Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations.
The health of the retinal pigment epithelium (RPE) can be estimated with autofluorescence (AF) imaging of lipofuscin, which accumulates as a byproduct of retinal exposure to light. Lipofuscin may be toxic to the RPE, and its toxicity may be enhanced by short-wavelength (SW) illumination. The high-intensity and SW excitation light used in conventional AF imaging could, at least in principle, increase the rate of lipofuscin accumulation and/or increase its toxicity. We considered two reduced-illuminance AF imaging (RAFI) methods as alternatives to conventional AF imaging. RAFI methods use either near-infrared (NIR) light or reduced-radiance SW illumination for excitation of fluorophores. We quantified the distribution of RAFI signals in relation to retinal structure and function in patients with the prototypical lipofuscin accumulation disease caused by mutations in ABCA4. There was evidence for two subclinical stages of macular ABCA4 disease involving hyperautofluorescence of both SW- and NIR-RAFI with and without associated loss of visual function. Use of RAFI methods and microperimetry in future clinical trials involving lipofuscinopathies should allow quantification of subclinical disease expression and progression without subjecting the diseased retina/RPE to undue light exposure.
Cideciyan
Artur V
AV
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia 19104, and Howard Hughes Medical Institute, University of Iowa Hospitals and Clinics, Iowa City 52242, USA. cideciya@mail.med.upenn.edu
Swider
Malgorzata
M
Aleman
Tomas S
TS
Roman
Marisa I
MI
Sumaroka
Alexander
A
Schwartz
Sharon B
SB
Stone
Edwin M
EM
Jacobson
Samuel G
SG
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008029:Lighting / Q000379:methods; D008062:Lipofuscin / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods*; D008875:Middle Aged; D015203:Reproducibility of Results; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D042262:Retinoscopy / Q000379:methods*; D012680:Sensitivity and Specificity
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; D008062:Lipofuscin