ophthalmic anomalies in the pediatric patient does my...

10/16/2009

1

Ophthalmic Anomalies in the Pediatric Patient

M k T D b O D F A A OMark T. Dunbar, O.D., F.A.A.O.Director of Optometric Services

Optometric Residency SupervisorBascom Palmer Eye Institute

University of Miami, Miller School of Medicine

Miami, Florida

Does my child see?y

Does my child see?

How well does a neonate/infant see?How do we determine vision in an infant or neonate?

Visual Acuity

Relatively poor in the 1st months to yrs of lifeAdult acuity not attained until 1-11/2Adult acuity not attained until 1-11/2

yrsWell below the standard for legal blindness

Development

Turn over by 2-3 monthsSit-up by 5-6 monthsReach for an object by 4 monthsReach for an object by 4 monthsPlay with objects in hand by 6 monthsHow well does the baby respond to other stimuli (touch, sound)?Is the baby floppy or hypotonic?

Birth HistoryBirth WeightFull-term vs PrematureWhat kind of deliveryWhat kind of delivery Complications

During pregnancy During delivery

HypoxiaBleeding

10/16/2009

2

Family History

Night blindnessColor visionHigh myopiaHigh myopiaNystagmusCataractsCNS disorders

Visual Acuity

Does the baby fixate while eating?Do the eyes followDo the eyes follow the parent’s face?Does the baby respond to light?Does the baby reach for objects

Good VisionParents will tell you the baby sees wellWill smile at a faceWill follow the fact of a parentWill fixate while eating

Bad VisionParents unsure if baby seesStares at bright lightlightNystagmusHand wavingEye pokingDisinterested in the environmentFailure to smile

Visual Acuity

Fixate and FollowCentral Steady and Maintained (CSM)Maintained (CSM)OKN (Optokinetic nystagmus) Familiar figures

Allen Figures

Fix and FollowFixate within days of birthFollow by 6 weeksBabies loose target after 5-10°

Pursuit movement not well establishedWatch for micro-saccadic eye movements

10/16/2009

3

Teller Acuity CardsPreferential Looking

Electrodiagnostic TestingERG

OKN

Answers the question “Does my child see?”my child see?Motor response used to assess a sensory functionCheck monocularly and vertical

Rotation of the Infant“Response to spin”

Assesses the vestibulo-ocular responseTests the ability to generate a saccadic eye movementsSlow drift of the eyes in the direction of the spinFast phase, jerk nystagmus in the opposite direction

Rotation of the Infant

Two observations made:Does the child develop a nystagmus in response to vestibulo-oculi stimuliWhat is the time interval that the baby dampens the nystagmus when swinging stopped

10/16/2009

4

Rotation of the Infant

Sighted child will visually inhibit the induced nystagmus in 3-5 seconds

Blind child cannot visually inhibit the nystagmus and it may continue for 15-20 seconds

Alignment of EOM’s

Cover testHirshberg

N l 0 5Normal 0.5 mm nasal

Krinsky Neutralizing the corneal light reflex with prism

Pupils

Extremely important – Never lie!Dim illuminationCheck size direct and consensualCheck size, direct and consensualCheck for “APD” Paradoxical pupil

Constriction in dim illumination, dilation in bright illumination

Nystagmus

Rhythmic oscillation of the eyesSign of poor vision

U til th iUntil proven otherwiseWill mimic focal neurologic disease

Nystagmus

Afferent visual pathway diseaseCongenital (1:10)Focal neurologic disease (CNS disorders)

Nystagmus

CataractsCorneal opacitiesHigh Rx errorsHigh Rx errorsFoveal hypoplasiaAlbinismAniridia

10/16/2009

5

Nystagmus

Bilateral macular scar (Toxoplasmosis)Leber’sCSNBROPON HypoplasiaAchromatopsia

Congenital Motor Nystagmus

Benign conditionPresent at birth (or shortly after)Pendular or jerkPendular or jerkSymmetricHorizontalHorizontal on up-gazeDampens on convergence

Congenital Motor Nystagmus

Latent componentNull pointHead turnHead turnNear visual acuity usually better

Paradoxical Pupil

Pupil constricts in darknessDilates in with bright lightSeen with:Seen with:

Leber’sCSNBON Hypoplasia

Neuro-Imaging Not Necessary

Poor visionAcquired nystagmusSluggish pupilSluggish pupilNormal appearing fundusParadoxical pupil

Neuro-Imaging Mandatory

Poor visionAcquired nystagmusBrisk pupil responseBrisk pupil responseNormal appearing fundusNo paradoxical pupil

10/16/2009

6

Nystagmus

Good case historyCharacteristicsVariabilityVariabilitySymmetryNull pointHead turnLatent component

Nystagmus

Afferent Visual Pathway Disease20/200 VisionIf you can superimpose an OKN overtopIf you can superimpose an OKN overtop of their nystagmus, visual prognosis is excellent

Children can be mainstreamed into regular schools

5 Month Old

Suspected blindness or poor visionNystagmus noted at 6 wks of ageSluggish pupilSluggish pupilCycloplegic retinoscopy + 5.00No family Hx of nystagmusNormal appearing fundus

Your Move

Work Up?

Only observation?Neuro-imaging?Electrodiagnostic testing?Electrodiagnostic testing?

5 Month Old

Additional InformationPhotophobiaERG performed

Depressed in both photopic and scotopic states

Leber’s Congenital Amaurosis

Rod cone dystrophyPresent at birth or shortly after10-15% of kids in schools for the blind10 15% of kids in schools for the blindPoor visionNystagmus or roving eye movementsPoor pupil response: Paradoxical pupilModerate HyperopiaAutosomal recessive

10/16/2009

7

Leber’s Congenital Amaurosis

FundusMay appear normalAttenuated vesselsAttenuated vessels10% bilateral macular dystrophy10% peripheral RPE changesOptic atrophyExtinguished ERG

Diagnostic Criteria

Leber’s Congenital AmaurosisDiagnosis of exclusionVisual dysfunction since birthVisual dysfunction since birthAbnormal ERGNystagmus or roving eye movementModerate – high hyperopia

ElectrodiagnosticsWhen to do in children:

Nystagmus or poor vision from birthNot due to obvious afferent visual pathwayNot due to obvious afferent visual pathway conditions

Overt, but nondiagnostic macular lesionGeneralized retinal degeneration present or suspectedDecreased VA of unknown cause

6 Month Old FemaleNo fix or followNo nystagmusBrisk pupils No afferent pupil defectBrisk pupils – No afferent pupil defectNo paradoxical pupilAbsent OKNNormal fundus exam

What are we missing?

6 Month Old Female

Case HistoryFull term pregnancyCardiac surgery at 4 monthsCardiac arrestCannot see upon awakening

Cortical Blindness

Loss of vision stemming from injury to the geniculostriate pathwayHypoxic insult to the posteriorHypoxic insult to the posterior pathway, occlusion of the post cerebral arteries

10/16/2009

8

Cortical Blindness

Generalized hypotensionCardiac surgeryBirth aphyxiaBirth aphyxiaHypotensive crisisHydrocephalusMetabolic derangements

Cortical Blindness

Positive historyNo visual responseNo NystagmusNo NystagmusAbsent OKNIntact pupil responseNo paradoxical pupilNormal fundus exam

Cortical Blindness

CNS DefectsMental retardationCerebral palsySeizure disorderHydrocephaly or microcephaly

Cortical Blindness

Radiologic findingsDiffuse atrophy of the occipital cortexBi-occipital lobe infarctionPeriventricular leukomalaciaParieto-occipital “watershed” infarction

Cortical BlindnessPrognosisTransient or permanentComplete restoration of VA rarep50% may show significant improvementRecovery is slow – months to yearsNLP -> LP -> Color -> Form perception->All will recover some visionNo tests accurate in prediction recovery

Cortical Blindness

Work-upMRICTERGPediatric neurological work-up

10/16/2009

9

The Wet Watery Eye

Nasal lacrimal duct obstruction (NLDO)(NLDO)Viral conjunctivitisHerpetic keratitisCongenital developmental anomalies

The Wet Watery Eye

DischargeInjection or rednessS lliSwellingCorneal involvementDoes the eye feel hotSystemic involvement

Nasal Lacrimal Duct Obstruction (NLDO)

Blockage at the lower end of the nasal lacrimal duct6% of babiesFailure of canalization of the epithelial cells

At the valve of HasnerChronic epiphora, mucopurulent discharge

NLDO80% spontaneously open by 6 monthsProbing after 6 monthsAdvise parents to massage lacrimal sacAdvise parents to massage lacrimal sac

Massage up to express mucous, then downto increase hydrostatic pressure

May need antibiotic for 2° infectionZymar, Polytrim

10/16/2009

10

Blepharoconjunctivitis in ChildrenChildren

Lorena 8 ½ yo Female

3 yr history of chronic “blepharitis”Last Dr rxed Bacitracin, Polytrim X 3 wksHad been on Cefaclor Max ung OcufloxHad been on Cefaclor, Max ung, Ocuflox Medical Hx unremarkable, twin

Sister did not have the same eye sxVA: 20/15 OUAnt Seg: L > R

Mild PEE RE and SEI RE – Photos LE

Rosacea: “Acne Rosacea”

A chronic acneiform skin disorder affecting cheeks, chin, nose, forhead, and eyeEtiology: Poorly understood

Dermatologic FindingsAxial facial erythema/hyperemiaTelangiectasisPapulesPustulesSebaceous gland hypertrophyRhinophyma

Ocular Rosacea FindingsMeibomian gland Dz

Foamy tearsRecurrent chalaziaChronic blepharitisChronic blepharitis

Staph blepharo-conjunctivitis Lid margin telangiectasia

Papillae, folliculesHyperemia

10/16/2009

11

Ocular Rosacea Findings

Corneal vascularizationSterile corneal infiltratesCorneal ulcerationCorneal perforationEpiscleritisScleritisIritis

Rosacea KeratitisRepresents more significant clinical problemCutaneous rosacea:

5 30% l i l t5-30% corneal involvementOcular rosacea:

75-85% corneal involvementInferior cornea usual siteCharacteristic “spade-shaped” infiltrates

Ocular Rosacea in Children

Erzurum SA, Feder RS, Greenwald MJ Arch of Ophthal 1993

3 Cases of Rosacea keratitis between 10-12 yoCharacteristic dermatologic findingsAll had ocular Sx > 6 mo duration2 bilateral, 1 unilateralTx oral TCN and/or Doxycycline

Ocular Rosacea in Children

Rybojad BE, Deplus S, Morel P. Ann Dermatol Venereol 199610 yo girl with red painful eye X 6mo10 yo girl with red painful eye X 6mo

Dxed with episcleritisErythematous papular and pustular eruption mid face X 1 mo Txed with oral antibiotics and erythromycin

Evaluation and treatment of children with ocular rosaceachildren with ocular rosacea

Cornea. 2007 Jan;26(1):42-6.Donaldson KE, Karp CL, Dunbar, MT

Patient CharacteristicsN = 20

Bilaterality 74% (usually asymmetric)Mean age of onset 6.3 yrs (range: 6 mos-17 yr)Mean age of diagnosis 9.2 yearsg g yMean time to diagnosis 2.6 yearsGender 70% female/ 30% maleSkin changes 40%Decreased vision 30%Family History 10% (not elicited)Mean length of follow-up 19.6 months (0-4 years)

10/16/2009

12

Symptoms

Redness - 65%Chronic chalazia – 40% Pain/irritation/burning – 39% Secretions – 28% Photophobia – 22% Tearing – 17% Itching – 11%Blurry vision – 5%Constant eye rubbing – 5% No complaints - 5%

Clinical Features

FEATURE INCIDENCEMGD/Blepharitis 95%C l P th l 90%Corneal Pathology 90%

PEE 70%Neovasc/Pannus/Scarring 80%

Conjunctival Hyperemia 85%Chalazia 40%

Rosacea in Children

Submitted to AJO – RejectedThey didn’t believe Rosacea in children really exists

29 Cases (16 girls, 13 boys)Mean age was 6 ½ y/o (range 2-12)

Archives of Ophthal. December 2005; 123:1667-1670Wills Eye Hospital

Blepharokeratoconjunctivitis in Children

Blepharokeratoconjunctivitis in Children

Underdiagnosed chronic inflammatory disorder observed in childrenRepresents a spectrum of clinical manifestations, ranging from:

Chronic eyelid inflammationRecurrent chalazia Conjunctival and corneal phylctenulesNeovascularization and scarring

Literature Ambiguous

No definitive etiology in the literature Many terms have been given including:including:

Nontuberculous or staphylococcal phlyctenular disease Childhood acne rosacea Blepharokeratitis Chronic blepharokeratoconjunctivitis,

Clinical FindingsBilateral in 28/29 (97%)

Significantly asymmetric in 6/29 (21%) Ambylopia attributed to BKC in 2/29 (7%) 100% h d lid i fl ti

Hammersmith, K. M. et al. Arch Ophthalmol 2005;123:1667-1670

100% had eyelid inflammation 16/29 (55%) had superficial punctate keratitis 15/29 (52%) corneal vascularization Corneal infiltration 8/29 (28%) 4 patients (14%) had classic phlyctenules Corneal scarring was seen in 11/29 (38%)

10/16/2009

13

Treatment

At the Time of Diagnosis:11/29 (38%) topical 1% prednisone or 0 1% dexamethasone at the time of Dx0.1% dexamethasone at the time of Dx4/29 (14%) were taking oral erythromycin


Treatment

Warm compresses were prescribed to all patients Topical antibiotic ointment was prescribed p pto 27 (97%) of 29 patients Oral therapy, in the form of erythromycin (n = 21) and doxycycline (n = 1), was prescribed to 22 (76%) of 29 patients. Length of oral therapy ranged from 1 to 14 months


TreatmentA Stepwise Approach

Step 1 – Lid HygieneStep 2 – Topical Medications

Low dose steroids (FML Blephamide PFLow-dose steroids (FML, Blephamide, PF, MP)Antibiotic ointment (Erythromycin)

Step 3 – Systemic antibioticsErythromycinDoxycycline

Treatment

Lid Hygiene (AT, LS, HC)Erythromycin or bacitracin ung lids hslids hsTopical CorticosteroidsTetracycline, 250 mg. QID PODoxycycline, 50-100 mg. BID POErythromycin, 250 mg. QID POTopical metroniadazole

Pablo

24 yo Hispanic MaleWants contact lenses -> has always been nearsightedbeen nearsightedHas never had good visionVA: 20/80 RE; 20/30 LERE: -17.00 -3.00 X 175LE: - 15.00 -1.00 X 180

Retinopathy of Prematurity (ROP)

Vasoproliferative retinopathy that occurs principally, but not exclusively, in premature infants

Largest cause of blindness < 1 yr age

10/16/2009

14

Retinopathy of Prematurity

Identified by Terry in 1942 and coined the name “Retrolental Fibroplasia (RLF)

Believed the pathologic process was proliferation of embryonic hyaloid system10 years became the largest cause of childhood blindness

1950’s the relationship b/w supplemental O2became understood and resulted in rigid curtailment O2 -> respiratory distress (RDS)

ROPLate 60’s early 70’s arterial blood gas analysis became standard resulted in drastic decline in RDSWith the development of neonatology, highest risk premature infants were now survivingSurvival infants with BW < 1000 g

1950: 8% Survival Today: >72% Survival

% of Survival < 1500 g

1960 -> 32%1971 -> 39%1982 -> 63%1992 -> 75%2003 -> 85%

Risk Factors for ROP

PrematurityLow birth weightComplex hospital courseComplex hospital courseProlonged supplemental O2

Not a significant factor since the 1970’sDue in part to arterial blood gas monitoring

Time for ROP Development

Critical Window for Development of ROP10 wk interval b/w -> 32-42 weeks postconception

95% ROP develops by 2 wks postterm, or 42 weeks postmenstrual ageScreenings mandated for infants weighing < 1500g or < 28 weeks gestational age

Exam should be done 4-6 weeks from birth or 31-33 wks postconceptional age

ROP and Birth Weight

BW > 1250 gms (2.75 lbs): odds are slimBW < 1250 gms: 10%BW < 1000 gms (2.2 lbs): 75% ROP

Approximately 500 new cases each year in US of blindness from ROP

10/16/2009

15

Classification of ROP

Not done since 1950’sIncreased ROP -> increased survival of low BW neonatesof low BW neonatesTreatment had reared its ugly head

Unifying Principle

The more posterior the disease process, and the greater the circumference, the

th iworse the prognosis

International Classification

LocationExtent

Clock hoursStage

ROP ClassificationStage I: Demarcation lineStage II: RidgeStage III:Stage III:

Retinal fibrovascular proliferationPlus disease

Stage IV: Retinal DetachmentMacula-On vs Macula-Off

Stage V: Total funnel RD

Stage I: Demarcation Line

Stage II: Ridge

10/16/2009

16

Stage III

Fibrovascular proliferation

Stage III Plus Disease

Stage IVMacula-on vs Macula-off

Stage V TotalTotal RD

ROP Natural History

90% spontaneously regress10% progress to Stage III or worse

Regressed ROPHigh myopia (often unilateral)Dragging of retinal vesselsLattice degenerationLattice degenerationPeripheral retinal foldsVitreoretinal interface changesRetinal thinningRetinal breaksRetinal detachment

10/16/2009

17

Treatment of ROP

Controversy surrounding value of Cryotherapy prompted the CRYO-ROP study 1985ROP study 1985Study stopped early as it proved the value of Cryo in threshold disease

45.4% vs. 26.9 % reduction in RD, Retinal folds, abnormal retinal tissueBlindness reduced from 61.7% to 47.1%

Treatment of ROP< Stage III threshold: monitor carefullyStage III threshold: Cryo vs laserStage IV:

Macula on: observation weekly/biweeklyMacula off: SBP

SBP 46-70% success reattaching retinaStage V: SBP/PPV/PPL for open funnel or bilateral RD’s

Treatment of ROPStage IV (Macular on and Macular off)

Chang/Yang Retrospective study of 23 eyes (18 infants) w/ Stage 4 A or B Tx y ( ) gwith SBP

Segmental buckle used in 15 eyes11 (79%) Achieved macular reattachment

Encircling buckle used in 9 eyes4 (44%) Achieved macular reattachmentOphthalmic Surg Lasers Sep-Oct 2000

Treatment of Stage V ROP

Anatomical and visual results of vitreoretinal surgery for stage 5 retinopathy of prematurity

Retina. 2006 Sep;26(7):729-35

601 infants with stage 5 ROP in at least one601 infants with stage 5 ROP in at least one eye 1977 and 2001 had surgery28% success, 5% partial success, 55% failure, and 11% lost eyeVisual function of > LP was achieved in 74%of the 183 eyes with data on visual acuity

(8 of 183) achieved visual acuity better than 5/200

10/16/2009

18

Surgical Results

50-70% of patients have attached retina’s with some useful vision

Stage IV, Mild Stage V

Stage V40-50% have some attached retina50% of attached retina have some useful vision

Natural Course of ROP90% spontaneous regression10% progress to Stage III or beyondExcellent prognosis for Stage IIIExcellent prognosis for Stage III thresholdGood prognosis for Stage IV macula onVery poor prognosis for Stage VApproximately 500 new cases each year in US of blindness from ROP

Pediatric Cataracts

When do you do a work-up?In clinically healthy children, an extensive peroperative evaluation isextensive peroperative evaluation is not necessary to establish the cause…

Congenital Cataract

Nonsurgical managementVA may improve afterVA may improve after dilationCycloplegiaAmblyopia patching therapy

Patch good eye

Congenital CataractSurgical Management

Only when visual function is jeopardizedBilateral Cataracts: Critical time forBilateral Cataracts: Critical time for achieving binocular vision: 6-8 wksUnilateral Cataracts: “Window of opportunity:” birth to 6 wks

Bilateral CataractsOperated by 8 weeks

60% > 20/60; 27% < 20/200Operated after 8 weeksOperated after 8 weeks

1 in 7 achieve better than 20/200No patient with nystagmus had > 20/200

10/16/2009

19

Surgical ManagementHistorical Perspective

NeedlingIntracapsular extractionIntracapsular extractionDiscision/aspiration anterior approachLensectomy/vitrectomyCapsulotomy/Anterior vitrectomyIOL’s

Focal PointsAAO 1999

Pediatric CataractsWhen to use IOL’s?

As late as 1991 IOL in children were controversial for children < 2 yo

Small globe sizeIncreased tissue reactivityMarked axial length changes

1994 study of 234 pedi ophthalmol, 46% indicated implanting IOL’s in children

Wilson et al (1994 J Cat Refract Surg)

IOL’s in Pediatric Cataracts

Why the trend towards younger ages?Better, smaller more flexible PMMA IOL’sProven biocompatibility > 40 yrsLonger follow up in adults give more confidence in “capsular fixation” of IOL’sAdvances in surgical technology -> smaller wounds etc…Better management of anterior/posterior capsules at the time of surgery

IOL’s in Pediatric Cataracts: Outcomes

Hutchinson et al (1998 J Cat Refract Surg)Reported on IOL children < 2 yrs of age

22 eyes of 17 pts operated 12 d– 22 mo22 eyes of 17 pts operated 12 d 22 moAxial length, complications, need for further surgeryEqual axial lengthsAmblyopia developed in most eyes

Kids still too young to accurately access VA


Hutchinson et al (1998 J Cat Refract Surg)Post op Rx error mean 1.5 D (-1.8 to 4.1)

Shot for hyperopiayp pNo difference rates in complicationsRecommended under-correcting IOL power to account for myopic shift

Leave kids hyperopic and anisometropicSafe alternative to Specs and CL’s

10/16/2009

20


Peterseim/Wilson July 2000 Ophthalmology

Bil l CE/PCIOL 30 (12 d 13 )Bilateral CE/PCIOL 30 eyes (12 d to 13 yrs)91% VA better than 20/40


Bilateral CE/PCIOL 30 eyes (12 d to 13 yrs)91% VA b h 20/40

Peterseim/Wilson July 2000 Ophthalmology

91% VA better than 20/40

Age # Pts 1st Pop Refract

F-upmo

Last Refraction

Change/Yr

< 2 8 +6.8 D 29 +0.8 D -2.5 D/yr2-4 3 +3.2 D 26 +1.8 D -0.8 D/yr5-6 6 +0.8 D 27 -0.8 -0.7 D/yr

Refractive Changes Following CE/IOL

52 eyes of 42 pts developmental catsAges 12 months – 18 years

Crouch et al. J AAPOS, Oct 2002

Ages 12 months 18 years85% 20/40 or better

95% VA > 20/30 10 eyes had surgery @ 12 mo to 2 yrs

-5.96 D myopic shift

Refractive Changes Following CE/IOL

Age # Eyes F-Up (yrs)

Change (dioptors)

Δ/Yr

Crouch et al. J AAPOS, Oct 2002

(yrs) (dioptors)

1-2 10 6.35 -5.96 -0.93 D3-4 7 4.42 -3.66 -0.82 D5-6 11 6.12 -3.40 -0.557-8 8 4.38 -2.03 -0.46


Study of 68 infants IOL’s implanted 1-18 months of lifeFollow up 7 yrsVA average 20/40 (20/20 to 20/1200)

Despite 3.5 mm axial growth

Focal Points 1999 AAO


Becoming “Standard” for > 2 yrs oldWarranted unilateral cataract > 1 year old

Still controversial for < 2 and much more controversial for < 1 yo

Change in globe size Greater post op inflammationRefractive changes Unpredictability of post op refractive error makes IOL calculations difficult/unreliable

10/16/2009

21


General ConsiderationsWhat IOL power to shot for?

Emmetropia? Get more myopia laterEmmetropia? Get more myopia laterLess problems with Amblyopia now and easier to manageMyopia later is easier to deal with

Hyperopia – expect shift toward myopiaProblems of amblyopia, anisometropiaMost surgeons aim 1-3 D hyperopia

What To Do With the Post Capsule?

Leave it in?High incidence of post operative

Leave it or take?

g p pcapsular opacification -> amblyopia

Take it out?Primary posterior capsulotomy (posterior capsulorhexis) or a central capsulotomy

Dictates where to put the IOL

IOL’s in Infants: When to Use?

12 dOld,1 day1 dayPost op

Focal PointsAAO 1999

Silsoft Contact Lens

+20 to + 32 D in 3 D steps+12 to +20 in 1D stepsBirth to 6 mo: overplus by 3 4 DBirth to 6 mo: overplus by 3-4 D6 mo to 2 yrs: overplus by 1-2 D> 2 yo: Plano to 1D

RetinoblastomaMost common intraocular malignancy in childhood90% diagnosed before 3 yo94% sporadic cases, 6% family history40% of all new pts have inheritable mutationAll bilateral RB’s have inheritable formAutosomal dominant (80%) penetrance

10/16/2009

22

RetinoblastomaLeukocoria (61%)Normal globe sizeWhite, gray tumorChalky calcificationNecrosisRetinal detachment

Retinoblastoma

Multiple or solitary tumor(s)Exophytic vs endophytic

Total exudative retinal detachmentTotal exudative retinal detachmentInvade choroid, optic nerve -> sub-arachnoid space -> brain1% spontaneous regression

Phthisis bulbi

Amber

7 mo old with leukocoria in both eyes and strabismus for 6 weeksReferred for evaluation of leukocoriaFHX: unremarkable

Amber

Bilateral, non-familial retinoblastomaRE Stage IV, LE Stage Vb

Treatment optionsTreatment optionsExternal beam radiotheraphySystemic chemotherapy with focal ablationEnucleation

Amber

External beam radiotherapy180 cGy single daily fractionsAnterior –lateral opposed wedge pairAnterior lateral opposed wedge pair planningTotal treatment dose: 4500 cGy

Focal laser hyperthermia/ablationArgon Green Laser Indirect

10/16/2009

23

Genetics and Molecular Pathophysiology

Normal cell division (regulation of cell growth and proliferation):

depends on a balance of activating and inhibiting growth regulators


Cancer results from an irreversible imbalance of these factors tilted

towards uncontrolled cell growth and proliferation


Rb gene (RB1) located on the long arm of chromosome 13 (at region 13q14)

It codes for Rb nucleoprotein (tumorIt codes for Rb nucleoprotein (tumor suppressor protein) which normally suppresses cell division

Protein also functions to inhibit cancer Not only in the eye, but throughout the body


Rb occurs when both copies of the Rb gene are mutationally inactivated

B h l d l ll l f hBoth maternal and paternal alleles of the RB gene are lostSo that RB protein is deficient

Knudson’s “Two-hit” Hypothesis

1 functional copy of Rb1 gene is required for normal embryogenesis2 normal genes provides double2 normal genes provides double protection1 abnormal gene renders the cell susceptible to development of Rb


Hereditary (Germline) RbOne Rb mutation is already present andOne Rb mutation is already present and therefore needs only one subsequent mutation

10/16/2009

24


The “2nd hit” inactivates the other copyUnlike the 1st mutation, the 2nd hit occurs at a higher frequency and is more sensitive to environment factors

Such as exposure to ionizing radiationIncreases the risk of tumorigenesis

It occurs frequently enough during retinal development that multiple tumors occur

Also tumors thought out the body

Retinoblastoma (Rb)

Nonhereditary (Somatic): 60-70% Rb1 gene occurs in a single retinal cellUnilateralUnilateralNo increased risk for cancers elsewhere

Hereditary (Germline) 30-40%Due to sporadic germline mutationsAutosomal dominant

RetinoblastomaHereditary (Germline) 30-40%

This type of mutation results in every cell in the body having only 1 normal chromosome (and 1 abnormal)

High risk of multiple bilateral tumorsLifelong predisposition to cancers throughout the body

Retinoblastoma2nd Malignant Neoplasms

External beam radiotherapy is associated with ↑ incidence of 2nd

malignancy in the irradiated fieldmalignancy in the irradiated field (dose related)35% of pts die by 40 yrs of age of 2nd

malignancyIncidence is greater if radiotherapy done before 12 months of age

Retinoblastoma2nd Malignant Neoplasms

If no external beam radiotherapy has been administered…..by age 40 yo

5% of patients (with Germline mutations) p ( )develop second malignant neoplasms

Osteosarcomas of skull and long bonesCutaneous melanomaSoft tissue sarcomasSlight ↑ incidence of breast Ca and Hodgkin’s disease

Retinoblastoma Treatment

EnucleationExternal beam radiationPlaque brachytherapy (radiotherapy)Plaque brachytherapy (radiotherapy) ChemoreductionChemothermotherapyCombinationCryo, Laser

10/16/2009

25

Rb TreatmentEnucleation

Unilateral RB > ½ RetinaAdvanced disease with bilateral RBAdvanced disease with no hope of useful visionEyes unresponsive to all forms of Tx

RB TreatmentPlaque Radiation

Small tumors Unilateral RB < ½ retinaBilateral RBBilateral RBMay use combination of other chemo-therapeutic agents

Chemothermotherapy

Involves IV carboplatinFollowed by transpupillary thermotherapy (TTT)thermotherapy (TTT)Combined effect of chemotherapy and heat treatment causes tumor destruction

Chemoreduction

Combination of carboplatin, vincristine, and etoposideGiven in hopes of either controllingGiven in hopes of either controlling tumor(s) or reducing size so more conservative Tx method can be usedVery large tumors with RD have shown a dramatic initial response

Genetics

One affected child: 6% riskTwo or more children: 50% chanceRB survivor with hereditary form: 50%RB survivor with hereditary form: 50%Linked to small arm of chromosome 13

10/16/2009

26

Retinoblastoma Prognosis

Overall 5 yr survival rate: > 92%Poor prognosis

Optic nerve involvementpMassive choroidal invasionOrbital invasion

Survival for metastatic RB: < 6 moVA 20/200 85% when macular or ON not involved

Trilateral Retinoblastoma

Primitive neural ectodermal tumor (PNET)Develops in 3% of germline mutationsDevelops in 3% of germline mutationsLocated in the pineal gland

May also arise in the parasellar regionHistological characteristics similar to retinoblastoma

Systemic Work Up

CT scan (follow up MRI) r/o PNETLP if ON involvementBone marrow aspiration if choroidalBone marrow aspiration if choroidal or orbital involvement

Persistent Fetal Vasculature (PFV)

“Persistent Hyperplastic Primary Vitreous” (PHPV)Failure of the primary vitreous to p yregressPlaque of fibrous tissue adherent to the posterior lensVariable degrees of vascularizationAnterior, posterior, both

PFV: AnteriorUnilateralLeukocoriaMicrophthalmiaMicrophthalmiaShallow anterior chamberVascularization of the retrolental membraneDrawn in ciliary processesClear lens

PFV: Posterior

May have all or none of the anterior features

May be isolate to posterior pole onlyMay be isolate to posterior pole onlyFold of condensed vitreous and retina running from the disc to ora serrataRetinal detachment

10/16/2009

27

PFV Management

Goal: avoid complications of glaucoma and phthisisEnucleation should be avoidedEnucleation should be avoidedLensectomy/VitrectomyManagement of amblyopia

Thank You!

ophthalmic anomalies in the pediatric patient does my...

Documents