Lack of fundus autofluorescence to 488 nanometers from childhood on in patients with early-onset severe retinal dystrophy associated with mutations in RPE65.
OBJECTIVE
Fundus autofluorescence is due to accumulation of lipofuscin in the retinal pigment epithelium (RPE) resulting from incomplete digestion of N-retinylidene-phosphatidyl-ethanolamine from shed photoreceptor outer segment discs. Alteration in autofluorescence reflects changes in lipofuscin content of the RPE. Mutations on both alleles of RPE65 result in absent or largely decreased formation of rhodopsin, due to a defect in all-trans retinol isomerization in the RPE. Autofluorescence could therefore be altered. This study was conducted to evaluate fundus autofluorescence in patients with early-onset severe retinal dystrophy (EOSRD, or early-onset rod-cone dystrophy) associated with mutations on both alleles of RPE65.


METHODS
Case series.


METHODS
Ten 10- to 55-year-old patients with EOSRD and compound heterozygous or homozygous mutations in RPE65. For comparison, 6 heterozygous parents and 2 patients with other forms of EOSRD were examined.


METHODS
Participants underwent, in addition to standard clinical and electrophysiological examination, autofluorescence imaging using a confocal scanning laser ophthalmoscope. Three of the patients were also examined by optical coherence tomography (OCT) to evaluate the status of retinal degeneration. Mutations in 7 patients have been reported previously; the other patients were investigated by polymerase chain reaction-single-strand conformation polymorphism and direct sequencing for mutations in RPE65 and lecithin retinol acyltransferase (LRAT).


METHODS
Fundus autofluorescence and OCT.


RESULTS
Absent or minimal autofluorescence was found in all patients with compound heterozygous or homozygous RPE65 mutations. Autofluorescence was normal in the heterozygous parents. Autofluorescence was present in 2 children with EOSRD not associated with mutations in RPE65 or LRAT, another gene involved in retinol recycling. Optical coherence tomography in younger patients revealed an intraretinal appearance similar to that of their healthy, heterozygous parents.


CONCLUSIONS
Lack of autofluorescence in patients with EOSRD associated with mutations in RPE65 is in accordance with the biochemical defect and can be used as a clinical marker of this genotype. Optical coherence tomography results in younger patients would indicate still viable photoreceptors despite the absence of autofluorescence.
Department of Paediatric Ophthalmology and Ophthalmogenetics, University of Regensburg, Germany. Birgit.Lorenz@klinik.uni-regensburg.de
Birgit
B
Lorenz
Bettina
B
Wabbels
Erika
E
Wegscheider
Christian P
CP
Hamel
Wolfgang
W
Drexler
Markus N
MN
Preising
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002352:Carrier Proteins; D002648:Child; D005136:Eye Proteins; D005260:Female; D005453:Fluorescence; D005654:Fundus Oculi; D005838:Genotype; D006801:Humans; D007834:Lasers; D008062:Lipofuscin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019721:Ophthalmoscopes; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011506:Proteins / Q000235:genetics*; D011726:Pyridinium Compounds / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism; D041623:Tomography, Optical Coherence; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D015415:Biomarkers; D002352:Carrier Proteins; D005136:Eye Proteins; D008062:Lipofuscin; D011506:Proteins; D011726:Pyridinium Compounds; D012176:Retinoids; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C112040:A2-E (N-retinylidene-N-retinylethanolamine)