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Purpose: To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss., Design: Retrospective, multicenter cohort study., Participants: A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe., Methods: Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss., Main Outcome Measures: Yearly change in VA., Results: The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P < 0.0001) per year overall, but the rate varied according to baseline VA: (1) eyes with baseline VA ≥20/25 (N = 53) declined at a rate of approximately 1.0 line per year; (2) eyes with VA between 20/25 and 20/70 (N = 65) declined at a rate of approximately 0.9 lines per year; (3) eyes with VA between 20/70 and 20/200 (N = 163) declined at a rate of 0.2 lines per year; and (4) eyes with VA worse than 20/200 (n = 49) improved at a rate of 0.5 lines per year. Older age of onset was associated with slower VA loss: Patients with onset age >30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years., Conclusions: Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the design and baseline characteristics of patients enrolled into 2 natural history studies of Stargardt disease (STGD1)., Design: Multicenter retrospective and prospective cohort studies., Participants: Three hundred sixty-five unique patients aged 6 years and older at baseline harboring disease-causing variants in the ABCA4 gene and with specified ocular lesions were enrolled from 9 centers in the United States and Europe., Methods: In the retrospective study, patients contributed medical record data from at least 2 and up to 4 visits for at least 1 examination modality: fundus autofluorescence (FAF), spectral-domain (SD) optical coherence tomography (SD OCT), and/or microperimetry (MP). The total observational period was at least 2 years and up to 5 years between single visits. Demographic and visual acuity (VA) data also were obtained. In the prospective study, eligible patients were examined at baseline using a standard protocol, with 6-month follow-up visits planned for a 2-year period for serial Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected VA, SD OCT, FAF, and MP., Main Outcome Measures: Design and rationale of a multicenter study to determine the progression of STGD1 in 2 large retrospective and prospective international cohorts. Detailed baseline characteristics of both cohorts are presented, including demographics, and structural and functional retinal metrics., Results: Into the retrospective study, 251 patients (458 eyes) were enrolled; mean follow-up ± standard deviation was 3.9±1.6 years. At baseline, 36% had no or mild VA loss, and 47% of the study eyes had areas of definitely decreased autofluorescence (DDAF) with an average lesion area of 2.5±2.9 mm(2) (range, 0.02-16.03 mm(2)). Two hundred fifty-nine patients (489 eyes) were enrolled in the prospective study. At baseline, 20% had no or mild VA loss, and 64% had areas of DDAF with an average lesion area of 4.0±4.4 mm(2) (range, 0.03-24.24 mm(2)). The mean retinal sensitivity with MP was 10.8±5.0 dB., Conclusions: The ProgStar cohorts have baseline characteristics that encompass a wide range of disease severity and are expected to provide valuable data on progression based on serial quantitative measurements derived from multiple methods, which will be critical to the design of planned clinical trials., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyze focal hyperreflective morphologic alterations in outer retinal layers in patients with type 2 idiopathic macular telangiectasia (MacTel type 2) using spectral-domain optical coherence tomography (SD OCT)., Design: Cross-sectional case-control study., Participants: Forty-one patients with MacTel type 2., Methods: Anatomic layers were evaluated and compared with those of controls of similar age. Simultaneous SD OCT scans were obtained with a combined confocal scanning laser ophthalmoscope for simultaneous tomographic and topographic in vivo imaging (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany)., Main Outcome Measures: Morphologic alterations in the retinal layers secondary to MacTel type 2., Results: Hyperreflective spots in the outer retina of MacTel type 2 patients were detected in all stages of disease using the SD OCT. Their presence was confined to the foveolar and parafoveolar region. The phenomenon also was detected in a monozygotic twin in an eye with no typical angiographic sign of the disease. A hyperreflective haze was detected in the vicinity of a disruption of the hyperreflective OCT line that is assumed to represent the line between the photoreceptor inner and outer segments and interdigitation of the outer segments and the retinal pigment epithelium. No corresponding pathologic features could be identified by biomicroscopy, time-domain OCT, or confocal scanning laser ophthalmoscope imaging. Crystalline deposits and intraretinal migration of pigmented cells were distinguishable because of differences in shape, reflectivity, and location., Conclusions: Hyperreflective spots were identified in outer retinal layers of patients with MacTel type 2 in all disease stages. It is suggested that this phenomenon represents an early sign of a neurodegenerative process. Secondary assumptions include extravasated deposits or vascular abnormalities. The pathologic features are indicative of an active disease process before the disease manifests by typical fluorescein angiographic signs., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the Bruch's membrane-retinal pigment epithelium (RPE) complex in pseudoxanthoma elasticum (PXE) by imaging techniques capable of visualizing deep retinal structures with high contrast., Design: Prospective cross-sectional study., Participants: Patients with PXE, confirmed by mutation analysis, skin histopathologic examination, or both., Methods: Sixteen patients were investigated by indocyanine green (ICG) and fluorescein angiography, confocal near-infrared (NIR) reflectance, and fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope (Spectralis HRA-OCT; Heidelberg Engineering, Heidelberg, Germany). Composite digital fundus photography also was performed., Main Outcome Measures: Characterization and topographic distribution of abnormalities detected by retinal imaging., Results: On late-phase ICG angiography, a central area of decreased fluorescence centered on the posterior pole was a characteristic finding in all patients. A second area characterized by increased fundus reflectivity on NIR reflectance imaging extended further into the periphery. A third and most eccentric area showed neither decreased ICG fluorescence nor increased fundus reflectivity. These 3 areas were separated by 2 transition zones, the second being the equivalent of peau d'orange. Angioid streaks did not extend into the third area., Conclusions: The abnormalities detected by this multimodal imaging approach suggest a centrifugal spread of the retinal pathologic features of the Bruch's membrane-RPE complex in PXE. Decreased fluorescence on late-phase ICG angiography is a consistent sign of retinal pathologic features in PXE. Bruch's membrane calcification may be the underlying cause for the increased reflectivity observed on NIR reflectance imaging., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To report findings in asymptomatic family members of patients with macular telangiectasia type 2., Design: Prospective, observational, cross-sectional case series., Participants: Four patients with symptomatic macular telangiectasia type 2 (index patients) and 5 relatives, including 2 sets of monozygotic twins., Methods: Screening of family members of participants in a non-interventional natural history study of macular telangiectasia type 2. Ophthalmologic examination included best-corrected visual acuity testing, fundus biomicroscopy, fluorescein angiography (FA), optical coherence tomography (OCT), and fundus autofluorescence (FAF) imaging., Main Outcome Measures: Evidence for macular telangiectasia type 2 in any of the imaging methods used and visual function of the family members studied., Results: In the first family, 2 of 3 daughters of a severely affected 68-year-old woman had features of macular telangiectasia type 2. Although one of the daughters was diagnosed by biomicroscopic examination, the second daughter was diagnosed only by subtle changes on OCT and FAF imaging. Both affected daughters were asymptomatic and were unaware that they had the condition. In the second family, clinical examination showed that the 60-year-old brother of the 75-year-old index patient obviously was affected, despite a lack of any subjective visual dysfunction. The 65-year-old monozygotic twin of the third index patient showed a slight retinal thinning within a small area temporal to the foveola in both eyes as well as minor staining on FA and a subtle monocular loss of macular pigment. The 56-year-old asymptomatic monozygotic twin of the last proband had opacification of the retina with leakage on FA in the right eye. The fellow eye was unremarkable except for an abnormal FAF signal that was present in both eyes., Conclusions: Macular telangiectasia type 2 may be more common than previously assumed, but patients may not seek ophthalmic care if their visual function is normal. The study of these early, asymptomatic cases may yield valuable insights into the pathogenesis of the condition. Further research is warranted to determine whether there is an underlying, dominantly inherited genetic abnormality in macular telangiectasia type 2 of variable penetrance and expressivity.

Purpose: To report the short-term effects of intravitreal bevacizumab in patients with type 2 idiopathic macular telangiectasia (IMT)., Design: Noncomparative, interventional, retrospective case series., Participants: Seven eyes of 6 patients with type 2 IMT were studied., Methods: Patients received 2 doses of intravitreal bevacizumab (1.5 mg) at 4-week intervals. Serial examinations included standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA), fluorescein angiography, and optical coherence tomography (OCT)., Main Outcome Measures: Assessments of OCT retinal thickness, angiographic characteristics, and VA were performed at baseline and at 4 and 8 weeks after the initial treatment., Results: A mean increase in VA of 8 ETDRS letters at 8 weeks was found (P<0.05). Visual acuity improved by more than 15 letters in 1 patient and by 10 to 15 letters in 2 patients and remained stable (-1 to +10 letters) in another 4 patients compared with baseline. All patients showed a reduction in extension and intensity of late-stage parafoveal hyperfluorescence on fluorescein angiography. In OCT imaging, mean retinal thickness showed a reduction in the foveal and in the parafoveal zones (P<0.01). The most pronounced effect (mean decrease, 22 microm) was in the parafoveal temporal zone. No significant ocular or systemic side effects were observed., Conclusions: Short-term results indicate that inhibition of vascular endothelial growth factor by intravitreal bevacizumab is associated with a decrease in retinal thickness and a reduction in angiographic leakage in type 2 IMT. Furthermore, intravitreal bevacizumab may improve VA in affected patients.

Objective: To compare 35-mm stereoscopic slide transparencies with digitized nonstereoscopic images (resolution 1024x768 pixels) for grading abnormalities in age-related maculopathy (ARM) and age-related macular degeneration (AMD)., Design: Comparative observational case series., Participants: Twenty-five patients (50 eyes) with ARM and/or AMD., Methods: Twenty-five patients with ARM/AMD in at least 1 eye were randomly selected from a large ongoing collection of clinical data and DNA in a tertiary referral United Kingdom population. Retinal photography was performed with mydriasis using the Zeiss FF-series 30 degrees fundus camera on Ektachrome slide transparency film. The images were centered on the macula. The color transparencies were then digitized. The grading process has been set up based on the International ARM Epidemiology Study Group. All images were independently graded by 3 retinal specialists. Both kappa statistics and exact agreement were calculated to assess agreement between and within observers and between the 2 master copies derived from the gradings of the color slides and digitized images., Main Outcome Measure: Agreement between the 2 master copies derived from the gradings obtained from stereoscopic slide transparencies and digitized nonstereoscopic images., Results: For small hard and intermediate soft drusen, agreement ranged between 77% and 91% (kappa, 0.56-0.72) and 83% and 93% (kappa, 0.31-0.64), respectively, for the 3 macular subfields. Agreement for the presence of hyperpigmentation was 12% to 56% (kappa, 0.00-0.27). Agreement was 94% to 96% (kappa, 0.80-0.82) for the presence of geographic atrophy and 93% (kappa, 0.78) for the area covered. For the presence of choroidal neovascularization (CNV), agreement was 94% to 98% (kappa, 0.81-0.88), and it was 95% (kappa, 0.83) for the area covered. For individual features of CNV, exact agreement was 88% to 96% (kappa, 0.22-0.49). In 3 cases of geographic atrophy and 2 cases of CNV, the lesion was missed on digitized images., Conclusions: Because of the close agreement for most categories between the grading of stereoscopic color slides and digitized images, digitized nonstereoscopic color images prove to be useful for grading ARM and AMD.