Dataset Information

SIBLING CONCORDANCE IN SYMPTOM ONSET AND ATROPHY GROWTH RATES IN STARGARDT DISEASE USING ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE.

ABSTRACT:

Purpose

To investigate concordance in symptom onset, area of dark autofluorescence (DAF), and growth rate (GR) between Stargardt disease siblings at an age-matched time point.

Methods

In this retrospective longitudinal study of sibling pairs with identical biallelic ABCA4 variants, age at symptom onset, best-corrected visual acuity, atrophy area, and effective radius of DAF on ultra-widefield fundus autofluorescence were recorded. Absolute intersibling differences for both eyes were compared with absolute interocular differences using the Mann-Whitney test.

Results

Overall 39 patients from 19 families were recruited. In 16 families, age-matched best-corrected visual acuity and DAF were compared between siblings. In 8 families, DAF GR was compared. The median (range) absolute difference in age at symptom onset between siblings was 3 (0-35) years. Absolute intersibling differences in age-matched best-corrected visual acuity were greater than interocular differences ( P = 0.01). Similarly, absolute intersibling differences in DAF area and radius were greater than interocular differences ( P = 0.04 for area and P = 0.001 for radius). Differences between absolute interocular and intersibling GR were not statistically significant ( P = 0.44 for area GR and P = 0.61 for radius GR).

Conclusion

There was significant discordance in age-matched best-corrected visual acuity and DAF beyond the expected limits of interocular asymmetry. Lack of significant intersibling differences in GR warrants further investigation.

SUBMITTER: Heath Jeffery RC

PROVIDER: S-EPMC9301984 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SIBLING CONCORDANCE IN SYMPTOM ONSET AND ATROPHY GROWTH RATES IN STARGARDT DISEASE USING ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE.

Heath Jeffery Rachael C RC Thompson Jennifer A JA Lo Johnny J Lamey Tina M TM McLaren Terri L TL De Roach John N JN Azamanov Dimitar N DN McAllister Ian L IL Constable Ian J IJ Chen Fred K FK

Retina (Philadelphia, Pa.) 20220424 8

<h4>Purpose</h4>To investigate concordance in symptom onset, area of dark autofluorescence (DAF), and growth rate (GR) between Stargardt disease siblings at an age-matched time point.<h4>Methods</h4>In this retrospective longitudinal study of sibling pairs with identical biallelic ABCA4 variants, age at symptom onset, best-corrected visual acuity, atrophy area, and effective radius of DAF on ultra-widefield fundus autofluorescence were recorded. Absolute intersibling differences for both eyes we ...[more]

PMID: 35344533

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Project description:ObjectiveTo study the longitudinal changes in autofluorescence in Stargardt disease to reveal aspects of disease progression not previously evident. Changes in autofluorescence reflect changing fluorophore compositions of lipofuscin and melanin in retinal pigment epithelial cells, which has been hypothesized to contribute to Stargardt disease pathogenesis.MethodsWe examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations.ResultsLongitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease.ConclusionsStargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.

Project description:Importance:Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. Objective:To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. Design, Setting, and Participants:A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye. Exposures:Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable. Main Outcomes and Measures:Yearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence. Results:A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion. Conclusions and Relevance:In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.

Project description:PurposeTo compare the detection rate of diabetic retinopathy (DR) lesions and the agreement of DR severity grading using the ultra-widefield color fundus photography (UWF CFP) combined with high-speed ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) or fluorescein angiography (FFA).MethodsThis prospective, observational study recruited diabetic patients who had already taken the FFA examination from November 2021 to June 2022. These patients had either no DR or any stage of DR. All participants were imaged with a 200° UWF CFP and UWF SS-OCTA using a 24 × 20 mm scan model. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal hemorrhage (IRH), non-perfusion areas (NPAs), intraretinal microvascular abnormalities (IRMAs), venous beading (VB), neovascularization elsewhere (NVE), neovascularization of the optic disc (NVD), and vitreous or preretinal hemorrhage (VH/PRH). Agreement of DR severity grading based on UWF CFP plus UWF SS-OCTA and UWF CFP plus FFA was compared. All statistical analyses were performed using SPSS V.26.0.ResultsOne hundred and fifty-three eyes of 86 participants were enrolled in the study. The combination of UWF CFP with UWF SS-OCTA showed a similar detection rate compared with UWF CFP plus FFA for all the characteristic DR lesions (p>0.05), except NPAs (p = 0.039). Good agreement was shown for the identification of VB (κ = 0.635), and very good agreement for rest of the DR lesions between the two combination methods (κ-value ranged from 0.858 to 0.974). When comparing the grading of DR severity, very good agreement was achieved between UWF CFP plus UWF SS-OCTA and UWF CFP plusr FFA (κ = 0.869).ConclusionUWF CFP plus UWF SS-OCTA had a very good agreement in detecting DR lesions and determining the severity of DR compared with UWF CFP plus FFA. This modality has the potential to be used as a fast, reliable, and non-invasive method for DR screening and monitoring in the future.

Project description:ImportanceSensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease.ObjectiveTo estimate the progression rate of atrophic lesions in the prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study over a 12-month period.Design, setting, and participantsThis multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. Patients who were affected by Stargardt disease, aged 6 years and older at baseline, and harboring disease-causing variants of the ABCA4 gene were enrolled at 9 centers in the United States, United Kingdom, and continental Europe. Data analysis occurred from November 2016 to January 2017.ExposuresAutofluorescence images obtained with a standard protocol were sent to a central reading center, and areas of definitely decreased autofluorescence, questionably decreased autofluorescence, and the total combined area of decreased autofluorescence were outlined and quantified. Progression rates were estimated from linear mixed models with time as the independent variable.Main outcomes and measuresYearly rate of progression, using the growth of atrophic lesions measured by autofluorescence imaging.ResultsA total of 259 study participants (488 eyes; 230 individuals [88.8%] were examined in both eyes) were enrolled (mean [SD] age at first visit, 33.3 [15.1] years; 118 [54.4%] female). Gradable images were available for evaluation for 480 eyes at baseline and 454 eyes after 12 months. At baseline, definitely decreased autofluorescence was present in 306 eyes, and the mean (SD) lesion size was 3.93 (4.37) mm2. The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm2. The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm2 per year (P < .001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm2 per year (P < .001). Both progression rates depended on initial lesion size.Conclusions and relevanceIn Stargardt disease, autofluorescence imaging may serve as a monitoring tool and definitely decreased autofluorescence and total area as outcome measures for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.

Dataset Information

SIBLING CONCORDANCE IN SYMPTOM ONSET AND ATROPHY GROWTH RATES IN STARGARDT DISEASE USING ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE.

Purpose

Methods

Results

Conclusion

Publications

SIBLING CONCORDANCE IN SYMPTOM ONSET AND ATROPHY GROWTH RATES IN STARGARDT DISEASE USING ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE.

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