Rule #3 Jay C Bradley MD Sandra M Brown MD

Case 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 History ? Bilateral OA Unable to drive legally; problem detected < 1 st grade

Examination 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 – x 95 OD – x 90 OS

Hereditary 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 < 1 st grade Thick glasses ET All blonde

Albinism 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 Differences Caucasians –Tyrosinase gene mutations African Americans –Intermediate phenotype –P gene mutations

Always on the Boards Chediak Higashi syndrome –White cell dysfunction –Recurrent infection Hermansky Pudlak syndrome –Bleeding diathesis –Increased frequency in Puerto Ricans

“Old Style” Albinism Genetics Type Location LocusGene ProductFunction OCA1 11q TYR TyrosinaseEnzyme OCA2 15q P P ProteinMembrane OCA3 9q TYRP1 TYRP1Enzyme OA1 Xp OA1 OA1 ProteinMembrane HPS1 10q HPS1 HPS1 ProteinVesicle HPS2 5q ADTB3A B-3A-adaptinVesicle CHS1 1q CHS1 CHS1 ProteinVesicle

New Thinking: Phenotype Spectrum “Chalky white” Acuity < 20/200 Sensory nystagmus “Ordinary” ~ 20/30

Leaky vs Non-Leaky Mutations Leaky mutations –Some enzyme production Non-leaky mutations –No enzyme production –OCA-1Bno activity“chalk white” –OCA-1Apartial activity“darkens down” Mom + Dad = net enzymatic deficiency

Rule #3 “Better Fit” Diagnosis – Mild Albinism –Fundus appearance –Hyperopia –Esotropia –Family history pigmentation “thick glasses” = high hyperopia Esotropia

A 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 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? 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 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