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156 PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 PHILIPPINE ACADEMY OF OPHTHALMOLOGY

PHILIPPINE JOURNAL OF

Ophthalmology OCTOBER - DECEMBER 2004VOL. 29 • NO. 4

EDITOR IN CHIEF

Patricia M. Khu, MD, MSc

ASSOCIATE EDITORS

Romulo N. Aguilar, MD, PhD

Marissa N. Valbuena, MD, MHPEd

ASSISTANT EDITORS

Jessica Marie R. Abaño, MD

Ruben Lim Bon Siong, MD

Santiago A.B. Sibayan, MD, PhD

Jocelyn L. Sy, MD

Joseph Anthony J. Tumbocon, MD

Harvey S. Uy, MD

MANAGING EDITOR

Carlos G. Naval, MD

EDITORIAL BOARD

Romeo V. Fajardo, MD

FOUNDING EDITOR, PHILIPPINES

Romeo B. Espiritu, MD

PHILIPPINES

Salvador R. Salceda, MD

PHILIPPINES

Rossina Lydia A. Ramirez, MD, MHSc

PHILIPPINES

Roger W. Beuermann, PhD

SINGAPORE/USA

Donald Tan, MD, FRCS

SINGAPORE

The PHILIPPINE JOURNAL OF OPHTHALMOLOGY (PJO), the officialjournal of the Philippine Academy of Ophthalmology, aims toprovide a venue for exchange of ideas and information amongophthalmologists and other physicians. It publishes peer-reviewedreports of original clinical and laboratory investigations,epidemiological studies done in the Philippines and other countries,

major reviews of specific topics, evaluation of diagnostic and surgical techniques,treatment methods, latest updates, and controversial issues in ophthalmology.

Published quarterly, Number One of Volume One is dated January–March 1969.Entered as a third-class mail matter at the Manila Post Office on February 13, 1969.

Journal International Standard Serial Number: PHISSN 0031 - 7659. Vol. 29No.1, March 2004.

Copyright 2004. All rights reserved.

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PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 157 PHILIPPINE ACADEMY OF OPHTHALMOLOGY


Ophthalmology

EDITORIAL

158 The eye on neuro-ophthalmologyA PJO issue devoted to neuro-ophthalmology is one way ofupdating local ophthalmologistson these unusual and interestingcases that they may occasionallyencounter in clinical practice.

ORIGINAL ARTICLES

167 Comparison of three-point andsix-point diurnal intraocular-pressure curvesM L Lat-Luna, et al.

171 Single-setting treatment protocolfor diode-laser transcleralcyclophotocoagulationJ P M Lirio, et al.

175 Fine-needle aspiration biopsy: avaluable test for malignancy oforbital tumorsA M Castro, et al.

CASE REPORT

189 Methanol-induced bilateral opticneuropathyJ M Ranche, et al.

BRIEF REPORTS

193 Surgically induced necrotizingscleritis after a routineextracapsular cataract extractionM A T Eltanal-Pascual, et al.

195 Usher syndromeM E P Fermin, J L Sy

REVIEW 160

A close look at optic-nerve meningiomaAC Arnold

Meningiomas affecting the optic nerve mayalso arise from the optic canal, and from theoptic-nerve sheath itself within the orbit. Thisreview focuses on such primary optic-nerve-sheath tumors.

VOL. 29 • NO. 4 OCTOBER - DECEMBER 2004

CASE SERIES 178

Möbius sequence with varied strabismus presentations in FilipinopatientsA P D Santiago, C S J Uy

Patients with typical Möbius sequence may have varying strabismuspresentations despite bilateral VI cranial-nerve involvement. Standard strabismusmanagement principles apply. These patients require a multidisciplinary teamfor optimal care.

CASE REPORT 186

Optic-nerve compression by the internalcarotid artery as a cause of “unexplained”optic atrophyR C Kho

Compressive optic neuropathy due to directpressure by the adjacent ICA should beconsidered as a possible etiology of occult,progressive visual loss in an otherwise healthypatient.


This issue of the PHILIPPINE JOURNAL OF

OPHTHALMOLOGY (PJO) is devoted to neuro-ophthalmology, a subspecialty still considered “minor”in terms of research and clinical practice in thePhilippines. It features a guest article by Dr. AnthonyArnold of the Jules Stein Eye Institute of the Universityof California in Los Angeles, a three-time guest speakerin local meetings. In addition, the issue highlightsreports on cases rarely seen in a generalophthalmologist’s practice, albeit not that rare inneuro-ophthalmic practice. Though nearly all of thecases have received wider attention in foreignliterature, they have not been reported locally. A PJO

issue devoted to neuro-ophthalmology is one way ofupdating local ophthalmologists on these unusual andinteresting cases that they may occasionally encounterin clinical practice.

Two other issues in local neuro-ophthalmic practicewarrant a second look.

Ethambutol-related optic neuropathy: a resurgence?A recent report by Tamesis and associates1 suggested

an apparent increase in the incidence of ethambutol(EMB)-related optic neuropathy. While no figurescurrently demonstrate this “resurgence,” it is worthdiscussing local issues in this clinical condition. In thePhilippines, the internist and the ophthalmologist oftendo not work synergistically in the management ofpatients undergoing quadruple anti-Koch’s treatmentfor pulmonary tuberculosis (PTB). When patients startexperiencing visual problems, they seek an ophthalmo-logist rather than the internist who prescribed the drug.

The internist is consequently not made aware of theadverse visual effects of the drug regimen, and that optic-nerve toxicity is rare. The ophthalmologist is left withthe difficult task of explaining why the patient’s visiondeteriorated with the anti-Koch’s therapy. While theinternist was not at fault in prescribing the regimen forPTB, his failure to warn the patient of the potential visualside effects of the drugs can not be ignored. The randomsurvey by Tamesis of 30 physicians (internists, pulmono-logists, family physicians) showed that while all 30respondents were aware of the potential optic-nervetoxicity, not one briefed their patients on the potentialvisual side effects of the drug or referred them to anophthalmologist prior to therapy.1

We need local studies looking into the relationshipbetween ethambutol intake and toxic optic neuropathy.Local literature on the topic is scant;1-2 there is nopublished incidence of EMB-related optic neuropathy.

Citron summarizes the recommendations of theJoint Tuberculosis Committee of the British ThoracicSociety for the management of these patients in a 10-point set of guidelines as follows:3

1. Determine pretreatment renal function. EMBshould be avoided in patients with impaired renalfunction.

2. Do not exceed recommended dose or treat-ment duration.

3. Record any history of eye problem.4. Record pretreatment visual acuity (VA). Avoid

EMB in patients with poor vision who may not noticefurther reduction in VA.

5. Inform patients that EMB may affect vision. Thedrug should be discontinued immediately once visualsymptoms occur. Even though the risk of thishappening is small, advise patients to comply.

6. Record that patient has been informed aboutthe ocular toxicity.

7. Inform the general practitioner that patientshave been given these instructions.

The eye on neuro-ophthalmology


Ophthalmology OCTOBER - DECEMBER 2004VOL. 29 • NO.4

GUEST EDITORIAL

Correspondence to

Richard C. Kho, MD

15 General de Jesus St. Heroes Hill

Quezon City, Philippines

Tel.: +63-2-6360762

Fax: +63-2-6385837

E-mail: [email protected]

We need local studies looking into the relationship between ethambutolintake and toxic optic neuropathy. Local literature on the topic is scant;there is no published incidence of ethambutol-related optic neuropathy.


8. Refer patients complaining of ocular symptomsduring treatment to an ophthalmologist for a detailedeye examination. Discontinue EMB.

9. Routine VA testing during treatment is not recom-mended (they may not detect early ocular toxicity).

10. Avoid EMB in children too young for objectiveeye exams and in patients with language or commu-nication problems that would make assessment difficult.

Documenting the local incidence and clinical profileof EMB-related optic neuropathy will eventually allowus to recommend similar guidelines1 to the Departmentof Health to be issued not just for ophthalmologists,but more importantly for internists. The Neuro-ophthalmology Club of the Philippines seeks to takethe lead in future collaborative studies on this topic.

The Optic Neuritis Treatment Trial (ONTT):A decade hence, still unheeded

It has been more than a decade since the one-yearresults of the Optic Neuritis Treatment Trial (ONTT),a multicenter randomized clinical trial sponsored bythe United States National Eye Institute, were published.4

The results of the study became a set of guidelines forclinical practice in the US. The main objectives of thestudy were to evaluate the efficacy of corticosteroidtreatment of acute optic neuritis and to investigate therelationship between optic neuritis and multiple sclero-sis. The major conclusions were: treatment with high-dose intravenous corticosteroids followed by oralcorticosteroids accelerated visual recovery but did notprovide any long-term benefit to vision; treatment with“standard-dose” oral prednisone alone did not improvethe visual outcome and was associated with an increasedrate of new attacks of optic neuritis.

It is quite clear from this study that oral prednisonealone should be avoided in patients with optic neuritis.However, we still encounter patients with a presumeddiagnosis of optic neuritis given oral steroids byophthalmologists. One may contend that the resultsof the ONTT might not apply to local setting as theclinical profile of local optic-neuritis patients does notmirror that seen in North America where multiplesclerosis is a commonly associated finding.5 A study byFajardo et al. even suggested that infectious etiologiesmight be the major culprit in many local optic-neuritispatients.6 Nevertheless, the results of the ONTTcurrently stand as the widely accepted publishedguidelines for clinical practice. In this age of mal-practice suits, there is no stopping a patient from chal-lenging the management based on personal researchof available medical literature. True enough, this

author last year encountered a patient (diagnosed withoptic neuritis and given oral prednisone by a localneurologist) who pulled out a 10-page printout of theONTT results obtained via the Internet, and chal-lenged the management of his neurologist by seekinga second opinion for a possible malpractice suit.

A survey in US recently looked into some of the post-ONTT practices of ophthalmologists and neurologistsby mailing a questionnaire to a random sample of 987ophthalmologists and 900 neurologists.7 With a 47%response, the study found that nearly all ophthalmolo-gists and neurologists reduced the use of oral prednisonealone in the treatment of optic neuritis —substituting aregimen that included intravenous methylprednisolone(IVMP). A similar survey attempted locally two years agogenerated less than 10% response, and was subsequentlydiscontinued.

The Philippine Optic Neuritis Treatment Trial isunderway at the St. Luke’s Medical Center Institute ofOphthalmology. This study aims to compare theefficacy of IVMP (a 3-day regimen would roughly costtwo month’s salary for a minimum-wage worker) vs. IVdexamethasone, a less expensive and more affordableregimen in the local setting (a primary reason for thepersistence of prescribing oral prednisone might beits miniscule cost compared with IVMP). Pending theresults of this study, however, the Neuro-ophthalmologyClub of the Philippines encourages local ophthalmo-logists to be guided by the results of the ONTT.

—Richard C. Kho, MDDepartment of Ophthalmology

and Visual SciencesUniversity of the PhilippinesPhilippine General Hospital

Manila, PhilippinesFor the Neuro-ophthalmology Club

of the Philippines

References

1. Tamesis JM Jr., Cloma A, Bascara A. Ethambutol toxic optic neuropathy in the

Philippines. Neuro-ophthalmol Jpn 2002; 19: 261-266.

2. Inocencio FP, Castillo TR. Toxic optic neuropathy secondary to ethambutol.

Philipp J Ophthalmol 1999; 24: 65-68.

3. Citron KM, Thomas GO. Ocular toxicity from ethambutol. Thorax 1986; 41:

737-739.

4. Beck RW, Cleary PA. Optic neuritis treatment trial: one-year follow-up results.

Arch Ophthalmol 1993; 111: 773-775.

5. Inocencio FP, Kho RC, Cruz RD, Cabrera BG. The clinical profile of optic

neuritis: a five-year retrospective study of cases seen at the neuro-

ophthalmology clinic of the Philippine General Hospital. Philipp J Ophthalmol

2001; 26: 28-31.

6. Fajardo RV, Noche RR, Litao RE, DeCastro FD. Retrobulbar neuritis among

Filipinos. Philipp J Ophthalmol 1981; 13: 41-43.

7. Trobe JD, Sieving PC, Guire KE, Fendrick AM. The impact of the optic neuritis

treatment trial on the practices of ophthalmologists and neurologists.

Ophthalmology 1999; 106: 2047-2053.


REVIEW


Ophthalmology OCTOBER - DECEMBBR 2004VOL. 29 • NO. 4

Taking a close look atoptic-nerve meningioma

Anthony C. Arnold, MD

Jules Stein Eye InstituteDepartment of OphthalmologyUniversity of California, Los Angeles

Correspondence to

Anthony C. Arnold, MD

Jules Stein Eye Institute

100 Stein Plaza, UCLA

Los Angeles, CA 90095-7005

Tel.: +1 (310) 8254344

Fax: +1 (310) 2671918

Email: [email protected]

The author has no proprietary or financial interest in any

product used or cited in this study.

Keywords: Optic-nerve-sheath meningioma, Optic-nerve tumors, Optociliary shunt vessels, Opticglioma, Stereotactic radiosurgery, 3D conformal fractionated stereotactic radiotherapy

PHILIPP J OPHTHALMOL 2004; 29(4): 160-166 © PHILIPPINE ACADEMY OF OPHTHALMOLOGY

ABSTRACTMENINGIOMAS, the most common benign intracranial neoplasms, most

often involve the visual pathways in the parasellar and orbital regions, withcompression or infiltration of the optic nerves or chiasm. Parasellar tumorsmay arise anteriorly, from the anterior clinoid, planum sphenoidale, or olfac-tory groove; posteriorly, from the dorsum or tuberculum sellae; or laterally,along the sphenoid wing. Meningiomas affecting the optic nerve may alsoarise from the optic canal, and from the optic-nerve sheath itself within theorbit. This review focuses on such primary optic-nerve-sheath tumors.

PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 161PHILIPPINE ACADEMY OF OPHTHALMOLOGY

CLINICAL PRESENTATIONOPTIC-NERVE-SHEATH meningiomas present most

frequently in middle-aged women; 61% of affected patientsare female, with a mean age at presentation of 41 yearsand only 4% under 20 years (age range 2.5-78 years).1 Thetumor typically produces slowly progressive, painlessmonocular visual loss which is insidious and may proceedundetected until substantial loss has occurred. Bilateralinvolvement is present at onset in 6%, usually in youngerpatients. Up to 23%1 report transient visual loss lasting forseveral seconds prior to the development of persistent visualloss, presumably due to compromise of the optic-nervevasculature by tumor compression. Gaze-inducedamaurosis occurs rarely due to distortion of the optic-nervevasculature by the tumor mass in eccentric gaze. Visualloss is usually the only presenting symptom, althoughfullness and vague discomfort due to orbital congestionmay occur; headache is not common. Rarely, facial painand numbness may be present if the trigeminal nerve isinvolved. Diplopia may be associated, but usually developslate, with tumors large enough to affect cranial nerves orextraocular muscles at the orbital apex.

Clinical examination reveals a visual-field defectconsistent with optic-nerve damage. The most commonpattern is diffuse depression with central loss (Figure 1);focal central scotomas and arcuate patterns are lessfrequent. Rarely, inferior altitudinal loss may result fromupward compression of the superior surface of the opticnerve against the falciform ligament at the proximal endof the optic canal. While this pattern of field loss maysuggest anterior ischemic optic neuropathy (AION), theusually slowly progressive visual loss and diffuse opticatrophy (as opposed to the acute loss with disc edema seenin AION) should raise suspicion for a compressive lesionat the optic canal. Visual acuity is decreased in 95%,1 andan afferent pupillary defect is nearly always seen. Proptosisis present in roughly 65%,1 but may not be evident untilsome time after visual loss. Optic-nerve-sheath tumors, dueto their intimate involvement with the nerve, may affectfunction early, before tumor volume is large enough toproduce noticeable proptosis. Ocular motility may becompromised either by direct mechanical involvement ofthe extraocular muscles by tumor mass, or by involvementof cranial nerves III, IV, or VI at the orbital apex; it isgenerally a late finding. Eyelid position is most oftennormal. Ptosis is occasionally present, but retraction isunusual and should prompt consideration of thyroid-related orbitopathy.

The optic disc most commonly is atrophic (49%), butmay be edematous (48%), or normal in appearance (3%);atrophy and edema may coexist.1 Typically, lesions at theorbital apex produce progressive optic atrophy withoutdisc edema, while more anteriorly located tumors result

Figure 1. Automated quantitative perimetry in a case of optic-nerve-sheath meningioma,

left eye, with generalized depression, worse nasally.

Figure 2. Color fundus photograph shows optic-disc edema and atrophy, with optociliary

shunt vessels (retinochoroidal collateral vessels) visible at the 8 and 12 o’clock positions.

(Reprinted, with permission, from Arnold AC, Focal Points: Clinical Modules for

Ophthalmologists, “Optic-Nerve Meningioma,” San Francisco: American Academy of

Ophthalmology; 2004.)

in optic-disc edema early, and may even be associated withcentral retinal-vein occlusion. Occasionally, the tumor mayinvade the optic-nerve head itself, with cellular infiltratevisible on the disc surface. Optociliary shunt vessels(retinochoroidal collateral vessels) are visible on the discsurface in about one third of patients, a reflection ofchronic compression and obstruction of central retinalvenous outflow; they may be present in atrophic or edema-tous optic discs (Figure 2). The clinical triad of visual loss,optic atrophy, and optociliary shunt vessels is the classicpresentation of optic-nerve-sheath meningioma.

DIFFERENTIAL DIAGNOSISThe differential diagnosis of optic-nerve-sheath

meningioma includes inflammatory, ischemic, infiltrative,and compressive etiologies.


Figure 4. MR orbital images in optic-nerve glioma, illustrating involvement of both sheath

and nerve substance without distinction between the two. Axial view (A), coronal view (B).

A

B

Figure 3. MRI of optic neuritis, with axial view demonstrating enhancement of the optic-

nerve substance without sheath involvement.

The most common inflammatory syndrome, demye-linative optic neuritis, presents with acute or subacute visualloss associated with pain, particularly on eye movement(92% in the Optic Neuritis Treatment Trial).2 Visual losstypically begins to recover in 2 to 3 weeks and most patientsregain excellent acuity within 3 to 4 months; graduallyprogressive painless visual loss (as occurs in optic-nervemeningiomas) is distinctly unusual. Neuroimaging showsenhancement and enlargement of the optic nerve, butthe sheath is not preferentially involved, as it is in menin-gioma (Figure 3).

Atypical optic neuritis, such as that associated withsarcoidosis, vasculitis (lupus), or specific infections(syphilis), may resemble optic-nerve-sheath meningiomain its presentation, with more gradual onset, variabledegree of pain, and slower or absent recovery of vision.

Sarcoid optic neuropathy, in particular, may demonstrateclinical and neuroradiologic features that are indis-tinguishable from meningioma.3 The presence of ocularinflammation such as uveitis and periphlebitis may aid indistinction. Selected patients may require systemicevaluation for granulomatous inflammation.

Orbital inflammatory disease (orbital pseudotumor) mayinvolve the optic nerve; it is almost always painful andusually shows features of external inflammation such aslid edema and conjunctival injection as well as proptosis.4

Neuroimaging usually shows signs of orbital fat and some-times extraocular muscle involvement with the inflam-matory process.

Ischemic optic neuropathy also typically presentsacutely, though without pain, and often shows segmentaldisc edema and altitudinal visual-field loss. It may be prog-ressive initially, but most often stabilizes within 4 to 6 weeks.

Infiltrative and compressive optic neuropathies aremore difficult to differentiate clinically from meningiomain that they may also cause gradually progressive visualloss, often with mild proptosis. Neuroimaging, however,provides clear differentiation of these entities. Orbitalinfiltrative processes such as lymphoma may affect theoptic nerve, but usually show more diffuse involvementof the orbital fat and extraocular muscles on neuro-imaging. Discrete orbital tumors of any origin maycompress the nerve extrinsically but are readily visualizedas distinct from the optic-nerve sheath. Disorders produc-ing extraocular muscle enlargement, especially thyroid-related orbitopathy, may result in proptosis and optic-nerve compression. Eyelid retraction and lid lag may betipoffs to this diagnosis. Sphenoid wing meningiomas,particularly in the medial portion, may present with


frequently associated with anterior (adjacent to the globe)or posterior (orbital apex) focal expansion (Figure 5).The increased size primarily represents thickening of theoptic-nerve sheath itself, though the optic-nerve paren-chyma may be infiltrated as the tumor grows. Sheathinvolvement is usually distinguishable from the nervesubstance as a bright, enhancing outline surrounding therelatively spared, less bright central nerve substance (so-called “tram-track” appearance on fat-suppressed axialviews (Figure 5), allowing differentiation from the diffuse,full-thickness involvement of both nerve and sheath tissuewith optic glioma (Figure 4). The type of kinking andbuckling of the nerve seen with glioma (Figure 6) isdistinctly unusual in meningioma. A focal cystic region

proptosis and gradually progressive optic neuropathy.Finally, primary optic-nerve tumors, most commonlyglioma, may masquerade as meningioma (Figure 4). Whilegliomas usually present in childhood, they may appear inyoung to middle-aged adults, and often are more aggres-sive at this age, with progressive visual loss over months.In all these entities, although the clinical presentation maymimic that of optic-nerve meningiomas, the neuroradiolo-gic features of each are characteristic, and aid in diagnosis.

In general, biopsy for tissue diagnosis is unnecessary andmay be detrimental. Full thickness biopsy is blinding, andpartial thickness or sheath biopsy, which may spare remain-ing vision, may be misleading, as arachnoidal proliferationsurrounding an optic- nerve glioma may be misdiagnosedas meningioma. In general, tissue biopsy is reserved foratypical cases in which an alternate diagnosis, such asmalignant glioma or sarcoid optic-nerve infiltration, issuspected on the basis of unusually rapid progression oratypical associated findings such as ocular inflammation.Neuroimaging is sufficient for diagnosis in most cases.5

NEURORADIOLOGIC FEATURESOptic-nerve-sheath meningiomas have a distinctive

radiologic appearance usually sufficient for specificdiagnosis;6 however, routine brain images, whethercomputed tomography (CT) or magnetic resonanceimaging (MRI), are inadequate to visualize the details ofthe optic nerve along its entire course. MRI of theparasellar region, with thin-section (1.5 mm) orbit views,utilizing fat-suppression technique and gadoliniumadministration, is essential for this purpose. Meningiomastypically demonstrate tubular, diffuse enlargement of theoverall diameter of the optic-nerve sheath/nerve complex,

Figure 5. “Tram-track sign” in meningioma (A), axial orbit MR image, with thickening and enhancement of the left optic-nerve sheath surrounding a relatively normal, darker optic-nerve

substance. “Ring sign” in meningioma (B), coronal orbit MR image shows similar sheath enhancement surrounding relatively normal, darker optic-nerve substance.

BA

Figure 6. CT axial view in glioma, with kinking of the tumor and cystic spaces within its

substance.


(perioptic cyst) may be present, often near the globe andsurrounding the nerve substance, representing a collect-ion of CSF presumably trapped by tumor obstruction offlow within the sheaths. This cystic component differs fromthe cystic spaces within gliomas, which are the result ofmucinous degeneration within the nerve substance itself(Figure 6). In more aggressive meningiomas, extraduralextension may produce an irregular, sometimes fluffy,margin representing breakthrough into the adjacentorbital fat. Meningiomas tend to be isointense or slightlyhyperintense relative to brain on both CT and MRI (T1and T2), and enhance prominently with contrast. This isanother point of distinction from gliomas, which may behyperintense on T2, and in some cases do not enhance asbrightly with contrast. The pattern of intracranialextension of meningioma also differs from that of glioma.Meningioma extension proceeds along the dura of theoptic canal and onto the planum sphenoidale, oftenanterior to the optic nerve and chiasm. There may belocalized nodular expansion of tumor, which extendssuperiorly into brain substance and away from the nerveitself. Glioma, on the other hand, extends intrinsicallywithin the nerve substance, expanding it along its course,which may include the chiasm and optic tract.

Several features are best demonstrated on CT: 5 up to50% of meningiomas may show calcification within theirsubstance, with an encircling band around the affectedportion of the nerve (noncontrast views are necessary tovisualize this pattern); adjacent bone, particularly the opticcanal or anterior clinoid process, may show hyperostosis;and finally, in rare cases, pneumosinus dilatans,7 a condi-tion in which enlarged, air-filled posterior ethmoid andsphenoid sinuses adjacent to tumor may be the first signof a meningioma, when the intracanalicular tumor is stilltoo small for detection.

HISTOPATHOLOGYMeningiomas of the optic-nerve sheath are thought to

arise from meningothelial “cap cells” lining the arachnoidvilli of the intracanalicular and intraorbital optic-nervemeninges. They tend to assume either (a) the meningo-thelial, or syncytial, pattern of sheets of polygonal cellswith interspersed vascular trabeculae, or (b) the transi-tional pattern, in which spindle or oval cells are arrangedin whorls and psammoma bodies are more common.Angioblastic and fibroblastic forms are usually seen onlyin primary intracranial tumors. The tumors proliferatewithin the subarachnoid space, often infiltrate the optic-nerve substance along pial septae and perivascular spaces,and may invade and extend through the dura into sur-rounding orbital tissues. They may invade bone, incitinghyperostosis and bony proliferation. They may extendintracranially to the chiasm and across the planum

sphenoidale to the contralateral optic nerve, but they donot tend to invade other brain structures. Tumors mayarise at multiple sites simultaneously, and thus it may bedifficult to assess whether large areas of involvement resultfrom spread from a single lesion or multiple separateorigins. Growth of the tumor compresses optic-nerveaxons, with resultant direct damage, as well as secondaryischemic damage due to obliteration of the pial vascularsupply.

NATURAL HISTORYUntreated, optic-nerve-sheath meningiomas generally

grow slowly, with gradually progressive loss of vision inthe affected eye over years, estimated in one series at 1 to3 Snellen lines acuity loss per year.8 The tumors do notmetastasize and only rarely invade the brain parenchyma;the mortality rate is essentially nil.9 The primary riskrelated to growth is that of visual loss, either in the affectedor the contralateral eye, the latter via spread along theplanum sphenoidale. There have been no reported casesof spread to the contralateral optic nerve from tumor thatpresented initially with involvement limited to one orbit.10

Canalicular tumors, however, show a higher rate ofbilaterality. Approximately 15% of these cases demonstrateextension of the tumor intracranially at presentation, andthe risk of growth to involve the contralateral nerve inthis instance is estimated at 2 to 4%.1

Alper11and Wright, et al.12 have both proposed thatoptic-nerve-sheath meningiomas in children tend to bemore aggressive, with higher recurrence and mortalityrates. Alper reported that 4 of 15 cases died with intra-cranial extension on follow-up. However, Dutton reportedthat deaths in this series resulted from operative compli-cations and late-onset secondary intracranial tumors—notthe original tumors—suggesting that the evidence formore aggressive course in children was inconclusive.1

Nevertheless, more careful observation of children forevidence of rapid growth seems appropriate. Additionally,investigation for evidence of neurofibromatosis (NF) inchildren presenting with sheath meningioma is indicated.As with optic gliomas (29%), the incidence of NF in casesof meningioma (12%) is higher than in the generalpopulation (0.05%).13 Conversely, 15% of NF patients areestimated to develop optic glioma;14 development of optic-nerve meningioma is less common, though precise figuresare not available. The influence of associated NF onclinical course of optic-nerve meningioma is uncertain.

TREATMENTTreatment options have included observation, surgical

excision of sheath tumor, surgical excision of sheath tumorand optic nerve, optic-nerve-sheath decompression, optic-canal decompression, hormonal therapy, standard


(fractionated) external beam radiotherapy, stereotactic(gamma knife, nonfractionated) radiosurgery, and morerecently, 3D conformal stereotactic (fractionated) radio-therapy. Surgical excision of tumor alone (preservingoptic-nerve tissue) has been attempted in anteriorlylocated extrinsic tumors, with occasional initial benefit,but in general, stripping of tumor from the optic nervecarries a high risk of sacrificing the pial circulation to thenerve, with loss of vision and incomplete tumor removal.15

Optic-nerve-sheath decompression has been attemptedin order to delay visual loss by reducing perineural pres-sure, but the procedure provides egress for tumor cells,and intraorbital spread and recurrence have been asso-ciated with this approach.1 Optic-canal decompression hasbeen proposed for certain intracanalicular tumors, againin an attempt to temporize and maintain vision byreducing compression without tumor removal. Very littlelong-term follow-up data are available for either of theseapproaches. Hormonal therapy has also been attemptedbased on initial observations that meningioma growth wasrelated to menstrual cycle and pregnancy, and later labora-tory evidence that meningioma cell growth could be inhi-bited by both progesterone (mifepristone) and estrogen(mepitiostane) antagonists. Mifepristone (RU-486) hasbeen the most extensively studied, primarily in unresec-table central-nervous-system (CNS) meningiomas,16 butthere are little data for effectiveness.

Surgical therapy of optic-nerve-sheath meningioma,with excision of tumor and optic nerve en bloc, has beenthe primary method of intervention to prevent spread tothe contralateral optic nerve or chiasm.12 There is no bene-fit to the affected eye, as therapy is blinding; there isgenerally no benefit to overall neurologic status andsurvival, as there is virtually no risk of other CNS or syste-mic involvement from the tumor. Surgical interventiontypically is only considered in the face of progressive visualloss, but the timing of intervention remains controversial.Some authors advocate early surgery if the tumor is limitedto the orbit, particularly anteriorly, as this situation affordsthe best opportunity for complete resection, possiblywithout the need for an intracranial approach. Otherspropose observation in this situation, as there is essentiallyno risk of extension to the contralateral nerve, and surgerymay be avoided entirely if the tumor is found to beindolent. The value of this approach is underscored by areport of Arnold et al.,10 demonstrating histopathologicevidence of meningioma cells at the chiasm in a case inwhich meningioma appeared on neuroimaging to belimited to the orbit, and which was nonprogressive overyears; a surgical approach was unnecessary in the face ofclinical stability and would have been ineffective toeliminate meningioma cells regardless. Many authorssuggest surgical excision for tumors presenting with

intracranial extension, but in the face of a small, stabletumor, which is not threatening the contralateral opticnerve, we typically recommend observation only.

Radiation therapy (standard external beam irradiation)of optic-nerve-sheath meningiomas was proposed by Smithin 198117 and was reported in isolated cases subsequentlythrough 1992, with 9 of 12 cases showing visual improve-ment, in some cases dramatically [from hand movement(HM) to 20/70 in Smith’s case, from counting fingers (CF)to 20/60 in another). The proximity of the sheath to intactoptic-nerve tissue and in some cases the infiltration oftumor into the nerve substance, however, creates risk ofradiation necrosis of the nerve, although meaningful dataon complication rates are lacking due to small numbersand limited follow-up. The development of stereotactictechniques has enabled better localization of radiationdose and sparing of surrounding tissues. Stereotacticradiosurgery (gamma knife) has been utilized withsubstantial benefit in CNS tumors, but the very high doseof radiation administered over a short time periodpotentially increases the risk of optic-nerve radionecrosis.Optic neuropathy has been reported in roughly 10% ofcavernous sinus meningiomas treated by this technique.18

Although a recent study by Stafford et al.19 reported anincidence of 2% for parasellar tumors, the risk for primaryoptic-nerve-sheath meningiomas, in which the tumor isintimately involved with the optic nerve, is felt to besubstantially higher; this modality is not frequently utilizedfor sheath tumors.

In recent years, 3D conformal stereotactic radiotherapyhas become the first option for cases requiring therapy.20

This technique, using fractionated rather than single-dosestereotactic techniques and intensity modulation to limitdose to surrounding tissue, has substantially improvedtherapeutic results. Multiple reports document visualimprovement in cases with previously progressive visualloss, and radionecrosis has been a rare occurrence evenwith prolonged follow-up.21-27 In cases with useful butdeteriorating vision or in which there is neuroimagingevidence of tumor growth toward the contralateral opticnerve, this is currently the preferred treatment. Thedecision whether to treat cases presenting initially withminimal or no intracranial spread and without progressivevisual loss remains controversial.

A recent large-scale multicenter study by Turbin et al.28

retrospectively reviewed the visual outcome and compli-cation rates for various therapeutic options, includingobservation, surgery only, radiotherapy only, and surgerywith radiotherapy. The series predated the developmentof the 3D conformal stereotactic technique. Patientsreceiving radiotherapy only demonstrated a significantlybetter visual acuity at follow-up than all other groups, withlower complication rate than cases that included surgical


therapy. While the study had limitations, it confirmed therecommendation that fractionated radiotherapy beconsidered as initial therapy in patients with useful vision.

MANAGEMENT GUIDELINESManagement of optic-nerve-sheath meningiomas

requires consideration of the patient’s age, visual function,degree of tumor extension, and the demonstrated clinicaland radiologic course (aggressive growth versus stability).Clinical examinations with visual acuity, visual field, andfundus evaluations at three- to six-month intervals arerecommended during the first 1 to 2 years, increasing theinterval to yearly if examinations are stable. MRI of thebrain with orbit-specific views using fat-suppressiontechnique and contrast administration is repeated at 6months, then yearly if stable.

Tumor limited to orbitIf useful vision is present and tumor is stable, obser-

vation alone is the usual first option. We currently reservetherapy for evidence of severe initial visual loss, progressivevisual loss, or tumor extension toward the contralateraloptic nerve on neuroimaging. If no useful vision remains,surgical excision has been the standard of care, althoughwith the advent of 3D conformal stereotactic radiation,consideration is now given to this modality to prevent prog-ression without the need for surgical intervention, particu-larly in view of the lack of evidence of reported spread tothe contralateral optic nerve in these cases.

Tumor with intracranial extensionSurgical excision has been proposed in the past for all

cases with intracranial extension, but more conservativeapproaches are now more common. If useful vision ispresent, intracranial extension is limited (not encroachingon the planum sphenoidale), and tumor is stable,observation alone is an option, although with the adventof 3D conformal stereotactic radiation, we advocate itsearly use in this situation. It is certainly indicated if thereis evidence of progressive visual loss or neuroimagingevidence of growth. With poor vision and intracranialextension with growth, most experts recommend surgicalexcision.

For any case, intraorbital or intracranial, in which pres-ervation of vision is possible, the use of 3D conformal ste-reotactic radiation must be considered as a primarytherapy; however, in all such cases, regardless of visual levelor clinical course, therapy must be selected on an indi-vidual basis.29 In all cases, age and general health of thepatient must be considered. Elderly or otherwise frailpatients may be poor surgical risks and more likely to becandidates for radiation or for observation only, whilechildren, in which the long-term risk for development of

References

1. Dutton JJ. Optic-nerve-sheath meningiomas. Surv Ophthalmol 1992; 37: 167-183.

2. Beck RW, Cleary PA, Anderson MM, and the Optic Neuritis Study Group. A

randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis.

N Engl J Med 1992; 326: 581-588.

3. Ing EB, Garrity JA, Cross SA, et al. Sarcoid masquerading as optic-nerve-sheath

meningioma. Mayo Clin Proc 1997; 72: 38-43.

4. Dutton JJ, Anderson RL. Idiopathic inflammatory perioptic neuritis simulating optic-

nerve-sheath meningioma. Am J Ophthalmol 1985; 100: 424-430.

5. Jakobiec FA, Depot MJ, Kennerdell JS, et al. Combined clinical and computed

tomographic diagnosis of orbital glioma and meningioma. Ophthalmology 1984;

91: 137-155.

6. Lindblom B, Truwit CL, Hoyt WF. Optic-nerve-sheath meningioma. Definition of

intraorbital, intracanalicular, and intracranial components with magnetic resonance

imaging. Ophthalmology 1992; 99: 560-566.

7. Hirst LW, Miller NR,Hodges III FJ, et al. Sphenoid pneumosinus dilatans. A sign of

meningioma originating in the optic canal. Neuroradiology 1982; 22: 207-210.

8. Sibony PA, Krauss HR, Kennerdell JS, et al. Optic-nerve-sheath meningiomas.

Clinical manifestations. Ophthalmology 1984;91:1313-1326.

9. Egan RA, Lessell S. A contribution to the natural history of optic-nerve-sheath

meningiomas. Arch Ophthalmol 2002; 120: 1505-1508.

10. Arnold AC, Hepler RS, Badr M, et al. Metastasis of adenocarcinoma of the lung to

optic-nerve-sheath meningioma. Arch Ophthalmol 1995; 113: 346-351.

11. Alper MG. Management of primary optic-nerve meningiomas. J Clin Neuro-

ophthalmol 1981; 1: 107-117.

12. Wright JE, McNab AA, McDonald WI. Primary optic-nerve-sheath meningioma. Br

J Ophthalmol 1989; 73: 960-966.

13. Dutton JJ. Optic-nerve gliomas and meningiomas. Neurol Clin 1991; 9: 163-177.

14. Lewis RA, Gerson LP, Axelson KA et al. Von Recklinghausen neurofibromatosis. II.

Incidence of optic gliomata. Ophthalmology 1984; 91: 929-935.

15. Kennerdell JS, Maroon JC, Malton M, et al. The management of optic-nerve-sheath

meningiomas. Am J Ophthalmol 1988; 106: 450-457.

16. Grunberg SM, Weiss MH, Spitz IM, et al. Treatment of unresectable meningiomas

with the antiprogesterone agent mifepristone. J Neurosurg 1991; 74: 861-866.

17. Smith JL, Vuksanovic MM, Yates BM, et al. Radiation therapy for primary optic-

nerve meningiomas. J Clin Neuro-ophthalmol 1981; 1: 85-89.

18. Girkin CA, Comey CH, Lunsford LD, et al. Radiation optic neuropathy after

stereotactic radiosurgery. Ophthalmology 1997; 104: 1634-1643.

19. Stafford SL, Pollock BE, Leavitt JA, et al. A study on the radiation tolerance of the

optic nerves and chiasm after stereotactic radiosurgery. Int J Radiation Oncology

Biol Phys 2003; 55: 1177-1181.

20. Eng TY, Albright NW, Kuwahara G, et al. Precision radiation therapy for optic-nerve-

sheath meningiomas. Int J Radiat Oncol Biol Phys 1992; 22: 1093-1098.

21. Lee AG, Woo Sy, Miller NR, et al. Improvement in visual function in an eye with a

presumed optic-nerve-sheath meningioma after treatment with three-dimensional

conformal radiation therapy. J Neuroophthalmol 1996; 16: 247-251.

22. Fineman MS, Augsburger JJ. A new approach to an old problem. Surv Ophthalmol

1999; 43: 519-524.

23. Klink DF, Miller NR, Williams J. Preservation of residual vision 2 years after

stereotactic radiosurgery for a presumed optic-nerve-sheath meningioma. J

Neuroophthalmol 1998; 18: 117-120.

24. Moyer PD, Golnik KC, Breneman J. Treatment of optic-nerve-sheath meningioma

with three-dimensional conformal radiation. Am J Ophthalmol 2000; 129: 694-696.

25. Andrews DW, Faroozan R, Yang BP, et al. Fractionated stereotactic radiotherapy

for the treatment of optic-nerve-sheath meningiomas: preliminary observations of

33 optic nerves in 30 patients with historical comparison to observation with or

without prior surgery. Neurosurgery 2002; 51: 890-904.

26. Narayan S, Cornblath WT, Sandler HM, et al. Preliminary visual outcomes after

three-dimensional conformal radiation therapy for optic-nerve-sheath meningioma.

Int J Radiat Oncol Biol Phys 2003; 56: 537-543.

27. Pitz S, Becker G, Schiefer U, et al. Stereotactic fractionated irradiation of optic-

nerve-sheath meningioma: a new treatment alternative. Br J Ophthalmol 2002; 86:

1265-1268.

28. Turbin RE, Thompson CR, Kennerdell JS, et al. A long-term visual outcome

comparison in patients with optic-nerve-sheath meningioma managed with

observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology

2002; 109: 890-900.

29. Miller NR. Radiation for optic-nerve-sheath meningiomas: is this the answer?

Ophthalmology 2002; 109: 833-834.

secondary malignancies with radiation therapy is greater,may be more likely candidates for surgery. Finally, surgi-cal excision in cases with poor vision may be consideredfor disfiguring proptosis or intractable pain.


ORIGINAL ARTICLE



Comparison of three-pointand six-point diurnal

intraocular-pressure curves

Ma. Margarita L. Lat-Luna, MDPaul I. Guerrero, MDJohn Vincent Policarpio D. Flores, MD, MS Epi

Department of Ophthalmology and Visual SciencesUniversity of the Philippines Philippine General HospitalManila

Correspondence to

Ma. Margarita Lat-Luna, MD

Department of Ophthalmology and Visual Sciences

University of the Philippines Philippine General Hospital

Taft Avenue, Ermita

1000 Manila, Philippines

Tel. +63-2-5218450 ext. 2174

Telefax +63-2-5210007

E-mail [email protected]

The authors have no proprietary or financial interest in

any product used or cited in this study.

ABSTRACT

ObjectiveThis study determined if three-point and six-point diurnal intraocular-

pressure (IOP) curves are comparable in terms of sensitivity, specificity, andaccuracy in detecting swings in IOP measurements of 6 mm Hg or higher.

MethodsThis is a retrospective cross-sectional study of 214 glaucoma patients (428

eyes) who underwent six-point diurnal IOP testing. The investigators reviewedtheir records and generated two sets of data—one for six-point and another forthree-point IOP measurements. Diurnal curves were constructed andcompared for each set of measurements using univariate analysis of variance.

ResultsThere was no statistically significant difference (p < .001) between three-

point and six-point IOP measurements in detecting IOP swings of 6 mm Hgor higher. The three-point determination has a comparable sensitivity of 70.9%,specificity of 100%, and accuracy of 87.6%. However, there is a likelihood forthe IOP change to be underestimated by 1.2 mm Hg in a three-pointdetermination.

ConclusionThe three-point determination (9 p.m., 1 p.m., and 5 p.m.) produces a

diurnal curve similar to that of a six-point determination and can be used as atool in detecting IOP swings in glaucoma patients.

Keywords: Intraocular pressure, Diurnal curve, Six-point determination, three-point determination,IOP swing



THE DETERMINATION of diurnal intraocular-pressure(IOP) curve, or phasing, is indispensable in the diagnosisand monitoring of patients with normal-tension glaucomaand ocular hypertension, patients with suspicious lookingdiscs without apparent IOP elevation, and diagnosed glau-coma patients who show progressive nerve damage despiteapparent control of IOP in the clinic.

The best method of detecting peaks in diurnal curvesis a 24-hour inpatient IOP monitoring. Initially, this wasdone to determine the diurnal curve in normal andglaucomatous patients.1-6 It also provides an accuratemeasure of the effectiveness of therapy because compli-ance is ensured.7-10 It is, however, not practical in theclinical setting as it interferes with sleep, and the hospitalenvironment is thought to influence or alter themagnitude of physiologic IOP variation in some patients.IOP was found to be significantly lower in hospitalizedpatients because of inactivity.11 An alternative is a phasingprocedure wherein IOP is measured at regular intervalsduring clinic hours.12 This was found to be adequate indetecting peak IOP and IOP swings.

At the University of the Philippines-Philippine GeneralHospital (UP-PGH) glaucoma clinic, the diurnal curve isdetermined by measuring the IOP at six points—every 2hours during clinic hours from 7 a.m. to 5 p.m. Severalclinical studies have shown that the probability of pressurepeaks occurring during this period ranges from 64 to80%.13-17 Clinical trials on newer topical antiglaucomamedications were done using this mode of diurnal-curvedetermination.18, 19 However, it is still tedious for patientswho have to stay in the clinic for prolonged periods.This artificial environment may also result in an under-estimation of the true IOP curve.

Some clinicians use a modified office-phasing proce-dure by taking the IOP at longer intervals and allowingpatients to leave the office while waiting for the next deter-mination. Although more practical because it does notrequire drastic modification of patient activity, the clinicalusefulness of this method needs to be evaluated. It is

important to assess whether modified phasing wouldproduce a diurnal curve comparable to that of standardphasing.

This study compared the diurnal IOP curves generatedfrom a three-point IOP measurement (modified officephasing) with a six-point IOP measurement (standardoffice phasing) from the same set of patients. Wedetermined the sensitivity, specificity, and accuracy of themodified office-phasing procedure in detecting IOPswings of 6 mm Hg or higher.

METHODOLOGYAll patients who were subjected to a six-point IOP deter-

mination (7 a.m., 9 a.m., 11 a.m., 1 p.m., 3 p.m., 5 p.m.)at the PGH glaucoma clinic from January 2000 to August2001 were included in the study. Inclusion criteria wereas follows: glaucoma suspects, normal-tension glaucoma,ocular hypertension, primary and secondary open-angleglaucoma, primary and secondary angle-closure glau-coma, with or without medications, pre- or postsurgery.Patients without any record of phasing procedure wereexcluded.

The investigators reviewed the records of the eligiblepatients. A precoded data collection tool was made toaddress the study objectives. Data gathered included age,sex, angle type, medications, surgical procedures, date ofphasing, and IOP measurements for both eyes. These wereentered into a computer database along with the six-pointapplanation tonometry (Goldmann, Haag-Streit, Bern,Switzerland) readings. A separate set of data taking onlythree of the six readings (9 a.m., 1 p.m., and 5 p.m.) wasconstructed. The corresponding diurnal curves weregenerated for each patient. Figure 1 shows a samplediurnal curve from a six-point IOP determination whileFigure 2 shows its derived three-point curve.

The significant IOP swing was defined as a differenceof 6 mm Hg or higher between the highest and lowestIOP value detected by each method of diurnal IOP-curvedetermination.

Figure 2. Sample diurnal IOP curve from three-point determination.

50 ----------------------------------------------------------------------------------------------------------------

40 ----------------------------------------------------------------------------------------------------------------

30 ----------------------------------------------------------------------------------------------------------------

20 ----------------------------------------------------------------------------------------------------------------

10 ----------------------------------------------------------------------------------------------------------------

0 ----------------------------------------------------------------------------------------------------------------

Intr

aocu

lar

Pre

ssure

7 a.m. 9 a.m. 11 a.m. 1 p.m. 3 p.m. 5 p.m.

Time

•

•

•

50 ----------------------------------------------------------------------------------------------------------------

40 ----------------------------------------------------------------------------------------------------------------

30 ----------------------------------------------------------------------------------------------------------------

20 ----------------------------------------------------------------------------------------------------------------

10 ----------------------------------------------------------------------------------------------------------------

0 ----------------------------------------------------------------------------------------------------------------

Figure 1. Sample diurnal IOP curve from six-point determination.

Intr

aocu

lar

Pre

ssure

7 a.m. 9 a.m. 11 a.m. 1 p.m. 3 p.m. 5 p.m.

Time

•

••

•

••


Univariate analysis of variance (p = .01) was used todetermine whether the curve produced by a three-pointdetermination would approximate that of a six-pointdetermination. The sensitivity, specificity, and accuracywere also determined. Kappa statistics were computed todetermine whether the results were due to chance alone.Pearson correlation coefficient was determined toestablish linearity of the relationship between the twodiurnal curves.

RESULTSA total of 214 patients (428 eyes) ages 10 to 88 years

(mean of 61), 55.6% female, was included in the study.66.8% had open-angle glaucoma, 9.3% angle-closure, and23.8% intermittent angle-closure glaucoma. 37.9% of theright and 42.1% of the left eyes were on medications. Morethan half of the right(55.6%) and left (52.3%)eyesunderwent glaucoma surgery.

Table 1 shows the mean and standard deviation of thedifferent IOP measurements in a six-point determination.Table 2 shows the range of IOP swings at each measurement.

There is no statistically significant difference (p < .001)in the ability of each method in determining IOP swingsof 6 mm Hg or higher. The three-point determinationshowed sensitivity of 70.9%, specificity of 100%, andaccuracy of 87.6% (Table 3). The kappa value was 0.74and Pearson correlation coefficient was 0.98.

DISCUSSIONAlthough IOP is not the only risk factor for the prog-

ression of optic neuropathy in glaucoma, it is currentlythe only factor that can be controlled. Studies have shownthat the degree of IOP fluctuation contributes significantlyto optic-nerve-damage progression more than the levelof IOP at a particular office visit. Gonzales et al. reportedthat significant IOP fluctuations occurred in 64% of caseswho developed visual- field loss.20 Asrani et al.21 showedthat in glaucoma patients with office IOP in the normalrange, large fluctuations in diurnal IOP are risk factorsfor progression independent of parameters obtained inthe office. The Advanced Glaucoma Intervention Study22

unraveled the protective role of persistently low IOP invisual-field deterioration. Therefore, the documentationof IOP fluctuation plays a vital role in the management ofglaucoma patients. This is achieved through diurnal IOP-curve determination.

Univariate analysis of variance for the two sets of datashowed a statistically significant similarity in the curves.There is a strong positive correlation (r = 0.98) betweenthe two curves. However, there is a likelihood for the IOPchange to be underestimated by 1.2 mm Hg in a three-point determination.

The sensitivity, specificity, and accuracy of the three-

point IOP determination are fairly accurate in detectingIOP swings of 6 mm Hg or more. Its kappa value was verygood, indicating that the similarity between the two curveswas not due to chance.

The results of this study are consistent with those instudies using conventional office diurnal measurements.Collectively, these studies showed that the probability ofpressure spikes during office hours (8 a.m. to 5 p.m.)ranged from 64% to 80% (Table 4), and stressed theimportance of varying office visits to detect these IOPswings. From these different office visits wherein the IOPswere taken at different times of the day, a diurnal curvecan be constructed, providing additional information on

Table 1. Mean IOP at each time period in a six-point determination.

Time

7 a.m.

9 a.m.

11 a.m.

1 p.m.

3 p.m.

5 p.m.

Right Eyes (n = 214) Left Eyes (n = 214)

15.68 ± 7.14 14.75 ± 5.46

15.56 ± 7.12 14.56 ± 5.50

15.15 ± 7.59 14.13 ± 5.27

15.58 ± 8.19 14.24 ± 5.58

14.94 ± 7.37 14.10 ± 5.56

14.46 ± 6.39 13.87 ± 5.39

Time

7 a.m.

9 a.m.

11 a.m.

1 p.m.

3 p.m.

5 p.m.

Table 2. Range of IOP swings (mm Hg) at each time period in a six-point

determination.

Right Eyes (n = 214) Left Eyes (n = 214)

0-12 5-12

0-14 4-10

0-10 1-12

0-12 3-12

1-12 3-12

0-12 3-12

Six-Point

Determination

IOP Swing

≥ 6mm Hg

129

53

182

Three-Point

Determination IOP

Swing Positive

Three-Point

Determination IOP

Swing Negative

Total

Six-Point

Determination

IOP Swing

< 6mm Hg

0

246

246

Total

129

299

428

Table 3. Two-by-two table for three-point determination.

Table 4. Probability of IOP swings in studies using conventional office

phasing.

Study

David et al.13

Yamagami17

Rota-Bartelink15

Pointer14

Sacca16

Probability of IOP

Swing (Percent)

65

78

80

64

65

Time When Most IOP

Swings Occurred

9 a.m. - 12 nn

8 a.m. - 4 p.m.

5 p.m.

12 nn

8 - 10 a.m.


References

1. De Venecia G, Davis M. Diurnal variation of intraocular pressure in the normal eye.

Arch Ophthalmol 1963; 69: 752-757.

2. Drance SM. The significance of diurnal-tension variations in normal and glaucoma-

tous eyes. Arch Ophthalmol 1960; 64: 46-53.

3. Drance SM. Diurnal variation in intraocular pressure in treated glaucoma. Arch

Ophthalmol 1963; 70: 302-311.

4. Horie T, Kitazawa Y. The clinical significance of diurnal-pressure variation in primary

open-angle glaucoma. Jpn J Ophthalmol 1979; 23: 310-333.

5. Kitazawa Y, Horie T. Diurnal variation of intraocular pressure in primary open-angle

glaucoma. Am J Ophthalmol 1975; 79: 557-566.

6. Phelps C, Woolson RF, Kolker AE, Becker B. Diurnal variation in intraocular pressure.

Am J Ophthalmol 1974; 77: 367-377.

7. Konstas AG, Lake S, Maltezos AC, et al. Twenty-four-hour intraocular-pressure

reduction with latanoprost compared with pilocarpine as third-line therapy in

exfoliation glaucoma. Eye 2001; 15: 59-62.

8. Konstas AG, Maltezos A, Bufidis T, et al. Twenty-four-hour control of intraocular

pressure with dorzolamide and timolol maleate in exfoliation and primary open-

angle glaucoma. Eye 2000; 1: 73-77.

9. Konstas AG, Mantziris DA, Maltezos A, et al. Comparison of 24-hour control with

Timoptic 0.5% and Timoptic XE 0.5% in exfoliation and primary open-angle

glaucoma. Acta Ophthalmol Scand 1999; 77: 541-543.

10. Konstas AG, Stewart WC, Toponzis F, et al. Brimonidine 0.2% given two or three

times daily versus timolol maleate 0.5% in primary open-angle glaucoma. Am J

Ophthalmol 2001; 31: 729-733.

11. Hyams S, Bergman D, Keroub C. The effect of hospitalization on intraocular pressure.

Am J Ophthalmol 1982; 94: 519-521.

12. Ritch R, Shields MB, Krupin T. The Glaucomas: Basic Science 2nd ed. Vol. 1. St.

Louis, MO: Mosby, 1996; 432.

13. David R, Zangwill L, Briscoe D, et al. Diurnal intraocular-pressure variations: an

analysis of 690 diurnal curves. Br J Ophthalmol 1992; 76: 280-283.

14. Pointer JS. The diurnal variation of intraocular pressure in nonglaucomatous subjects:

relevance in a clinical context. Ophthalmic Physiol Opt 1997; 17: 456-465.

15. Rota-Bartelink AM, Pitt A, Story I. Influence of diurnal variation on the intraocular

pressure measurement of treated primary open-angle glaucoma during office hours.

J Glaucoma 1996; 5: 410-415.

16. Sacca SC, Rolando M, Marletta A, et al. Fluctuations of intraocular pressure during

the day in open-angle glaucoma, normal-tension glaucoma, and normal subjects.

Ophthalmolgica 1998; 212: 115-119.

17. Yamagami J, Araie M, Aihara M, Yamamoto S. Diurnal variation in intraocular

pressure of normal-tension glaucoma eyes. Ophthalmology 1993; 100: 643-650.

18. Stewart WC, Day DG, Stewart JA, et al. The efficacy and safety of latanoprost

.005% once daily versus brimonidine .2% twice daily in open-angle glaucoma or

ocular hypertension. Am J Ophthalmol 2001; 131: 631-635.

19. Stewart WC, Sharpe ED, Stewart JA, et al. Additive efficacy of unoprostone isopropyl

.12% to latanoprost .005%. Am J Ophthalmol 2001; 131: 339-344.

20. Gonzalez I, Pablo LE, Pueyo M, et al. Assessment of diurnal tensional curve in

early glaucoma damage. Int Ophthalmol 1996-1997; 20: 113-115.

21. Asrani S, Zeimer R, Wilensky J, et al. Large diurnal fluctuations in intraocular

pressure are an independent risk factor in patients with glaucoma. J Glaucoma

2000; 9: 134-142.

22. The AGIS Investigators: The advanced glaucoma intervention study (AGIS): 7. The

relationship between control of intraocular pressure and visual-field deterioration.

Am J Ophthalmol 2000; 130: 429-440.

the range of IOPs and peak IOPs. Information on whenthe glaucoma medications were instilled should also beavailable to address the adequacy of IOP control.

We chose 9 a.m., 1 p.m., and 5 p.m. as our three-pointdetermination based on the common clinic hours ofophthalmologists and the even intervals between thesehours. Further studies determining the best possiblecombination of these hours and the optimum number ofhours needed to detect maximum IOP swings can be done.

In summary, the three-point determination (9 a.m., 1p.m., 5 p.m.) produces a diurnal curve similar to thatgenerated from a six-point determination and can be usedas a tool in detecting IOP swings in diagnosed glaucomapatients in an outpatient setting. This study suggested thatit is fairly accurate and convenient.

PHILIPP J OPHTHALMOL VOL 29 NO.4 OCTOBER - DECEMBER 2004 171PHILIPPINE ACADEMY OF OPHTHALMOLOGY

ORIGINAL ARTICLE



Single-setting treatment protocolfor diode-laser transscleral

cyclophotocoagulation

John Patrick M. Lirio, MD1

Jose Ma. Martinez, MD1

Jesus Altuna, MD1

Jay League, MD2

Rigo Daniel Reyes, MD2

1East Avenue Medical CenterQuezon City, Philippines

2University of the East-Ramon Magsaysay Memorial Medical CenterQuezon City, Philippines

Correspondence to

Jose Ma. Martinez, MD

Glaucoma Section, Department of Ophthalmology

East Avenue Medical Center

East Avenue, Diliman

1104 Quezon City, Philippines

Telefax: +63-2-9288550


Presented at the Annual Meeting of the Philippine

Academy of Ophthalmology, November 2003.



ABSTRACTObjective

To determine the efficacy of diode-laser transcleral cyclophotocoagulation(TSCPC) using a standard treatment protocol in the treatment of Asianpatients with refractory glaucoma.

MethodsThis is a prospective, noncomparative, interventional case series involving

35 eyes of 35 patients with refractory glaucoma and no previous cycloablation.After clinical examination and intraocular-pressure (IOP) measurements, diodelaser TSCPC was performed using a standard protocol (30 shots over 270o at1500 mW x 1500 msec). Patients were followed up at one day postoperatively,weekly for the first month, then every four weeks for 48 weeks. Complete successwas defined as IOP less than 22mm Hg or an IOP reduction of at least 30%from pretreatment level. The pre- and posttreatment IOPs were analyzed bypaired student t-test and the probability of success at different follow-up periodswas determined by Kaplan-Meier survival analysis.

ResultsMean pretreatment IOP was 50.9 ± 12.8 mm Hg. Mean posttreatment IOP

was 26.9 ± 10.7 mm Hg (45% reduction) at 24 weeks and 27.8 ± 10.9 mm Hg(40% reduction) at 48 weeks. The cumulative success rate was 80% at 24 weeksand 77% at 48 weeks. Twelve eyes (34 %) were retreated. Medications werereduced from a mean of 1.8 pretreatment to 0.4 at the end of the study period.Among the 28 patients who completed the 48-week follow-up period, visual-acuity score remained stable in 18 (64%) and deteriorated in 9 (32%). Onepatient experienced a 1-Snellen line improvement. Treatment complicationsincluded hyphema, tilting of an intraocular lens, severe inflammation, andconjunctival chemosis. No cases of phthisis, hypotony, or sympatheticophthalmia were encountered.

ConclusionThe diode-laser treatment protocol using fixed settings (30 shots over 270o

at 1500 mW x 1500 msec) was effective in controlling IOP in patients withrefractory glaucoma. There was minimal risk of hypotony.

Keywords: Glaucoma, Diode laser, Transscleral cyclophotocoagulation, Intraocular pressure



CILIARY body ablation in end-stage glaucoma hadpreviously been performed with cryotherapy and neody-mium:yttrium aluminum garnet (Nd:YAG) laser. Bothtechniques frequently involved considerable pain andpostoperative inflammation, with an unpredictable finalintraocular pressure (IOP) and a significant risk ofphthisis.1 Since the advent of the 810 nm semiconductordiode-laser, transcleral cyclophotocoagulation (TSCPC) hasbecome the method of choice for ciliary-body destructionin refractory glaucoma.2

A standard laser dose has yet to be established to effectadequate IOP reduction while maintaining an acceptablemargin of safety from overtreatment. Various treatmentparameters utilize different combinations of power andduration settings as well as extent of treated area.3, 4, 5 Someauthors adjusted the power settings intraoperativelydepending on the presence or absence of an audible“pop.” But this crude method of “dosimetry,” thought bysome to represent ciliary body disruption, may not exactlybe a sound basis for titrating power and duration settings.6

Setting the optimum treatment parameters has indeedbecome difficult considering the variability amongpublished treatment protocols. The more pigmented Asianeye may yet present another variable in calculating theamount of energy delivered since abundance of pigmentin these eyes may result in greater tissue absorption. Lowerenergy settings may therefore be justified.

This study evaluated the efficacy of TSCPC in reducingthe IOP in patients with refractory glaucoma using a fixedenergy setting in a sample of Asian eyes. We investigatedthe IOP reduction achieved over 48 weeks using a set treat-ment protocol, the number of medications used to controlglaucoma, and the adverse effects of treatment. We alsocompared visual acuity before and 48 weeks after diodetreatment.

METHODOLOGYThis is a prospective, noncomparative, interventional

case series involving 35 patients of Asian descent recruitedfrom the glaucoma section of the East Avenue MedicalCenter (EAMC) and the University of the East-RamonMagsaysay Memorial Medical Center (UERMMMC) fromJuly 2001 to August 2002. Included in the study werepatients who have refractory glaucoma despite maximumtolerable medical treatment and were deemed poorcandidates for or have refused filtering surgery, andpatients who have failed glaucoma surgery. All patientshad best-corrected visual acuity of ≤ 20/100 (6/30).Excluded were patients who have undergone previouscycloablative procedures.

The study complied with the requirements of theDeclaration of Helsinki and was approved by theInstitutional Review Boards of EAMC and UERMMMC.

All participants gave informed consent.Diode-laser cyclophotocoagulation was performed as

follows. Anesthesia was administered via a 2 to 4 ml retro-bulbar injection of an equal mixture of 2% lidocaine HCl(Elin Pharmaceuticals, Quezon City, Philippines) and 0.5%bupivacaine HCl (Sensorcaine, AstraZeneca, London,United Kingdom) accompanied by topical instillation ofproparacaine HCl (Alcaine 0.5%, Alcon Laboratories, FortWorth, TX, USA). Laser treatment was performed usingthe IRIS Medical OcuLight SLX (810 nm) diode-laserwith G-Probe (IRIS Medical Instruments, Iridex Corpo-ration, Mountain View, CA, USA). The laser energy wasdelivered through a 600 µm diameter quartz fiber withinthe G-probe handpiece to apply treatment 1.2 mm behindthe limbus. Each laser application was spaced approxi-mately 2 mm apart, using half the width of the G-probefootplate as a guide. A single-treatment setting of 1500 mwpower and 1500 msec duration (2.25 J) was used for eachapplication. Thirty shots were applied over 270o of thecircumference of the limbus, sparing the supero-nasalquadrant. This setting was not altered during the course ofthe treatment session even if audible “pops” were noted.

Postoperatively, all previous glaucoma medications werediscontinued and patients were prescribed prednisoloneacetate 1.0% eye drops (Pred Forte 1%, Allergan, Irvine,CA, USA) every 4 hours. Follow-up examinations, whichincluded visual acuity, IOP determination, and slit-lampbiomicroscopy, were performed on the first postoperativeday, weekly for the first month, and every four weeksthereafter for the duration of the 48-week follow-upperiod. IOP-reducing medications were reintroduced asneeded. Repeat diode-laser treatment was given at least 5weeks following initial laser treatment to those whose firsttreatment failed. Repeat treatment consisted of additional30 shots at the same power setting applied to the previouslytreated 270o and another 5 shots applied to 45o of previouslyuntreated area.

Differences in pre- and posttreatment IOP wereanalyzed using the paired student t-test. The probabilityof success at different follow-up periods was determinedby Kaplan- Meier survival analysis. Complete success wasdefined as IOP less than 22 mm Hg or a reduction of atleast 30% from baseline levels. Qualified success wasdefined as IOP reduction at least 20% but less than 30%.A reduction of less than 20% was considered failure.Differences in initial and final visual-acuity scores and inthe number of antiglaucoma medications required wereevaluated using Wilcoxon-signed-rank test.

RESULTSThirty-five eyes of 35 patients of Asian descent (14 males,

21 females) with a mean age of 53 years (range 18 to 79years) were included in the study. Most of the patients

PHILIPP J OPHTHALMOL VOL 29 NO.4 OCTOBER - DECEMBER 2004 173PHILIPPINE ACADEMY OF OPHTHALMOLOGY

(18) had neovascular glaucoma. Twelve of the 35 eyes wereretreated (Table 1).

The mean IOP at 4, 24, and 48 weeks of follow-up waslower than at pretreatment (p < 0.001) (Table 2). A signi-ficant drop in IOP was seen during the first 4 weeksposttreatment, and the level was sustained (Figure 1).There was no statistically significant difference among thefour follow-up measurements compared with baseline.

Thirty-three (94.2%) of the 35 eyes seen at the fourthweek of follow-up met the criteria for complete success.This dropped to 23 at 24 weeks and 21 at the end of the48-week follow-up period (Table 3).

Using the Kaplan-Meier life table analysis, the meanfinal IOP of the 28 eyes that completed 48 weeks of follow-up was 27.8 mm Hg ± 10.9. The cumulative probability ofcomplete success was 80% at 24 weeks and 77% at 48 weeksafter diode-laser TSCPC (Figure 2). The cumulativeprobability of qualified success was 83% at 24 weeks and83% at 48 weeks.

The mean number of treatment sessions was 1.2(range 1-2). Twenty-three out of 35 eyes (65.7%) hadsingle treatment while 12 eyes (34.3%) had repeattreatment (Table 1). Retreatment of the 12 eyes resultedin 8 complete successes, one qualified success, and onefailure at 48 weeks. Two patients from the retreated groupfailed to report for follow-up. The IOP at 24 and 48 weeksin each group did not differ significantly (Table 4). Allretreatments were done between the 5th and 20th weeks.

At 48 weeks , 32% (9/28) of subjects suffered deterio-ration in visual acuity (Table 5).

The mean number of medications was 1.8 at baseline,which was significantly reduced to 0.4 at 48 weeks (p < 0.001).By the end of the study period, 64.3% (18/28 patients) ofthe remaining subjects were maintained without anytopical or oral medication. At four weeks post-TSCPC, 87%(30/35 patients) were able to discontinue oral acetazo-lamide (Diamox, Wyeth Pharmaceuticals, Collegeville, PA,USA). After 48 weeks, 93% (26/28 patients) weremaintained without oral acetazolamide.

In terms of adverse effects, 12 subjects reported post-treatment redness, foreign body sensation, and moderateeye discomfort. However, the symptoms were transient andresolved spontaneously after the first week of follow-up. Onepatient had severe inflammatory reaction with chemosisduring the first week of follow-up. Another developed grade1 hyphema, which resolved after the first week of follow-

Figure 1. Mean intraocular pressure at baseline and follow-up. Percent decline from

baseline shown in parentheses.

Baseline 4 weeks 12 weeks 24 weeks 48 weeks

Intr

ao

cu

lar

Pre

ssu

re (

mm

Hg

) •

�

� � � �

• •

• •• •

• • •

(52%) (52%) (45%)(40%)

70 -----------------------------------------------------------------------------------------------------------

60 -----------------------------------------------------------------------------------------------------------

50 -----------------------------------------------------------------------------------------------------------

40 -----------------------------------------------------------------------------------------------------------

30 -----------------------------------------------------------------------------------------------------------

20 ------------------------------------------------------------------------------------------ -----------------

10 -----------------------------------------------------------------------------------------------------------

0 -----------------------------------------------------------------------------------------------------------

Figure 2. Kaplan-Meier survival analysis. The cumulative probability of success defined

as IOP reduction >30% from baseline was 0.80 at 24 weeks and 0.77 at 48 weeks.

Weeks

Cu

mu

lati

ve P

rob

ab

ilit

y

1.00 – – – – –

0.75 – –

– – –

0.50 – – – – –

0.25 – – – – –

0.00 –

0.0 12.5 25.0 37.5 50.0

– – – – – – – – – – – – – – – – – – – –

(n=35)(n=30)

(n=28)

a. defined as IOP <22 mm Hg or ≥30% IOP reduction from

baseline

b. ≥20% but <30% IOP reduction from baseline

c. <20% IOP reduction from baseline

Table 2. Mean intraocular pressure at baseline and follow-up.

Mean IOP(mm Hg)

50.9 ± 12.8

24.9 ± 12.0

26.9 ± 10.7

27.8 ± 10.9

Time of Follow-up

Baseline (n=35)

4 weeks (n=35)

24 weeks (n=30)

48 weeks (n=28)

Percent Decline

52.1 ± 18.1

44.9 ± 22.3

40.4 ± 25.5

ANOVA

p value

< 0.001

< 0.001

< 0.001

Single Treatment

(n=23)

10

7

3

1

0

1

1

Diagnosis/

Glaucoma Type

Neovascular (NVG)

Absolute

Primary Open Angle

Chronic Angle Closure

Angle Recession

Secondary Open Angle

Secondary Angle Closure

Retreatment

(n=12)

8

0

2

1

1

0

0

18

7

5

2

1

1

1

Table 1. Treated eyes by type of glaucoma.

(51.4%)

(20.0%)

(14.3%)

(5.7%)

(2.8%)

(2.8%)

(2.8%)

Total

(n=35)

Time of Success Failurec Dropout Total at

Follow-up Completea Qualifiedb Total Follow-up

4 weeks 33 (94.2%) 0 33 (94.3%) 2 (5.7%) 0 35 (100%)

24 weeks 23 (65.7%) 2 (5.7%) 25 (71.4%) 5 (14.3%) 5 (14.3%) 30 (85.7%)

48 weeks 21 (60.0%) 3 (8.6%) 24 (68.6%) 4 (11.4%) 7 (20.0%) 28 (80.0%)

Table 3. Treatment results.


refractory glaucoma, costly treatment is difficult to justifygiven the limited benefit for the patients. Diode-laserTSCPC effectively decreases medication requirement andalmost abolishes the need for systemic medications(acetazolamide). This simple, minimally invasive, modestlyexpensive procedure may be the best choice for patientwith limited financial capacity.

A persistent issue with diode TSCPC is a significant rateof visual deterioration after the procedure. In this study,32% experienced visual deterioration while 64% had nochange. Bloom et al., using the same settings, reported thatvisual acuity was worse in 29% and remained unchangedin 60% of their patients.4

Most patients in this study had neovascular glaucomasecondary to retinal ischemia and advanced glaucomatousdamage. It is difficult, as in other studies, to equate thevisual deterioration with the procedure itself. Properlydesigned studies should be done to investigate the potentialof this procedure when used in eyes with better prognosis.

Studies involving new procedures generally suffer fromlimited application, small sample size, and limitedduration of observation. In the future, as this procedureenters the mainstream of glaucoma treatment, we hopeto see studies involving more patients, longer follow-up,and standard protocols.

The single-setting protocol used in this study for diode-laser TSCPC is effective in reducing IOP in Asian eyesand decreasing the number of glaucoma medications atthe 48-week follow-up period, while exposing the patientto minimal risk of complications.

References

1. Assia EI, Hennis HL, Stewart WC, et al. A comparison of neodymium:yttrium

aluminum garnet and diode-laser transscleral cyclophotocoagulation and

cyclocryotherapy. Invest Ophthalmol Vis Sci 1991; 32: 2774-2778.

2. Samples, JR. Laser cyclophotocoagulation for refractory glaucomas. Ophthalmol

Clin North Am 1995; 8: 401-410.

3. Walland MJ. Diode-laser cyclophotocoagulation: dose-standardized therapy in end-

stage glaucoma. Aust N Z J Ophthalmol 1998; 26: 135-139.

4. Bloom PA, Tsai JC, Sharma K, et al. Cyclodiode: transscleral-diode laser

cyclophotocoagulation in the treatment of advanced refractory glaucoma.

Ophthalmology 1997; 104: 1508-1519.

5. Spencer AF, Vernon SA. Cyclodiode: results of a standard protocol. Br J Ophthalmol

1999; 83: 311-316.

6. Gaasterland D. Diode-laser transscleral cyclophotocoagulation: treating refractory

glaucoma with the OcuLight SLX and G-Probe. Iris Medical Newsletter 2002; 7: 1-6.

7. Gaasterland DE, Pollack IP. Initial experience with a new method of laser transscleral

cyclophotocoagulation for ciliary ablation in severe glaucoma. Trans Am Ophthalmol

Soc 1992; LXXXX: 225-246.

8. Brancato R, Leoni G, Trabucchi G, et al. Histopathology of continuous wave

neodymium:yttrium aluminum garnet and diode-laser contact laser transscleral

lesions in rabbit ciliary body. A comparative study. Invest Ophthalmol Vis Sci 1991;

32: 1586-1592.

9. McKelvie PA, Walland MJ. Pathology of cyclodiode laser: a series of nine enucleated

eyes. Br J Ophthalmol 2002; 86: 381-386.

10. Kosoko O, Gaasterland DE, Pollack IP, Enger CL. The Diode-Laser Ciliary Ablation

Study Group. Long-term outcome of initial ciliary ablation with contact diode-laser

transscleral cyclophotocoagulation for severe glaucoma. Ophthalmology 1996; 103:

1294-1302.

up. One subject developed tilting of the lens after repeatdiode therapy. At last visit, there were 2 patients who notedoccasional recurrent eye pain that spontaneously resolved.No hypotony (IOP <5 mm Hg) or phthisis bulbi occurred.

DISCUSSIONHistopathologic studies in animals and humans have

shown the relative selectivity of 810 nm diode-laser treat-ment for ciliary tissue.7, 8 However, significant damage topars plicata and pars plana has been observed in a studyof enucleated, postcyclodiode eyes.9 Determining theoptimum dose in a procedure where tissue reaction cannotbe directly observed is difficult.

Our general approach has been to adopt the lowestpossible dose given the more pigmented Asian eye andapply it consistently hoping to establish a definite dose-response relationship. Interestingly, IOP reduction, cumu-lative success rates, and retreatment rates in this study weresimilar to those in other studies that used variable settings.Bloom et al., using the same treatment settings of between20 to 40 shots, reported that 66% of their patients werecontrolled at 10 months. The mean number of treatmentsin their study was 1.75.4 Walland also used the sametreatment settings, but treated the entire limbus (40 shotsto 360 degrees). He reported 90% control at 10 months.3

Thus, it is probably easier to determine the amount ofenergy delivered in the “single-setting” strategy andpropose the optimum dose for a particular patient.

Another important aim of treatment is to decrease therequirement for antiglaucoma medications. In end-stage

Table 5. Visual acuity outcome at 48 weeks post-TSCPC.

Eyes Percent

3.6

64.2

10.7

17.9

3.6

100.0

1

18

3

5

1

28

Outcome

Improved by 1 Snellen line (20/200 to 20/100)

Remained the same

Deteriorated by 2 grades (HM to NLP)

Deteriorated by 1 grade

CF1 to HM = 1

HM2 to LP = 2

LP3 to NLP4 = 2

Deteriorated by 5 grades (20/100 to NLP)

Total

1counting fingers2hand movement3light perception4no light perception

Mean IOP

(mmHg)

Baseline

47.2 ± 11.0

56.6 ± 15.6

Treatment

Group

Single treatment (n=23)

Retreated (n=12)

24 weeks

29.8 ± 11.5 (36.6)

26.2 ± 10.9 (44.0)

Mean IOP (mm Hg) Post-TSCPC

(%decrease)

48 weeks

29.9 ± 9.2 (36.7)

27.2 ± 10.9 (40.0)

Table 4. Single treatment versus retreatment.


ORIGINAL ARTICLE



A valuable test for malignancyof orbital tumors

Alberto M. Castro, MDGloria D. Lim, MDLawrence Marlon H. Pe, MD

East Avenue Medical CenterQuezon City, Philippines

Correspondence to

Alberto M. Castro, MD

East Avenue Medical Center

East Avenue, Diliman


Tel. +63-2-3731685




ABSTRACT

ObjectiveThis study determined the effectiveness of fine-needle aspiration biopsy

(FNAB) in detecting malignancy in orbital lesions compared with sectionbiopsy. Its sensitivity, specificity, and positive predictive value were determined.

MethodsThis is a nonrandomized, prospective, comparative study of 33 (20 males

and 13 females, ages 11 months to 71 years) with orbital lesions who underwentFNAB. The cytologic results were correlated with the histologic results.Different pathologists who were blinded as to study lesions read the cytologicand histologic smears.

ResultsTwenty-three patients whose smears had high yield of cells were included

in the study. Excluded were 2 with poor yield smears, 3 hemorrhagic smears,and 5 without section biopsies of which 2 presented with pyogenic granu-loma. FNAB is 87.5% sensitive and 100% specific, with a positive predictivevalue of 100%. No statistical difference was found between FNAB and sectionbiopsy in detecting ocular malignancy (p < 0.05) in this study.

ConclusionFNAB has a good sensitivity and specificity in diagnosing ocular malignancy

and is a useful tool in the diagnosis of orbital tumors.

Keywords: Fine-needle aspiration biopsy, section biopsy, malignancy, orbital tumors


Fine-needle aspiration biopsy


SECTION biopsy, the removal of the whole or a part ofthe mass, is considered the “gold standard” in the diagnosisof orbital lesions. An incisional or excisional biopsy isperformed depending on the size of the mass. Thisdiagnostic and therapeutic procedure is selected fortumors suspected to be malignant.

Fine-needle aspiration biopsy (FNAB) or aspiration-biopsycytology is widely used for morphologic diagnosis oftumors.1 It has the advantage of possibly obviating majorsurgeries. It requires the removal of a sample of cells usinga fine needle to predict the nature of the entire lesion,assuming that the lesion is homogenous. It is a cytologicrather than a histologic technique. It has other advantages:it is easy to perform and does not require extensivepreparations such as hospitalization or anesthesia, resultsare fast, and costs are lower. Reported complicationsinclude pain and anxiety, minor bleeding, vasovagalreaction, seizures, nerve damage, local anaphylaxis, andinfection.1

In this study we determined the effectiveness of FNABin detecting malignancy in orbital lesions compared withsection biopsy. We determined its sensitivity, specificity,and positive predictive value.

METHODOLOGYPatients with orbital lesions who underwent FNAB at

the Orbit Section of the Department of OphthalmologyEast Avenue Medical Center from January 2001 to June2003 were included into the study. Those who did notundergo section biopsy, or had poor yield or hemorrhagicsmears were excluded.

FNAB was performed as follows: Computed-tomography(CT) plates were examined and the position of the mass

noted. The skin was cleansed with povidone iodine. Noanesthetic was used. A gauge 23, 1.5-inch needle attachedto a 10 cc disposable plastic syringe was carefullyintroduced into the lesion, avoiding blood vessels. Afterentering the mass, suction was applied and maintainedwith the syringe. The needle was moved in and out, in acutting motion within the lesion, to obtain adequatesample. At the conclusion of the procedure, the suctionwas released, and the needle was pulled straight out. Steriledressing was applied on the puncture site and pressureapplied. Aspirates were smeared on a glass slide and fixedwith 95% ethyl alcohol. Slides were stained withPapanicolau and analyzed under a microscope.

A section biopsy was subsequently done under standardtechniques. The cytologic results were correlated with thehistologic results. Different pathologists who were blindedas to study lesions read the cytologic and histologic smears.

RESULTSThirty-three patients (20 males and 13 females, ages

11 months to 71 years) underwent FNAB but only 23whose smears had high yield of cells were included.Excluded were 2 with poor yield smears, 3 hemorrhagicsmears, and 5 without section biopsies, two of whompresented with pyogenic granuloma that responded toantibiotics.

Table 1 shows the comparison between the cytologicdiagnosis from FNAB and the histologic diagnosis fromthe section biopsy. Eight of the cytologic results showedmalignancy with one false negative. On the other hand,all 15 cases that had negative malignancy on section biopsyalso showed negative on FNAB.

Results showed that FNAB is 87.5% sensitive and 100%

Table 1. Comparison between FNAB and section biopsy results.

FNAB (Cytologic Diagnosis)

Positive for malignant cells. Cytomorphologic findings consistent with lymphoproliferative disorder.

Positive for malignant cells. Cytomorphologic findings consistent with carcinoma, probably glandular in origin.

Positive for malignant cells. Cytomorphologic findings consistent with carcinoma.

Positive malignant cells. Cytomorphologic findings consistent with malignant blue cell tumor.

Considerations: 1) small cell CA 2) primitive neuroectodermal tumor (PNET)/Ewing’s sarcoma.

No malignant cells seen. Cytomorphologic findings consistent with epidermal inclusion cyst.

No malignant cells seen.

No malignant cells seen. Lymphoproliferative disorder. Favor benign process.

No malignant cells seen.

No malignant cells seen. Cytomorphologic findings consistent with a chronic inflammatory process.

Positive for malignant cells.

Positive malignant cells.

No malignant cells seen. Cytomorphologic findings consistent with tumor of neurogenic origin.

Section Biopsy

(Histologic Diagnosis)

Lymphoma

Adenoid cystic carcinoma

Nasopharyngeal carcinoma

Malignant tumor consistent

with poorly differentiated

adenocarcinoma

Epidermal inclusion cyst

Conjunctival cyst

Inflammatory pseudotumor

Squamous hyperplasia with

keratosis and sclerosis

Dermoid cyst

Rhabdomyosarcoma

Small cell CA with neuroendocrine

differentiation; consider

metastatic small cell CA of the

lung or primary Merkel tumor

Shwannoma (Neurilemoma)

Number

of Cases

2

1

2

1

1

3

5

1

4

1

1

1


specific, with a positive predictive value of 100% (Table2). When compared with corresponding incisional biopsyusing Fishers Exact Test, no statistical difference was foundbetween FNAB and section biopsy in detecting ocularmalignancy (p < 0.05).

DISCUSSIONFNAB is a well-recognized technique in the diagnosis

of tumors of the head, neck, lung, in various abdominaland prostatic tumors, and more recently, in tumors of thebone and eyelid.2 Remulla, et.al. found that FNAB was auseful technique in the diagnosis of retinoblastoma,3

which confirmed findings by Das et al. in 3 cases ofretinoblastoma in children.4 These studies showed thatFNAB is a useful tool in the diagnosis of orbital tumors,which can be performed as an outpatient procedure withminimal discomfort and cost to the patient. Cytologicresults from the biopsy give a preliminary idea of whetherthe lesion is malignant or benign so that appropriate treat-ment can be planned before contemplating a moreinvasive procedure.

Our results showed that FNAB has high sensitivity andspecificity for detecting ocular malignancy and that theconcordance between the two procedures is good thoughthe sample size is small. Other studies have shown similarresults.2-5 Caution, however, must be exercised in theinterpretation of cytologic results of FNAB.2 The bestindication for FNAB is detection of malignant orbitaldisease.5 It is not helpful in tumors or inflammatory diseasewith a high fibrous content.5 Lesions that are suspectedpseudotumors are not recommened for FNAB since theyare notoriously difficult to distinguish from well-differentiated lymphocytic malignant lymphoma even inhistologic sections.5 For instance, one patient in this seriesshowed cytomorphologic findings consistent with alymphoproliferative disorder, which was confirmed witha histologic diagnosis of malignant lymphoma (Figure 1).However, 5 smears with the same cytomorphologic

References

1. DeMay, R.M. The Art and Science of Cytopathology, Vol. 2. Chicago: ASCP Press,

1996; 464-481.

2. Kennerdell JS, Dubois PJ, Dekker A, Johnson BL. CT-guided fine-needle aspiration

biopsy of orbital optic nerve tumors. Am J Ophthalmol 1980; 87:491-496.

3. Remulla JC, Espiritu RB, Abelardo AD, et al. Fine-needle aspiration biopsy in the

diagnosis of retinoblastoma. Philipp J Ophthalmol 1999; 24: 86-88.

4. Das DK, Das J, Chachra KL, Natarajan R. Diagnosis of retinoblastoma by fine-

needle aspiration and aqueous cytology. Diagn Cytopathol 1989; 5: 203-206.

5. Kennerdell JS, Dekker A, Johnson BL, Dubois PJ. Fine-needle aspiration biopsy:

its use in orbital tumors. Ophthalmology 1979; 97: 1315-1317.

6. Gupta S, Sood B, Gulati M, et al. Orbital mass lesions: US-guided fine-needle

aspiration biopsy: experience in 37 patients. Radiology 1999; 213: 568-572.

findings had a histologic diagnosis of inflammatorypseudotumor. In these cases, an incisional biopsy isrecommended.

In our study, we detected 7 cases of malignant tumorsby FNAB that correlated with the histologic diagnoses(Table 2). Only 1 case of lymphoproliferative disorderfavoring reactive process on FNAB was diagnosed asHodgkin’s lymphoma. This supported previous studies onthe difficulty of FNAB in differentiating lymphomas frominflammatory diseases.

FNAB is relatively safe. The concern about implantingtumor cells during the procedure is as old as aspirationbiopsy itself.1 There is no direct evidence that aspirationbiopsy causes an increase in distant metastases or adverselyaffects the survival of the patients.1 In our study, only onecomplication (retrobulbar hemorrhage because of a deep-seated retrobulbar mass) was encountered. The hemor-rhage was appropriately managed and resolved after 7days. To avoid serious complications, ultrasound-guidedFNAB or use of other imaging techniques is recommendedprior to or during the procedure. The positive yield willalso be higher with less chance of hemorrhage.

In summary, fine-needle aspiration biopsy is a usefultool in the diagnosis of orbital tumors. It is 87.5% sensitiveand 100% specific, with a positive predictive value of 100%.No statistical difference was found between FNAB andsection biopsy in detecting ocular malignancy (p < 0.05)in this study of 23 cases.

Figure 1. Cytomorphologic findings consistent with lymphoproliferative disorder showing

large lymphoid cells with round to oval nuclei.

Table 2. Comparison of FNAB with incisional biopsy.

Positive

Malignancy

7

1

8

Negative

Malignancy

0

15

15

Total

7

16

23

Positive Malignancy

Negative Malignancy

Total

F

N

A

B

Incisional Biopsy


CASE SERIES


Ophthalmology OCTOBER - DECEMBBR 2004VOL. 29 • NO. 4

Möbius sequence with variedstrabismus presentations in

Filipino patients

Correspondence to

Alvina Pauline D. Santiago, MD

Motility and Pediatric Ophthalmology Section


University of the Philippines-Philippine General Hospital

Taft Avenue, Ermita


Tel.: +63-2-5218450 ext. 2174

Fax: +63-2-5210007

Email: [email protected]

Presented at the Annual Meeting of the Philippine

Academy of Ophthalmology, November 2003.

The author has no proprietary or financial interest in any

product used or cited in this study.

ABSTRACTObjective

To report various presentations of patients diagnosed with Möbius sequence,discuss theoretical basis for the findings, and present treatment options.

MethodsConsecutive cases of patients meeting the minimum criteria of VI and VII

cranial-nerve diplegia seen from January 2003 to June 2003 were included inthis case series. Their strabis-mus presentations and associated systemic findingswere presented. All patients underwent a comprehensive ophthalmologicexamination.

ResultsSeven patients aged six months to eight years, five males and two females,

were identified. Patients were born to mothers 28 to 38 years old with varyingparities. First trimester insults in the form of tobacco and alcohol exposure,upper respiratory and varicella infections were seen in three patients. Whileall patients had bilateral abduction deficit consistent with bilateral VI cranial-nerve palsy, the strabismus deviations varied. Four patients had large-angleesotropia exceeding 40 PD, one of whom had dissociated vertical deviation(DVD), ptosis, and lid fissure narrowing on attempted adduction. The othershad 20 PD of exotropia, 10 PD of intermittent esotropia with DVD, and onewas orthotropic. Four patients had limb abnormalities, including three withtalipes equinovarus or clubfoot and one with absent distal phalanges. Fourpatients, two of them females, suffered from mental retardation. Two patientshad seizure disorder.

ConclusionPatients with typical Möbius sequence may have varying strabismus present-

ations despite bilateral VI cranial-nerve involvement. Standard strabismusmanagement principles apply. These patients require a multidisciplinary teamfor optimal care.

Keywords: Cranial-nerve-VI and -VII diplegia, Hanhart syndrome; Möbius sequence/syndrome,Moebius/Möbius, Poland-Möbius syndrome, Strabismus


Alvina Pauline D. Santiago, MDChristopher Sebastian J. Uy, MD

Department of Ophthalmology and Visual SciencesUniversity of the Philippines Philippine General HospitalManila, Philippines


THE CONSTELLATION of findings often referred toas Möbius (or Moebius) syndrome is more appropriatelydiscussed as Möbius sequence, consistent with a cascadeof secondary events after an embryonic insult fromhetero-genous causes.1 There is general agreement thatthe timing of insult or trigger factors occur during thefourth to sixth weeks of gestation during which time thecranial nerve nuclei undergo the most rapid deve-lopment.2 No common cause has been found but ahistory of benzodiazepine and misoprostol use, bleedingduring pregnancy, spontaneous abortion, and chorionicvillus sampling in the second month of gestation havebeen documented.3,4

Palsy of the sixth and seventh cranial nerves is the mini-mum diagnostic criteria for Möbius sequence.5 Clinicallyit is characterized by a large-angle esotropia and absenceof facial expression (facial lines). Typically, the strabismusdeviation is observed during the first six months of lifewith bilateral limitation in abduction.6 There may be otherassociated ocular and orbital findings (Table 1).7,8

In many cases, an expanded Möbius sequence isobserved with variable cranial-nerve-III to IX involve-ment.1 Cases consisting primarily of cranial-nerve involve-ment are known as Möbius syndrome while those withassociated limb abnormalities are known as Hanhart orPoland-Möbius syndrome.9 Simultaneous disruption ofnormal blood flow in developing facial arterial networkscould account for hypoplasia of the eye, ear, and jaw. Con-comitant disruption of the subclavian artery, around thesixth week of embryonic development, could cause theterminal transverse limb defects and Poland syndrome.10

Patients with typical Möbius facies with varied strabis-mus alignment, including large-angle esotropia describedabove, are presented in this case series. Theoretical basisfor the varied presentations and treatment options arediscussed.

METHODOLOGYConsecutive series of patients with typical Möbius facies

seen at the pediatric ophthalmology clinic of the Universityof the Philippines-Philippine General Hospital (UP-PGH)from January 2003 to June 2003 were identified. AllMöbius sequence diagnoses were confirmed by pediatricgenetics specialists at the University of the Philippines-National Institutes of Health.

All patients underwent a complete ophthalmologicevaluation consisting of gross examination, visual-acuitytesting, full cycloplegic refraction, biomicroscopic exami-nation, sensorimotor (strabismus) and amblyopia evalua-tion, and dilated fundoscopy with both direct and indirectophthalmoscopes. All refractions were performed follow-ing cycloplegia with 0.5 to 1.0% atropine given thrice aday for three days prior to objective refraction. Whenever

possible, alternate-prism-cover testing was the preferredmethod for measuring misalignment with the appropriatecorrection glasses in place, if necessary. In uncooperativepatients, strabismus measurements were estimated byKrimsky/Modified Krimsky method.

RESULTSSeven cases with typical Möbius sequence were

included. Their profiles are summarized in Tables 2 and 3.

Case 1A five-year-old male was born full term via spontaneous

vaginal delivery to a 38-year-old multigravid [G6P5 (5-0-0-5)]. There was no identified insult—viral or otherillness, teratogenic drug intake, or radiation exposure—during pregnancy. Esotropia, poor suck, and bilateraltalipes equinovarus (clubfoot) were noticed at birth. Thepatient’s feet underwent repair at age 4 months. Thoughdevelopmentally at par with his peers, the patient hadpersistent esotropia that prompted consultation at ourinstitution.

There was bilateral eccentric fixation with best-corrected vision of 6/9 (20/30) OU and slight right-eyepreference. Cycloplegic refraction was +5.50 -1.00 x 90°OD and +6.00 -3.00 x 90° OS. He had prominentepicanthal folds with epiblepharon. The poor orbicularisoculi and oris tone were confirmed. There was lagoph-thalmos with preservation of upgaze and good Bell’sphenomenon. Cranial-nerve-VII palsy was total, but he hadintact gross hearing. Gag and corneal reflexes were alsointact. His tongue deviated to the right on protrusion.There was 60 PD of esotropia with absence of horizontalgaze (Figure 1). Maximum tolerated plus prescription wasgiven with minimal improvement in ocular alignment.Bilateral transposition surgery with medial rectusweakening was recommended.

• VI cranial-nerve palsy with decreased abduction ability

• Small palpebral fissure

• Epicanthal folds

• Hypertelorism

• Esotropia [E+] [up to 100 prism diopters (PD)]

• Exposure keratitis due to lagophthalmos

• Situs inversus of retinal vessels and tortuous retinal vasculature

• Mild to moderate refractive errors

• Entropion

• Ptosis

• Anomalous head posture

• Head tilt if vertical strabismus is present

• Amblyopia and decreased binocular vision

• III and IV cranial-nerve palsies

• Generally preserved vertical eye movements and convergence

• Normal pupillary function, occasionally poorly reactive and miotic

Table 1. Ocular and orbital findings in Möbius syndrome.7, 8


Featu

res

Age(yrs.)/S

ex

Ma

tern

al A

ge

Pre

-/pe

rina

tal e

xpo

sure

Be

st-corre

cted

visua

l

acu

ity

Cyclo

ple

gic re

fractio

n

Pre

scriptio

n g

lasse

s

Stra

bism

us d

evia

tion

in

prim

ary g

aze

An

om

alo

us h

ea

d

positio

n

La

tera

l ga

ze

Vertica

l gaze

Ab

du

ction

limita

tion

Ad

du

ction

limita

tion

Eye

lids

Fu

nd

us F

ind

ing

s

Case 1

5/M

38

No

kno

wn

exp

osu

re

OD

: 6/9

; OS

: 6/9

OD

: +5.5

0 -1

.00 x 9

0°O

S: +

6.0

0 -3

.00 x9

0°O

D: +

4.5

0 -1

.00 x9

0°O

S: +

4.0

0 -1

.00 x9

0°

60 P

D5 E

T6

Rig

ht h

ea

d tu

rn,

Rig

ht h

ea

d tilt

Abse

nt

Inta

ct

OU

None

Epica

nth

us,

Ep

ible

ph

aro

n,

La

go

ph

tha

lmo

s

Norm

al

Case 2

1/M

33

8m

os: To

ba

cco,

alco

ho

l, UT

I 1

OU

: tracts lig

ht

OD

: +2.7

5

OS

: +2.5

0

OD

: +2.7

5

OS

: +2.5

0

45 P

D5 E

T6

None

Abse

nt

Inta

ct

OU

None

Epica

nth

us,

Ep

ible

ph

aro

n,

La

go

ph

tha

lmo

s

Norm

al

Case 3

0.5

/F

38

6m

os: U

TI, 1 7

mo

s: UR

TI 2

OU

: inco

nsiste

nt d

azzle

(flat V

ER

3)

OD

: +1.5

0

OS

: +1.2

5

No

ne

give

n

40-6

0 P

D5 E

T6

None

Abse

nt

Inta

ct

OU

None

Epica

nth

us,

Ep

ible

ph

aro

n,

La

go

ph

tha

lmo

s

Norm

al

Case 4

4/M

28

6m

os: M

eclizin

e H

Cl

OD

: 6/9

; OS

: 6/1

2

OD

: +2.0

0

OS

: +2.0

0

OD

: +2.0

0

OS

: +2.0

0

65 P

D5 E

T6 w

ith D

VD

7

Rig

ht h

ea

d tu

rn,

Rig

ht h

ea

d tilt

Abse

nt

Inta

ct

OU

None

Epica

nth

us, E

pib

lepharo

n

La

go

ph

tha

lmo

s,

Lid

-fissure

na

rrow

ing

on

atte

mp

ted

ad

du

ction

, Rig

ht p

tosis

Norm

al

Case 5

8/M

38

1m

o:U

RT

I 2 w/ fe

ver;

3 m

os: va

ricella

infe

ction

OD

: 6/6

; OS

: 6/6

OD

: +2.0

0

OS

: +2.0

0

OD

: +1.0

0

OS

: +1.0

0

20 P

D5 X

T8

None

Abse

nt

Inta

ct

OU

OU

Epica

nth

us,

Ep

ible

ph

aro

n

Norm

al

Case 6

6/F

35

2m

os: U

RT

I 2 w/ fe

ver

OU

: tracts lig

ht; C

SM

4

OD

: +1.5

0 -0

.50 x1

80°

OS

: +1.5

0

No

ne

give

n

10 P

D5 E

(T)9 w

ith D

VD

7

None

Abse

nt

Inta

ct

OU

OU

partia

l

Epica

nth

us,

Epib

lepharo

n,

Lagophth

alm

os,

Trich

iasis

Optic-n

erve

pallo

r OU

Tab

le 2

. De

mo

gra

ph

ic a

nd

oc

ula

r find

ing

s in

a s

erie

s o

f Mö

biu

s s

eq

ue

nc

e p

atie

nts

.

Case 7

3/M

27

No

kno

wn

exp

osu

re

OU

: fing

er p

lay a

t 6 m

ete

rs

OD

: +3.0

0

OS

: +3.0

0

OD

: +1.5

0

OS

: +1.5

0

Orth

otro

pic

Le

ft he

ad

tilt

Abse

nt

Inta

ct

OU

OU

partia

l

Epica

nth

us,

Ep

ible

ph

aro

n,

Trich

iasis

Norm

al

1. U

rina

ry tra

ct in

fectio

n; 2

. Up

pe

r resp

irato

ry tra

ct in

fectio

n; 3

. vis

ua

l-evo

ke

d-re

sp

on

se

; 4. c

en

tral, s

tea

dy, m

ain

tain

ed

; 5. p

rism

dio

pte

rs; 6

. eso

trop

ia; 7

. dis

socia

ted

ve

rtical d

evia

tion

; 8. e

xotro

pia

9. in

term

itten

t esotro

pia

Case 6

Bila

tera

l & co

mp

lete

Norm

al B

AE

R

Inta

ct ga

g re

flex

Ton

gu

e d

evia

ted

to

righ

t on

pro

trusio

n

None

Ye

s

Norm

al

Norm

al

Case 7

Bila

tera

l & co

mp

lete

Inta

ct gro

ss he

arin

g

Inta

ct ga

g re

flex

Ton

gu

e m

idlin

e o

n

pro

trusio

n

None

None

Ab

sen

t left n

ipp

le, a

bse

nt

pecto

ralis m

uscle

Rig

ht ta

lipe

s eq

uin

ova

rus

Case 4

Bila

tera

l; com

ple

te le

ft;

partia

l right

Inta

ct gro

ss he

arin

g

Inta

ct ga

g re

flex

Ton

gu

e d

evia

ted

to rig

ht

on

pro

trusio

n

None

None

Norm

al

Bila

tera

l talip

es

eq

uin

ova

rus

Case 5

Bila

tera

l & co

mp

lete

Inta

ct gro

ss he

arin

g

Inta

ct ga

g re

flex

Ton

gu

e a

trop

hy

Ye

s

Ye

s

Norm

al

Norm

al

Featu

res

CN

1 VII p

alsy

CN

1 VIII

CN

1 IX-X

CN

1 XII

Seizu

re d

isord

er

Me

nta

l reta

rda

tion

Chest F

indin

gs

Extre

mitie

s

Case 1

Bila

tera

l & co

mp

lete

Inta

ct gro

ss he

arin

g

Inta

ct ga

g re

flex

Ton

gu

e d

evia

ted

to

righ

t on

pro

trusio

n

None

None

Norm

al

Bila

tera

l talip

es

eq

uin

ova

rus

Case 2

Bila

tera

l & co

mp

lete

Norm

al B

AE

R2

Inta

ct ga

g re

flex

No

t teste

d; to

ng

ue

atro

ph

y no

ted

None

Ye

s

Norm

al

Norm

al

Case 3

Bila

tera

l & co

mp

lete

Inta

ct gro

ss he

arin

g

Inta

ct ga

g re

flex

Not te

sted

Ye

s

Ye

s

Norm

al

Abse

nt/u

nderd

eve

loped

dista

l ph

ala

ng

es b

oth

ha

nd

s; ab

sen

t dista

l

ph

ala

nx o

f left b

ig to

e;

ab

sen

t toe

na

ils of 2

nd

an

d 3

rd d

igits o

f left

foo

t an

d rig

ht b

ig to

e.

Table

3. N

on

op

hth

alm

olo

gic

find

ing

s in

Mö

biu

s s

eq

ue

nc

e p

atie

nts

.

1. c

ran

ial n

erv

e; 2

. bra

inste

m-a

ud

itory

-evo

ke

d re

sp

on

se


Case 2A one-year-old male was born full-term to a 33-year-old

multigravid [G5P3 (3-0-1-3)] mother assisted by a midwife.The mother smoked one pack of cigarettes a day up todelivery and drank brandy and whisky, about 750 ml persession, twice or thrice weekly up to the third month ofgestation. There was maternal urinary-tract infection(UTI)) at 8 months of gestation treated with amoxicillinfor a week. Soon after giving birth, the mother noted thebaby had poor suck and spilled milk when fed. Dropperfeeding was required to sustain nutrition. At one month,expressionless facies, esotropia, and monotone voice oncrying were noted. The baby had no lateral gaze. Eyelasheswere misdirected toward the cornea with bilateral epible-pharon of the medial third of eyelids and epicanthal folds.

The mother first brought the child for consultation atfive months of age. Expressionless facies was observed.He was able to fixate at objects, but tracking of movementswas difficult to assess because of bilateral abduction defi-cits. A 45 PD of esotropia was documented with slight right-eye preference. Corneal and gag reflexes appeared intact.Tongue atrophy was noted but tongue deviation on pro-trusion was not elicited. There was good gross sound lat-eralization confirmed by a normal brainstem-auditory-evoked response (BAER). Refraction was +2.75D OD and+2.50D OS. Patient was given full cycloplegic refractionand started on patching therapy for amblyopia. Transpo-sition surgery was suggested.

Case 3A six-month-old female was born post term via sponta-

neous vaginal delivery after induction of labor to a 38-year-old [G3P2 (3-0-0-2)] mother at a tertiary-care facility.Pregnancy was confounded by UTI at six months ofgestation, treated by a full course of amoxicillin, andupper-respiratory-tract infection (URTI) at seven monthstreated with paracetamol intake. No first-trimester insultwas identified.

Figure 1. Gaze composite. A 60 PD esotropia with absence of horizontal gaze was evident. Bilateral eccentric fixation and slight right-eye preference were pesent. Esotropia increased

on up and down gaze. Vertical eye movements were preserved.

Figure 2. A: Both hands have absent or underdeveloped distal phalanges. Bilateral simian

crease was also noted. B: The distal phalanx of the left big toe is absent. Also missing are

the toenails of the second and third digits of the left foot and the right big toe. Rocker

bottom feet were also noted.

At birth, the patient had poor cry and poor suck, withsubsequent development of seizures described as general-ized tonic-clonic associated with upward rolling of eyeballsnecessitating prolonged hospital confinement. All upperextremities had absent or underdeveloped distal phalanges(Figure 2A). The distal phalanx of the left big toe was absentas well as the toenails of the second and third digits of leftfoot and the right big toe (Figure 2B). Simian crease, higharched palate, and rocker bottom feet were also identified.

Visual-acuity assessment showed inconsistent dazzlereflex to bright halogen test light. A visual-evoked-responserecording revealed no evidence of conduction along thevisual pathway. There was bilateral epiblepharon andepicanthus managed conservatively with bland ointments.Variable esotropia ranged between 40 to 60 PD by Krimsky

A

B


method. No abduction was elicited. Latest refraction at 7months old was +1.50D OD and +1.25D OS. Because ofpoor vision OU, no further treatment except vision stimu-lation exercises was recommended.

Case 4A four-year-old male was born full term via spontaneous

vaginal delivery to a 28-year-old primigravid assisted by aphysician at a local hospital. The mother took meclizineHCl (Bonamine, Pfizer, New York, NY, USA) at 6 monthsof gestation, but no insult during the first trimester wasidentified. Bilateral abduction deficit with large-angleesotropia was apparent at birth. Some degree of facialmuscle movement was noted on the right side, no move-ment on the left (Figure 3A-B). Beginning at age 4 months,patient consulted repeatedly for esotropia, facial asym-metry, and frequent drooling.

At last evaluation at age 4, best-corrected visual acuitywas 6/9 (20/30) OD, 6/12 (20/40)OS with refraction of+2.00D OU. He had spontaneous alternating fixation withslightly better vision OD. He preferred the right-head turnto assume left gaze, maximizing the use of his right eye.However, because of the right-sided congenital blepharop-tosis on forced primary gaze, left-eye fixation was preferredin this position. He also had epicanthus, epiblepharon,and a 65 PD of esotropia with dissociated vertical deviation.Tongue deviates to the right on protrusion (Figure 3B).On attempted left gaze, there was associated lid-fissurenarrowing on the right with globe retraction of the righteye. Ptosis of the right upper lid was noted on down gaze(Figure 3C). He was started on full hyperopic prescriptionand patching of the right eye to treat the amblyopia in

Figure 3. A: Left-eye fixating is evident on forced primary gaze. The patient has bilateral

epicanthus and epiblepharon. Downward sloping of upper lip and incomplete closure of

mouth with dental caries are evident. B: Attempting to smile. Bilateral cranial-nerve-VII

palsy is evident with some degree of facial muscle movement on the right side, no movement

on the left. The left nasolabial fold is shallow compared to the right. Only right eyelids can

close, indicating residual facial-nerve function on the right side. C: Gaze composite. Note

65 PD of esotropia on primary gaze with left eye fixating. Bilateral abduction deficit apparent

on side gazes. On attempted left gaze, there was associated lid-fissure narrowing on the

right with globe retraction of the right eye. Ptosis of the right upper lid was noted on down

gaze and left gaze. Some degree of vertical gaze movement appears to be preserved.A B

C

the left eye. Bilateral transposition surgery with medialrectus weakening may be required.

Case 5An eight-year-old male was born full term via spon-

taneous vaginal delivery to a 38-year-old [G4P3 (3-0-0-3)]at home assisted by a midwife. At around 3 months ofgestation, the mother developed systemic varicella infection(chicken pox). There was no known exposure to radiation;mother denied intake of potential teratogens or other drugs.

Patient had episodes of seizure starting on the thirdday after birth, recurring monthly and associated withfever, upper-respiratory-tract infection as well as aspirationfrom frequent regurgitation, poor suck, and inadequateswallowing reflexes.

The patient came for an eye examination at 8 years old.At this time, the visual acuity was 6/6 (20/20) OU withoutcorrection. Cycloplegic refraction was +2.00D OU. Therewas 20PD of exotropia on primary gaze with some degreeof limited lateral versions (Figure 4). Patient had bilateralpartial abduction deficit and bilateral complete cranial-nerve-VII palsy. Atrophy of the tongue was noted. Therewas bilateral epicanthus that needed no intervention. Atrial of +1.00D OU was given to evaluate effect ofcorrection of small hyperopia on his alignment. Patienthad not followed up since then.

Case 6A six-year-old female was born full term and thickly

meconium-stained to a 35-year-old multigravid [G5P4 (4-0-0-4)] via spontaneous vaginal delivery. At 2 months ofgestation, the mother experienced a 38-40°C fever asso-


ciated with cough and colds. She self-medicated with amoxi-cillin, paracetamol, and dextromethorphan-paracetamol-phenylpropanolamine HCl (Tuseran Forte) combination.Fever allegedly lasted for 15 days without medical super-vision. No other first-trimester insults could be elicited.

At birth, facial asymmetry was noted. No consultationswere made until age one year. Throughout her first fewyears, the patient had feeding difficulties implicatingcranial-nerve-IX-X involvement, contributing to hermalnutrition.

Patient had profound mental retardation with lack ofverbal response. Best qualitative visual-acuity test showedboth eyes can maintain central and steady fixation, but witha right-eye preference. There was no associated nystagmus.Mask-like facies with bilateral trichiasis, epicanthus, andepiblepharon was apparent on gross examination. BAERwas normal. Gag reflex was intact. Tongue deviated tothe right on protrusion with tongue atrophy on the leftside. Cycloplegic refraction was +1.50 -0.50 x 180° ODand +1.50D OS. Ten PD of intermittent esotropia wasdocumented on alternate prism cover test. Vertical up-and-down gaze was intact, with a tendency for spontaneousupward deviation suggestive of dissociated vertical

deviation. The esodeviation increased on attempted lateralgaze. Fundus evaluation showed minimal pallor of theoptic-nerve head with a small cup, but otherwise withinnormal limits.

Patient had associated severe global developmentaldelay so that delayed visual maturation was also consi-dered. With intermittent esodeviation in the monofixationrange and fairly good motor fusion in primary gaze(Figure 5), no intervention was recommended at this time.The patient remains under the care of a multidisciplinaryteam.

Case 7A three-year-old male was born full term to a 27-year-

old primigravid via Caesarian section secondary to cepha-lopelvic disproportion. There was no maternal illness orexposure to teratogens or radiation.

At birth, patient had good cry, movement, and color.There was note of syndactyly of the left hand from secondto fifth digits and right talipes equinovarus. The left nippleand pectoralis muscle were absent. Clubfoot was operatedon prior to consultation at our institution.

Evaluation done at 3 years of age revealed finger play

Figure 4. Gaze Composite. A small angle of 20PD of exotropia on primary gaze with some degree of limited lateral versions was evident. There is mild “X” pattern with increase in angle

of exotropia on straight up and down gaze. Patient had bilateral partial abduction deficit.

Figure 5. Gaze Composite. A 10 PD of intermittent esotropia was documented on alternate prism cover test. The esodeviation increases on attempted lateral gaze. Small lateral

excursion on straight upgaze noted, with a small binocular field of vision apparent on primary and slight upgaze. Vertical up and down gaze somewhat preserved, with a tendency for

spontaneous upward deviation suggestive of dissociated vertical deviation. Left eye moves up on attempted right gaze. Either upshoot or dissociated vertical deviation was considered.


at 6 meters OU, with bilateral epiblepharon, trichiasis,and epicanthus. There was intact gross hearing. Tonguewas midline on protrusion with intact gag reflex. Pupillaryand fundus evaluation were normal. In primary gaze,patient was orthotropic without refixation movement onalternate prism cover test. Esotropia was noted only onup-and-down gaze but represented target convergence(Figure 6). Abduction was absent. Cycloplegic refractionwas +3.00D OU. Reduced hyperopic prescription of+1.50D OU was given, with plans of bilateral blepharo-plasty for trichiasis.

DISCUSSIONAplasia or hypoplasia of the cranial nerves is believed

to result from an ischemic event during the first trimesterof pregnancy, usually at about the fourth to the sixth weekof gestation. Interruption of the blood supply fromcompression of fetal vessels near developing cranial-nervenuclei VI and VII leads to a vascular insufficiency, hencea clinical picture with VI-VII cranial-nerve diplegia.11 Thispresents as typical mask-like facies known as Möbiussequence. Multiple causes of blood-flow interruptioninclude trauma, placental abruption,2 maternal illness,and drug ingestions such as benzodiazepines,13 thalido-mide,7 and misoprostol.4 Anomalous development ofcerebral circulation has also been implicated.12 Thesubclavian-artery-supply-disruption-sequence theory(SASDS) alludes to an interruption of embryonic bloodsupply during the sixth week of gestation. This theory issupported by the histologic documentation of symmetriccalcification (in a vascular distribution) of the dorsaltectum at the midbrain-pons junction, presumably causinghypoxia and ischemia of the affected neural tissues.2,14

In this series, first-trimester insults were identified onlyin three patients (42.9%), with Case 2 exposed to tobaccoand alcohol throughout gestation. The two other casesonly had a vague history of maternal URTI, although onehad confirmed varicella infection. The older maternal age

at the time of delivery (mean of 33.9 years) may beindicative of a relative vascular insufficiency and may becontributory.

Most cases appear sporadic but there have been reportsexhibiting autosomal-dominant, autosomal-recessive, andX-linked inheritance transmissions.15 Familial transmissionhas been reported in 26 patients.16 A gene was localizedin chromosome 3q by linkage analysis in one family withautosomal-dominant Möbius sequence.17 Deletion in thelong arm of chromosome 13 has also been described.18

Whether these are inherited defects or the result of a trig-ger event has not yet been clarified.

Recurrence rate in siblings of about 2% in typical isolatedcases has been reported.19 If associated with skeletal defects,the recurrence rate is very low.7 The syndrome affects bothsexes equally.17 In this series, male patients outnumberedfemale patients 5 to 2 (2.5:1). Typical bilateral VI cranial-nerve involvement consistently gives a large-angle deviationexceeding 40 PD,6 and may even reach up to 100 PD,7,8

especially if associated with secondary changes on themedial rectus muscles. In this series, however, this typicalpresentation of a large-angle deviation was seen only inCases 1 to 4.

That other mechanisms may be responsible is suggestedby Case 4. Associated lid-fissure narrowing on attemptedadduction was present, prompting the patient to preferhis left eye, despite loss of 1 line of Snellen acuity. Thesefindings allude to the presence of cocontraction as thatoccurring in Duane syndrome.3,11,14 Cocontraction mayexplain why Case 5 presented as an exotropia (despitebilateral abduction deficit), intermittent esotropia, andorthotropia. The possibility of an aberrant nerve regene-ration occurring in some cranial-nerve palsies cannot beexcluded.20 In fact, in a 1999 series, orthotropia in primarygaze was reported in 10 out of 25 cases, exotropia in 2,and esotropia in only 7.5

Bilateral facial-nerve involvement was seen in allpatients except Case 4, which had complete left facial-

Figure 6. Gaze composite. Patient is orthotropic on primary gaze without refixation movement on alternate prism cover test. Note slight increased esotropia on up and down gaze that

may be due to target convergence and preservation of accommodation. There is absence of abduction. Some vertical movements noted.


References

1. Peleg D, Nelson GM, Williamson RA, Widnes JA. Expanded Möbius syndrome.

Pediatr Neurol 2001; 4: 306-309.

2. D’Cruz OF, Swisher CN, Jaradeh S, et al. Möbius syndrome: evidence for a vascular

etiology. J Child Neurol 1993; 8: 260-265.

3. Stromland K, Sjogreen L, Miller M, et al. Möbius sequence: a Swedish multidiscipline

study. Eur J Paediatr Neurol 2002; 6: 35-45.

4. Vargas FR, Schuler-Faccini L, Brunoni D, et al. Prenatal exposure to misoprostol

and vascular disruption defects: a case-control study. Am J Med Genet 2000; 95:

302-306.

5. Miller MT, Stromland K. The Möbius sequence: a relook. J Am Assoc Pediatr

Ophthalmol Strab 1999; 3: 199-208.

6. Spierer A, Barak A. Strabismus surgery in children with Möbius syndrome. J Am

Assoc Pediatr Ophthalmol Strab 2000; 4: 58-59.

7. Elsahy NI. Möbius Syndrome associated with the mother taking thalidomide during

gestation: case report. Plast Reconstr Surg 1973; 51: 93-95.

8. Laby DM. Möbius syndrome. In: Rosenbaum A and Santiago AP, eds. Clinical

Strabismus Management: Principles and Surgical Techniques. Philadelphia: W.B.

Saunders, 1999; Chap. 26: 358-362.

9. Herrmann J, Pallister PD, Gilbert EF, et al. Studies of malformation syndromes of

man XXXXI B: nosologic studies in the Hanhart and the Möbius syndrome. Eur J

Pediatr 1976; 122: 19-55.

10. Abramson DL, Cohen MM, Mulliken JB. Möbius Syndrome: classification and grading

system. Plast Reconstr Surg 1998; 102: 961-967.

11. Miller MT, Ray V, Owens P, Chen F. Möbius and Möbius-like syndromes (TTV-

OFM, OMLH). J Pediatr Ophthalmol Strab 1989; 26: 176-188.

12. Carr MM, Ross DA, Zuker RM. Cranial-nerve defects in congenital facial palsy. J

Otolaryngol 1997; 26: 80-87.

13. Courtens W, Vamus E, Hainaut M, et al. Möbius syndrome in an infant exposed to

benzodiazepines. J Pediatr 1992; 121: 833-834.

14. St Charles S, DiMario FJ, Grunnet M. Möbius syndrome: further in vivo support for

the subclavian artery supply disruption sequence. Am J Med Genet 1993; 47: 289-

293.

15. Kumar D. Möbius syndrome. J Med Genet 1990; 27: 122-126.

16. MacDermont KD, Winter RM, Baraitser M. Oculofacial bulbar palsy in mother and

son: review of 26 reports of familial transmission within the Möbius spectrum of

defects. J Med Genet 1991; 28: 18-26.

17. Kremer H, Kuyt LP, van den Helm B, et al. Localization of a gene for Möbius

syndrome in chromosome 3q by linkage analysis in a Dutch family. Hum Mol Genet

1996; 5: 1367-1371.

18. Slee JJ, Smart RD, Viljoen DL. Deletion of chromosome 13 in Möbius syndrome. J

Med Genet 1991; 28: 413-414.

19. Cronemberger MF, de Castro Moreira JB, Brunoni D, et al. Ocular and clinical

manifestations of Möbius syndrome. J Pediatr Ophthalmol Strab 2001; 38: 156-

162.

20. Moffie D. Aberrant nerve fibres within the central nervous system. Clin Neurol

Neurosurg 1992; 94: Sl27-S129.

21. Richards RN. The Möbius syndrome. J. Bone Joint Surg 1953; 35A: 437-444.

22. Baraitser, M. Genetics of Möbius syndrome. J Med Genet 1977; 14: 415-417.

23. Zucker RM, Goldberg CS, Manktelow RT. Facial animation in children with Möbius

syndrome after segmental gracilis muscle transplant. Plast Reconstr Surg 2000;

106: 1-8.

24. Foster RS. Vertical muscle transposition augmented with lateral fixation. J Am Assoc

Pediatr Ophthalmol Strab 1997; 1: 20-30.

25. Santiago AP, Rosenbaum AL. Selected transposition procedures. In: Rosenbaum

A and Santiago AP, eds. Clinical Strabismus Management: Principles and Surgical

Techniques. Philadelphia: W.B. Saunders, 1999; Chap. 36: 476-489.

26. Britt MT, Velez FG, Thacker N, et al. Partial rectus muscle-augmented transposition

in abduction deficiency. J Am Assoc Pediatr Ophthalmol Strab 2003; 7: 325-332.

nerve palsy but partial paresis only on the right. This canbe observed as facial asymmetry or mask-like facies, down-ward sloping of upper lip, incomplete closure of mouth,and lagophthalmos. The involvement of bilateral VIIcranial nerve, together with bilateral VI cranial nerve, isnecessary before a diagnosis of Möbius sequence can bemade. Involvement of the IX-X cranial nerves was gleanedfrom feeding difficulties, recurrent regurgitation, andaspiration, often complicated with malnutrition as well.In 4 patients, the involvement of the XII cranial nervewas evident with tongue atrophy or deviation.

Limb anomalies consistent with Hanhart (Poland-Möbius) syndrome were seen in four (57%) patients.Findings such as syndactyly, talipes equinovarus, absenceof unilateral nipple, breast, and pectoralis muscles, as wellas absence or underdevelopment of distal phalanges ofhands and absence of toenails were seen. This compareswell with the 43% reported by Croenemberger in hisseries.19 There are experts, however, who recognize theseabnormalities of extremities and trunk as essential featureof Möbius sequence.21,22 Nonetheless, there was no corre-lation between limb abnormalities and extent of cranial-nerve involvement.23

Mental retardation in this series was seen in 57% ofpatients (4/7) compared with 75% in a much larger seriesof 16 patients.19 Notably, seizure disorder was seen in 2patients and poor control may have also contributed topoor cortical and visual function.

The typical VI cranial-nerve palsies in Möbius sequencegive a large-angle deviation that exceeds 40 PD. Invariably,the medial rectus muscle develops a contracture (Cases 1to 4). In patients with partial VI nerve function, a recessionof the medial rectus combined with a resection of thelateral rectus may suffice.6,8 Bimedial rectus recession initself, however, is usually inadequate.6 In patients with totalabduction deficit, especially with preservation of verticalgaze, the superior rectus muscle and the inferior rectusmuscle may be transposed beside the lateral rectus muscle.Our preferred procedure is lateral augmentation. Thisprocedure, however, may result in overcorrections.8,24,25

We reserve medial rectus weakening as a second proce-dure, and prefer chemodenervation of the contractedmedial rectus muscle. A partial transposition with lateralaugmentation to decrease the strength of the procedure,as well as preserve a second ciliary blood supply per verticalrectus muscle, has been described.26 This procedure mayprove useful for these patients.

Management of refractive errors, amblyopia, and stra-bismus follows existing guidelines in treatment.

Many patients with Möbius sequence have multiple

problems aside from age deviation, eating and communi-cation difficulties resulting from facial palsy, cleft palate,and tongue anomalies. Cranial-nerve-IX-XII involvement,for example, leads to feeding and speech problems, aswell as malnutrition. Developmental delay, seizuredisorder, and dental caries all require specialists’ care. Therecognition and reinforcement of strengths and resi-liencies such as family support, faith, sense of self, specialskills, determination, and networking help maximize theirpersonal and professional success as adults.


CASE REPORT



Richard C. Kho, MD


Correspondence to:

Richard C. Kho, MD

15 General de Jesus St., Heroes Hill


Tel: +63-2-6360762

Fax: +63-2-6385837




ABSTRACT

ObjectiveTo present a case of bilateral optic neuropathy secondary to optic-nerve

compression by the internal carotid artery (ICA).

MethodsObservational case report; single patient seen in private practice.

ResultsCompression of the optic nerves by the ICAs as the etiology of unexplained

progressive optic neuropathy is reported. The patient refused further inva-sive procedures after diagnosis.

ConclusionCompressive optic neuropathy due to direct pressure by the adjacent ICA

should be considered as a possible etiology of occult, progressive visual loss inan otherwise healthy patient. Although rare, the clinical picture of progres-sive optic neuropathy backed by evidence of magnetic resonance imaging(MRI) should clinch the diagnosis early and spare the patient from furtherunnecessary ancillary work-up.

Keywords: Compressive optic neuropathy, Internal carotid artery, Dolichoectatic artery,Fusiform enlargement


Optic-nerve compressionby the internal carotid arteryas a cause of “unexplained”

optic atrophy


PROGRESSIVE loss of vision secondary to optic-nervecompression by the supraclinoid portion of the internalcarotid artery (ICA) became known before the age ofcomputed tomography.1-3 Neurosurgical exploration wasfrequently utilized to evaluate the etiology of occultprogressive optic neuropathy.2 With the advent of andsubsequent advances in neuroimaging techniques, interestin this clinical entity was revived with noninvasive methodsof assessing the anatomic relationship between the opticnerve and the supraclinoid ICA.4-6 This clinical conditionas a cause of unexplained chronic, progressive visual losshas not been reported in the Philippines. Clinical andneuroradiological correlation of these cases is crucial incorrectly making the initial diagnosis before otherwisehealthy patients presenting with “unexplained” visual lossare either subjected to various unnecessary work-up, orworse, left in the dark about the etiology of theirprogressive blindness.

The author presents a case in which the diagnosis ofoptic-nerve compression by the intracavernous ICAs asthe cause of slowly progressive visual loss eluded cliniciansfor several years before a review of the patient’s old mag-netic resonance imaging (MRI) plates and repeat scansconfirmed the diagnosis.

CASE REPORTA 79-year-old hypertensive male was referred for bila-

teral optic atrophy. The patient had undergone phaco-emulsification with posterior chamber intraocular lens(IOL) implantation on the left eye (OS) in 1997. Best-corrected visual acuity on this eye was 20/40 at the time.The right eye (OD) underwent the same procedure in2001. Optic-nerve pallor was initially noted on the righteye at the time after the patient complained of gradualand progressive blurring of vision. Ancillary proceduresconducted revealed the following: MRI of the orbits andoptic nerves (Figure 1) was read as within normal, fluores-cein angiogram (FA) was normal, visual-evoked response(VER) showed severe conduction defect in OD and mildconduction defect in OS, electroretinography (ERG)revealed reduced cone (macula) responses and normalrod responses in both eyes (OU), automated achromaticperimetry showed diffuse depression greater in ODcompatible with advanced optic-nerve damage. Routinecardiovascular and blood chemistry did not yield anyinsights as to the etiology of the visual loss.

At the time of consultation, best-corrected visual acuitywas 20/200 OD and 20/40 OS. Slit-lamp examinationshowed normal anterior chambers with a centrally placedposterior chamber IOL in both eyes. Intraocular pressureswere normal and motility examinations were withinnormal limits. Fundus examination with a 78D lensrevealed bilateral optic-nerve pallor, greater in OD. The

vascular arcades and the rest of the posterior pole did notshow any gross abnormalities. A review of MRI scansperformed two years prior to the consultation showed thatthe intracavernous portion (Figure 1) of the ICA impingedon the chiasm, with slightly greater indentation on theright side. These scans were sent to a neuroradiologist forreview and new MRI scans of the orbit/optic nerves wererequested for comparison. Figure 2 shows a coronal sectionthrough the chiasmal portion of the optic nerves on therepeat MRI. The supraclinoid and cavernous ICAs arebilaterally tortuous and mildly ectatic. Both ICAsdemonstrate vascular segments which are more mediallyand superiorly located than the average patient, abuttingthe optic chiasm bilaterally, as well as a significant portionof the prechiasmatic segments of both optic nerves. Theright side of the optic chiasm/proximal right optic nerveis superiorly displaced and draped around the subjacent

Figure 2. Repeat MRI ( August 26, 2004). T1-weighted coronal section shows both ICAs

(black arrows) pushed up against the chiasm (white arrow), greater on the right side (right

optic nerve literally wrapped over the convexity of the artery).

Figure 1. First MRI (October 9, 2002). T1-weighted coronal section through the chiasm

(white arrow) and intracavernous internal carotid arteries (black arrows).


right intracranial ICA segment. The optic chiasm appearssmaller than average and probably represents atrophyfrom chronic compression by the intracavernous ICAs.The patient refused further invasive treatment, includingscant neurosurgical options, which have not been tried inthe Philippines.

DISCUSSIONUnilateral or bilateral optic neuropathy secondary to

fusiform enlargement or “dolichoectasia” of the ICA as acause of occult, slowly progressive loss of vision haspreviously been reported in foreign literature.1-3 In thisage of high-resolution neuroimaging techniques, renewedinterest in the intimate anatomic relationship between theoptic nerve and the supraclinoid ICAs has emerged. Golnikand associates analyzed the MRIs of 20 patients presentingwith unexplained optic-nerve dysfunction and speculatedthat the anatomic proximity between the optic nerve andthe ICA may be important in the development of opticneuropathy.4 Jacobson and associates further elucidatedon this anatomic relationship by analyzing the MRIs of100 patients who underwent the procedure for a varietyof reasons unrelated to visual loss or optic neuropathy.5

The authors presented a grading scheme to classify theirappearance on neuroimaging as follows: Grade 0, nocontact; Grade 1, contact but without distortion of the opticnerve (i.e., contact but no compression); Grade 2, contactwith distortion of the optic nerve contour (i.e., compres-sion). Surprisingly, contact (no compression) between thetwo structures occurred at a high frequency (70%), whilecompression was noted at a much lower frequency (30%)in these asymptomatic patients. It should be noted fromthis study that neuroradiological evidence of contact orcompression of the optic nerves need not be accompaniedby clinically evident optic neuropathy. In a follow-up paper,Jacobson described symptomatic compression of the opticnerve in 24 eyes of 18 patients with radiologic evidence ofcontact and compression.6 Hypertension (present in ourpatient) was noted in 10 of 18 patients in this series.

In our patient, it was evident that optic-nerve contactand compression by the ICA (Grade 2 on the right; Grade1-2 on the left) was already present when the first MRI wastaken almost two years before this consultation (Figure 1).The arterial ectasia and optic-nerve compression in theright eye appear to be worse than in the left eye, clinicallyevident as worse optic-nerve dysfunction on this side(Figure 2). This diagnosis was missed on the first MRIwhen the optic nerves were read as within normal limits.Several ophthalmologists who evaluated the patient at thetime could not identify the etiology of the opticneuropathy after subjecting the patient to various ancillaryprocedures. Discussions with local neuroradiologistsconfirmed that contact between these structures is

occasionally seen on MRI but is neither considered norreported as a potential cause of progressive “unexplained”optic neuropathy in the local setting. Armed with MRIplates returned as “normal,” attending ophthalmologistsconsequently do not consider this etiologic possibility forthe optic neuropathy. A review of the local literature didnot yield any report on this condition. To our knowledge,this is the first local report.

The prognosis for visual improvement in this patient(who refused further invasive procedures) was not encou-raging. Although isolated reports of visual improvementwith neurosurgical procedures to decompress optic-nervecompression by the ICA have been published,7 it is stillunclear whether these procedures are beneficial at all inthe reversal of existing visual loss or prevention of furtheroptic neuropathy.2, 6 These procedures should not beexpected to reverse the optic neuropathy if ischemia fromcompression is its predominant mechanism.

The rate of visual loss in these cases without surgicalintervention tends to be very slow.6 Subsequent follow-upsshould give the clinician an idea of the course of the opticneuropathy, which may be slowly progressive or static.Improvement in the cardiovascular status shouldtheoretically be beneficial, as ageing and hypertension arecorrelated with an increase in arterial diameter. Indeed,Jacobson et al. noted that the estimated odds of com-pression were increased by a factor of 2.54 for eachmillimeter increase in the diameter of the carotid artery.5

Thin-section, T1-weighted, coronal cuts constitute theoptimal MRI protocol for identifying optic-nerve compres-sion by the ICA (Figures 1 and 2). Presented with clinicalfindings of progressive optic neuropathy and evidence ofcompression on MRI (not just contact), the clinician mayspare the patient from unnecessary ancillary tests anddelay in diagnosis. Certainly, these MRI techniques shouldbe performed on any patient presenting with progressiveoptic neuropathy of unknown etiology. Though rare andunreported locally, optic-nerve compression by the supra-clinoid carotid artery should be kept in mind as a potentialcause of “unexplained” progressive optic neuropathy.

References

1. Bergaust B. Unusual course of internal carotid accompanied by bitemporal

hemianopsia. Acta Ophthalmol (Scand) 1963; 41: 270-274.

2. Mitts MG, McQueen JD. Visual loss associated with fusiform enlargement of the

intracranial portion of the internal carotid artery. J Neurosurg 1965; 23: 33-37.

3. Manor RS, Ouaknine GE, Matz S, Shalit MN. Nasal visual field loss with intracranial

lesions of the optic nerve pathways. Am J Ophthalmol 1980; 90: 1-10.

4. Golnik KC, Hund PW III, Stroman GA, Stewart WC. Magnetic resonance imaging

in patients with unexplained optic neuropathy. Ophthalmology 1996; 103: 515-520.

5. Jacobson DM, Warner JJ, Broste SK. Optic-nerve contact and compression by the

carotid artery in asymptomatic patients. Am J Ophthalmol 1997; 123: 677-683.

6. Jacobson DM. Symptomatic compression of the optic nerve by the carotid artery:

clinical profile of 18 patients with 24 affected eyes identified by magnetic resonance

imaging. Ophthalmology 1999; 106: 1994-2004.

7. Colapinto EV, Cabeenn MA, Johnson LN. Optic nerve compression by a

dolichoectatic internal carotid artery: a case report. Neurosurgery 1996; 39: 604-

606.


CASE REPORT



Joseph M. Ranche, MDRaul D. Cruz, MDFroilan P. Inocencio, MD


Correspondence to

Joseph M. Ranche, MD


University of the Philippines

Philippine General Hospital

Taft Avenue, Ermita


Tel: +63-2-5218450 ext. 2178




ABSTRACTObjective

To emphasize the importance of diagnosing cases of methanol toxicity,demonstrate the value of electrophysiologic testing as an adjunct in the diag-nosis, and provide a framework for intervention.

MethodsThis is a case report.

ResultsThe patient’s visual-evoked-response tracing showed failure of transmission

while electroretinogram waveforms were normal. The findings were consis-tent with bilateral optic neuropathy from ingestion of methanol.

ConclusionComplete clinical history and ophthalmologic examination are vital to the

diagnosis of methanol toxicity. Respiratory assessment and support andtreatment of acidosis are the cornerstone of its management. Currently, theprimary therapeutic approach is the use of competitive inhibitors of alcoholdehydrogenase.

Keywords: Methanol toxicity, Methanol-induced optic neuropathy, Alcohol-related ocular toxicity


Methanol-induced bilateraloptic neuropathy


LAMBANOG, a local liquor manufactured fromcoconut, is common in many areas in the Philippines.There have been anecdotal reports of alcohol-inducedblindness (popularly referred to as gin bulag) incommunity health centers and provincial hospitalsattributed to intake of lambanog that had been laced withmethanol to enrich its alcohol strength. To our knowledge,such cases have never been reported in local scientificliterature.

We report a case of a 72-year-old female with methanol-induced blindness to:

1. emphasize the importance of a thorough clinicalhistory and physical examination in the diagnosis ofmethanol toxicity,

2. review the significant findings in methanol toxicity,3. illustrate the current pathophysiologic concepts in

methanol toxicity, and4. outline current and potential areas of intervention

and study in the treatment of methanol toxicity.

CASE HISTORYA 72-year-old female, regular alcohol drinker, consulted

at the General Clinic of the Department of Ophthal-mology, University of the Philippines-Philippine GeneralHospital (UP-PGH) after becoming blind following intakeof locally manufactured lambanog.

Seventeen days prior to consultation, the patient andsix other female relatives drank lambanog. She consumedabout 1 liter of the liquor over a 9-hour drinking session.The next day, she experienced sudden clouding of visionwith associated headache, nausea, and abdominaldiscomfort. Three days later, she became blind.

Medical and family history was unremarkable. Initialexamination revealed vital signs within normal limits(BP 120/80; HR 78; RR 20). Patient had no lightperception in both eyes (OU). Pupils were dilated at 5mm and nonreactive to light. Intraocular pressureswere normal. There was a 2+ nuclear sclerosis withposterior subcapsular cataract OU. Dilated fundoscopicexamination showed distinct disc borders with gene-ralized disc pallor, a cup-disc ratio of 0.3 OU, an artery-to-vein caliber ratio of 2:3. No hemorrhages or exudateswere seen. The rest of the neurologic examination wasnormal.

Optic neuropathy secondary to methanol toxicity wasconsidered.

Further work-up included chromatographic analysis ofthe liquor sample, which revealed the presence ofmethanol. Visual-evoked response (VER) showed failureof optic-nerve conduction while electroretinogram (ERG)was normal. Cranial computed tomography (CT) showedphysiologic calcifications in the basal ganglia, particularlyin the area of the lentiform nucleus.

DISCUSSIONMethanol (CH3OH, wood alcohol) is a common addi-

tive solvent in fuel, windshield washing fluids, photo-copying fluids, and paint removers. It has also been usedas an adulterant to bootleg liquor.1, 2 Ingestion of liquorhas been implicated in methanol toxicity as early as 1904,with the publication of Wood and Buller’s report on 153cases of blindness caused by methyl alcohol poisoning.3 Amajor catastrophe in 1951 documented 323 cases ofmethanol toxicity after intake of bootleg whiskey contain-ing 35-40% methanol, later published as a comprehensivestudy by Benton and Calhoun in 1953. Most recent was acase in December 2000 of a Finn developing visualdeterioration resulting in monocular blindness (countingfingers in the left eye) following ingestion of locallyproduced coconut liquor in Indonesia.4 Halavaraa et al.reiterated the importance of history-taking and thepresence of neuro-ophthalmologic findings as central inthe diagnosis of methanol toxicity.4 A high index ofsuspicion to the possibility of toxic alcohol ingestion inthe setting of ethanol intoxication is important asmethanol toxicity may mimic ethanol intoxication earlyon.4, 5, 6

Our patient presented initially with nausea, vomiting,and central-nervous-system (CNS) depression, symptomsthat are nonspecific and may be attributed to the directtoxic effects of methanol.1, 7 She experienced blurring ofvision 18 hours after ingesting the poison. This is explainedby the lag time needed for the body to metabolize thepoison to formic acid, an inhibitor of mitochondrialcytochrome oxidase that causes metabolic acidosis andtissue injury.1, 7 ,8

Human and animal models of methanol ocular toxicityhave shown particular vulnerability of the optic nerve andthe retina; 9, 10, 11, 12, 13, 14 the mechanism of injury, however,remains obscure. It has been theorized that this may bedue to:

1. the differentially larger oxygen demand in thesestructures (Zitting et al. 1982, as cited by Liesivuori J &Savolainen H. 1991),8

2. low cytochrome-oxidase activity combined withselective accumulation of formate in the said structures,9 or

3. differential mitochondrial uptake.14

It is generally accepted that the final common pathwayfor nerve or retinal damage is mitochondrial toxicitycaused by the metabolite formic acid.8, 9, 14

Initial fundus findings reveal optic-disc hyperemia oredema with associated blurring of vision resulting frommitochondrial disruption, leading to histotoxic anoxia.If uncorrected, this can progress to cell death observedas pseudoglaucomatous changes or optic atrophy4, 6, 8, 10 asseen in our patient. Optic-nerve and retinal pathologymanifests as attenuation or loss of VER or ERG waveforms.


Our patient presented with loss of VER waveforms(Figure 1), and normal ERG (Figure 2), indicating thedamaging effect of formic acid was solely in the opticnerve.

Loss of mitochondrial function and the ensuingmetabolic acidosis also predisposes certain areas of thebrain to hemorrhage, necrosis, and calcifications, owingto disrupted membrane integrity.8, 9, 14 These pathologicchanges as seen in T2 weighted images via gradient spinecho technique are helpful in the diagnosis of methanoltoxicity.4

A framework (Figure 3) for understanding the patho-physiologic mechanism of methanol-induced injury ispresented.8, 9, 14 Methanol may exert its effect on the CNSas a direct depressant. Approximately 90% of methanol ismetabolized by alcohol dehydrogenase to formaldehyde.This is the rate-limiting step in methanol metabolismfollowing first order kinetics at small concentrations,eventually reaching saturation and a shift to zero orderkinetics at methanol levels of 20mg/dL. Formaldehyde isfurther oxidized to formic acid, the toxic metabolite ofmethanol.

Formic acid is eliminated by the body through itsentrance in the one carbon unit transfer utilizing folateas a co-factor. Formate combines with tetrahydrofolatethrough formyl-THF synthetase to form 10-formyl-THF,which undergoes further oxidation to create CO2 andH2O. Alcoholics have been documented to have lowerlevels of folate, which may predispose them to thedamaging effects of formate owing to its slowermetabolism.

Formate does damage in a milieu of high-anion-gapmetabolic acidosis (HAGMA). More importantly, it is adirect inhibitor of the mitochondrial cytochrome oxidase,thereby disrupting the oxidative process occurring in therespiratory chain. This leads to anoxia, which is morepronounced in areas of high ATP dependence like theoptic nerve and retina. Anoxia leads to membranedisruption leading to the morphologic changes noted onthe level of the mitochondria. Acidosis aggravates theseas protons increase the production of membrane-damaging reactive oxygen species as well as the influx ofCa++ through membranes.

Based on the pathophysiology of methanol toxicity, thereare several approaches to treatment (Figure 3).1, 8, 9, 14, 15, 16

The cornerstone of poisoning management is respiratoryassessment and support, and the treatment of acidosis.The presence of formate has been shown to correlate withfindings indicative of HAGMA and decreased serumbicarbonate.

Currently, the primary therapeutic approach is the useof competitive inhibitors of alcohol dehydrogenase(ADH). Intravenous or oral ethanol has long been utilized

Figure 1. Visual-evoked-response tracing.

Figure 2. Representative electroretinogram tracings.


because of its greater affinity for ADHthan methanol. It blocks formateproduction, allowing the respiratoryand renal routes of excretion ofmethanol to set in. Recently, analternative inhibitor 4-methylpyrazole (Fomepizole, Antizole,Orphan Medical, Minnetonka, MN,USA) has clinically been shown to beeffective in the treatment of methanolpoisoning.16

Other approaches to managementof acute intoxication are:1, 14, 15

1. Hemodialysis to enhancemethanol elimination. There areconflicting findings on the role ofdialysis in formate elimination.1

2. Bicarbonate treatment tocounter metabolic acidosis.

3. Treatment with folic acid orfolinic acid to counter the metabolismof formate.

Other approaches undergoinganimal studies are:13, 14, 15

1. Photobiomodulation using redto near-infrared wavelengths toupregulate cytochrome oxidase,thereby overcoming the inhibition byformate. Photobiomodulation usinglight-emitting diode may provide acheap alternative in methanol toxicityand retinal and optic-nerve conditionswhere the final common pathway liesin the inhibition of cytochrome ordisruption in the respiratory chain.14

2. Use of antioxidants as adjunctin treatment. They act as scavengersof oxygen radicals created by theproton-rich milieu.

References

1. Dyer S. Methanol Update. Clinical Toxicology Review

1998: http://www.maripoisoncenter.com/ctr/

9802methanol.html (accessed May 2004).

2. Davis LE, Hudson O, Benson BE, et al. Methanol

poisoning exposures in the United States: 1993-

1998. Clin Toxicol 2002; 40: 499-505.

3. Hayreh MS, Hayreh SS, Baumbach GL, et al. Methyl

alcohol poisoning: ocular toxicity. Arch Ophthalmol

1977; 95: 1851-1858.

4. Halavaraa J, Valanne L, Setälä K. Neuroimaging

supports the clinical diagnosis of methanol poisoning.

Neuroradiology 2002; 44:924-928.

5. Weinberg L, Stewart J, Wyatt JP, et al. Unexplained

drowsiness and progressive visual loss: methanol

poisoning diagnosed at autopsy. Emerg Med 2003;

15: 97-99.

6. Cursiefe C, Bergua A. Acute bilateral blindness

caused by accidental methanol intoxication during

fire “eating”. Br J Ophthalmol 2002; 86: 1064-1065.

7. Kerns W II, Tomaszewski C, McMartin K, et al.

Formate kinetics in methanol poisoning. Clin Toxicol

2002; 40: 137-143.

8. Liesivuori J, Savolainen H. Methanol and formic acid

toxicity: biochemical mechanisms. Pharmacol Toxicol

1991; 69: 157-163.

9. Martin-Amat G, Trephly TR, McMartin KE, et al.

Methyl alcohol poisoning, development of a model

for ocular toxicity using the rhesus monkey. Arch

Ophthalmol 1977; 95:847-850.

10. Baumbach GL, Cancilla PA, Martin-Amat G, et al.

Methyl alcohol poisoning, alterations of the

morphological findings of the retina and optic nerve.

Arch Ophthalmol 1977; 95: 1859-1865.

11. Mbia JE, Guerit JM, Haufroid V, Hantson P.

Fomepizole therapy for reversal of visual impairment

after methanol poisoning: a case documented by

visual-evoked-potential investigation. Am J

Ophthalmol 2002; 134: 914-916.

12. Plaziac C, Lachapelle P, Camanova C. Effects of

methanol on the retinal function of juvenile rates.

Neurotoxicology 2003; 24: 255-260.

13. Seme MT, Summerfelt P, Nietz J, et al. Differential

recovery of retinal function after mitochondrial

inhibition by methanol intoxication. Invest Ophthalmol

Vis Sci 2001; 42: 834-841.

14. Treichel JL, Henry MM, Shumutz CMB, et al.

Formate, the toxic metabolite of methanol, in cultured

ocular cells. Neurotoxicology 2003; 24: 825-834.

15. Eells JT, Henry MM, Summerfelt P, et al. Therapeutic

photobiomodulation for methanol-induced retinal

toxicity. Proc Natl Acad Scie U S A 2003; 100: 3439-

3444.

16. Brent J, McMartin K, Philips S, et al. Fomepizole for

the treatment of methanol poisoning. N Engl J Med

2001; 344: 424-429.

Figure 4. Pathophysiology of methanol toxicity showing sites of potential interventions.

Eliminated

via Lungs &

Kidneys

Methanol Formaldehyde Formic Acid CO2 + H

20

bicarbonate

HAGMA Inhibits

Cytochrome

Oxidase

1. Increased

ROS7

2. Increased

Ca++ influx

Loss of

Membrane

Integrity

Arrest of

Cellular

Respiration

Cell death

A

D

H1

F

D

H2

T

H

F3

��

� � �

�

Direct

Toxicity:

CNS5

depression

GI6

�

��

� �

�

ETOH,4

4-methyl

pyrazole

Supportive

Antioxidant

Folate,

folinic acid

Photobio-

modulation

Dialysis

1. Alcohol Dehydrogenase

2. Formaldehyde Dehydrogenase

3. Tetrahydrofolate Reductase

4. Ethanol therapy

5. Central nervous system

6. Gastrointestinal

7. Reactive oxygen species

��



OphthalmologyLETTERS

OCTOBER - DECEMBER 2004VOL. 29 • NO.4

On the new PJO format

EDITOR’S REPLY: Thank you for your interestand support of the PJO. Your continualsupport of the Philippine Academy ofOphthalmology (PAO) with payment of theannual dues entitles you to a one-yearsubscription (4 issues) of the PJO. The orderform enclosed in the journal is for those whowish to subscribe but are not members ofthe PAO.

Undoubtedly, only a few teaching institu-tions in our country are involved in qualityresearch. We hope this scenario will changein the near future when research will be apart not only of an academic’s life but aclinician’s as well. Research results from

keen observation of diseases encountered in the clinicsand is a source of continuing medical education. Thosewho claim to be experts in particular fields not only haveextensive experience but also do research.

On the article The diagnostic properties of a nerve-fiberanalyzer in glaucoma,1 the conclusion mentioned that theGDx 400 is primarily used as a screening tool to detectthe presence or absence of glaucoma because of the fairsensitivity and specificity obtained. When one studies thediagnostic properties of an instrument, one deals withsensitivity, specificity, predictive values, and likelihoodratios. These were extensively discussed in the paper.

I trust that you read the whole article and was able toglean the message imparted.

Patricia M. Khu, MD

Editor in Chief

DEAR EDITOR: Thank you on theefforts done. Your journal is oneof the best ophthalmology jour-

nals. I hope you give me the chance to followthe journal.

Munsour Agroum, MD

[email protected]

�

�

Welcome changes, but why are authors mostly from PGH?

DEAR EDITOR: Congratulationson the “new” PJO. The latestchanges introduced are very

welcome, specifically the utilization of color.Vol 29 No 2 has improved further when youused colored pictures. The present form ofPJO makes it more inviting to read; it looksmore vibrant. What a great job!

I would like to thank you for sendingcopies to me. But I’m wondering if the first2 issues are just “sample” issues because thereis an order form enclosed in each issue. Doesthat mean that if I don’t place an order, Iwon’t receive the subsequent issues? All thewhile I thought the PJO is free to all membersin good standing, meaning those who pay their annualdues. Right now, the only thing tangible that I get fromPAO (in exchange for my annual dues) is PJO.

I noticed that most of the papers are from PGH doctors.Does that mean that only a few doctors from otherhospitals submit papers?

Comment on the article The diagnostic properties of a nerve-fiber analyzer in glaucoma:1 In contrast to all the otherarticles, in its abstract, the objective and the conclusiondo not match or meet. The conclusion does not answerthe objective.

Matabai A. Lim, MD

Cotabato City

[email protected]

1. Khu PM, et al. The diagnostic properties of nerve-fiber analyzer in glaucoma. Philipp

J Ophthalmol 2004; 29: 66-72.

EDITOR’S REPLY: Thank you for your interest andsupport of the PJO. The Editorial Board strives togive our readers quality and relevant articles inthe field of Ophthalmology and Visual Science.We hope to serve the educational needs of prac-ticing ophthalmologists in the Philippines.

Patricia M. Khu, MD

Editor in Chief



OphthalmologyINDEX


AAbduction, 180, 182, 184 Adduction, 178, 180Aberrations

comparison of higher order in low to moderatemyopia, 33

measurement of wavefront, 34Abscess

postsurgical suppurative scleral, 194Achromatic perimetry, 64ADH. See alcohol dehydrogenaseAdrenergic response

induced by cortocosteroid, 10Advanced Glaucoma Intervention Study,

implications on clinal practice, 99, 105,on the protective role of IOP lowering, 169

Age-related macular degeneration as a cause of blindness, 47

AGIS. See Advanced Glaucoma Intervention StudyAIDS

ocular toxoplasmosis in patients with, 92AIGS. See Association of International Glaucoma

SocietiesAION. See ischemic optic neuropathyAlcohol dehydrogenase

use in management of alcohol-induced opticneuropathy, 189

Alstrom syndrome, 95Alstrom’s disease, 196Amaurosis, 161Amblyopia, 46, 141, 179Amphotericin B, 28Amvisc Plus, 12Aniridia, 141–142Ankyloblepharon, 146Anophthalmos, 145Antifibrotic agent

factors to consider when using, 86Anti-Koch’s treatment

as a cause of optic neuropathy (editorial), 158See also ethambutol-induced optic neuropathy

Aplasia, 184Applanation tonometry

See Goldmann applanation tonometryApoptosis

in human retinal pigment epithelium cells in vitro, 6

Subject index to volume 29Apoptotic cells

quantification of, 9Arachnoid villi, 164Argon laser

sequential argon-YAG compared with Nd:YAG, 132Aspergillus flavus, 26–28Aspiration-biopsy cytology, 176–177Association of International Glaucoma Societies

recommendations on assessment of optic nerveand management of glaucoma, 77

Astigmatism, 97Atovaquone, 92Atrophy

macular, in Usher syndrome, 195of the retinal pigment epithelium and

choriocapillaries in Usher syndrome, 195optic, in methanol-induced neuropathy, 190

Atypical optic neuritis, 162

BBAER. See Brainstem-auditory-evoked responseBardet-Biedl syndrome

a case of, 94associated with deafness and pigmentary

retinopathy, 196diagnostic criteria for, 95–96differential diagnoses, 95management of, 97manifestations of, 94, 95ophthalmologic problems in patients with, 97

BBS. See Bardet-Biedl syndromeBevel down technique, 119Biemond II syndrome, 95Blindness

alcohol-induced, 190causes of, 47DOH Prevention of Blindness Program, 44, 45childhood, 47, 141in systemic lupus erythematosus, 18prevalence in the Philippines, 43results of first national blindness survey, 45Second National Blindness Survey, 44

Brachydactyly,in Möbius sequence, 96–97

Brainstem-auditory-evoked response, 181


CCandida parasilopsis, 26–28Capsulorhexis, 121Cataract

blindness, 46–47brunescent, 119childhood, 141chopping techniques for brunescent, 118–121dense/hard, 118familial, 141idiopathic, 141–142in infancy, 141posterior subcapsular, 17prevalence of operable, 47profile of childhood cases at Philippine General

Hospital, 140secondary, 142surgery/surgery rate, 12, 46–47, 122case of postsurgical scleritis, 193

See also surgically induced necrotizing scleritis aftercataract surgery

Cat’s eye reflex, 136–137CCT. See central corneal thicknessCentral corneal thickness

correlation with IOP among Filipinos, 79predictive factor in the development of primary

open-angle glaucoma, 100Central nervous system

abnormalities, 142Central-retinal-vein occlusion, 161Central serous chorioretinopathy

characteristic, 7epinephrine-induced, 10mechanism of cause, 7prevalence, 7

Cerebral palsy, 142Chipping technique, 133Chopping technique, 119CIGTS. See Collaborative Initial Glaucoma Treatment

StudyCiliary body ablation in end-stage glaucoma, 172Coats’ disease, 149Cockayne’s syndrome, 196Collaborative Initial Glaucoma Treatment Study, 65, 99,

103Congenital

anomalies, 150cataract, 141coloboma of the eyelids, 146deafness, 195eye defects, 145heart defects, 142neurosensory deafness, 196

Congenital rubella syndromeas a cause of cataract, 142

Conjunctivamelanoma of, 147

Cornealbirefringence, 70endothelial edema, 132injury, 15scar, 47

Cranial computed tomographyuse in diagnosing methanol-induced optic

neuropathy, 190Cranial nerve

involvement in Möbius sequence, 179–185Cryopexy

indications for use, 125Cryotherapy

in management of melanoma of the conjunctiva,148

Cryptophthalmosa case of, 144associated anomalies, 146management of, 144, 146pathogenesis of, 146

CSCR. See central serous chorioretinopathy

DDemyelinating optic neuritis, 162Dexamethasone

for treatment of toxoplasmic retinochoroiditis, 92in relation to apoptosis in human retinal pigment

epithelium cells in vitro, 6Diabetic retinopathy, 47Diffuse depression, 161Diode-laser transscleral cyclophotocoagulation

single-setting treatment protocol, 171Disc edema, 161Diurnal intraocular-pressure, 168Diurnal curves

comparison of three-point and six-pointdetermination, 167

peaks, 168Dolichoectasia of the internal carotid artery, 188Down syndrome, 140, 142Duovisc, 12

EEarly Manifest Glaucoma Trial, 65, 99, 101Electromagnet

for extraction of metallic intraocular foreignbodies, 38–41

Electrophysiologic testing, 189Elmycin, 26, 28


EMB. See ethambutolEMGT. See Early Manifest Glaucoma TrialEndothelial

cell count, 12cell loss, 15

Epiblepharon, 179–185Epicanthus, 184–185Epilepsy, 142Epinephrine

in apoptosis in human retinal pigment epitheliumcells in vitro, 6

Error of refraction, 46, 47Esotropia in Möbius sequence, 179–185Ethambutol (editorial), 158Ethambutol-related optic neuropathy (editorial), 158Exotropia, 182-–183Extracapsular cataract extraction, 193Extraepithelial proliferation

in malignant melanoma of the conjunctiva, 147Eye care

stages of programs in, 47movement in the Philippines, 46

Eye injuriescaused by metallic objects, 39

FFacies, 179, 181, 183, 185Fibrovascularization

in orbital implants, 31Filtration surgery

causes of failure, 84Fine-needle aspiration biopsy

advantages of, 176a valuable test for malignancy of orbital tumors, 175

First national blindness survey, 45See also blindness

Flynn-Aird syndrome, 196FNAB. See fine-needle aspiration biopsy.Folic/folinic acid

in treatment of methanol-induced optic neuropathy,192

Formaldehyde, 191Formate, 191, 192Formic acid, 191Fraser syndrome, 146Friedreich’s ataxia, 196Fungal keratitis

current treatment protocol for, 27incidence, 27in vitro evaluation of natamycin 5% suspension

for, 26Fusarium solani, 26–28Fusiform enlargement, 186, 188

GGalactosemia

association with cataract, 141Glaucoma

advanced primary open-angle glaucoma 105as a complication of corticosteroid treatment, 20as one of the leading causes of blindness, 47as ocular manifestation of systemic lupus

erythematosus, 17causes of failure of filtration surgery, 84central corneal thickness and intraocular pressure

correlation, 79ciliary body ablation in end-stage, 172detecting the disease early, 71diurnal IOP curves, 167filtering surgery, 103gold standard in diagnosis, 64Hemifield Test, 103implications of randomized, controlled clinical

trials, 99neovascular, 174normal-tension, 168primary angle-closure, 132primary open-angle, 100progression of optic neuropathy in, 169refractory, 171resulting from expansion of perfluoropopane, 126spectrum of damage in, 70surgical management of, 84

Glioma, 163Goldmann applanation tonometry

correlation with central corneal thickness, 79See also glaucoma, central corneal thickness

measurements confounded by central cornealthickness, 99

HHanhart syndrome, 185Helen Keller International, 44–45Hidden eye

a case of, 144See also cryptophthalmos

Histotoxic anoxia, 190Horizontal chopping technique, 119Hydroxyapatite, 22Hypogenitalism, 95, 97Hypoplasia, 184Hypotony, 171

IICA. See internal carotid arteryImmunosuppressives

rapid response of patients with SINS to, 194


Implantsbiocompatibility, 129causes of migration, 22characteristics of ideal, 22extrusion, 22, 130fibrovascularization, 31freeze-dried human cancellous bone as orbital, 29hollow polymethylmethacrylate, 21hydroxyapatite 22, 30ostrich eggshell implant as an onlay graft substitute

for orbital blow-out fractures, 127Infection

incidence with eggshell implant, 130Infiltrative and compressive optic neuropathies, 162Internal carotid artery, 186–188Intracranial neoplasms, 160Intraocular foreign body

penetrating injuries to the eye, 39extraction using a low-cost electromagnet, 38-41magnetic extraction of metallic, 39

Intraocular surgery, 80Intraocular pressure

accurate measurement of, 80beneficial effect of reduction in open-angle

glaucoma, 99control of, 131fluctuation, 169gold standard for clinical measurement of, 80in diode-laser transscleral cyclophotocoagulation,

171outcome measure in cataract surgery, 12posttrabeculectomy, 83swings, 167

Intraocular-pressure curvescomparison of three-point and six-point diurnal

measurements, 167Intravenous corticosteroids, 159Intravenous methylprednisolone, 159IOFB. See intraocular foreign bodiesIOP. See intraocular pressureIridotomy, 131–132Iris

bleeding, 132perforation, 131perforation-success rate, 132pigmentation, 132

Ischemic optic neuropathy, 162IVMP. See intravenous methylprednisolone

JJoint Tuberculosis Committee of the British Thoracic

Society, 158Jose Rizal Memorial Lecture, 42

KKeans-Sayne syndrome, 196Keratitis

See also fungal keratitisfungal, incidence, 27fungal, treatment protocol, 27prevention in cryptophthalmos, 144in Möbius sequence, 179

Keratoconjunctivitis sicca, 17

LLagophthalmos, 179, 180, 185Lambanog, 190LASEK. See laser-assisted subepithelial keratectomyLaser-assisted subepithelial keratectomy, 37Laser-diode transscleral cyclophotocoagulation

optimum dose, 174single-setting treatment protocol, 171

Laser in situ keratomeleusiscomparison of wavefront-guided and standard laser

in low to moderate myopia, 33–37Laser iridotomy

comparison of Nd:YAG and sequential argon-YAGin Filipino eyes, 131

patency, 131–132success rates, 132

Laser trabeculoplastyin the Early Manifest Glaucoma Trial, 102,in the Collaborative Interventional Glaucoma

Treatment Study, 103LASIK. See laser in situ keratomeleusisLattice degeneration

effect on anatomic outcome of pneumaticretinopexy, 124

Laurence Moon syndrome, 95Leukocoria

bilateral, 148–149in retinoblastoma, 136–137

Lid coloboma, 144Lid edema, 162Low vision, 46, 47Lowe syndrome, 140, 142LTP. See laser trabeculoplastyLupus erythematosus. See systemic lupus erythematosusLupus retinopathy. See systemic lupus erythematosus

MMaloney’s supracapsular flip, 119Melanoma of the conjunctiva

a case of, 147differential diagnosis, 147management of, 148metastasis, 148


MeningiomasSee also optic-nerve meningioma

of the optic-nerve, 160pattern of intracranial extension, 164sphenoid wing, 162

Metabolic acidosis, 191–192Methanol

metabolism, 191toxicity, 190–192cause of bilateral optic neuropathy, 189

Methanol-induced bilateral optic neuropathya case of, 189 approaches to treatment, 191pathophysiologic mechanism, 191–192

MFC. See minimum fungicidal concentrationMIC. See minimum inhibitory concentrationMicrophthalmos, 145Minimum fungicidal concentration, 26–28Minimum inhibitory concentration, 26–28Mitochondrial function

loss of 191–192Mitomycin-C

comparison of outcomes of trabeculectomies usingconcentrations of 0.4 mg/ml and 0.2 mg/ml,83-87

for management of malignant melanoma of theconjunctiva, 148

Möbius sequenceabsence of facial expression in, 179–184cranial-nerve involvement in, 179–185demographic and ocular findings in a series of

Filipino patients, 181diagnostic criteria, 179strabismus presentations in Filipino patients, 178

Modified office-phasing procedurein intraocular-pressure monitoring, 168, 169

NNatacyn, 26–28National Council on Blindness, 44National Institutes of Health, 115National Sight Plan, 44Nd:YAG. See Neodymium: Yttrium-Aluminum-GarnetNecrotizing scleritis, 193–194Neodymium: Yttrium-Aluminum-Garnet

comparison with argon-YAG, 132in ciliary body ablation, 172–173

Nerve-fiber analyzerSee also Scanning laser polarimetry

diagnostic properties of the GDx 400, 66, 68GDx 400, 66, 67, 70, 74–75GDx number, 67

improving the accuracy of the GDx 400, 71issues relating to GDx measurements, 69issues relating to validity, 70potential use as a screening tool, 66receiver operating characteristics 67reliability analyses of, 73reliability of the GDx 400, 73, 74

Neuro-ophthalmology, 158Neuro-ophthalmology Club of the Philippines, 159Neurofibromatosis in optic-nerve meningioma, 164Neuroimaging, 162Newborn screening, 141, 143Norrie’s disease, 150Nuclear fragmentation, 118Nuclear sclerosis, 121Nyctalopia, 195

OOAG. See open-angle glaucomaObesity, 97Ocular hypertension. See glaucoma, intraocular pressureOcular Hypertension Treatment Study, 65, 99Ocular toxoplasmosis

treatment during pregnancy, 88Ocular ultrasonography, 149OHTS. See Ocular Hypertension Treatment StudyOnchoceriasis, 47ONH. See optic-nerve head.Open-angle glaucoma

beneficial effect of IOP lowering in, 99See also glaucoma

Ophthalmic services, 47Ophthalmologist-population ratio, 47Optic atrophy

in systemic lupus erythematosus, 17unexplained/caused by optic-nerve compression by

the internal carotid artery, 186Optic disc, 161Optic-canal decompression, 164Optic-disc

hyperemia, 190–192progression, 101

Optic-nerve compression, 187–188Optic-nerve meningioma

a close look, 160distinction from glioma, 164natural history, 164treatment options, 164

Optic-nerve-damage progressionin glaucoma, 169

Optic-nerve head, 64Optic-nerve-head stereophotography, 100


Optic-nerve-sheathmeningiomas, 161meningiomas in children, 164thickening of, 163

Optic-nerve vasculature, 161Optic Neuritis Treatment Trial, 159, 162Optic neuropathy

case secondary to optic-nerve compression, 186anterior ischemic, 161secondary to fusiform enlargement, 188

Orbital floor fractures, management of, 128Orbital implant. See implantOrbital inflammatory disease, 162Orbital lesions, 176–177Orbital mass, 136–137

See also retinoblastomaOrbital pseudotumor, 162Orbital tumors, 175

See also retinoblastoma, optic-nerve meningioma

PPalpebral fissure, 145PAM. See primary acquired melanosisPars plana vitrectomy, 92, 124Periorbital edema, 17Peripheral anterior synechiae, 132Periphlebitis, 162Persistent hyperplastic primary vitreous, 149Phacoemulsification

chopping technique that attacks the posteriorplate, 117

See also cataractPhilippine Board of Ophthalmology, 45Philippine Optic Neuritis Treatment Trial, 159Photobiomodulation for treatment of alcohol-induced

optic neuropathy, 192Photorefractive keratectomy, 37, 80PHPV. See persistent hyperplastic primary vitreous PlanoScan, 33PMMA, See polymethylmethacrylatePneumatic retinopexy

causes of failure, 122, 123potential complications, 126use of intravitreal gas in, 123compared with scleral buckling, 124

POAG. See glaucoma.Poland-Möbius syndrome, 179Polymethylmethacrylate, 22

See also implantsPolyethylene, 22, 30Positive predictive value, 70Postaxial hexadactyly, 97

Presbyopia, 47Primary acquired melanosis,

in melanoma of the conjuctiva, 147Proliferative vitreoretinopathy

failure of pneumatic retinopexy in eyes with, 122–126Proptosis, 136, 137, 162, 163Prostaglandin analogues, 103PSC. See cataractPterygium, 193Ptosis, 178, 179, 182Pulmonary tuberculosis, 158PVR. See proliferative vitreoretinopathy.

RRadiologic appearance, 163Radiological examination, 128Reconstructive surgery, 146Refractive surgery, 34Refsum’s disease, 196Renal dysfunction, 97Research

importance of (editorial), 115output of developing countries (editorial), 116

Retina, 190–192Retinal densitometry, 196Retinal detachment, 122Retinal dysplasia

a case of, 148association with congenital anomalies and

chromosomal abnormalities, 150differential diagnosis in leukocoria, 150pathogenesis of, 150

Retinal nerve-fiber layerassessment of, 67, 73, 74birefringence, 70changes in thickness, 74“double-hump” profile, 70measurement, 73, 74

Retinal pigment epithelium apoptosis in RPE cells in vitro, 6atrophy of, 195functions of, 7in retinitis pigmentosa, 96loss of pigment in Usher syndrome, 195

Retinitis pigmentosa, 96, 195, 196Retinoblastoma

age of onset, 137epidemiological and clinical patterns at the

Philippine General Hospital, 136familial incidence, 138gender distribution, 137incidence, 136, 138


malignancy of childhood, 149ocular manifestation at consultation, 137

at onset, 136, 137tumor classification, 137

Retinopathy of prematurity, 149Rhegmatogenous retinal detachment, 123RNFL. See retinal nerve-fiber layerRPE. See retinal pigment epitheliumRubella

congenital, 142as cause of cataract, 141–142

SSarcoidosis, 162Scanning laser polarimetry, 67, 74

See also nerve-fiber analyzerScleral buckling

compared with pneumatic retinopexy, 124Scleritis, 193Section biopsy, 175–177Sequential argon-Nd:YAG laser iridotomy, 133Short wavelength automated perimetry, 71Sight conservation and blindness prevention, 42SINS. See surgically induced necrotizing scleritisSLE. See systemic lupus erythematosusSLEDAI. See Systemic Lupus Erythematosus Disease

Activity IndexSLP. See scanning laser polarimetrySphenoid wing meningiomas, 162Standard central corneal thickness, 80Staphylococcus epidermidis, 145Steinert chopper, 119Stereotactic radiation, 166Storz Millennium, 119Strabismus, 46, 137, 178, 179, 193Struthio camelus, 128Subclavian-artery-supply-disruption-sequence theory,

184Sulfonamides, 92Surgical excision of sheath tumor, 164Surgically induced necrotizing scleritis after

cataract surgery, 193SWAP. See short wavelength automated perimetrySyndactyly, 183, 185Syphilis, 162Systemic lupus erythematosus

estimated incidence, 18ocular manifestations of, 17–21

Systemic Lupus Erythematosus Disease ActivityIndex, 18

TTalipes equinovarus, 178, 180, 183, 185Thalidomide, 184Third National Survey on Blindness, 47, 141Tono-Pen, 80Toxoplasma retinochoroiditis

causes of, 89Toxoplasmic retinochoroiditis

recurrence of, 91Trabeculectomy

comparison of outcomes with 0.4 mg/mland 0.2 mg/ml mitomycin concentrations, 83-87

Trachoma, 47Transcleral cyclophotocoagulation

single-setting treatment protocol for, 171–174 treatment with corticosteroids, 194Trichiasis, 184–185Trisomy, 13, 150TSCPC. See Transcleral cyclophotocoagulationTumor. See optic-nerve meningioma, retinoblastoma

UUltrasonic pachymetry, 79Upper-respiratory-tract infection, 178, 181, 184Urinary-tract infection, 181, 184URTI. See upper-respiratory-tract infectionUsher syndrome

a case of, 195diagnosis, 196fundus findings in, 195

UTI. See urinary-tract infectionUveitis

as a cause of secondary cataract, 142cause of posterior, 89

VVaricella

as a cause of childhood cataract, 140in Möbius sequence, 182

VEMs. See viscoelastic materialsVertical cutting, 119Viscoat, 12–15Viscoelastic materials

comparison of Amvisc Plus, Duovisc, and Viscoaton the corneal endothelium after cataractsurgery, 12

Vision 2020, 48Visual loss

in optic-nerve meningioma, 161Visual impairment

causes of, 46, 47


Vitamin Adeficiency, cause of blindness, 47slows down decline in ERG responses, 97

Vitreouspersistent hyperplastic primary, 149

Vitritis, 121

WWeiss syndrome, 95

XX-linked recessive disorder, 142Xerophthalmia, 47

ZZernike

coefficient, 36modes, 36–37

Zonulysis, 120Zyoptix, 33–35


Author index to volume 29Agahan, A. L. D., 21Agulto, M. B., 66, 73, 131Altuna, J., 99, 171Ang, R. E., 12Aquino, M. V., 83Arnold, A. C., 160Arroyo, M. H., 122Bacsal, K. M. E., 12, 131Brucelas, A. G., 193Castro, A. M., 175Castro, J. J. R., Jr., 38Chan, P. S., 12Chuanico, R. U., 38Cordero, C. P., 66, 73Cristobal, S., 127Cruz, R. D., 189Cua, I. Y., 33Cubillan, L. D. P., 17, 26De Jesus, A. A., 136De Leon, A. S., 42Dizon, G. R., 147Dorotheo, E. U., 66, 73Eckert, E., 6Eltanal-Pascual, M. A. T., 193Espiritu, R. B., 136, 148Fermin, M. E. P., 195Flaminiano, R. E., 122Flores, J. D. G., 12, 17Flores, J. V. P. D., 79, 83, 167

Foster, C. S., 88Gabel, V. P., 6Guerrero, P. I., 79, 167Guevara, G., 193Inocencio, F. P., 189Joaquin-Quino, R. M., 144Kho, R. C., 158, 186Khu, P. M., 64, 66, 73, 99, 115Kobuch, K., 6Kump, L. I., 88Lat-Luna, M. M. L., 79, 83, 131, 167League, J., 171Leser, R., 6Lim Bon Siong, R., 33, 144Lim, G. D., 127, 175Lirio, J. P. M., 171Lising, R. S., 17Lo, K. T., 94Mangubat, L. R., 144, 147Martinez, J. M. G., 99, 171Mercado, G. V., 136Monzer, J., 6Nievera, L. F., 26Oro, M. M., 33Paredes, I., 88Pe, L. C. 127Pe, L. M. H., 175Peczon, I. V., Jr., 29Ranche, J. M., 189

Remulla, J. C., 17, 94Reyes, M. C. D., 118Reyes, R. D., 171Roces, J. E. G., 33Romero, H., 127Salido, E. O., 17Salvosa, F. A. M., 26Santiago, A. P. D., 94, 140, 178Sarmiento, J. M., 33Sibayan, S. A. B., 6Spiegel, D., 6Sunico, A. T. C., 127Sy, J. L., 195Sy, M. E. A., 148Sy, R. T., 122Tamesis-Villalon, P., 122Tan, A. D., 21, 29, 147Tecson, J. V., III, 140Tee, M. L., 17Tinio, L., 66, 73Tumbocon, J. A. J., 99Uy, C. S. J., 178Uy, H. S., 12Valdez, A. M., 127Valenton, M. V., 17Valera, E. G., 136Verzosa, L. G., 118Villar, W. L., 33Yadao, R. A., 127

PJO Reviewers, 2004Patricia M. Khu, MD, MScRomulo N. Aguilar, MD, PhDMarissa N. Valbuena, MD, MHPeDJoseph Anthony J. Tumbocon, MDSantiago A.B. Sibayan, MD, PhD

Ruben Lim Bon Siong, MDHarvey S. Uy, MDJessica Marie R. Abaño, MDJocelyn L. Sy, MDCarlos G. Naval, MD

Jose Maria G. Martinez, MDFranklin Kleiner, MDRichard Kho, MDRaul D. Cruz, MD



OphthalmologyACADEMY NEWS


Eye doctors urged to get out of comfort zonesSOCIAL welfare and development secretary Corazon

“Dinky” Soliman has called on Filipino ophthalmologiststo help bring not just good eyesight but hope to peoplewho need it most and in the process help fuel a much-needed “national transformation.”

Keynoting the opening session of the annual meetingof the Philippine Academy of Ophthalmology (PAO) onNovember 18, Sec. Soliman urged members of the PAOto think of their work not just in terms of providing eyecare but also of helping people see “the possibilities tomake our [national] vision come true.” “As eye doctorsyou can help [bring about] a compassionate society andarticulate our vision of transformation for our country,”she said.

Stressing that the ophthalmology profession cannot beisolated from the rest of society, the former nongovern-ment organization leader asked ophthalmologists andother medical professionals to help bring about a corrupt-free government, deliver basic social services to all citi-

zens, and make justice reign in the country.“We must all help in seeing the potentials in our country

and not be blind to the needs of our own people,” shesaid even as she called attention to what she called a“doctor deficit” prevailing in many parts of the country.

Sec. Soliman was referring to the overseas exodus ofFilipino doctors and other health workers in search offinancial stability, which has aggravated the dearth ofhealth-care services especially in the rural areas.

“We have a doctor deficit especially in rural areas,[owing in part to the] government’s inability to givecompetitive salaries for professionals in the medicalprofession,” she said, noting that a government doctorreceives roughly PhP15,000 a month while a Filipinonurse working in the United States gets as much asP200,000 a month—“which is why we have doctorstraining to become nurses.”

Sec. Soliman noted that one rarely finds a doctor—especially an eye doctor—in the rural areas on a regular


basis, which is one of the reasons why vision impairmentis also common in the rural areas.

She said the most common eye disease of the poor iscorneal blindness due to infection. “Obviously theinfection comes from the polluted environment that wehave and the lack of knowledge on how to care for theeyes—because eye care is the least available health care inthe rural areas,” she explained.

She commended PAO for its commitment to encou-rage its members “to remain in the country and providehealth-care services where they are at the moment.”

Said Sec. Soliman: “This is the challenge for eye doctors.Each one of us is called upon to serve—to move out ofour comfort zones, to move out of what is familiar, and goto the places you think are dangerous, where you mightthink people will not accept you or people will harm you.”

In opening the convention, Dr. Marcelino Banzon, PAOpresident, spoke of the same challenge. Said he: “Let mechallenge all of us to do our share, to get out once in awhile from our comfort zones, do charity work, and giveback and share to society the blessings we have been given.”

“My community, my responsibility remains our battlecry,” he said. “The prevention of childhood blindness isour moral and social responsibility as eye specialists. It isalso our commitment to help in the international commu-nity’s efforts in fighting remediable blindness worldwide,”he added.

The meeting, which had Look the Future in the Eye for itstheme, focused on “pediatric ophthalmology and strabis-mus in a global perspective.”

“Children are our hope, our future. But their future looksbleak,” said Dr. Banzon, noting that about 1.5 millionchildren worldwide are blind, one million of them in Asia.He said nearly half of these could have been prevented withproper ophthalmic care. In the Philippines, children below15 years of age make up 37 percent of the population.Among them, the prevalence of blindness 0.9 per 1,000.

“An estimated 100 children lose their sight every week”because of causes that are preventable like poor nutrition,measles, and premature birth, lamented Dr. Banzon.

To help address the problems, the PAO and the Philip-pine Pediatric Society have joined hands for a vision-screening program for children so that vision problemscan be addressed early. During the convention, the twosocieties issued a Joint Policy Statement on Retinopathyof Prematurity Screening, which came on the heels of thePPS Policy Statement on Pediatric Blindness Preventionand Vision Screening.

These are meant to boost the Elimination of AvoidableChildhood Blindness Project launched in 2003 and theFive-Year Strategic Plan for Vision 20/20 launched inAugust 2004 to bring down the national blindnessprevalence rate to less than 0.5 percent in five years.


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PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 iPHILIPPINE ACADEMY OF OPHTHALMOLOGY

INSTRUCTIONS TO AUTHORS

SUBMISSIONThe PHILIPPINE JOURNAL OF OPHTHALMOLOGY adheres to

the policies set forth in the “Uniform Requirements forManuscripts Submitted to Biomedical Journals” writtenby the International Committee of Medical Journal Editors(N Engl J Med 1997; 336:309-314).

The journal publishes articles in the followingcategories:

• Original Articles, including clinical or laboratoryinvestigations, clinical epidemiology, and evaluation ofdiagnostic and surgical techniques

• Evidence-Based Medicine (EBM), includingsystematic review and metaanalysis

• Lectures and Symposiums• Case Reports and Case Series• Brief Reports• Special Matters Letters, correspondence, and guest editorials may also

be published.Manuscripts submitted to the journal must be original

material that has not been published or accepted for pub-lication elsewhere. All papers are submitted to a panel ofexperts for peer review. Manuscripts may be sent to:

Editor in ChiefPhilippine Journal of OphthalmologyUnit 815 Medical Plaza MakatiAmorsolo Street, corner Dela Rosa Street1229 Makati City, Metro ManilaPhilippines

Other Contact DetailsPhone: +63-2-8135324Fax: +63-2-8135331E-mail: [email protected]

MANUSCRIPT PREPARATIONSubmitted manuscripts should not exceed 18 double-

spaced typewritten pages (paper size 8.5 x 11 inches),including references, legends, tables, and figures(approximately 6-7 published pages). Use Times NewRoman font size 12. Submit 3 hard copies of the manuscriptand a digital copy in a compact disc (CD-ROM) or 3 .5floppy diskette. Manuscripts should begin each componenton a new page and be in the following order: (1) title page,(2) abstract, (3) text, (4) acknowledgments, (5) references,(6) legends for tables/figures, (7) tables, (8) figures(photographs, illustrations and graphs). A copyrighttransfer form with original signature and transmittal lettershould accompany the manuscript.

TITLE PAGEThe title page should include:1. Title of the article which should be informative,

concise, meaningful, as brief as possible, and no longerthan 135 characters.

2. Name of each author with his or her highestacademic degree(s) and complete address of institutionalaffiliation.

3. Financial support, if any. Provide the agency nameand city, company name and city, fellowship name, andgrant number.

4. Proprietary interest statement. Each author isexpected to disclose any type of financial interest relatedto the manuscript, including stock or ownership of abusiness entity connected to a product described in thepaper, paid consulting for the company or competingcompanies, travel support or patent rights to a drug orpiece of equipment.

5. List of any meeting(s) where the material is underconsideration for presentation or has been previouslypresented. Indicate name, place, month, and year of themeeting.

6. Corresponding author’s name, mailing address,telephone, fax, and e-mail address. The correspondingauthor will be responsible for all questions about themanuscript and for reprint requests. Only one author isto be designated corresponding author and he/she doesnot need to be the first author on the manuscript.

7. Appropriate footnotes.8. Five keywords.

ABSTRACTProvide a structured abstract of 300 words or less with

the following four headings:

Objective: State the purpose or objective of the study.

Methods: The following must be included:• Study Design: Identify the study design using a

phrase such as randomized or nonrandomized clinicaltrial, case-control study, cross-sectional study, cohortstudy, case series, case report, systematic review, meta-analysis, review, experimental study, or historicalmanuscript. Additional modifiers can be included(consecutive, retrospective, prospective, observational,interventional, nonconsecutive, etc).

• Setting: Such as multicenter, institutional, clinicalpractice, etc.

• Participants, Patients or Study Population: Num-ber of patients/eyes, selection procedures, inclusion/


Ophthalmology

ii PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 PHILIPPINE ACADEMY OF OPHTHALMOLOGY

clusion criteria, randomization procedure, and mask-ing.

• Intervention or Observation Procedure(s)• Main Outcome Measure(s)• Data and Statistical Analyses

Results: Briefly summarize the principal outcome mea-surements/data obtained. Results should be accompaniedby data with confidence intervals and the exact level ofstatistical significance.

Conclusions: Provide brief and concise conclusion(s)directly supported by the data.

TEXTNumber the pages of the manuscript consecutively,

beginning with the title page as page one. The text should,in general, not exceed 18 double-spaced typewritten pages.

Organize and prepare the manuscript to include thefollowing sections:

Introduction: The Introduction, without a heading,should refer only to the most pertinent past publicationsand should not be an extensive review of the literature.Include a brief background, the research question and/or rationale, objectives/purposes of the study, and majorhypothesis to be tested, if any.

Methods: Methods should be written with sufficientdetail to permit others to duplicate the work. Thefollowing should be included:

• Study Design: Identifies the study design using aphrase such as randomized or nonrandomized clinicaltrial, case-control study, cross-sectional study, cohortstudy, case series, case report, systematic review,metaanalysis, review, experimental study, or historicalmanuscript. Additional modifiers may be included (e.g.consecutive, nonconsecutive, retrospective, prospect-ive, observational, interventional).

• Setting: (e.g. multicenter, institutional, clinicalpractice)

• Participants, Patients, or Study Population: Numberof patients/eyes, selection procedures, inclusion/exclu-sion criteria, randomization procedure, and masking.

• Intervention or observation procedure(s)• Main and secondary outcome measure(s)• Data and statistical analyses.

For clinical studies, statements regarding adherence tothe Declaration of Helsinki, approval by InstitutionalReview Board (IRB)/Ethics Committee, and descriptionof the informed consent process should be included. For

animal research, the Association for Research in Visionand Ophthalmology (ARVO) guidelines for animalresearch should be followed and adherence to the saidguidelines should be stated. Previously publishedprocedures should be identified by reference only.

Results: Results must be concise. Provide demographicdata of the study population. Describe outcomes andmeasurements in an objective sequence with minimumdiscussion. Data should be accompanied by confidenceintervals (usually at the 95% interval) and exact p valuesor other indications of statistical significance.

Discussion: The Discussion should be restricted to thesignificant findings presented. Avoid excessive generali-zation and undue speculation. Digressions and theorizingare not appropriate. Elucidate on (but do not reiterate)the results, provide responses to other and contradictoryliterature, identify limitations or qualifications of the study,and state the conclusions that are directly supported bythe data. Give equal emphasis to positive and negativefindings, whether and what additional study is required,and conclude with the clinical applications or implicationssupported by the study. The conclusion(s) is (are) incor-porated into the end of the discussion and should be directlysupported by the results. Authors should avoid makingstatements on economic benefits and costs unless theirmanuscript includes economic data and analyses. Avoidclaiming priority of the content unless you provide theliterature search protocol used.

BRIEF REPORTSA brief report is an original contribution (generally an

interesting case, a case series, surgical technique, orexperimental study) with a concise message. Manuscriptmust adhere to the PJO format guidelines, except that theabstract should contain no more tha 150 words and thebody no more than 1,000 words. References should belimited to 5.

ACKNOWLEDGMENTSAcknowledge statistical consultation and assistance

(when provided by someone other than an author) in anacknowledgment at the end of the article, before thereferences. Include the name, degree, and affiliation of theindividual. Consultants (other than statistical consultants),editorial assistants, photographers, artists, laboratory asso-ciates, and others who assist in preparation of a manuscriptare not to be acknowledged, however valuable their service.

Because readers may infer their endorsement of thedata and conclusions, all persons acknowledged must havegiven permission to be acknowledged and this must beconfirmed in the cover letter.

PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 iiiPHILIPPINE ACADEMY OF OPHTHALMOLOGY

APPENDIXAn appendix should be used very sparingly. However,

it is appropriate to provide survey forms, to list the mem-bers of a study group, or explain complex formulas orinformation.

In studies involving a study group, the writing groupauthors should be listed along with the group name (e.g.Smith TT, Jones JJ on behalf of the Pediatric AmblyopiaStudy Group) on the title page. Other group membersshould be listed in an appendix. When the study groupname alone is listed on the title page, the Copyright Trans-fer Agreement requires only the original signature of theCorresponding Author. When a series of authors is listedon the title page in conjunction with the study groupname, the Copyright Transfer Agreement must includethe original signatures of these authors.

REFERENCESList only references that are pertinent to the manu-

script. Cite only published studies as references. Cite/Quote from the entire study, not the abstract. You mayacknowledge “unpublished data” or submitted articleswithin parentheses in the text. Reference to a “personalcommunication” within parentheses in the text must beaccompanied by a signed permission letter from the indi-vidual being cited.

References should be numbered consecutively in thetext and in the reference list. In the text, referencenumbers are entered as superscripts. The referencesmust be verified by the author(s) against the originaldocuments. PubMed (http://www.ncbi.nlm.nih.gov)offers a useful reference checker. References to journalarticles should include: the author or authors (for morethan four authors, list only the first three followed by“et al.”), title, journal name (as abbreviated in IndexMedicus), year, volume number, and inclusive pagenumbers.

References to books should include: the author orauthors, chapter title (if any), editor or editors (if any),book title, edition (other than the first), city of publication,publisher, copyright year, and inclusive pages of thechapter or section cited.

Web site references must include author (or web siteowner), title of article, date article was posted, publication(if applicable), complete web site address, and dateaccessed.

ExamplesJournal Article (If four or fewer authors, list all)Fishman GA, Alexander KR, Milam AH, Derlacki DJ.

Acquired unilateral night blindness associated with anegative electroretinogram waveform. Ophthalmology 1996;103: 96-104.

Journal Article (If five or more authors, list only the firstthree and add et al.)

Vail A, Gore SM, Bradley BA, et al. Clinical and surgicalfactors influencing corneal graft survival, visual acuity, andastigmatism. Br J Ophthalmol 1996; 103: 41-49.

Chapter in a BookParks MM, Mitchell PR. Cranial nerve palsies. In: Tasman

W, Jaeger EA, eds. Duane’s Clinical Ophthalmology, revised ed.Philadelphia: JB Lippincott, 1993; v. 1, chap. 19: 550-551.

BookMiller NR. Walsh and Hoyt’s Clinical Neuro-Ophthalmology,

4th ed. Vol. 4. Baltimore: Williams & Wilkins, 1991; 2102-2114

Web siteWorld Health Organization. Hospital infection control

guidelines for severe acute respiratory syndrome. April16, 2003: http://www.who.int/csr/sars/infectioncontrol/en (accessed April 24, 2003).

TABLESTables should follow references. Each table must be

titled and numbered consecutively using Arabic numbersas mentioned in text. The title should be brief and fullyunderstandable without reference to the text. Each tablecolumn and row must have a heading. Tables that indi-cate the mean should have the corresponding standarddeviation. Legends must identify all symbols that appearon the tables and graphs.

FIGURES (PHOTOGRAPHS, ILLUSTRATIONS, ANDGRAPHS)

Submit three (3) identical complete sets of prints anda digital copy if available. Each print must be separatelylabeled with the author’s name, figure number and anindication (arrow) as to orientation (up). Put allinformation on a separate label on the back of theillustration to avoid writing on or damage to the prints.

Prints of figures (clinical photographs, fluoresceinangiograms, CT, MRI, X-ray, photomicrographs, TEM,SEM, graphs, etc.) must be large enough to be easily read,preferably 4 x 6 inches. The digital copy of eachphotograph or illustration should be saved in individualfiles in either TIF or JPEG format with a resolution of atleast 300 dpi. Photographs and illustrations saved in“Power point” or “Word” format are not acceptable.Graphs may be submitted in “Power Point” or “Excel”format. Text in figures must not be smaller than 10 pointswhen finally reproduced in the Journal.

Each figure must be numbered consecutively in Arabicnumerals by order of citation in the text. Each should

iv PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 PHILIPPINE ACADEMY OF OPHTHALMOLOGY

have a brief explanatory legend. Legends must identifyall symbols or letters that appear on the prints. Histologicfigures, stains, and magnifications should be noted in thelegend. Graphs that indicate the mean should include thestandard deviation. Any figure that has been publishedelsewhere should have an acknowledgment to the origi-nal source. A copy of the release to publish the figuresigned by the copyright holder must also be submitted.

Clinical photographs should be masked when possibleto prevent identification of the patient. Clinical photo-graphs that permit identification of an individual mustbe accompanied by a signed statement by the patient orguardian granting permission for publication of the pic-tures for educational purposes.

Color reproduction of figures will be published at theauthor’s expense based on prevailing rates. Check with thePAO office for exact cost. If a manuscript has been reviewedand accepted with color photos, it must be published withcolor photos. The author may opt to have them printed inblack and white at no expense.

ABBREVIATIONSRestrict abbreviations to those that are widely used and

understood. Avoid abbreviations that have meaning onlyin the context of your specific manuscript. If an abbrevia-tion is to be used, it should appear in parentheses imme-diately after the term or phrase to which it refers when itis stated for the first time in the text.

INSTRUMENTS, DRUGS, AND MANUFACTURERNAMES

Use generic names only in the text body. State the tradename of a particular drug cited in parentheses including

manufacturer’s name, city, state and/or country when firstmentioned in the text. With regard to instruments uti-lized in the study, enclose in parentheses the specificmodel, manufacturer’s name, city, state and/or country.

TRANSMITTAL LETTEREach submission must be accompanied with a letter to

the editor in chief. It must identify the correspondingauthor, list any meetings where the material is underconsideration for presentation or has been previouslypresented and disclose any conflict of interest. Thetransmittal letter must include a copyright transfer. Theeditorial office must be supplied with phone and faxnumbers for the corresponding and first author(s), ande-mail addresses, if available.

COPYRIGHTConsideration of manuscripts for publication in the

PHILIPPINE JOURNAL OF OPHTHALMOLOGY is dependent onthe assurance that the material (in whole or part) is notunder consideration by another journal, is not in press inany other format, and has not been previously published.Each author must sign a statement transferring copyrightownership to the Philippine Academy of Ophthalmology.Manuscripts which have been accepted for publicationmay be published in another journal after securing awritten consent from the editor in chief of the PHILIPPINE

JOURNAL OF OPHTHALMOLOGY.

These instructions may be downloaded from the PJO web site at www.pao.org.ph

PHILIPP J OPHTHALMOL VOL 29 NO. 4 OCTOBER - DECEMBER 2004 vPHILIPPINE ACADEMY OF OPHTHALMOLOGY

COPYRIGHT TRANSFER

Title of Article________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________

Authors1. ________________________________2. ________________________________3. ________________________________4. ________________________________5. ________________________________

In submitting the above-titled article, I/we hereby transfer, assign, or otherwise convey all copyright ownershipto the Philippine Academy of Ophthalmology in the event that such work is published in the PHILIPPINE JOURNAL

OF OPHTHALMOLOGY (PJO). Such conveyance covers any product, whether print or electronic, that may derive fromthe published journal. I/We affirm that this article has not been previously published in or submitted for pub-lication to another journal, except under circumstances communicated to PJO in writing at the time the articlewas first submitted.

Each author must sign a Copyright Release form. The signatures need not appear on the same page. All manuscripts submittedbecome the property of the journal.

Name (print) Proprietary Signature Dateor Financial Interest (Yes/No*)

1. _____________________________ _____________ _____________________________ ________________2. _____________________________ _____________ _____________________________ ________________3. _____________________________ _____________ _____________________________ ________________4. _____________________________ _____________ _____________________________ ________________5. _____________________________ _____________ _____________________________ ________________*If yes, please explain on the title sheet. See instructions to authors for details.

Submit this signed transfer with your manuscript to:

The Editor in ChiefPhilippine Journal of OphthalmologyUnit 815 Medical Plaza MakatiAmorsolo Street, corner Dela Rosa Street1229 Makati City, Metro ManilaPhilippines

Other Contact DetailsPhone: +63-2-8135324Fax: +63-2-8135331E-mail: [email protected]

This form may be downloaded from the PJO web site at www.pao.org.ph


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