Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations.
OBJECTIVE
To quantify the residual vision in Leber congenital amaurosis (LCA) caused by RPE65 mutations.


METHODS
Patients with RPE65-LCA (n = 30; ages, 4-55) were studied using electroretinography (ERG), full-field stimulus testing (FST), kinetic and static threshold perimetry, and optical coherence tomography (OCT).


RESULTS
All patients with RPE65-LCA had abnormal ERGs even at the youngest ages. There were no detectable rod ERGs and only reduced cone ERGs. By chromatic FST, however, 59% of patients had measurable rod- and cone-mediated function. The remaining 41% had only cone-mediated function. Extent of kinetic fields varied widely in the first two decades of life but, by the end of the third decade, there was very little measurable field. Regional patterns of visual loss were evident using dark-adapted static threshold perimetry. The mildest dysfunctions showed relatively homogeneous sensitivity loss beyond the central field. Mid-peripheral dysfunction was a later feature; finally, only central and peripheral islands remained. Colocalized measures of visual function and retinal structure by OCT showed that visual function was detectable when a photoreceptor layer was detectable.


CONCLUSIONS
Residual rod as well as cone function is detectable in RPE65-LCA. The finding of different regional patterns of visual loss in these patients suggests that the optimal retinal site(s) for subretinal gene delivery to achieve efficacy are likely to change with disease progression.
Jacobson
Samuel G
SG
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. jacobsos@mail.med.upenn.edu
Aleman
Tomas S
TS
Cideciyan
Artur V
AV
Roman
Alejandro J
AJ
Sumaroka
Alexander
A
Windsor
Elizabeth A M
EA
Schwartz
Sharon B
SB
Heon
Elise
E
Stone
Edwin M
EM
D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology*; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000235:genetics / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase