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Contrast sensitivity deficits in patients with mutation-proven inherited retinal degenerations
摘要： Background: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity. Methods: Seventeen patients (30 eyes) with IRD and visual acuity of 20/40 or better, and 18 controls (18 eyes) without any ocular condition underwent slit lamp examination, visual acuity testing via standard Snellen chart testing, CS testing via the Quick Contrast Sensitivity Function (QCSF), and Spectral Domain Optical Coherence Tomography (SD-OCT). CS were measured at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). T tests with general estimated equations were used to compare CS between groups. Wald chi square followed by pairwise comparisons was used to compare CS between multiple groups. Results: We included 12 patients with rod-cone dystrophy (RCD), 3 patients with Stargardt disease (STGD) and 2 patients with Best disease. Patients with IRD had significantly worse CS than controls (p < 0.001) in all spatial frequencies. Patients with STGD had more marked deficits in CS than patients with Best disease (p < 0.001) and RCD (p < 0.001) despite having similar visual acuities. Conclusion: Patients with IRD, especially patients with STGD with relatively preserved visual acuity have marked deficits in CS when measured across a range of spatial frequencies. We recommend that clinical trials for STGD incorporate CS measured over a range of spatial frequencies as a secondary clinical endpoint for monitoring visual function. CS may provide an explanation for complaints of visual dysfunction when visual acuity is not significantly altered.
关键词： Best disease,Contrast sensitivity,Retinal dystrophy,Retinitis Pigmentosa,Stargardt disease
更新于2025-09-23 15:23:52
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Factors influencing the choice of low-vision devices for visual rehabilitation in Stargardt disease
摘要： Background: Stargardt disease is the most common cause of juvenile macular degeneration leading to early central visual loss. Dispensing of correct low-vision devices based on the residual visual function and specific visual requirements of a patient can result in a positive outcome. It is important to know the factors involved in the selection of these devices. This study was undertaken to assess these factors. Methods: Patients with Stargardt disease referred to a low-vision clinic underwent evaluation of visual status, disease stage, visual requirements and lifestyle. They were evaluated for suitability for successful use of various low-vision devices. Their education level and occupation were noted. They were counselled regarding the proper use of the devices and lifestyle modifications. For patients with extensive use of computers, modifications related to contrast, font size and audio software were explained. Results: Among the 97 patients in the study (age range 7–66 years, mean 23.7 ± 13.1), there were 49 (50.5 per cent) students, 36 (37.1 per cent) employed, eight (8.2 per cent) unemployed, and four (4.2 per cent) homemakers. Except for seven patients (7.2 per cent), all were literate, with education ranging from primary school to college graduation. The presenting visual acuity for distance was 0.10–1.47 (0.79 ± 0.28), and for near was N4–N40 (N9.95 ± 6.65). This acuity showed positive correlation with age (p < 0.0001, R2 = 0.16) and with magnification required (p < 0.0001, R2 = 0.26). Patients above 40 years preferred higher adds and half-eye glasses, whereas younger patients preferred dome magnifiers. The occupation also influenced the choice. Disease stage was seen to affect the choice with advanced stages requiring higher magnifiers (p = 0.03, R2 = 0.11). Duration of disease and the magnification of low-vision devices showed a positive correlation (p = 0.03, R2 = 0.049). Conclusions: Age, presenting visual acuity, disease stage, duration, education and occupation influenced the choice of low-vision devices in patients with Stargardt disease. However, they appear to be interdependent and a larger, controlled study is required to provide information on the individual effect.
关键词： occupation,visual rehabilitation,heredomacular degeneration,Stargardt disease,low vision rehabilitation,low vision devices
更新于2025-09-23 15:23:52
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Cross-Sectional and Longitudinal Assessment of Retinal Sensitivity in Patients With Childhood-Onset Stargardt Disease
摘要： Purpose: We assess cross-sectional and longitudinal microperimetry and full-field static perimetry-derived retinal sensitivity with conventional and volumetric indices of retinal function in childhood-onset Stargardt disease (STGD1). Methods: Subjects with molecularly confirmed childhood-onset STGD1 underwent full-field static perimetry and/or microperimetry using custom designed grids. Mean sensitivity (MS) and total volume (VTOT) were computed for each microperimetry test. MS, VTOT, and central field volume (V30) were computed for each full-field static perimetry test. Subjects under 18 years old at baseline were classified as children and subjects 18 years or older as adults. Results: A total of 43 children (mean age at baseline, 13.0 years; range, 8–17) and 13 adults (mean age at baseline, 23.1 years; range, 18–32) were included in the analysis. For full-field static perimetry and microperimetry for both subgroups, intraclass correlation coefficient results for MS and volumetric indices were good to excellent, indicating strong test–retest reliability. Interocular symmetry in terms of baseline measurements and the annual rate of progression was observed. A greater rate of progression was observed in childhood. Conclusions: To our knowledge, this is the first prospective study of retinal sensitivity in a large cohort of molecularly confirmed subjects with childhood-onset STGD1 demonstrating that children with STGD1 can reliably undertake detailed functional testing. Moreover, using custom designed grids and subsequent topographic analysis, volumetric indices of retinal function provide a reliable measure of retinal sensitivity.
关键词： endpoints,Stargardt disease,retina,clinical trials,ABCA4,perimetry,visual field,STGD1,Retinal sensitivity
更新于2025-09-23 15:22:29
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Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration
摘要： Recessive Stargardt disease (STGD1) is an inherited blinding disorder caused by mutations in the Abca4 gene. ABCA4 is a flippase in photoreceptor outer segments (OS) that translocates retinaldehyde conjugated to phosphatidylethanolamine across OS disc membranes. Loss of ABCA4 in Abca4?/? mice and STGD1 patients causes buildup of lipofuscin in the retinal pigment epithelium (RPE) and degeneration of photoreceptors, leading to blindness. No effective treatment currently exists for STGD1. Here we show by several approaches that ABCA4 is additionally expressed in RPE cells. (i) By in situ hybridization analysis and by RNA-sequencing analysis, we show the Abca4 mRNA is expressed in human and mouse RPE cells. (ii) By quantitative immunoblotting, we show that the level of ABCA4 protein in homogenates of wild-type mouse RPE is about 1% of the level in neural retina homogenates. (iii) ABCA4 immunofluorescence is present in RPE cells of wild-type and Mertk?/? but not Abca4?/? mouse retina sections, where it colocalizes with endolysosomal proteins. To elucidate the role of ABCA4 in RPE cells, we generated a line of genetically modified mice that express ABCA4 in RPE cells but not in photoreceptors. Mice from this line on the Abca4?/? background showed partial rescue of photoreceptor degeneration and decreased lipofuscin accumulation compared with nontransgenic Abca4?/? mice. We propose that ABCA4 functions to recycle retinaldehyde released during proteolysis of rhodopsin in RPE endolysosomes following daily phagocytosis of distal photoreceptor OS. ABCA4 deficiency in the RPE may play a role in the pathogenesis of STGD1.
关键词： Stargardt disease,retinal pigment epithelium,lipofuscin,ABCA4,bisretinoid
更新于2025-09-23 15:21:21
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[Essentials in Ophthalmology] Advances in Vision Research, Volume II (Genetic Eye Research in Asia and the Pacific) || Genetics and Susceptibility of Retinal Eye Diseases in India
摘要： As per the World Health Organization, genetic eye disorders are one of the top ten major causes of global ocular health burden. AMD and DR take major share of the adult eye diseases component that particularly affects the neurovascular retina. More than 100 genes are known to cause Mendelian types of retinal degenerations including syndromic and non-syndromic RP, and it is presumed that this constitutes only 60% of all the genes known so far, and the remaining are yet to be identified. The burden of genetic disorders in India is significant, and very many significant genes like RPE65 have been identified with consanguineous autosomal recessive pedigrees obtained from this region.
关键词： Visual cycle,Phototransduction pathway,Stargardt disease,Retinitis pigmentosa,Leber congenital amaurosis
更新于2025-09-23 15:21:21
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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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Flecks in Recessive Stargardt Disease: Short-Wavelength Autofluorescence, Near-Infrared Autofluorescence, and Optical Coherence Tomography
摘要： PURPOSE. We evaluated the incongruous observation whereby ?ecks in recessive Stargardt disease (STGD1) can exhibit increased short-wavelength auto?uorescence (SW-AF) that originates from retinal pigment epithelium (RPE) lipofuscin, while near-infrared AF (NIR-AF), emitted primarily from RPE melanin, is usually reduced or absent at ?eck positions. METHODS. Flecks in SW- and NIR-AF images and spectral-domain optical coherence tomography (SD-OCT) scans were studied in 19 STGD1 patients carrying disease-causing ABCA4 mutations. Fleck spatial distribution and progression were recorded in serial AF images. RESULTS. Flecks observed in SW-AF images typically colocalized with darkened foci in NIR-AF images; the NIR-AF pro?les were larger. The decreased NIR-AF signal from ?ecks preceded apparent changes in SW-AF. Spatiotemporal changes in ?eck distribution usually progressed centrifugally, but in one case centripetal expansion was observed. Flecks in SW-AF images corresponded to hyperre?ective deposits that progressively traversed photoreceptor-attributable bands in SD-OCT images. Outer nuclear layer (ONL) thickness negatively correlated with expansion of ?ecks from outer to inner retina. CONCLUSIONS. In the healthy retina, RPE lipofuscin ?uorophores form in photoreceptor cells but are transferred to RPE; thus the SW-AF signal from photoreceptor cells is negligible. In STGD1, NIR-AF imaging reveals that ?ecks are predominantly hypo?uorescent and larger and that NIR-AF darkening occurs prior to heightened SW-AF signal. These observations indicate that RPE cells associated with ?ecks in STGD1 are considerably changed or lost. Spectral-domain OCT ?ndings are indicative of ongoing photoreceptor cell degeneration. The bright SW-AF signal of ?ecks likely originates from augmented lipofuscin formation in degenerating photoreceptor cells impaired by the failure of RPE.
关键词： lipofuscin,fundus auto?uorescence,recessive Stargardt disease,optical coherence tomography,retinal pigment epithelium,ABCA4,scanning laser ophthalmoscope
更新于2025-09-09 09:28:46
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Quantitative Fundus Autofluorescence and Optical Coherence Tomography in <i>ABCA4</i> Carriers
摘要： PURPOSE. To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus auto?uorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort. METHODS. Seventy-?ve individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9–82 years) were recruited as family members of affected patients from 46 unrelated families. For comparison, 57 affected family members with biallelic ABCA4 mutations (mean age, 23.4 years; range, 6–67 years) and two noncarrier siblings were also enrolled. Auto?uorescence images (308, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal ?uorescent reference. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magni?cation, and normative optical media density to yield qAF. Horizontal SD-OCT scans through the fovea were obtained and the thicknesses of the outer retinal layers were measured. RESULTS. In 60 of 65 carriers of ABCA4 mutations (age range, 9–60), qAF levels were within normal limits (95% con?dence level) observed for healthy noncarrier subjects, while qAF levels of affected family members were signi?cantly increased. Perifoveal ?eck-like abnormalities were observed in fundus AF images in four carriers, and corresponding changes were detected in the outer retinal layers in SD-OCT scans. Thicknesses of the outer retinal layers were within the normal range. CONCLUSIONS. With few exceptions, individuals heterozygous for ABCA4 mutations and between the ages of 9 and 60 years do not present with elevated qAF. In a small number of carriers, perifoveal ?eck-like changes were visible.
关键词： heterozygous carrier,retinal pigment epithelium,lipofuscin,recessive Stargardt disease,optical coherence tomography,quantitative fundus auto?uorescence,Abca4,scanning laser ophthalmoscope
更新于2025-09-04 15:30:14