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Quantitative Fundus Autofluorescence and Optical Coherence Tomography in <i>PRPH2/RDS</i> - and <i>ABCA4</i> -Associated Disease Exhibiting Phenotypic Overlap
摘要： PURPOSE. To assess whether quantitative fundus autofluorescence (qAF), a measure of RPE lipofuscin, and spectral-domain optical coherence tomography (SD-OCT) can aid in the differentiation of patients with fundus features that could either be related to ABCA4 mutations or be part of the phenotypic spectrum of pattern dystrophies. METHODS. Autofluorescence images (308, 488-nm excitation) from 39 patients (67 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference and were quantified as previously described. In addition, horizontal SD-OCT images through the fovea were obtained. Patients were screened for ABCA4 and PRPH2/RDS mutations. RESULTS. ABCA4 mutations were identified in 19 patients (mean age, 37 ± 12 years) and PRPH2/RDS mutations in 8 patients (mean age, 48 ± 13 years); no known ABCA4 or PRPH2/RDS mutations were found in 12 patients (mean age, 48 ± 9 years). Differentiation of the groups using phenotypic SD-OCT and AF features (e.g., peripapillary sparing, foveal sparing) was not reliable. However, patients with ABCA4 mutations could be discriminated reasonably well from other patients when qAF values were corrected for age and race. In general, ABCA4 patients had higher qAF values than PRPH2/RDS patients, while most patients without mutations in PRPH2/RDS or ABCA4 had qAF levels within the normal range. CONCLUSIONS. The high qAF levels of ABCA4-positive patients are a hallmark of ABCA4-related disease. The reason for high qAF among many PRPH2/RDS-positive patients is not known; higher RPE lipofuscin accumulation may be a primary or secondary effect of the PRPH2/RDS mutation.
关键词： scanning laser ophthalmoscope,PRPH2/RDS,optical coherence tomography,quantitative fundus autofluorescence,retinal pigment epithelium,lipofuscin,recessive Stargardt disease,ABCA4,pattern dystrophy
更新于2025-09-11 14:15:04
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Monoallelic <i>ABCA4</i> Mutations Appear Insufficient to Cause Retinopathy: A Quantitative Autofluorescence Study
摘要： PURPOSE. To investigate the effect of ABCA4 mutation status on lipofuscin-related quantitative autofluorescence (qAF) in humans and on bisretinoid accumulation in mice. METHODS. Genotyped parents (n ? 26; age 37–64 years) of patients with biallelic ABCA4-related retinopathy underwent in-depth retinal phenotyping including qAF imaging as a surrogate measure for RPE lipofuscin accumulation. In addition, bisretinoids as the main components of autofluorescent lipofuscin at the ocular fundus were quantified in Abca4(cid:2)/(cid:2), Abca4t/(cid:2), and wild-type mice. RESULTS. Index patients showed a retinal phenotype characteristic for ABCA4-related retinopathy, including increased qAF levels. In contrast, qAF measures in carriers of only one ABCA4 mutation were not different from age-matched controls in this sample, and there was no difference between truncating and missense mutations. Also, none of these carriers presented an abnormal phenotype on conventional imaging. One parent with ABCA4-related retinopathy and increased qAF carried an additional ABCA4 mutation, explaining the phenotype under a recessive disease model (pseudodominance). Biochemical analysis in the mouse model revealed direct downstream products (A2PE-H2, at-RALdimer-PE) of the ABCA4 substrate N-Ret-PE to be similar in wild-type and Abca4t/(cid:2) mice. Both bisretinoids were 12- to 18-fold increased in Abca4(cid:2)/(cid:2) mice. Levels of A2E and A2PE in Abca4t/(cid:2) mice were in between those measured in wild-type and Abca4(cid:2)/(cid:2) mice. CONCLUSIONS. This study indicates that carriers of monoallelic ABCA4 mutations are phenotypically normal. However, biochemical analysis in the Abca4-deficient mouse model suggests detectable effects of one mutation in ABCA4 on the molecular level. The findings may have implications for therapeutic approaches such as gene replacement therapy.
关键词： quantitative fundus autofluorescence,carrier,monoallelic,phenotype,Abca4
更新于2025-09-11 14:15:04