1. UNEXPLAINED VISUAL LOSS Neuro-ophthalmology Service Wills Eye Hospital Philadelphia, Pensylvania USA Survey of Ophthalmology 48(6) 626-630

2. 20y, male, reduced VA 8y: myopia/ ‘eyes not perfect’ 17y: low VA Retina specialist+ neuroophth. VF, FFA, Fundoscopy, MRI: normal No medication/ No toxic exposure Negative family eye history Well balanced diet No tobacco/ occasional alcohol HISTORY:

3. VA: 6/12 R, 6/18L (-2.5 -0.5 90°) Pupils: brisk reactions/ No RAPD Ishihara: 6/10R, 7/10L Orthophoria D/N Full ductions/ versions Normal ant. segment IOP:14 R+L Fundus: tilted discs+ mild temporal pallor+ thinned papillomacular bundle VF: subtle cecocentral scotoma R+L CLINICAL EXAMINATION:

4. DD: COMPRESSION/ INFILTRATION DEMYELINATION DOA TOXIC NEUROPATHY MACULAR DISEASE (CONE DYSTROPHY)

5. DIRECT QUESTIONING FOR: Endocrine dysfunction MS NF1

6. DIAGNOSTIC WORKUP: MRI (fat supression, FLAIR, contrast) F-M 100: tritan axis LP ERG

7. DIAGNOSIS: DOA PROGNOSIS: VA gradual  with age but most >3/60 No recovery No Rx Good longterm

8. DISCUSSION I: CRITERIA: AD INSIDIOUS ONSET <10y Bilateral mild to moderate/ asymmetric Central, para- or centrocecal scotoma (subtle),pseudobitemp. hemianopia Aquired tritan dyschromatopsia (94%) Temporal disc pallor/ excavation (triangular)

9. DISCUSSION CONT.: Commonest heretodegenerative opt. neuropathy: 1:10,000 Inter/intra-familial variation in VA Mental retardation Nystagmus Hearing loss Ganglion cell degeneration/ ascending atrophy OPA1 gene: GTP-ase (mitoch. Biogenesis/membrane integrity)