Diabetic Retinopathy Screening Using Smartphone-Based Fundus Photography and Deep-Learning Artificial Intelligence in the Yucatan Peninsula: A Field Study.

BACKGROUND: To compare the performance of Medios (offline) and EyeArt (online) artificial intelligence (AI) algorithms for detecting diabetic retinopathy (DR) on images captured using fundus-on-smartphone photography in a remote outreach field setting. METHODS: In June, 2019 in the Yucatan Peninsula, 248 patients, many of whom had chronic visual impairment, were screened for DR using two portable Remidio fundus-on-phone cameras, and 2130 images obtained were analyzed, retrospectively, by Medios and EyeArt. Screening performance metrics also were determined retrospectively using masked image analysis combined with clinical examination results as the reference standard. RESULTS: A total of 129 patients were determined to have some level of DR; 119 patients had no DR. Medios was capable of evaluating every patient with a sensitivity (95% confidence intervals [CIs]) of 94% (88%-97%) and specificity of 94% (88%-98%). Owing primarily to photographer error, EyeArt evaluated 156 patients with a sensitivity of 94% (86%-98%) and specificity of 86% (77%-93%). In a head-to-head comparison of 110 patients, the sensitivities of Medios and EyeArt were 99% (93%-100%) and 95% (87%-99%). The specificities for both were 88% (73%-97%). CONCLUSIONS: Medios and EyeArt AI algorithms demonstrated high levels of sensitivity and specificity for detecting DR when applied in this real-world field setting. Both programs should be considered in remote, large-scale DR screening campaigns where immediate results are desirable, and in the case of EyeArt, online access is possible.

Reproducibility of Fixed-luminance and Multi-luminance Flicker Electroretinography in Patients With Diabetic Retinopathy Using an Office-based Testing Paradigm.

BACKGROUND: We evaluated the reproducibility of office-based flicker electroretinography (ERG) in patients with nonproliferative diabetic retinopathy (NPDR). METHODS: An observational study was conducted in which ultra-widefield fluorescein angiography (UWF-FA) was performed on 20 patients with mild-to-moderate NPDR; images were graded by the Fundus Photography Reading Center (Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, USA). Fixed- and multi-luminance flicker ERG was repeated four times (greater than or equal to seven days apart). Recording consistency was assessed using intra-class correlation coefficients (ICCs), coefficients of variation, and Pearson correlations. RESULTS: 82.5% and 17.5% of eyes had mild and moderate NPDR using UWF-FA; 90% of the angiograms were given a high confidence grade. Fixed-luminance phase values were highly reproducible (ICC: 0.949; P < .001). There was a significant negative correlation between fixed-luminance phase and log-corrected ischemic index values (-0.426; P = .015). CONCLUSIONS: Office-based, fixed-luminance phase values are highly reproducible and negatively correlate with retinal ischemia in NPDR, suggesting that global retinal dysfunction may be reliably quantified early in patients with diabetes.

Evaluation of a combination digital retinal camera with spectral-domain optical coherence tomography (SD-OCT) that might be used for the screening of diabetic retinopathy with telemedicine: A pilot study.

AIMS: Pilot study to determine whether an instrument combining a non-mydriatic retinal camera and spectral domain optical coherence tomography (SD-OCT) is effective for screening patients with diabetic retinopathy (DR). METHODS: Case series conducted between 2012 and 2013. DR imaged with a retinal camera/SD-OCT instrument viewed remotely was compared to a dilated examination by a retina specialist. RESULTS: The combination instrument was better than the retina specialist in detecting more severe retinopathy, primarily because of the SD-OCT. For severe retinopathy (grade ≥ 3), the image grader had better sensitivity (87.3% [95% CI: 75.5%, 94.7%]) than the retina examiner (76.4% [95% CI: 63.0%, 86.8%]). Specificities were similar between the instrument grader (96.0% [95% CI: 86.3%, 99.5%]) and retina examiner (100.0% [95% CI: 92.9%, 100.0%]). When identifying diabetic macular edema (ME), the retina examiner only identified 47.6% (20/42) of eyes with ME detected by SD-OCT. The instrument was better than a dilated retinal examination in detecting ME and not as good at detecting mild or proliferative retinopathy. CONCLUSIONS: As used in this study, the instrument was more effective in identifying DR than was the current recommendation of a dilated and comprehensive eye examination. SD-OCT is needed to accurately identify DR in a screening setting.

Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical Trial.

IMPORTANCE: Studies have established the efficacy and safety of aflibercept for the treatment of macular edema due to central retinal vein occlusion. Bevacizumab is used off-label to treat this condition despite the absence of supporting data. OBJECTIVE: To investigate whether bevacizumab is noninferior to aflibercept for the treatment of macular edema secondary to central retinal or hemiretinal vein occlusion. DESIGN, SETTING, AND PARTICIPANTS: The SCORE2 randomized noninferiority clinical trial was conducted at 66 private practice or academic centers in the United States, and included 362 patients with macular edema due to central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive aflibercept or bevacizumab. The first participant was randomized on September 17, 2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data available as of December 30, 2016. INTERVENTIONS: Eyes were randomized to receive intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg; n = 180) every 4 weeks through month 6. MAIN OUTCOMES AND MEASURES: The primary outcome was mean change in visual acuity (VA) letter score (VALS) from the randomization visit to the 6-month follow-up visit, based on the best-corrected electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0-100; higher scores indicate better VA). The noninferiority margin was 5 letters, and statistical testing for noninferiority was based on a 1-sided 97.5% confidence interval. RESULTS: Among 362 randomized participants (mean [SD] age, 69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2] [approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6) in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the aflibercept group (model-based estimate of between-group difference, -0.14; 97.5% CI, -3.07 to ∞; P = .001 for noninferiority), meeting criteria for noninferiority. Ocular adverse events in the aflibercept group included 4 participants with intraocular pressure (IOP) more than 10 mm Hg greater than baseline; ocular adverse events in the bevacizumab group included 1 participant with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma not attributed to the study drug or procedure. CONCLUSIONS AND RELEVANCE: Among patients with macular edema due to central retinal or hemiretinal vein occlusion, intravitreal bevacizumab was noninferior to aflibercept with respect to visual acuity after 6 months of treatment.

Topical Squalamine 0.2% and Intravitreal Ranibizumab 0.5 mg as Combination Therapy for Macular Edema Due to Branch and Central Retinal Vein Occlusion: An Open-Label, Randomized Study.

BACKGROUND AND OBJECTIVE: To evaluate the effects of squalamine (OHR-102; Ohr Pharmaceuticals, New York, NY) and ranibizumab (Lucentis; Genentech, South San Francisco, CA) on macular edema (ME) secondary to retinal vein occlusion (RVO). PATIENTS AND METHODS: Twenty consecutive, treatment-naïve patients with RVO-related ME received topical squalamine and intravitreal ranibizumab 0.5 mg for 10 weeks, followed by randomization to continue or discontinue squalamine. Groups received as-needed ranibizumab from weeks 2 through 34. The primary endpoint was the proportion of eyes gaining 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 38. Safety and tolerability were assessed. Data from 13 treatment-naïve control eyes previously enrolled in three similar trials evaluating monthly ranibizumab 0.5 mg for RVO-related ME were included for comparison. RESULTS: At baseline, mean best-corrected visual acuity (BCVA) measures were 55.6 ETDRS letters and 55.0 ETDRS letters in the squalamine and control groups, respectively. At week 38, BCVA improved 25.6 letters in the squalamine group; at month 9, BCVA improved 16.3 letters in the control group. This corresponds to a between-treatment-group difference of 9.2 letters. Squalamine and ranibizumab combination therapy was well-tolerated. CONCLUSIONS: In patients with RVO-related ME, topical squalamine combined with early, as-needed ranibizumab appears to enhance visual recovery versus ranibizumab alone. Combination therapy appears safe and was well-tolerated. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:914-923.].

Pegaptanib sodium for macular edema secondary to branch retinal vein occlusion.

PURPOSE: To assess the efficacy and safety of intravitreous pegaptanib sodium (Macugen; EyeTech Pharmaceuticals/Pfizer Inc, New York, New York, USA) for macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: Prospective, randomized, dose-finding study. METHODS: Twenty subjects from three clinical practices in the United States with BRVO of more than 1 month's and fewer than 6 months' duration; best-corrected visual acuity (BCVA) 70 to 25 Early Treatment Diabetic Retinopathy Study letters inclusive (approximately 20/40 to 20/320 Snellen); and central foveal thickness of 250 microm or more were included. Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3 or 1 mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48. Principal efficacy outcomes were change from baseline to week 54 in BCVA, center point thickness, central subfield thickness, and macular volume as measured by optical coherence tomography. RESULTS: Fifteen subjects received pegaptanib 0.3 mg and 5 received pegaptanib 1 mg. Eighteen subjects completed the 54-week follow-up. Results were similar in both the 0.3- and 1-mg groups. Overall improvements from baseline to week 54 occurred in mean BCVA (+14 +/- 13 letters), center point thickness (-205 +/- 195 mum), central subfield thickness (-201 +/- 153 mum), and macular volume (-2.2 +/- 1.6 mm(3)). The response was rapid after the first injection, with a mean BCVA improvement of 11 +/- 7 letters at 1 week from the baseline of 56 +/- 12 letters (approximately 20/80 Snellen). One retinal detachment and no cases of endophthalmitis or traumatic cataract were seen. CONCLUSIONS: Intravitreous pegaptanib offers a promising alternative as a treatment for macular edema secondary to BRVO.

Pegaptanib sodium for macular edema secondary to central retinal vein occlusion.

OBJECTIVES: To assess the safety and efficacy of intravitreous pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO). DESIGN: This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n=33; sham, n=32). MAIN OUTCOME MEASURE: Visual acuity at week 30. RESULTS: In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects (P= .48 for 0.3 mg and P= .35 for 1 mg of pegaptanib sodium vs sham). In secondary analyses, subjects treated with pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P= .03 for 0.3 mg and P= .01 for 1 mg of pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs -3.2 letters with sham; P= .09 for 0.3 mg and P= .02 for 1 mg of pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg pegaptanib sodium groups by 269 microm and 210 microm, respectively, vs 5 microm with sham (P< .001). CONCLUSIONS: Based on this 30-week study, intravitreous pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO. APPLICATION TO CLINICAL PRACTICE: Benefits accrued with intravitreous pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00088283.