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Purpose Photic retinal toxicity induced by exposure to arc welding can lead to irreversible vision loss. Serial multimodal imaging is characterized in a patient with outer retinal damage secondary to welder's maculopathy. Methods A single case was retrospectively reviewed. Results Spectral domain optical coherence tomography acutely revealed disruption of the ellipsoid zone, hyperreflective bands through the outer nuclear layer, and outer retinal cavitation consistent with phototoxicity. Subsequently, disruption and hypertrophy of the subfoveal retinal pigment epithelium developed. Autofluorescence depicted central hypoautofluorescence. Conclusion We report serial multimodal imaging in welder's maculopathy to better characterize the evolution of lesions. Multimodal imaging including spectral domain optical coherence tomography in arc welding phototoxicity may share features with other forms of phototoxicity such as hand-held laser maculopathy.

PURPOSE: To report on the safety of the first five cohorts of a gene therapy trial using recombinant equine infectious anemia virus expressing ABCA4 (EIAV-ABCA4) in adults with Stargardt Dystrophy (SD) due to mutations in ABCA4. DESIGN: Nonrandomized multicenter phase I/IIa clinical trial. METHODS: Patients received a subretinal injection of EIAVABCA4 in the worse-seeing eye at three dose levels and were followed for three years after treatment. MAIN OUTCOME MEASURES: The primary end point was ocular and systemic adverse events. The secondary endpoints were best-corrected visual acuity (BCVA), static perimetry (SP), kinetic perimetry (KP), total field hill of vision (V(TOT)), full field electroretinogram (ffERG), multifocal ERG (mfERG), color fundus photography (CFP), short-wavelength fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT). RESULTS: The subretinal injections were well-tolerated by all 22 patients across three dose levels. There was one case of a treatment-related ophthalmic serious adverse event in the form of chronic ocular hypertension. The most common adverse events were associated with the surgical procedure. In one patient treated with the highest dose, there was a significant decline in the number of macular flecks as compared to the untreated eye. However, in six patients hypoautofluorescent changes were worse in the treated eye than the untreated eye. Of these, one patient had retinal pigment epithelium (RPE) atrophy that was characteristic of tissue damage likely associated with bleb induction. No patients had any clinically significant changes in BCVA, SP, KP, V(TOT), ffERG, or mfERG attributable to the treatment. CONCLUSIONS: Subretinal treatment with EIAV-ABCA4 was well tolerated with only one case of ocular hypertension. No clinically significant changes in visual function tests were found to be attributable to the treatment. However, 27% of treated eyes showed exacerbation of RPE atrophy on FAF. There was significant reduction in macular flecks in one treated eye from the highest dose cohort. Additional follow-up and continued investigation in more patients will be required to fully characterize the safety and efficacy of EIAV-ABCA4.

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

Purpose To determine the sensitivity and specificity of OCT angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Design Prospective case series. Subjects A prospective series of 72 eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. Methods All eyes underwent OCTA with a spectral domain OCT. The 3-dimensional angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. Main Outcome Measure The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography and OCT was determined for structural spectral domain OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. Results Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage and sensitivity improved to 94% for both graders if eyes with subretinal hemorrhage were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. Conclusions Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of fluorescein angiography with OCT, and it is better than en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV detection. False positives from structural OCT can be mitigated with the addition of flow information with OCTA.

To evaluate the clinical, anatomic and functional effects of conversion to aflibercept following ranibizumab and/or bevacizumab in patients with neovascular age-related macular degeneration (AMD).A retrospective review of patients with neovascular AMD treated with intravitreal ranibizumab and/or bevacizumab who were switched to aflibercept was performed. The primary outcome was change in injection frequency in the year following the change. Secondary outcomes included change in central macular thickness (CMT) at 6 months and 1 year, presence of intraretinal and subretinal fluid at 6 months and visual acuity at 1 year.A total of 109 eyes with neovascular AMD were switched to aflibercept and met inclusion criteria. Overall, aflibercept injection frequency was unchanged with patients receiving 7.4 antivascular endothelial growth factor (VEGF) injections the year prior to conversion compared with 7.2 aflibercept injections in the year following (p=0.47). However, the change to aflibercept was associated with improvement in CMT from 324 to 295 μm (p=0.0001) at 6 months and 299 μm (p=0.0047) at 1 year. There was no effect on visual acuity at 1 year. In a subgroup analysis, patients who had received ≥10 anti-VEGF injections in the year prior had fewer injections (11.1 to 8.4, p0.0001) and clinic visits (13.9 to 9.6, p0.0001) as well as a significant decrease in CMT (-35 μm, p=0.02).In our population, switching to aflibercept therapy was not associated with a change in injection frequency nor improved visual acuity, but was associated with improved CMT at 6 months and 1 year. In patients who received at least 10 anti-VEGF injections in the year prior, transitioning to aflibercept was associated with a reduced injection frequency and CMT, suggesting potential cost savings in this population.

Adaptive optics (AO) has been increasingly used to study retinal disease.1–26 Until recently, the application of AO technology in ophthalmic imaging has been restricted to custom-built systems that require extensive technical infrastructure, which limits their use in a typical clinical setting. Now with commercially available AO imaging systems, such as the flood-illuminated rtx1 from Imagine Eyes (Orsay, France), the Compact AO retinal imager from Physical Sciences, Inc. (Andover, MA, USA), and an AO scanning laser ophthalmoscope from Canon, Inc. (Tokyo, Japan), AO-aided imaging is becoming a more clinically viable tool for assessing retinal disease.27–30 We used the rtx1 flood-illuminated AO camera from Imagine Eyes to develop a protocol for imaging and sampling cone density from a large macular area in healthy subjects. Previous studies have used the rtx1 to examine retinal diseases,12,21,22,31–36 study the healthy eye,37–40 and optimize AO imaging parameters.41,42 However, the practicality and limitations of using the rtx1 and other commercial systems have not been well established. Most studies have sampled density in small, manually selected areas of high image quality, even though a major advantage of flood-illuminated AO imaging is to allow for large areas of the retina to be imaged quickly. The density analysis methods typically used are also prohibitively labor intensive when analyzing large datasets with extensive retinal areas. Therefore, the clinical and research utility of adaptive optics remains limited by a lack of automated cone sampling and density representation methods. Additionally, although some studies have explored the effect of different-sized sampling windows on measurements of cone density,43 it is still unclear how to best represent or sample cone density most accurately and consistently. We describe our process for image acquisition, processing, and cone density analysis using the rtx1. We evaluated three methods of automatically sampling cone density, assessed the repeatability of our measurements, and compared our cone density values to histological studies,44,45 adding our data to previous studies that have used AO imaging systems to characterize the normal photoreceptor mosaic.37,38,46–52