Diagnostic accuracy of disorganization of the retinal inner layers in detecting macular capillary non-perfusion in diabetic retinopathy.

BACKGROUND: Disorganization of the retinal inner layers (DRIL) on optical coherence tomography (OCT) is thought to represent retinal capillary non-perfusion (CNP) in eyes with diabetic retinopathy. This study was designed to evaluate the ability of DRIL to accurately predict CNP. DESIGN: Retrospective masked reliability and diagnostic accuracy study performed in the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre, London, UK SAMPLES: Retinal images of patients with diabetic retinopathy METHODS: The OCT images from 90 separate areas of angiographically confirmed perfused and non-perfused areas of the macula from 37 eyes of 31 patients were anonymized and coded. Two masked graders independently graded these OCT scans for the presence or absence of DRIL to determine the intergrader reliability. The diagnostic accuracy of DRIL in identifying CNP was evaluated from the results obtained. MAIN OUTCOME MEASURES: Sensitivity and specificity of DRIL in accurately detecting CNP RESULTS: The intergrader agreement was high with a Cohen's kappa of 0.909. DRIL was present in 84.4% (38/45) of non-perfused retina and none in perfused retina (0/45). The sensitivity and specificity of DRIL in detecting angiographic evidence of CNP was 84.4% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 86.5%. CONCLUSIONS: The presence of DRIL is a reliable predictor of areas of macular CNP. However, DRIL is not a universal finding of non-perfusion, with some cases exhibiting absence of DRIL despite angiographic CNP.

The clinical relevance of ultra-widefield angiography findings in patients with central retinal vein occlusion and macular oedema receiving anti-VEGF therapy.

AIMS: To report, using ultra-widefield angiography (UWFA) the area, distribution, and change in retinal capillary nonperfusion (RCNP) at baseline and 100 weeks in eyes with central retinal vein occlusion (CRVO) receiving anti-VEGF for macula oedema. METHODS: Prospective longitudinal multi-centre cohort study. Adults with CRVO treated with anti-VEGF therapy for macular oedema underwent UWFA at baseline and week-100. The area, distribution, and change in total, peripheral and posterior pole RCNP were determined. RESULTS: Of 153 eyes at baseline, mean area of RCNP was 34.3DA and 12 (7.8%) had ≥75DA RCNP. More than 10DA RCNP was present in the temporal periphery in 75.8% of eyes vs. 10.5% in the nasal periphery. At week-100, mean RCNP was 42.1DA with a median change from baseline of 3.3DA 95% CI [0.4, 7.3]; p < 0.01. Of 146 eyes with ≤10DA of posterior pole RCNP at baseline, 16/146 (11.0%) progressed to >10DA at week-100. These eyes had a median increase in total RCNP of 69.7DA [95% CI 27.2-85.4] vs 0DA [0.0-1.4]; p < 0.001 for those who did not, and two developed neovascular glaucoma. Larger baseline area of RCNP and history of glaucoma were risk factors for posterior pole RCNP developing. CONCLUSIONS: With UWFA, significant baseline RCNP was identified in the majority of CRVO patients, notably in the temporal periphery, but large increases over 100 weeks were uncommon. Development of >10DA posterior pole RCNP is a marker for widespread RCNP and in such cases the risk of anterior segment neovascularisation is not abolished by concomitant anti-VEGF therapy.

Retinal Nonperfusion in the Posterior Pole Is Associated With Increased Risk of Neovascularization in Central Retinal Vein Occlusion.

PURPOSE: To review the definition of ischaemic central retinal vein occlusion (CRVO) and stratify the risk of neovascular complication based on wider areas of visible retinal non-perfusion. DESIGN: Retrospective consecutive case series and image analysis study. METHODS: Setting: Moorfields Eye Hospital, London, United Kingdom. STUDY POPULATION: Forty-two consecutive treatment-naïve eyes with CRVO imaged with ultra-widefield angiography with a minimum of 12 months follow-up. OBSERVATION PROCEDURE: The spatial location and total area of retinal nonperfusion (measured in disc areas, DA) were determined using the validated concentric rings method. The area was corrected for projection distortion. The images were graded by 2 retinal physicians and average measurements used. MAIN OUTCOME MEASURES: Development of neovascular complications. RESULTS: The percentage of eyes developing new vessels increased from none in eyes with less than 10 DA of nonperfusion in total to 14.3% in eyes with 10-30 DA, 20.0% for 30-75 DA, and 80% risk with 75-150 DA of nonperfusion. From 13 (31.0%) eyes with a perfused posterior pole (an area encompassing a 5 disc diameter radius centered at the fovea) and more than 10 DA of nonperfusion isolated in the periphery (beyond the posterior pole), only 1 (7.7%) eye developed new vessels, odds ratio (OR) 0.12 [95% confidence interval (CI): 0.01, 1.03]. Comparatively, for 13 (31.0%) eyes with more than 10 DA of nonperfusion in the posterior pole, 11 (84.6%) developed new vessels, OR 74.25 [95% CI: 9.26, 595.30], P < .001. CONCLUSION: With ultra-widefield angiography, we have ascertained that posterior pole nonperfusion of more than 10 DA remains the key risk factor for new vessel development compared to areas of nonperfusion confined to the periphery.

Real-World Outcomes of Ranibizumab Treatment for Diabetic Macular Edema in a United Kingdom National Health Service Setting.

PURPOSE: To determine visual acuity (VA) and spectral-domain optical coherence tomography (OCT) outcomes with intravitreal ranibizumab for diabetic macular edema (DME) in a United Kingdom National Health Service clinical setting. DESIGN: Retrospective interventional case series. PARTICIPANTS: Consecutive patients with DME, treated with the first ranibizumab injection between August 2013 and March 2014 across 4 sites of Moorfields Eye Hospital, London. METHODS: Two hundred eyes of 164 consecutive patients with center-involving DME and VA ≤79 ETDRS letters, central subfield macular thickness (CST) ≥350 µm on Topcon 3D OCT 2000, initiated on a loading phase of 3 intravitreal ranibizumab injections and who had at least 6 months follow-up were reviewed. Subsequent retreatment was guided by VA and OCT with the aim of treating to stability. VA, OCT CST, and macular volume (MV) were recorded at baseline and monthly to 12 months. RESULTS: The mean VA, mean CST, and mean MV at baseline were 54.4 (± 15.26) letters, 490.16 (± 116.54) µm, and 10.46 (± 2.28) mm3. The mean VA change at 12 months was +6.6 (± 13.35) letters (P = .0003). A total of 40.3% of patients (n = 77) gained ≥10 letters and 25.1% (n = 48) gained ≥15 letters; 8.9% (n = 17) lost ≥10 letters and 6.3% (n = 12) lost ≥15 letters. At 12 months, the mean change in CST and MV were -133.9 (± 160.12) µm (P = .0001) and -1.5 (± 1.96) mm3 (P = .0001), respectively. An average of 7.2 (± 2.3) injections were given over 12 months. CONCLUSIONS: Outcomes with 3 loading injections of 0.5 mg ranibizumab given monthly followed by pro re nata retreatment in a clinical setting are comparable with outcomes from clinical trials.

Validation of Concentric Rings Method as a Topographic Measure of Retinal Nonperfusion in Ultra-Widefield Fluorescein Angiography.

PURPOSE: To validate the use of concentric rings as a method to measure topographic area of retinal nonperfusion in ultra-widefield angiography with the ischemic index method, which is the most frequently used method to measure nonperfusion in ultra-widefield angiography. DESIGN: Validation study and reliability analysis. METHODS: setting: Single-center study performed at National Institute for Health Research Moorfields Biomedical Research Centre, London, United Kingdom. STUDY POPULATION: Twenty-eight ultra-widefield angiogram images of eyes with central retinal vein occlusion. OBSERVATION PROCEDURE: The concentric rings method consists of 6 macula-centered concentric rings divided into 12 segments each. Each image was graded by 5 graders using both the concentric rings and the ischemic index methods. MAIN OUTCOME MEASURES: Agreement between the 2 methods was calculated using the intraclass correlation coefficient. Intertest agreement, intergrader agreement, test-retest reliability, and the time taken to grade using these 2 methods were compared. RESULTS: The intertest agreement between concentric rings method and ischemic index method was 0.965. The intergrader agreement was 0.910 for the concentric rings method and 0.898 with the ischemic index method. The test-retest reliability was 0.975 for the rings and 0.979 for the ischemic index. Average grading time per image was 187 s and 297 s for the concentric rings method and ischemic index method, respectively, P < .001. CONCLUSION: The concentric rings method has an "almost-perfect" intergrader agreement and intertest agreement with the ischemic index method, with a shorter grading time.