Longitudinal and cross-sectional study of patients with early-onset severe retinal dystrophy associated with RPE65 mutations.
OBJECTIVE
To quantify retinal function longitudinally and cross-sectionally in patients with autosomal-recessive early-onset severe retinal dystrophy (EOSRD) associated with RPE65 mutations.


METHODS
The ocular phenotype was characterized in four children from three families up to the second decade of life, and in three siblings from one family aged 43-54 years carrying compound heterozygous or homozygous mutations in RPE65. Standard clinical examination included colour vision testing, fundus photography and Goldmann visual fields (GVF). Full-field ERGs (in all) and multifocal ERGs (in two patients) were also recorded. Visual performance and fundus appearance were compared to literature data.


RESULTS
In childhood, visual acuity (VA) ranged from 0.1 to 0.3, and GVF for target V4 was well preserved. VA and GVF were measurable in only one of the three adult siblings. Nystagmus was present in two of four children and two of three adults. Photophobia was absent in childhood and developed in adulthood. Funduscopic changes were discrete during the first decade of life in three of four children; one patient had clear macular changes already at age 5 years. All three adult siblings had distinct retinal changes including the macula. Bone spicules were not a feature. Residual colour vision was present in all patients with measurable VA. Rod ERGs were absent at any age; cone ERGs were detectable in early childhood. To date, VA data have been reported in 51 patients, visual fields in 29 patients, and a detailed fundus description in 34 patients. For all three parameters, data were comparable to the results in our patient cohort.


CONCLUSIONS
In childhood, patients with RPE65 mutations have better visual functions than typically seen in Leber congenital amaurosis. The phenotype shows a common progressive pattern with intrafamilial and interfamilial variation. The data suggest a preserved retinal morphology at young ages, arguing for vision-restoring gene therapy trials in childhood.
Paunescu
Karina
K
Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, University of Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany.
Wabbels
Bettina
B
Preising
Markus N
MN
Lorenz
Birgit
B
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins; D002648:Child; D003117:Color Vision Defects / Q000235:genetics / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005500:Follow-Up Studies; D005808:Genes, Recessive; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011446:Prospective Studies; D012160:Retina / Q000503:physiopathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D035781:Siblings; D014792:Visual Acuity; D014794:Visual Fields / Q000502:physiology; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase