COLE EYE INSTITUTETHE CLEVELAND CLINIC

3 PUZZLER

A 46-year-old male presents with progres-sively blurry vision over12 hours. Learn moreabout his symptomsand decide what wouldbe your diagnosis.

OphthalmologyUpdate

2 4 7DRUSEN REMOVAL

Studies of the proteincomposition of drusenat the Cole Eye Institutehave been advanced bya new drusen-removaltechnique.

ANTI-OXIDANTTHERAPY

Recent proof of thevalue of anti-oxidanttherapy dovetails wellwith the ongoingresearch of JonathanE. Sears, M.D.

CATCHING THEWAVE

Wavefront imagingtechnology helps deliverthe most personalizedlaser vision correctionavailable.

Spring 2002

Horizontal illumination of drusen that shows a bright iridescent foamy-like texture. Story, page 2

Page

analyzed after using this collection tech-nique, he was able to find those eightplus 29 additional proteins.

“We proved the technique worked and showed its utility,” Dr. Hollyfield says.

Part of Dr. Hollyfield’s challenge incollecting large numbers of drusen sam-ples was that most eye banks only accepteyes from younger, healthier patients.However, he has been able to access about400 pairs of frozen cadaver eyes from 70-to 103-year-old patients from the NationalDisease Research Interchange.

“We started with the hypothesis thatsome normal eyes have drusen and thatremoving the retinal pigment epithelium(RPE) and choroid would allow us to getright to them,” Dr. Hollyfield explains.“And we were right — we can isolate themdirectly from the site where they reside,on Bruch’s membrane.”

He explains that the retrieval pro-cedure requires dexterity to perform thecareful dissection from the back of theeye, but otherwise it is not difficult toreplicate. He says that as the drusen aregathered, differences in their appearanceare immediately apparent.

“We divide them by color and otherdefining characteristics so we can studyour next hypothesis, which is that differentappearance of the drusen is due to differ-ences in molecular composition. We hopethis will help us discover the pathwaysthat lead to drusen formation,” he adds.

Once drusen samples are collected,the proteins in drusen are cut with en-zymes into small pieces. Mass spectralanalysis of these fragments provides datathat allow identification of the proteins bycomparison with databases of all knownprotein sequences, Dr. Crabb says.

The next step is a crucial one, he explains, as researchers try to determinehow and why the identified proteins ac-cumulated in drusen. Dr. Crabb suggeststhat protein oxidative damage may be involved in this process.

“We are working our way throughabout 40 protein identifications now todetermine their origin,” Dr. Hollyfield says.

Dr. Lewis says he is hopeful thatthese findings will soon be translated intobenefits for patients.

ALTHOUGH DRUSEN ARE THE HALLMARK

OF AGE-RELATED MACULAR DEGENERATION

(AMD), VERY LITTLE IS KNOWN ABOUT

THEIR COMPOSITION OR HOW THEY FORM.

In order to develop treatments or ways to prevent AMD, Hilel Lewis,M.D., Chairman of the Cole Eye Insti-tute, recruited a team of scientists toconduct a study of drusen that eventu-ally could lead to major breakthroughs.The members of this team are Joe G.Hollyfield, Ph.D., Director of Research,Cole Eye Institute, and faculty membersin the Department of Ophthalmic Re-search, John W. Crabb, Ph.D., and AlanD. Marmorstein, Ph.D.

Their studies of drusen have beenrecently advanced by a new drusen-isolation technique developed by Dr.Hollyfield and by mass spectrometricproteomic applications in Dr. Crabb’slaboratory.

Dr. Crabb is looking for modifica-tions of proteins that could alter theirfunction and is also studying whendrusen appear, how they change withage and where they are located. This research could provide essential infor-mation on how drusen form, why somepatients develop AMD and why patientswith AMD develop the atrophic or exudative form of the disease, saysDr. Lewis.

“We hope that our work on under-standing drusen composition opens thedoor to the creation of the first animalmodel of macular degeneration andeventual development of drug pathwaysto treat it,” Dr. Hollyfield explains.

Dr. Hollyfield devised a procedurein which drusen are manually dissectedfrom normal donor eyes and those withAMD. This technique, known as DrusenIsolation for Composition Analysis, al-lows collection of hundreds of particleson which researchers can perform massspectrometric analyses.

Previously, only eight proteinswere known to be present in drusen.With just the first sample Dr. Crabb

Narrowing in on DrusenThe Hallmark of Age-Related Macular Degeneration

Fragment of the choroid-Bruch'smembrane complex from the posteri-or segment of a 95-year-old normaldonor eye in which the retina andretinal pigment epithelium have beenremoved. Large choroidal vessels arepresent. This image shows severaldrusen on the surface of Bruch'smembrane

Drusen from the sample describedabove that have been dissected fromBruch's membrane and placed in adepression slide for photography

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Drusen such as these are the hallmarkof age-related macular degeneration

Isolated Bruch’s membrane complexfrom the same tissue viewed withtransmitted light compound mi-croscopy showing amber-to-brownhemispherical lesion

Irregular-shaped drusen with a centralcore from a 91-year-old normal donor

Ophthalmic Puzzler

By Eric Sputh, M.D.,

and Scott D. Smith, M.D., M.P.H.

A 46-year-old male presented with a chief complaintof blurry vision. Subjectively, the right eye was worsethan the left, and his symptoms were progressive overa period of 12 hours. He complained of loss of pe-ripheral vision. Pertinent positive findings includedheadache, nausea and one episode of emesis. Perti-nent negative findings included lack of ocular pain,diplopia, photopsias, floaters and photophobia. Ocularhistory was negative, with the patient stating he pre-viously had 20/20 visual acuity without correction.

Ocular exam revealed visual acuity of countingfingers at 4 feet in both eyes. Pupillary exam was re-markable for mydriasis and sluggish reaction in botheyes, and an afferent pupillary defect in the righteye. Confrontational visual fields showed bitemporalhemianopsia and inferior nasal defects. Tonometry,versions, color vision and cranial nerves III-XII wereall normal. Slit-lamp exam and dilated fundoscopicexams were both normal.

A CT scan was obtained (see Figure 1).What is the diagnosis? Turn to Page 5.

CME Objective To describe

the latest research on har-

vesting drusen and analyz-

ing its protein composition.

Figure 1 CT scan obtained from a46-year-old male presenting witha chief complaint of blurred vision

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metabolic byproducts of oxidative phosphorylation, known as reactive oxygenspecies, can be stimulating free radical formation.

“In all cells, especially in the eye,” adds Dr. Sears, “the most fundamental an-tioxidation defense involves the tripartite interaction between glutathione, ascorbate(vitamin C), and tocopherol (vitamin E). Dr. George Hoppe, Dr. Yuh-Cherng Chai andI have identified a protein called glutaredoxin that couples glutathione homeostasis to ascorbate recycling. This protein is responsible for releasing glutathione from itsprotective bond with protein cysteine residues. We hypothesize that during oxidativestress, glutathione binds proteins at cysteine residues. This stabilizes the oxidized proteins to prevent free-radical propagation.

“Glutaredoxin is prevented from breaking these protective bonds because itcontains a redox-sensitive switch responsive to oxidized ascorbate, called dehy-droascorbate. Once the cell returns to a normal reduced state, at a lull from oxida-tive stress, glutaredoxin is reactivated to allow reduction of the mixed disulfidebonds in order to remove the glutathione adducts and restore the protein’s function.The trick is to show this effect in cells, not just in the test tube. It is a beautiful example of oxidation-stimulated cell signaling, which will lead to development of a molecular assault on macular degeneration.”

Dr. Sears offers a few caveats regarding the use of high anti-oxidant therapy. He says ophthalmologists should encourage patients who are following such aregimen to be monitored by their internists for any effects.

“Also, any agent given in massive doses that has not been tested in a dose-response analysis may have a beneficial effect that is independent of the intendedmechanism of therapeusis,” he points out. “Therefore, it is absolutely critical that weinvestigate and understand the basic mechanism of anti-oxidant protection in eye.”

Slowing the Progression of Macular DegenerationUnderstanding the Role Anti-Oxidant Therapy Can Play

CME Objective To identify

how the key findings of the

Age-Related Eye Disease

Study can be applied to other

research into retinal disease.

Figure 1 Schema adaptedfrom Winkler, et al., (Win-kler et al. 1994) showselectron transport that ul-timately facilitates the re-duction of lipid peroxidesand the theoretical role ofglutaredoxin (GRX) in sus-taining ascorbate regener-ation. Glutaredoxin mayreduce oxidized ascorbate(dehydroascorbate) to as-corbate. An increased poolof reduced ascorbate mayplay a role in increasingpools of reduced vitaminE, which is necessary forquenching lipid peroxides.GSSG — glutathione disul-

fide, GSH — glutathione, AA —ascorbic acid, DHA — dehydro-ascorbate; LOOH — lipid peroxidesand LOH — reduced lipid peroxideshypothetically derived from pho-toreceptor disc membranes

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RESEARCH ON THE VALUE OF ANTI-OXIDANT

THERAPY IN REDUCING A PATIENT’S RISK

OF PROGRESSION OF AGE-RELATED MACU-

LAR DEGENERATION (AMD) MADE HEAD-

LINES RECENTLY. THE NEWS FROM THE

AGE-RELATED EYE DISEASE STUDY (AREDS)

WAS ESPECIALLY WELCOME TO JONATHAN

E. SEARS, M.D., OF THE COLE EYE INSTITUTE,

WHOSE RESEARCH INVOLVES THE STUDY OF

OXIDATION IN THE PATHOGENESIS OF AMD.

“The AREDS demonstrated a mod-est but definite therapeutic benefit ofvitamin antioxidant supplementation as prevention of AMD. An exact under-standing of the cellular response to oxidation may enable us to augmentknown or develop new therapies for theprevention of AMD,” explains Dr. Sears,a vitreoretinal surgeon and basic scien-tist who joined the Institute in 1998.

AREDS researchers found thatwhen patients who had intermediate or advanced AMD took high doses ofvitamins C and E, beta-carotene, zincand copper, they reduced their risk ofdisease progression by 28 percent. Thisdevelopment applies to both the wetand dry forms of AMD.

“In the highly oxidative environ-ment of the outer retina and retinalpigment epithelium, redox protectivemechanisms are relevant to cell sur-vival, especially because there is limitedregenerative capability of either celltype,” says Dr. Sears. “For example, theretina has one of the highest rates ofoxygen consumption when comparedwith other tissues, approaching 2 moloxygen/mg dry weight per hour.”

Light can concomitantly add to thestimulus of radical production. In con-cert with the high rate of metabolismand the pro-oxidant effect of light, theretinal pigment epithelium is exposedto a large quantity of polyenolic fattyacids, which become a substrate forlipid peroxyl radical formation. The

The anti-oxidant dose levels used in the Age-Related Eye DiseaseStudy were:

� Vitamin C: 500 mg� Vitamin E: 400 IU� Beta-carotene: 15 mg� Zinc: 80 mg

(as zinc acetate)� Copper: 2 mg

(as cupric oxide)

Ophthalmic PuzzlerSolution to Part I (page 3)

Diagnosis and treatment

The CT scan showed a large mass in the sella turcica. The diagnosis of pituitary apoplexy was made, and an MRI image wasobtained emergently (Figure 2). Neurosurgical consultation wasobtained and the patient underwent transsphenoidal tumor resection.

Visual acuity improved in the postoperative period to 20/40 inthe right eye and 20/25 in the left eye. The patient’s afferent pupil-lary defect resolved. The bitemporal hemianopsia and inferior altitu-dinal defects improved, but remain on Humphrey visual field testing.A dilated fundoscopic exam revealed bilateral optic disc pallor thatdeveloped three months after presentation.

Pituitary apoplexyPituitary apoplexy is an important diagnosis to make. Mis-

diagnosis is common; the condition can be confused with migraineheadaches, optic neuritis or subarachnoid hemorrhage. Importantsigns and symptoms include headache, vomiting, visual field loss,diplopia, ptosis and altered mental status.

Apoplexy is defined as an abrupt pituitary hemorrhage, classi-cally in the setting of a nonsecreting pituitary adenoma. Secretingadenomas are commonly diagnosed earlier due to the signs andsymptoms produced by the hormone in overproduction. The inci-dence of pituitary apoplexy has been reported to be 1.9% of all pituitary adenomas. Factors that place patients at higher risk for pituitary apoplexy include diabetes mellitus, atherosclerosis andanticoagulation.

The prognosis for visual recovery is good with timely surgicaldecompression of the optic chiasm. Most patients are left withsome degree of compressive chiasmal injury, but 88% to 95% ofpatients show visual acuity and visual field improvement after surgical intervention.

Pituitary apoplexy is an important diagnosis to consider in patients with acute visual loss. Knowledge of the signs and symp-toms of pituitary apoplexy combined with an appropriate index ofsuspicion based on the clinical presentation will facilitate the diag-nosis. These patients need timely evaluation with CT and/or MRimaging. Proper diagnosis and subsequent triage are critical to thepatient’s survival and the preservation of vision.

Reference

Bills D C, Meyer F B, Laws E R et al. A Retrospective Analysisof Pituitary Apoplexy. Neurosurgery 33: 602-609, 1993.

Figure 2 MRI image obtained froma patient with newly diagnosed pituitary apoplexy

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Also, he says the LADARWave boasts the longest track record of commercialtesting and is furthest along in Food andDrug Administration trials for approval ofcustom cornea treatments. The Cole EyeInstitute will be one of about five centersparticipating in the next phase of testingbeginning later this year.

Study to Assess AberrationsInduced by Creating a Flap

THE COLE EYE INSTITUTE IS ENROLLING

PATIENTS IN A STUDY TO ASSESS WHAT

ABERRATIONS, IF ANY, ARE INDUCED SOLELY

BY THE PROCESS OF MAKING THE LASIK FLAP.

IN THIS STUDY, PATIENTS WILL HAVE A FLAP

CUT, THEN REPLACED, WITHOUT TREATMENT.

THE FLAP WILL BE LIFTED A MONTH LATER FOR

CUSTOM CORNEA IMAGING FOLLOWED BY A

STANDARD ABLATION TREATMENT.

Patients are being offered financialincentives in exchange for agreeing tothis delay between flap creation andcornea reshaping.

“We hope to use the informationwe gain from studying what subtle aber-rations are created solely by the flap to perfect LASIK treatments in the future,”explains Ronald R. Krueger, M.D., MedicalDirector of The Department of RefractiveSurgery at the Cole Eye Institute.

He hopes to enroll about 50 patientsin this study.

Comparing how a particular wavefront imaging pattern deviates from the pattern of a “perfect eye”shows where a patient’s aberrations are. This information can be captured by the LADARWave device on a disk and input into a compatible excimer laser to generate the ideal laser shot patternfor each individual patient

Wavefront Technology at Cole Eye InstitutePromises Superior Refractive Surgery Outcomes

COLE EYE INSTITUTE REFRACTIVE SURGEONS RECENTLY ACQUIRED A WAVEFRONT IMAGING

DEVICE THAT IS HELPING THEM DELIVER THE MOST PERSONALIZED, ACCURATE LASER VISION

CORRECTION CARE AVAILABLE.

Ronald R. Krueger, M.D., explains that surgeons at the Cole Eye Institute are usinga new LADARWave device as a diagnostic tool to measure higher-order aberrationsbefore and after LASIK. Their next step will be to use the machine to devise a person-alized or custom ablation shot pattern on the excimer laser.

“Use of this machine can facilitate achieving better corrected visual acuity than standard LASIK alone,” Dr. Krueger says.

Not only will coupling the machine to the laser help surgeons correct more existing aberrations than standard LASIK, it will help avoid inducing new ones, he explains. It is also a useful diagnostic tool if a patient does not have satisfactory vision after refractive surgery.

“In centers where this machine has been used for diagnostic and surgical purpos-es, it has been shown that LASIK does indeed induce aberrations and that inducedaberrations can be minimized or prevented by using wavefront technology,” he says.

The free-standing wavefront machine, known as LADARWave, is a Shack-Hart-mann-style device that directs low-intensity, non-damaging infrared laser light intothe eye while the patient focuses on it. The scattered light that bounces off the maculais directed onto a series of lenses that focuses each section of the wavefront into anarray of spots.

Comparing how a particular spot pattern deviates from the pattern of a “perfecteye” shows where the patient’s aberrations are. This information can be captured ona disk and input into the excimer laser to generate the ideal laser shot pattern foreach patient.

Taking the time to conduct this additional preoperative test may not initiallyinterest refractive surgeons who are happy with their current outcomes, but Dr. Kruegerpredicts they will embrace the technology as they learn to utilize it efficiently.

Several other wavefront-measuring devices utilize similar Shack-Hartmann technology, including the WaveScan and Zywave systems. The LADARWave system,however, has one of the highest numbers of focused spots at the pupillary plane.This is second only to the Meditec/Wavefront Sciences device, which is coupled to a broader-beam scanning laser that is less refined at correcting aberrations.

“Although the number of focused spots isn’t the only factor in evaluating thesedevices, if you have too few of them, you won’t be able to characterize the full aber-ration pattern accurately,” Dr. Krueger explains.

6

BLINDNESS REPRESENTS A SERIOUS PUBLIC

HEALTH PROBLEM FOR MANY DEVELOPING

NATIONS, WHERE 90 PERCENT OF THE

WORLD’S BLIND POPULATION LIVES. UP TO

80 PERCENT OF GLOBAL BLINDNESS IS PRE-

VENTABLE, AND THE WORLD HEALTH OR-

GANIZATION AND OTHERS HAVE LAUNCHED

AN INITIATIVE TO ERADICATE PREVENTABLE

BLINDNESS BY 2020.

In identifying its primary targets, WHO named the more traditional culprits —cataract, trachoma and onchocerciasis — as well as one that is less commonly thoughtof as a public health issue: uncorrected refractive error.

The desire to help patients who have severe refractive errors but little or no accessto glasses led a Cole Eye Institute refractive surgeon to travel to Nepal late last year tohelp establish a laser vision correction center there.

“For many people in Nepal, glasses are unaffordable and inaccessible. Breaking an existing pair can force a person to live with poor vision for months or even years.This can translate into a vicious cycle of unemployment and increased poverty,” ex-plains Ronald R. Krueger, M.D.

“These people don’t have another way to see,” he adds. “Myopia is a preventabledisease that limits vision in the developing world much as cataracts do. LASIK offers aquick, permanent solution that can transform the lives of these people and free themfrom worrying about glasses again.”

Dr. Krueger, Medical Director of Refractive Surgery at the Cole Eye Institute,spent eight days in Katmandu performing the first LASIK procedures there. He treated17 patients and helped train local surgeon Dr. Sanduk Ruit to perform the procedurein what Dr. Krueger says “may be the first step in providing LASIK as a means of cor-recting preventable blindness in the developing world.”

“I saw young, healthy people who were highly myopic whose vision became20/20,” Dr. Krueger says. “One 35-year-old man whose vision was -9 D and -15 Drode his bicycle around town without correction. He had never worn glasses and toldus that he had been unable to read the blackboard at school when he was young.After undergoing LASIK, he said, ‘So that’s what the world looks like.’”

Indications for treatment at Dr. Ruit’s clinic have been limited to myopia andastigmatism, but Dr. Krueger anticipates hyperopia will be added. The patients treatedduring his visit ranged from 19 to 55 years old; nine were female and eight weremale. All were treated bilaterally for a wide range of errors, initially by Dr. Kruegerand then by Dr. Ruit. Most had acuity of 20/20 or 20/30 after surgery.

The average income in Nepal is $275 per year. Although some patients at Dr.Ruit’s clinic make small payments for their refractive surgery, some pay nothing. Thatis possible, in part, because the excimer laser was donated by Alcon Laboratories.

Now that LASIK is available in Nepal, Dr. Krueger would like to see other devel-oping nations have access to it as well. “I really believe refractive surgery can play abig role in world efforts to eradicate curable blindness,” he concludes.

Refractive Surgery Can Contribute to Fight Against Preventable Blindness

Dr. Sanduk Ruit performsLASIK in his clinic in Katman-du, Nepal. Although refractivesurgery is largely a luxury itemin the United States, it can bea way to combat preventableblindness from high refractiveerror in areas where glassesare prohibitively expensive orare inaccessible

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The Cole Eye Instituteis proud to announce thelaunch of its new Website at:

WWW.CLEVELANDCLINIC.ORG/EYE

The site features information of interestto professionals and consumers.

Physicians and researchers can usethe site to:

• Find upcoming Continuing Medical Education or Distinguished Lecture Series events to attend.

• Learn about new and ongoing ClinicalTrials at the Eye Institute.

• Read past issues of Ophthalmology Update.

• Meet the physicians who make up the clinical staff. Also, meet the principal investigators who lead the research teams and find out what their labs are working on.

• Link to a variety of ophthalmic organizations and publications.

CURRENTLY RECRUITING

GENETICS

STUDIES OF THE MOLECULAR GENETICS OF EYE DISEASES

Objective To map the genes for inheritedeye diseases. To screen candidate genesfor mutations in a variety of geneticocular disorders, including ocular malfor-mations, congenital cataracts and retinaldystrophies. Contact E. Traboulsi, M.D., 216/444-4363or S. Crowe, C.O.T., 216/445-3840

GENETICS AND MOLECULAR ANALYSIS OF RETINAL DISEASES

Objective The Cole Eye Institute isrecruiting patients with a family historyof macular degeneration to participate in a genetic study. Our goal is to find thegene that causes macular degeneration.Participants must have at least two familymembers who have been diagnosed withmacular degeneration who are willing toparticipate in our study. There is no agelimit and it does not matter if you havethe wet or dry type of AMD. Contact Ellen Simpson, R.N., 216/445-9886

THE GENETICS OF STRABISMUS

Objective To discover the genes thatcause some strabismus syndromes, includ-ing those for accommodative esotropia,congenital esotropia, congenital ocular fibrosis syndrome, intermittent exotropia,Brown syndrome and Duane syndrome. Contact E. Traboulsi, M.D., 216/444-4363or S. Crowe, C.O.T., 216/445-3840

PEDIATRICS AND STRABISMUS

CONGENITAL ESOTROPIA OBSERVATIONSTUDYObjective To observe the early course ofcongenital esotropia in order to determinethe probability of spontaneous resolutionand to try to correlate this finding withvarious aspects of esotropia.

Eligibility Criteria Patients between 9and 17 weeks old, gestational age lessthan 37 weeks and birth weight less than2,000 grams (4 lb., 6 oz.), neurologicallyand developmentally normal.Contact E. Traboulsi, M.D., 216/444-4363or S. Crowe, C.O.T., 216/445-3840

COMPARISON OF LEA GRATING PADDLESWITH TELLER ACUITY CARDS FOR EVALUATIONOF VISUAL ACUITY IN PREVERBAL PATIENTS

Objective Pediatric ophthalmologists areinvestigating a new method of checkingvisual acuity in preverbal children. Thismethod uses the principle of preferentiallooking. Infants' acuity is tested usingTeller acuity cards and Lea Grating Cardsduring the same clinical visit. The investi-gators are trying to determine if Lea Grat-ing Cards are accurate and if they offerany advantage over the widely acceptedTeller Acuity Cards.Contact E. Traboulsi, M.D., 216/444-4363,or D. Peralta, M.D., 216/444-4363

COLOR SORT TEST

Objective This project compares an individual's performance on four tests of color vision.Contact E. Traboulsi, M.D., 216/444-4363

REFRACTIVE SURGERY

OPTICAL COHERENCE TOMOGRAPHY (OCT)

Objective Optical coherence tomographyis a non-invasive way of imaging tissuewith light. Several projects are under wayto refine this machine's ability to imagethe anterior segment of the eye.Eligibility Criteria Subjects must bemore than 18 years of age, eligible forLASIK and have narrow-angle glaucomaor pathology in the anterior segment.Contact Scott D. Smith, M.D., M.P.H.,216/444-4821 or J. Finkenthal, C.O.A.,Clinical Research Coordinator, 216/444-2566

PARTNERSHIP FOR RESEARCH IN OPTICAL COHERENCE TOMOGRAPHY (OCT)

Objective To use optical coherence tomography (OCT) to measure cornealchanges after LASIK.Eligibility Criteria Patients eligible forLASIK.Contact D. Huang, M.D., Ph.D., 216/444-0848 or J. Finkenthal, C.O.A.,216/444-2566

THE HUANG SMALL LETTER CONTRAST SENSITIVITY TEST

Objective To improve the understandingof how LASIK affects the quality of vision. Eligibility Criteria Subjects must be be-tween 20 and 60 years age and be eligiblefor LASIK surgery with best corrected vision of 20/20 prior to surgery. Subjectswill be paid $225 at completion of study.Contact D. Huang, M.D., Ph.D., 216/444-0848, or J. Finkenthal, C.O.A.,Clinical Research Coordinator, 216/444-2566

THE EFFECT OF CREATING A LASIK FLAP ASDETERMINED BY WAVEFRONT ANALYSIS

Objective To determine the effect of creating a LASIK flap.Eligibility Criteria Subjects more than 18years age and eligible for LASIK.Contact R. Krueger, M.D., 216/444-8158or J. Finkenthal, C.O.A., Clinical ResearchCoordinator, 216/444-2566

ANTERIOR SEGMENT IMAGING USING OPTICAL COHERENCE TOMOGRAPHY (OCT)AND ULTRASOUND BIOMICROSCOPY,A COMPARISON STUDYObjective Optical coherence tomography(OCT) and ultrasound biomicroscopy areused to image and measure the anteriorstructures of the eye. The variance ofthese measurements will be examined.Contact D. Huang, M.D., Ph.D., 216/444-0848 or J. Finkenthal, C.O.A.,Clinical Research Coordinator, 216/444-2566

MODELING THE CORNEA EPITHELIAL SMOOTHING FUNCTION AFTER LASER SURGERY

Objective Corneal topography and optical coherence tomography are used tomeasure corneal changes after LASIK. Amathematical model will be developed topredict changes and design laser ablationprofiles to compensate for them.

Cole Eye Institute

Clinical Trials All studies have been approved by the Institutional Review Board.

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Contact D. Huang, M.D., Ph.D., 216/444-0848, or J. Finkenthal, C.O.A.,Clinical Research Coordinator, 216/444-2566

USE OF WAVEFRONT DEVICE FOR DIAGNOSTIC MEASUREMENTS

Objective The Custom Cornea WavefrontDevice from Alcon Summit Autonomouswill be evaluated for repeatability and accuracy of measurements as comparedwith manifest refraction and topography.Eligibility Criteria Must be 18 years ofage or older. Participants will have eyesdilated. Must be eligible for LASIK, PRKor AK.Contact R. Krueger, M.D., 216/444-0848,or J. Finkenthal C.O.A., 216/444-2566

LASIK SURGERY

Objective To evaluate the ability of theCustom Cornea Device in its ability to improve keratorefractive surgery. CustomCornea is a new method of measuring thevisual system of the eye. These measure-ments are used in conjunction with theexcimer laser system to customize the application of the laser beam to the indi-vidual needs. This allows the excimerlaser to reshape the cornea so that lightentering the eye is properly focused. Ifthis technology proves reliable, it standsto improve keratorefractive surgery byminimizing or eliminating common post-operative side effects such as glare, halos,double vision, night vision difficulties andresidual refractive error.Contact Ronald Krueger, M.D., at216/444-8158 or Josel Finkenthal, C.O.A.,Clinical Research Technician, at 216/444-2566

VISION THERAPY: A PROGRESSIVE CON-TROLLED STUDY ON THE EFFECTIVENESS OF VISION THERAPY IN ELIMINATING AS-THENOPIA IN A SYMPTOMATIC POPULATION

Eligibility Criteria Patients who are 18to 35 years old and have any of the fol-lowing symptoms: eye strain, occasionalblurred vision when using a computer orperforming other near work, occasionalheadaches, have words run together orfall asleep when doing prolonged comput-er work or near work. If eligible, partici-pation will involve approximately threevisual assessments at the Cleveland ClinicDivision of Ophthalmology at Beachwood

and required equipment for therapy. Compensation of $100 will be allotted fortravel expenses.Contact D. Tucker, O.D., 216/831-0120, or K. Danko, C.O.T., 216/831-0120

RETINAL DISEASES

DIABETIC RETINOPATHY TRIAL

Introduction Doctors throughout the United States are working together in astudy to see if a new investigational drugis effective in delaying the progression of diabetic retinopathy and the need forlaser treatment for diabetic eye disease.Goal To determine if a once-a-day pillcontaining an investigational drug canslow or prevent the worsening of diabeticeye disease.Eligibility Criteria Patients must be age18 or older, have either type 1 or 2 dia-betes, have good blood pressure control if hypertensive, do not intend to becomepregnant or be nursing, have 20/125 visu-al acuity or better in the eye under inves-tigation and have moderate to very severediabetic retinopathy without evidence ofabnormal new blood vessel growth.Contact Cherrie (Rosario) Rosal, R.N., at 216/445-1256

EYE001 INTRAVITREAL INJECTION

Objective To determine the safety and efficacy of EYE001 to treat choroidal neovascularization in patients with age-related macular degeneration (AMD). Eligibility Criteria Patients must havethe wet (exudative) form of AMD. Visualacuity must be 20/40 to 20/230.Contact Hilel Lewis, M.D., 216/444-0430or L. Schaaf, R.N., 216/445-4086

TRANSPUPILLARY THERMOTHERAPY (TTT) OFOCCULT SUBFOVEAL CHOROIDAL NEOVAS-CULAR MEMBRANES IN PATIENTS WITH AMDObjective To determine if a diode laserwith lower power will close abnormalvessels, yet preserve normal retina.Eligibility Criteria Patients must havethe wet (exudative) form of AMD, havevisual acuity of 20/50 to 20/400 and beage 50 or older.Contact P. Kaiser, M.D., 216/444-6702, or L. Schaaf, R.N., 216/445-4086

POSTERIOR SUB-TENON'S CORTICOSTEROIDINJECTION VERSUS FOCAL LASER PHOTO-COAGULATION FOR THE TREATMENT OF DIABETIC MACULAR EDEMA

Objective To compare the effectiveness of steroid injections with focal laser thera-py in the treatment of clinically significantmacular edema. The study will involverandomly assigning patients with clinicallysignificant macular edema to treatmentwith either steroid injection or laser thera-py. Patients will undergo follow-up visitsfor at least 1 year after treatment. Thehope is that steroid injection will be aseffective with less severe side effects andlower costs than laser therapy.Contact P. Kaiser, M.D., 216/444-6702, or L. Holody, C.O.A., 216/445-3762

OCULEX: DEXAMETHASONE POSTERIOR SEGMENT DRUG DELIVERY SYSTEM IN THETREATMENT OF PERSISTENT MACULAREDEMA

Objective To determine the safety and effectiveness of the intraocular, biode-gradable Dexamethasone PosteriorSegment Drug Delivery System in thetreatment of persistent macular edema.Eligibility Criteria Patients must beage 12 or older and have vision between20/40 and 20/200 and a diagnosis of per-sistent macular edema associated with diabetic retinopathy, uveitis, retinal veinocclusion or Irvine-Gass syndrome. Contact Hilel Lewis, M.D., 216/444-0430or Laura Holody, C.O.A., 216/445-3762

VER: VERTEPORFIN IN EARLY RETREATMENT

Objective This is a photodynamic thera-py study for “wet" macular degenerationto determine if early retreatment will slowthe progression of vision loss.Contact Peter Kaiser, M.D., 216/444-6702or Laura Holody, C.O.A., 216/445-3762

VIM: VISUDYNE IN MINIMALLY CLASSICSUBFOVEAL CHOROIDAL NEOVASCULARIZA-TION (CNV) SECONDARY TO AGE-RELATED MACULAR DEGENERATION (AMD)

Objective A photodynamic therapy studyfor wet macular degeneration to under-stand the disease better and to study itseffect in AMD patients who have a typeof lesion called minimally classic.Contact Peter Kaiser, M.D., 216/444-6702or Laura Holody, C.O.A., 216/445-3762

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BAUSCH & LOMB PHARMACEUTICALS,BPL 415-001 UVEITIS

Objective This 3-year multi-centercontrolled study is designed to evaluatethe safety and efficacy of intravitreal fluocinolone acetonide implants and tocompare the 0.5 mg and 2 mg doses to be delivered in the treatment of non-infectious posterior uveitis.Contact Careen Lowder, M.D., Ph.D., at 216/444-3642 or Mary Escano Preda,R.N., at 216/445-3641

ANTERIOR SEGMENT

CORNEA DONOR STUDY

Objective To determine whether thegraft-failure rate over a 5-year period is equivalent with corneal tissue fromdonors older than 65 years of age com-pared with that from younger donors. To assess the relationship betweendonor:recipient ABO compatibility andgraft failure due to rejection. To assesscorneal endothelial cell density as an indicator of the health of the cornea andas a surrogate outcome measure.Eligibility Criteria Patients must be age40 to 80 years. They must have a condi-tion associated with endothelial dysfunc-tion, including pseudophakic/aphakiccorneal edema, Fuchs’ dystrophy, posteri-or polymorphous dystrophy, interstitial keratitis (nonherpetic) or perforatingcorneal injury.Contact D. Meisler, M.D., 216/444-8102or L. Holody, C.O.A., 216/445-3762

GLAUCOMA

THE TRAVATAN STUDY

We are seeking glaucoma patients to par-ticipate in a 4-week trial using Travatan0.004% Ophthalmic Solution. Travatan is an FDA-approved eye drop used in the treatment of glaucoma. Patients willtake Travatan in both eyes at night for 4weeks and come in for two clinic visits(the first at the time of study entry andthe second at study exit). At both clinicvisits, eye pressure will be checked. Eyemedication, clinic visits and parking arecovered during the study.Contact E. Rockwood, M.D., S. Smith,M.D., or D. Dueker, M.D., at 216/444-1995or L. Wash, C.O.T., 216/444-6497

GLAUCOMA DIAGNOSIS BY OPTICAL COHERENCE TOMOGRAPHY ANALYSIS OFRETINA AND OPTIC NERVE

Objective The purpose of this study is to evaluate the ability of the OpticalCoherence Tomography Unit Model 2010and the Optical Coherence TomographyUnit Model 3000 to measure accuratelyand reproduce measurements of the opticnerve head excavation, retinal fiber thick-ness layer and the perifoveal retinalthickness in patients suspected of havingglaucoma or patients with glaucoma.Contact J. Finkenthal, C.O.A., 216/444-2566

FOLLOW-UP PHASE ONLY

RETINAL DISEASE

PROTEIN KINASE C INHIBITOR B DIABETICMACULAR EDEMA STUDY (PKC STUDY)

Eligibility Criteria Patients must have a diagnosis of diabetic retinopathy withmacular edema that is not vision-threat-ening, be age 18 years or older with typeI or II diabetes mellitus and have visualacuity better than 20/32.Treatment Patients will be randomly assigned to receive a placebo or LY33353. Contact H. Lewis, M.D., 216/444-0430, P. Kaiser, M.D., 216/444-6702, or C. Rosal,R.N., 216/445-1256

PROTEIN KINASE C INHIBITOR B DIABETICRETINOPATHY STUDY (PKC STUDY)

Eligibility Criteria Patients must have adiagnosis of severe or very severe diabeticretinopathy with no previous scatter lasertreatment for diabetic retinopathy. Theymust be age 18 or older with type I or IIdiabetes mellitus and have visual acuitybetter than 20/100.Treatment Patients will be randomly assigned to receive placebo or LY33353Contact H. Lewis, M.D., 216/444-0430, P. Kaiser, M.D., 216/444-6702, or C. Rosal,R.N., 216/445-1256

COLLABORATIVE OCULAR MELANOMASTUDY (COMS)

Objective Two randomized controlled trials to compare enucleation versusradiation therapy for medium tumors andstandard enucleation versus enucleationpreceded by radiation therapy for largetumors. Follow-up phase only.

Contact F. Gutman, M.D., 216/444-5888or L. Holody, C.O.A., 216/445-3762

TAP STUDY EXTENSION—TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH PHOTODYNAMIC THERAPY

Objective To collect long-term follow-updata on patients with age-related maculardegeneration enrolled in the TAP trial. Contact H. Lewis, M.D., 216/444-0430or L. Holody, C.O.A., 216/445-3762

SUBMACULAR SURGERY TRIALS

Eligibility Criteria Diagnoses of choroidalneovascularization (CNV) due to age-re-lated macular degeneration, ocular histo-plasmosis or idiopathic causes; evidenceof new or recurrent subfoveal CNV; visualacuity of 20/50 to 20/800; age 18 yearsor older.Treatment Patients are randomly assignedto surgery or observation. Contact H. Lewis, M.D., 216/444-0430 or L. Schaaf, R.N., 216/445-4086

SAFETY AND EFFICACY OF VITRASE FOR OPHTHALMIC INTRAVITREAL INJECTION FOR CLEARANCE OF SEVERE VITREOUS HEMORRHAGE (PHASE III STUDY)

Objective To determine the safety and efficacy of Vitrase to clear severe vitreoushemorrhages.Eligibility Criteria Patients must havesevere vitreous hemorrhage (20/200 orworse vision) and be 18 or older. Contact P. Kaiser, M.D., 216/444-6702 or C. Rosal, R.N., 216/445-1256

GLAUCOMA

COLLABORATIVE INITIAL GLAUCOMA STUDY (CIGTS)

Objective To determine the best initialtreatment for glaucoma. Six hundred patients across the country randomly assigned to either surgery or medication. Contact E. Rockwood, M.D., 216/444-1995or L. Wash, C.O.T., 216/445-6497

5-FU VERSUS MMCObjective Comparing the surgical out-comes of two antimetabolite drugs usedduring trabeculectomies with 5-FU andMMC.Contact E. Rockwood, M.D., 216/444-1995or L. Wash, C.O.T., 216/445-6497

Clinical Trials continued

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7

Hilel Lewis, M.D.Director and Division ChairmanSpecialty/Research Interests Vitreoretinalsurgery for complicated retinal detachmentand trauma, age-related macular degenera-tion, diabetic retinopathy, retinal photoco-agulation, instrument development

Bela Anand-Apte, M.B.B.S., Ph.D.Research Interest Angiogenesis

John W. Crabb, Ph.D.Research Interests Age-related macular degeneration, inherited retinal diseases

David K. Dueker, M.D.Specialty/Research Interests Glaucoma,glaucoma drainage procedures, reducing risk of infection

Froncie A. Gutman, M.D.Specialty Interests Retinal vascular dis-eases, laser therapy, diabetic retinopathy

Stephanie A. Hagstrom, Ph.D.Research Interests Inherited forms of reti-nal degeneration, including macular degen-eration and retinitis pigmentosa

Joe G. Hollyfield, Ph.D.Research Interests Retinal degeneration,retinal diseases

David Huang, M.D., Ph.D.Specialty/Research Interests Keratorefrac-tive surgery, instrumentation and equipmentdevelopment, corneal disease, cataract/ante-rior segment surgery

Peter K. Kaiser, M.D.Specialty/Research Interests Vitreoretinaldiseases, age-related macular degeneration,retinal detachment, diabetic retinopathy,endophthalmitis, posterior segment compli-cations of anterior segment surgery

Ronald R. Krueger, M.D.Specialty/Research Interests Refractivesurgery, lasers, refractive corneal pathology,lamellar corneal transplants, investigationalclinical trials

Roger H.S. Langston, M.D.Specialty Interests Cornea and externaldisease, corneal transplantation

Careen Y. Lowder, M.D., Ph.D.Specialty/Research Interests Uveitis, in-traocular inflammatory diseases, pathology

Alan D. Marmorstein, Ph.D.Research Interest Development of newtreatments for age-related macular degen-eration through understanding proteinfunction in inherited retinal degenerativediseases, such as Best macular dystrophy

David M. Meisler, M.D.Specialty/Research Interests Corneal and external disease, inflammatory andinfectious diseases of the cornea, cornealtransplantation, refractive surgery

Neal S. Peachey, Ph.D.Research Interest Treating visual loss associated with hereditary retinal degen-eration

Julian D. Perry, M.D.Specialty/Research Interests Aestheticfacial surgery/fat transplantation andrepositioning, acellular human dermalgraft matrix, new bovine hydroxyapatiteorbital implant, thyroid eye disease/rateof strabismus after decompression surgeryfor dysthyroid orbitopathy

Edward J. Rockwood, M.D.Specialty Interests Glaucoma, glaucomalaser surgery, combined cataract and glau-coma surgery, glaucoma filtering surgerywith antimetabolite therapy, glaucomatousoptic nerve damage

Jonathan E. Sears, M.D.Specialty/Research Interests Pediatricand adult vitreoretinal diseases, pediatricretinal detachment, inherited vitreoretinaldisorders, retinopathy of prematurity,other acquired proliferative diseases

Scott D. Smith, M.D., M.P.H.Specialty/Research Interests Glaucoma,cataract, prevention of eye disease, inter-national ophthalmology

Elias I. Traboulsi, M.D.Specialty/Research Interests Oculardiseases of children, genetic eye diseases,strabismus, retinoblastoma, congenital cataracts, childhood glaucoma

Cole Eye Institute

Staff

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REGIONAL OPHTHALMOLOGY

Philip N. Goldberg, M.D.Specialty Interests Comprehensive ophthal-mology, cataract, glaucoma

Gregory S. Kosmorsky, D.O.Specialty Interests Neuro-ophthalmology,cataract, refractive surgery

Andreas Marcotty, M.D.Specialty Interests Pediatric ophthalmol-ogy, adult strabismus

Michael Millstein, M.D.Specialty Interests Cataract, glaucoma,laser refractive surgery (LASIK)

Allen S. Roth, M.D.Specialty Interests Corneal transplantation,laser refractive surgery, cataract and implantsurgery

David B. Sholiton, M.D.Specialty Interests Cataract and implantsurgery, glaucoma, oculoplastics

O. David Solomon, M.D.Specialty Interests Contact lens research,cataract surgery, retinal laser surgery

216/444-2020The Cleveland ClinicCole Eye Institute

Visit The Cleveland Clinic online atwww.clevelandclinic.org and the Cole Eye Institute atwww.clevelandclinic.org/eye

Faculty Disclosure *Faculty members who haveindicated having a relationship which, in thecontext of their articles, could be perceived as a potential conflict of interest: None.

The following faculty has indicated they haveno relationship which, in the context of theirarticle, could be perceived as a potential con-flict of interest: John W. Crabb, Ph.D., Joe G.Hollyfield, Ph.D., Hilel Lewis, M.D., Alan D.Marmorstein, Ph.D., and Jonathan E. Sears, M.D.

Cole Eye Institute Staff Members Present Findings at

American Academy of Ophthalmology Meeting

Many Cole Eye Institute staffmembers presented researchfindings at the 2001 meeting

of the American Academy of Ophthal-mology in New Orleans. Here are someof the highlights of those presentations.

LIMITED MACULAR TRANSLOCATION WITH DIAGONAL OUTPOUCHING OF THE SCLERA USING CLIPS

Sr. Author Motohiro Kamei, M.D.,Osaka, University Medical School,Osaka, JapanCo-Authors Hilel Lewis, M.D., Cole EyeInstitute, and Yasuo Tano, M.D., OsakaUniversity Medical School, Osaka, Japan

In this study, 24 consecutive patientswith subfoveal neovascularization un-derwent limited macular translocation.The researchers used clips to outfold the sclera diagonally for chorioscleralshortening. Visual acuity improved by 2 or more lines in 9 patients (37.5 per-cent). Acuity was unchanged in 12 pa-tients (50 percent) and worsened in 3patients (12.5 percent). The mean dis-tance of foveal displacement was 1012microns. Surgery-induced astigmatismranged from 0 D to 2.5 D (mean: 0.9 D).No complications were associated withthe clipping. The researchers concludedthat limited macular translocation withdiagonal outfolding of the sclera allowedimprovement of vision with less defor-mity of the eye.

PEDIATRIC MACULAR HOLES: ETIOLOGIESAND THE ROLE OF VITRECTOMY

Sr. Author Linda A. Lam, M.D., ColeEye InstituteCo-Authors Jonathan E. Sears, M.D.,Peter K. Kaiser, M.D., and Hilel Lewis,M.D., all of the Cole Eye Institute

This retrospective study looked at fivepediatric patients with macular holesthat were repaired via vitrectomy. Fourof five patients had traumatic macularholes. An optic nerve pit was associatedwith the remaining macular hole. Infour of five patients, the macular holewas closed after one vitreoretinalsurgery. One patient required an addi-tional vitrectomy for hole closure. Mac-ular hole closure was achieved in allfive patients. Visual acuity improved inthree of five patients. The researchersconcluded that vitreoretinal surgery canimprove vision in some children withmacular holes of varying etiologies.

OPTICAL COHERENCE TOMOGRAPHY EVALUATION OF MACULAR EDEMA IN PATIENTS WITH UVEITIS

Sr. Author Careen Yen Lowder, M.D.,Ph.D., Cole Eye InstituteCo-Authors Marc Estafanous, M.D., and Peter K. Kaiser, M.D., of the Cole Eye Institute

This prospective case series looked at92 uveitic eyes in 52 patients. Ocularcoherence tomography (OCT) demon-strated macular edema in 49 percent ofeyes. The macular edema was associatedwith cystoid macular edema in 82 per-cent of eyes, subretinal fluid in 33 per-cent, hyaloidal traction in 10 percent,epiretinal membranes in 8 percent, sub-foveal lesions in 5 percent, pigment epithelial detachment in 2 percent andepiretinal lesions in 2 percent. Retinalthickness averaged 275 ±132 micronsand correlated well with vision (P <.001) but was not predictive of macularedema. Sensitivity and specificity ofOCT compared with fluorescein angiog-raphy were 76 percent and 79 percent,respectively. OCT demonstrated eightpatterns of macular edema in uveitis.

RISK FACTORS AND CHARACTERISTICS OF ENDOGENOUS ENDOPHTHALMITIS: AN 18-YEAR REVIEW

Sr. Author Peter K. Kaiser, M.D., Cole Eye InstituteCo-Authors Monica Binder, M.D., Cleve-land Clinic Foundation Department of Infectious Disease; Darius M. Moshfeghi,M.D., Cole Eye Institute; and Jimmy Chua,M.D., and Carlos Isada, M.D., ClevelandClinic Foundation Department of Infec-tious Disease

This retrospective review of culture-positive endogenous endophthalmitis (EE)was designed to evaluate risk factors andcharacteristics of EE. Twenty-seven pa-tients (34 eyes) were identified. They hada mean age of 64 years. Risk factors in-cluded immunosuppression (23 percent),diabetes (35 percent) and heart valves (19percent). Clinical features include iritis (62 percent), hypopyon (35 percent),chorioretinitis (88 percent), bilaterality (26 percent) and retinal detachment (6percent). Fungal (53 percent), gram-posi-tive (42 percent) and gram-negative (5percent) organisms were recovered. Visionimproved in 57 percent of eyes, stabilizedin 21 percent and declined in 21 percentafter vitrectomy (78 percent), antibioticinjection (4 percent) or systemic therapyalone (18 percent). Final vision was <20/200 in 56 percent. The researchersconcluded that fungal EE is common, especially in diabetic and immunosup-pressed patients.

TRANSCARUNCULAR-APPROACH ORBITALAPEX DECOMPRESSION FOR TREATMENT OFDYSTHYROID OPTIC NEUROPATHY

Sr. Author Julian D. Perry, M.D., Cole Eye Institute

Dr. Perry conducted this study to deter-mine the efficacy of medial wall decom-pression for dysthyroid compressive

12

ophthalmopathy via a transcaruncular approach. Decompression was performedprospectively via a transcaruncular ap-proach on 5 consecutive patients (6 or-bits). Preoperative visual acuity rangedfrom 20/40 to counting fingers; colorplate testing ranged from 0/10 to 9/10.Postoperative visual acuity ranged from20/20 to 20/30. Color plates were 10/10 in all 6 cases. Visual fields improved tofew nonspecific changes or within normal limits in all 6. There were nocomplications. Dr. Perry concluded thatthe transcaruncular approach appears todecompress the orbital apex effectivelyfor treatment of dysthyroid compressiveoptic neuropathy.

IMPROVEMENT IN STEREO ACUITY (SA) IS LESS THAN EXPECTED AFTER TREATMENT OFANISOMETROPIC AMBLYOPIA IN CHILDRENWITHOUT STRABISMUS

Sr. Author Blanca I. Riemann, M.D.,Cincinnati Eye InstituteCo-Authors Christopher D. Riemann,M.D., Cincinnati Eye Institute; and SueCrowe, C.O.T. and Elias I. Traboulsi, M.D.,Cole Eye InstituteThis study was designed to determine the relationship between visual acuity and stereo acuity in children with ani-sometropic amblyopia (AA). Visual acuityand stereo acuity measurements taken before and after treatment for amblyopiawere analyzed retrospectively in 44 chil-dren with AA. Expected stereo acuityafter amblyopia treatment was mathemat-ically modeled using internal control data.The study found that visual acuity inamblyopic eyes improved from 0.3±0.2 to 0.5±0.3 (P < .00000001). Stereo acuityimproved from 200 to 152 degrees ofstereo arc (P = .004). Expected post-treat-ment stereo acuity was 91 degrees ofstereo arc (P = .007). Median follow-upwas 11 months. Stereo acuity improvedless than expected for the observed in-crease in visual acuity. The researchersconcluded that this suggests the existenceof “stereoscopic amblyopia” as a distinctentity, possibly less responsive to treat-ment than AA in orthotropic children.

OCULAR FINDINGS IN CHILDREN WITHMYOTONIC DYSTROPHY

Sr. Author Elias I. Traboulsi, M.D.,Cole Eye InstituteCo-Authors Valerie Kattouf, O.D.,Illinois College of Optometry; Brian W.Arthur, M.D., Wilkes-Barre, PA; Jane D.Kivlin, M.D., Milwaukee, WI; Natalie C.Kerr, M.D., Memphis, TN; and MichaelA. Kipp, M.D., Wheaton, IL

This study was designed to describe theocular findings in infants and youngchildren with myotonic dystrophy (MD).Ocular examination of 11 children withMD included refraction, motility andslit-lamp biomicroscopy. All children (5 boys and 6 girls with an age rangeof 4 months to 7 years; mean 2.6 years)were hypermetropic (+1.00 D to +12.5D, mean +7.25 D). Six had esotropia, 4had ptosis, 3 had amblyopia (2 bilateralametropic and 1 unilateral strabismic),2 had characteristic multicolored lensopacities, 2 had strabismus surgery and1 had ptosis repair. The researchersconcluded that hypermetropia appearsto be universal in infants and youngchildren with MD. It is accompanied byesotropia and/or amblyopia in a signifi-cant proportion of patients.

NOVEL RDS/PERIPHERIN GENE MUTATIONASSOCIATED WITH A BUTTERFLY-SHAPEDPATTERN DYSTROPHY OR ADULT-ONSETFOVEAL MACULAR DYSTROPHY

Sr. Author Scott O’Connor, M.D., ColeEye InstituteCo-Authors Darius M. Moshfeghi, M.D.,Yang Li, M.D., Zhengha Yu, M.D., NealPeachey, Ph.D., all of the Cole Eye Institute; Samuel G. Jacobson, M.D.,Ph.D., Scheie Eye Institute, Philadelphia;Donald J. Zack, M.D., Ph.D., WilmerEye Institute, Baltimore; and KangZhang, M.D., Ph.D., Cole Eye Institute

This study was designed to describe novel RDS/peripherin mutation result-ing in a butterfly-shaped pattern dys-trophy (BPD) or adult-onset fovealmacular dystrophy (AOFMD). Two

kindreds were examined. Mutationalscreening was performed by directsequencing of PCR-amplified DNA frag-ments corresponding to the 3 exons ofthe gene. Four of the 5 patients in 1family and 8 of 23 patients in a secondfamily with AOFMD demonstrated mac-ular and angiographic changes consis-tent with BPD and AOFMD, respectively.Sequence analysis demonstrated an A-to-G change, predicting a novelTyr141Cys substitution. The researchersconcluded that the Tyr141Cys substitu-tion in the RDS/peripherin gene can result in different clinical phenotypessuch as BPD and AOFMD.

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Ophthalmic

Continuing Medical Education

14

Course Description and Objectives

This program provides a scientificforum to present clinical and basic sci-ence research of the residents, fellows,alumni and staff of the Cleveland ClinicFoundation Division of Ophthalmology.The goal of this meeting is to pursueand present the highest-quality, origi-nal, thought-provoking clinical andresearch papers. In addition to the edu-cational aspects of the program, thisevent offers an excellent opportunity torenew old friendships, meet the currentresidents and fellows, and learn aboutnew and ongoing investigations withinthe Division.

After completion of this course, participants should be able to:

• Recognize the most up-to-dateconcepts and treatments in researchand clinical ophthalmology.

• Identify current basic science research in age-related maculardegeneration.

• Explain the rationale and status of the most current treatments for age-related macular degeneration.

• Discuss outcomes of complicated glaucoma and cataract surgery.

• Describe the latest techniques in refractive surgery.

Annual Residents and AlumniMeeting

Thursday, June 20, and Friday, June 21, 2002

Thursday (poster session) 5 p.m. to 7:30 p.m.Cole Eye Institute Skyway

Friday (Speakers and Posters) 7 a.m. to 5:30 p.m.James P. Storer AuditoriumCole Eye Institute

Friday evening reception, dinner, graduation/awards ceremony and residents skit6 p.m. Ritz-Carlton Ballroom, Downtown Cleveland

Course Directors

Hilel Lewis, M.D.Chairman, Division of OphthalmologyDirector, Cole Eye Institute

Careen Y. Lowder, M.D., Ph.D.Uveitis DepartmentCole Eye Institute

Keynote Speaker

Neil R. Miller, M.D.Professor of Ophthalmology, Neurology,and Neurosurgery, Johns Hopkins Med-ical Institutions, and Frank B. WalshProfessor of Neuro-Ophthalmology,Wilmer Eye Institute

Lecture

Advances in the Diagnosis and Management of Carotid-CavernousSinus Fistulas

A question-and-answer period is incor-porated in the time allotted each speak-er. Audience interaction is stronglyencouraged.

Registration deadline isJune 7, 2002.

To register or for more information, contact KelliMeeks at 216/444-2010.

Distinguished Lecture Series

ALL PROGRAMS WILL BE HELD IN THE JAMES P. STORER TELECONFERENCE ROOM ON THE FIRST

FLOOR OF THE CLEVELAND CLINIC COLE EYE INSTITUTE FROM 5:30 TO 6:30 P.M. NO REGISTRATION

IS NECESSARY. FOR MORE INFORMATION, CALL 216/444-5832.

Thursday, June 27, 2002 (changed from June 20, 2002)

CONTROL OF ION AND FLUID TRANSPORT IN THE RETINAL PIGMENT EPITHELIUM

Sheldon S. Miller, Ph.D.Professor, Department of Visual Sciences and Molecular Cell Biology, University of California, Berkeley

Thursday, July 18, 2002TRANSGENIC ANIMAL MODELS AND STRATEGIES FOR THE STUDY AND TREATMENT OF INHERITED RETINAL DISEASES

Dean Bok, Ph.D.Professor of Neurobiology and Dolly Green Professor of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles

Thursday, August 15, 2002NOVEL THERAPEUTIC STRATEGIES TO CONTROL OCULAR ANGIOGENESIS

John S. Penn, Ph.D.Professor and Vice Chairman, Department of Ophthalmology and Visual Sciences,Vanderbilt University School of Medicine, Nashville, TN

Thursday, September 19, 2002REGULATION OF PHOTORECEPTOR GENE EXPRESSION: FROM CIS ELEMENTS TO RETINAL DEGENERATION

Donald J. Zack, M.D., Ph.D.Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology, Departments of Ophthalmology, Molecular Biology and Genetics, and Neuroscience, Johns Hopkins University School of Medicine

Thursday, October 17, 2002COLOR VISION: FROM GENES TO BEHAVIOR

Maureen Neitz, Ph.D.Professor, Department of Ophthalmology, Medical College of Wisconsin

Thursday, November 21, 2002MASSIVE LIGHT-DRIVEN MOVEMENT OF THE G-PROTEIN TRANSDUCIN FROM THE ROD OUTER SEGMENT: A NOVEL MECHANISM OF PHOTORECEPTOR LIGHT ADAPTATION

Edward N. Pugh, Ph.D.Jules and Doris Stein Research to Prevent Blindness, Professor F. M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, School of Medicine, University of Pennsylvania

15

Ophthalmology Update, a publication of The ClevelandClinic Cole Eye Institute, provides information forophthalmologists about state-of-the-art diagnosticand management techniques and current research.Please direct any correspondence to:

Scott D. Smith, M.D., M.P.H.Cole Eye Institute / i32The Cleveland Clinic Foundation9500 Euclid AvenueCleveland, Ohio 44195Phone 216/444-4821Fax 216/445-8475

Director and Division ChairmanHilel Lewis, M.D.

Editor-in-ChiefScott D. Smith, M.D., M.P.H.

Editorial BoardDavid Huang, M.D., Ph.D.Alan D. Marmorstein, Ph.D.Julian D. Perry, M.D.Jonathan E. Sears, M.D.

Managing Editor Beth Thomas Hertz Graphic Designer Barbara Ludwig ColemanPhotographers Don Gerda and Tom Merce

The Cleveland Clinic Foundation is an independent,not-for-profit, multispecialty academic medical center.It is dedicated to providing quality specialized careand includes an outpatient Clinic, a hospital with approximately 927 staffed beds, an Education Divisionand a Research Institute.

Ophthalmology Update is written for physicians andshould be relied upon for medical education purposesonly. It does not provide a complete overview of thetopics covered and should not replace the independentjudgment of a physician about the appropriateness orrisks of a procedure for a given patient.

Physicians who wish to share this information withpatients need to make them aware of any risks orpotential complications associated with any procedures.

Release date June 1, 2002Expiration date September 1, 2002The Cleveland Clinic Foundation, 2002

Ophthalmic Pearl

THE PAST FEW YEARS HAVE SEEN THE INTRODUCTION OF SEVERAL NEW OPTIONS

IN THE MEDICAL TREATMENT OF GLAUCOMA. THE NEWEST FAMILY OF GLAUCOMA

MEDICATIONS, THE PROSTAGLANDINS, COME NOT ONLY WITH A POTENTIALLY

POTENT OCULAR HYPOTENSIVE EFFECT, BUT ALSO WITH A NEW SET OF POSSIBLE

ADVERSE EFFECTS AND CLINICAL CONSIDERATIONS.

First, we must remember that the bulk of available data and docu-mented clinical experience with these drugs is in patients with open-angleglaucoma. While it is possible that reduction in intraocular pressure mayoccur in individuals with primary or secondary angle-closure glaucoma,this remains an off-label use. In addition, these drugs have the potential of inducing intraocular inflammation and should be avoided in cases of uveitic or neovascular glaucoma. Prostaglandins also have the potentialto increase retinal vascular permeability. These drugs should, therefore, beused with caution in patients with diabetic macular edema and in patientsundergoing cataract surgery who may be at risk of developing cystoidmacular edema.

Another difference from other classes of glaucoma medications is theapparent variation in clinical response that may be observed in a particularpatient between specific drugs in the class. With beta-blockers, if a poor re-sponse is seen, it is generally unproductive to try switching to a differentbeta-blocker. In contrast, a poor response to one prostaglandin does not nec-essarily preclude a good response to a different member of the same family.

The addition of prostaglandins to our armamentarium has made a significant impact in the medical treatment of glaucoma. By keeping inmind the important differences in mechanism of action and adverse effects,we can use them to the greatest advantage in our patients with glaucoma.

Non-Profit Org.U.S. Postage

PAIDCleveland, OH

Permit No. 4184

9500 Euclid Avenue / W14

Cleveland, OH 44195