Rule #3Rule #3

Jay C Bradley MDJay C Bradley MD

Sandra M Brown MDSandra M Brown MD

CaseCase

• Chief Complaint: left eye crosses

• HPI– 18 month old healthy girl– Left eye crossing intermittently for 4-5 mos– More noticeable when tired– Worsening overall

• PMH– Normal pregnancy, delivery, development

Family HistoryFamily History

?

Bilateral OA

Unable to drive legally; problem detected < 1st grade

ExaminationExamination

• Normal visual attention for age• Bruckner – large superior crescents OU• ITT

– One refixation OD– No movement OS

• Motility– Orthophoria at distance– Orthotropia with 8-10 PD esophoria at near– Versions full w/o oblique overaction

• Penlight exam– Normal OU

• Fundus exam– Small optic nerves with indistinct borders OU– Mild macular hypoplasia OU– Lightly pigmented throughout

• Refraction– +5.50 + 1.00 x 95 OD– +6.00 + 1.00 x 90 OS

Hereditary Optic Nerve AtrophyHereditary Optic Nerve Atrophy

• Bilateral gradual loss of central vision– VA 20/40 to 20/100– Long term prognosis – rarely < 20/200

• Generally starts in first decade

• Dyschromatopsia

• Ceocentral or paracentral scotomas with preserved peripheral field initially

• Optic discs– Temporal pallor– Triangular temporal excavation

• Inheritance– Usually autosomal dominant– Occasionally autosomal recessive– Phenotype varies by rate of vision loss

• Brown’s Rules of Pediatric Ophthalmology– #1 Don’t make the child cry– #2 Don’t let the child make you cry– #3 Everything in pediatric ophthalmology

makes sense

• Lee Jampol’s Clinic Rule– Try not to give the patient more than one

disease

• McCartney’s Rule– A patient may have as many diseases as they

wish

?

Bilateral OA

Unable to drive legally; problem detected < 1st grade

Thick glasses ET

All blonde

AlbinismAlbinism

• Foveal hypoplasia– Critical clinical feature

• Iris transillumination defects– Very difficult to detect in young kids

• Minimal fundus pigmentation

• Light-skinned– Doesn’t tan easily– “very light hair when young”

• Sensory nystagmus– Foveal function in infancy < 20/200 OU

• High hyperopia

• Accommodative esotropia

• Poor binocular stability– Abnormal ganglion cell decussation

• Amblyopia

Racial DifferencesRacial Differences

• Caucasians– Tyrosinase gene mutations

• African Americans– Intermediate phenotype– P gene mutations

Always on the BoardsAlways on the Boards

• Chediak Higashi syndrome– White cell dysfunction– Recurrent infection

• Hermansky Pudlak syndrome– Bleeding diathesis– Increased frequency in Puerto Ricans

““Old Style” Albinism GeneticsOld Style” Albinism Genetics

Type Location Locus Gene Product FunctionOCA1 11q TYR Tyrosinase EnzymeOCA2 15q P P Protein MembraneOCA3 9q TYRP1 TYRP1 EnzymeOA1 Xp OA1 OA1 Protein MembraneHPS1 10q HPS1 HPS1 Protein VesicleHPS2 5q ADTB3A B-3A-adaptin VesicleCHS1 1q CHS1 CHS1 Protein Vesicle

New Thinking: New Thinking: Phenotype SpectrumPhenotype Spectrum

“Chalky white”

Acuity < 20/200Sensory nystagmus

“Ordinary”

~ 20/30

Leaky vs Non-Leaky MutationsLeaky vs Non-Leaky Mutations

• Leaky mutations– Some enzyme production

• Non-leaky mutations– No enzyme production– OCA-1B no activity “chalk white”– OCA-1A partial activity “darkens down”

• Mom + Dad = net enzymatic deficiency

Rule #3Rule #3

• “Better Fit” Diagnosis – Mild Albinism– Fundus appearance– Hyperopia– Esotropia– Family history

• pigmentation • “thick glasses” = high hyperopia• Esotropia

A Cruel Genetic LotteryA Cruel Genetic Lottery• Might our patient have inherited AD optic

nerve atrophy too?

• Nothing rules it out.

• Watch for disc pallor

• Watch for decreased visual acuity resistant to refraction

Albinism TreatmentsAlbinism Treatments• Glasses for refractive error

– UV protection medically indicated

• Patching for amblyopia– Atropine – must consider UV issues

• Surgery for residual esotropia• Surgery for compensatory head turns• Education about sunblock• Education about genetics

Can This Get Better on Its Own?Can This Get Better on Its Own?

• YES!– Subset of patients with seemingly total foveal

hypoplasia at < 1 yo– Gradual production of foveal pigment over

first 5 years of life– Nystagmus slows down, might “stop”

• Difficult to predict which kids will improve

• Clinical observation: very smart kids

The Amarillo EffectThe Amarillo Effect

• Many referrals for “can’t refract to 20/20”

• Tow-headed kid and sibs/mom

• Mild foveal hypoplasia– Normal “light end of spectrum” peripheral

pigmentation for a Caucasian

• Mild to moderate hyperopia– Not enough to cause bilateral amblyopia

• Especially boys