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A. V. Cideciyan, M. Swider, T. S. Aleman, M. I. Roman, A. Sumaroka, S. B. Schwartz, E. M. Stone, S. G. Jacobson; Macular Disease Sequence in Patients With ABCA4-Associated Retinal Degenerations. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3671.
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ABCR encoded by the ABCA4 gene facilitates removal of all-trans-retinal from light-exposed photoreceptors. Abnormal ABCR function is hypothesized to trap retinoids which accumulate as autofluorescent lipofuscin or melanolipofuscin granules in the RPE and cause retinal degeneration and dysfunction. We have supporting evidence for this hypothesized disease sequence in the extra-macular region of patients with ABCA4 mutations. In the current study, earliest detectable features of macular disease due to ABCA4 mutations were defined.
Patients with Stargardt disease and ABCA4 mutations were included. To avoid confounding the natural history of ABCA4 disease with high intensity illumination typically used in conventional AF imaging, a reduced illuminance autofluorescence imaging (RAFI) method was developed. RAFI was performed with near-infrared (NIR) or short-wavelength (SW) excitation. Retinal thickness was quantified with OCT and retinal function was examined with microperimetry. All modalities were spatially registered and compared to normal results.
SW-RAFI results were qualitatively and quantitatively comparable to conventional AF imaging but they were obtained with lower light dose and greater patient comfort. NIR-RAFI results were consistent with the hypothesis of AF signal originating from melanin and/or melanolipofuscin located at the RPE and/or choroid. Estimate of depth of NIR light penetration obtained from OCT was used to discard retinal regions with evident choroidal NIR-RAFI signals. The earliest detectable macular disease feature was hyper-autofluorescence with SW- and NIR-RAFI modalities at macular regions where retinal appearance, cross-sectional structure and microperimetric function was normal. This subclinical macular disease stage is similar to that observed in the extra-macular retina. Unexpectedly, boundary regions between subclinical and clinically overt disease showed hyper-autofluorescence and loss of retinal function with normal retinal structure.
Human macular retina may react differently to accumulation of lipofuscin than extra-macular retina. Use of RAFI methods, OCT and microperimetry allow detection and quantitation of subclinical macular disease expression and monitoring of progression without subjecting the diseased retina/RPE to undue light exposure.
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