Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.
OBJECTIVE
To evaluate genotypic and macular morphologic correlations in patients with RPE65-, CEP290-, GUCY2D-, or AIPL1-related Leber congenital amaurosis (LCA) using spectral-domain optical coherence tomography (SD-OCT).


METHODS
SD-OCT macular scans were performed in 21 patients, including 10 with RPE65, 7 with CEP290, 3 with GUCY2D, and 1 with AIPL1 mutations. An image processing software was used to manually draw segmentation lines by three observers. Lamellar structure was evaluated based on the number of retinal layers on segmented images. Total retinal thickness was measured at the central macular and perifoveal areas by using an automated algorithm.


RESULTS
All three patients with GUCY2D mutations (age range, 20-53 years) retained six retinal layers with visible photoreceptor inner/outer segment juncture (PSJ). However, the preservation of lamellar structures did not parallel better visual acuity. Patients with other mutations had poorly defined PSJ and disorganized retinal lamellar structures, where only one to three retinal layers could be observed. Patients with CEP290 mutations trended to have retention of the outer nuclear layer at the fovea and macular thickening, especially at younger ages. In patients with RPE65 (age range, 20-71 years) and AIPL1 mutations (age, 22 years), macular thickness was markedly decreased. Disorganization of retinal lamellar structures in the RPE65 group trended toward a worsening with increasing age.


CONCLUSIONS
Variations of macular microstructures were observed among LCA patients with different genotypes. Disorganization of retinal lamellar structure was generally age related. Preservation of retinal microanatomic structures may not be associated with better visual acuity.
Pasadhika
Sirichai
S
Department of Ophthalmology and Visual Sciences, University of Illinois Medical Center, Chicago, Illinois, USA.
Fishman
Gerald A
GA
Stone
Edwin M
EM
Lindeman
Martin
M
Zelkha
Ruth
R
Lopez
Irma
I
Koenekoop
Robert K
RK
Shahidi
Mahnaz
M
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003598:Cytoskeletal Proteins; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000175:diagnosis* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface / Q000235:genetics*; D012160:Retina / Q000473:pathology*; D041623:Tomography, Optical Coherence; D055815:Young Adult; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C403625:AIPL1 protein, human; C493903:Cep290 protein, human; C110715:guanylate cyclase 1