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

Nicholson, Luke; Vázquez-Alfageme, Clara; Ramu, Jayashree; Triantafyllopoulou, Ioanna; Patrao, Namritha; Muwas, Mahdi; Islam, Farrah; Hykin, Philip; Sivaprasad, Sobha

doi:10.1016/j.ajo.2015.09.003

Cited by 26 publications

(43 citation statements)

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“…In order to assess spatial location and quantity of non-perfusion and area of new vessels, a concentric rings template was applied to each image in accordance with previously described methods. 80 In brief, this validated method incorporates a macular ring with a radius of 2.5 DDs and five additional concentric rings (rings 1-5), each with a 2.5-DD increment in radius. Each of the six rings (ring M and rings 1-5) was divided into 12 segments.…”

Section: Ultrawide Field Fundus Fluorescein Angiographymentioning

confidence: 99%

Intravitreal aflibercept compared with panretinal photocoagulation for proliferative diabetic retinopathy: the CLARITY non-inferiority RCT

et al. 2018

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Background Panretinal photocoagulation (PRP) has been the standard of care for patients with proliferative diabetic retinopathy (PDR) for the last 40 years. It prevents severe visual loss in PDR but is also associated with adverse effects on visual functions. Objectives The clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (CLARITY) trial evaluated the clinical efficacy, mechanisms and cost-effectiveness of intravitreal aflibercept (Eylea®, Regeneron, Tarrytown, NY, USA/Bayer Pharma AG, Berlin, Germany therapy for PDR. Design A multicentre, prospective, individually randomised, single-masked, active-controlled trial with concurrent economic evaluation that tested the non-inferiority of intravitreal aflibercept versus standard care PRP at 52 weeks. A subset of the participants enrolled in a mechanistic evaluation substudy. Setting 22 UK NHS clinical sites. Participants Patients aged at least 18 years having either treatment-naive PDR or active retinal neovascularisation (NV) despite prior PRP requiring treatment and best corrected visual acuity (BCVA) of 54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or better in the study eye were included. Eyes with evidence of macular oedema at baseline confirmed by central subfield thickness > 320 µm on spectral-domain optical coherence tomography were excluded. Intervention In the intervention arm, intravitreal aflibercept injections were given at baseline, 4 and 8 weeks and patients were subsequently reviewed every month and injected pro re nata based on the treatment response defined by degree of regression of retinal NV. In the comparator arm, PRP was completed in 2-weekly sessions and then supplemented if necessary at 8-weekly intervals. Main outcome measures The primary outcome was the mean change in BCVA at 52 weeks utilising a linear mixed-effects model incorporating data from both week 12 and week 52. Results A total of 232 participants (116 per arm) were recruited between August 2014 and November 2015. A total of 221 and 210 participants contributed to the intention-to-treat (ITT) model and per-protocol (PP) analysis, respectively. Economic evaluation was undertaken on 202 participants (101 per arm) with complete cost and outcome data. Aflibercept was non-inferior and superior to PRP in both the ITT population [mean BCVA difference 3.9 letters, 95% confidence interval (CI) 2.3 to 5.6 letters; p < 0.0001] and the PP population (difference 4.0 letters, 95% CI 2.4 to 5.7 letters; p < 0.0001). From a public sector multiagency perspective that covers health and social care services, treatment with aflibercept costs more in terms of total resource use (mean adjusted total additional cost per patient = £5475, bootstrapped 95% CI £5211 to £5750) than PRP over a 12-month follow-up period. There were a small number of important safety events in each arm. Patients were more satisfied with aflibercept than PRP. Limitations This study is limited to 1 year of follow-up. Conclusions At an additional cost, the study shows that intravitreal aflibercept is an effective alternative treatment option for PDR in the first year. Future work Future research is needed to evaluate the long-term benefits of aflibercept in comparison with PRP and other anti-vascular endothelial growth factor agents for this condition. Trial registration Current Controlled Trials ISRCTN32207582. Funding This project was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanistic Evaluation programme, a Medical Research Council and NIHR partnership. Aflibercept was supplied by Bayer Plc (Reading, UK). The study was sponsored by NIHR Moorfields Biomedical Research Centre and supported by the UK Clinical Research Network. The research was supported by the NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College London Institute of Ophthalmology, the NIHR Moorfields Clinical Research Facility and the UK Clinical Reasearch Collaboration-registered King’s Clinical Trials Unit at King’s Health Partners, which is partly funded by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King’s College London.

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Section: Ultrawide Field Fundus Fluorescein Angiographymentioning

confidence: 99%

Intravitreal aflibercept compared with panretinal photocoagulation for proliferative diabetic retinopathy: the CLARITY non-inferiority RCT

et al. 2018

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“…To determine whether the observed changes were due to the laser treatment or diabetes itself, the amount of ischemia was quantified using the mean perfused ratio. The mean perfused ratio was calculated by the concentric rings method utilized by Nicholson et al 19 Compared to the standard ischemic index method wherein the grader draws the ratio of area perfused to the total area graded, the concentric rings method utilizes a set template. It has a perfect agreement with the ischemic index method, a higher inter-grader agreement, and a short-grading time.…”

Section: Discussionmentioning

confidence: 99%

“…It has a perfect agreement with the ischemic index method, a higher inter-grader agreement, and a short-grading time. 19 Using the concentric rings method, it was observed that at 12 and 24 months post laser, PRP laser resulted in a significant increase in the perfusion of the eye, whereas the control eyes showed no change. The result suggests that although diabetes remains a contributing factor, the improvement and changes in ischemia are most likely the result of the laser treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Two graders quantified the amount of ischemia in each patient using the concentric rings method that has been previously described in detail. 19 In this method, the innermost circle was first centered on the optic nerve to be sized proportionately and then repositioned to be foveacentered. The 12 segments in each of the rings were graded as, 'perfused', or 'non-perfused', if 450% of the segment showed either a perfused or non-perfused morphology.…”

Section: Optical Coherence Tomographymentioning

confidence: 99%

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Structural and functional changes to the retina and optic nerve following panretinal photocoagulation over a 2-year time period

Filek

Hooper

Sheidow

et al. 2017

Eye

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PurposeTo evaluate long-term structural and functional changes to the retina and optic nerve following panretinal photocoagulation (PRP) in diabetic retinopathy (DR) patients.MethodsParticipants were patients with DR requiring PRP and control patients with DR not requiring PRP. The Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT) were performed to analyze the optic nerve and macula. Best-corrected visual acuity (BCVA) and visual field (VF) testing were done to measure central and peripheral vision. Wide-field fluorescein angiogram was performed to monitor the progression of diabetic ischemia. The primary outcome measure was to determine the degree of retinal and optic nerve changes before and after PRP.ResultsThere was a non-significant thickening of the macula and retinal nerve fiber layer at 6 months post laser that recovered by 24 months. Mean perfused ratio was significantly increased (P=0.02) at 12 and 24 months post laser. Independently grading patient stereophotographs, grader 1 indicated there was a non-significant increase in cup to disk ratio post laser, while grader 2 indicated a significant increase at 6 (P=0.04), 12 (P=0.02), and 24 months (P=0.005). There was a significant VF decrease (P≤0.02) at 12 and 24 months post laser with BCVA showing a non-significant trend of deteriorating results.ConclusionDespite an improvement in peripheral perfusion, there was a significant progressive decline of peripheral VF over the study period. Clinical grading of the optic nerve was more unreliable following PRP, despite the absence of significant morphological changes as detected by the OCT and HRT.

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“…The concentric rings template then was added to each image according to previously described methods. 26 This validated method incorporates a macular ring with a radius of 2.5 disc diameters (DD) and five additional concentric rings (rings 1-5), each with a 2.5 DD increment in radius. Each of the six rings (Rings M and 1-5) was divided into 12 segments.…”

Section: Image Processingmentioning

confidence: 99%

The Relationship Between Retinal Vessel Oxygenation and Spatial Distribution of Retinal Nonperfusion in Retinal Vascular Diseases

Nicholson

Vázquez-Alfageme

Hykin

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We study the relationship between retinal vessel oxygenation and the spatial distribution of retinal nonperfusion using ultrawide field angiography in eyes with retinal vascular diseases. METHODS. This prospective single center study recruited 57 eligible eyes from 44 patients with retinal vascular diseases. Retinal oximetry measurements were obtained using the Oxymap T1 device to determine the arteriovenous (AV) difference. Retinal nonperfusion was measured from ultrawide field angiography images taken with the Optos 200TX system and superimposing the images with the concentric rings template to determine the area and distribution of retinal nonperfusion. RESULTS. Seven (12.3%) eyes had a diagnosis of a branch or hemiretinal vein occlusion, 24 (42.1%) with central retinal vein occlusion and 26 (45.6%) with diabetic retinopathy (11 [19.3%] nonproliferative and 15 [26.3%] proliferative diabetic retinopathy). The correlation between the total area of retinal nonperfusion with the AV difference controlling for age was not statistically significant (R ¼ À0.103, P ¼ 0.449). However, when analyzing the correlation of AV difference with the area of retinal nonperfusion in the posterior pole controlling for age and peripheral nonperfusion, this was significant (R ¼ À0.295, P ¼ 0.029). This was not significant for the area of retinal nonperfusion in the periphery while controlling for posterior pole nonperfusion and age (R ¼ 0.124, P ¼ 0.368). CONCLUSIONS. Retinal nonperfusion has a negative correlation with AV difference measured on retinal oximetry. This correlation is significant in the posterior pole, but not in the peripheral retina.

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

Cited by 26 publications

References 20 publications

Intravitreal aflibercept compared with panretinal photocoagulation for proliferative diabetic retinopathy: the CLARITY non-inferiority RCT

Intravitreal aflibercept compared with panretinal photocoagulation for proliferative diabetic retinopathy: the CLARITY non-inferiority RCT

Structural and functional changes to the retina and optic nerve following panretinal photocoagulation over a 2-year time period

The Relationship Between Retinal Vessel Oxygenation and Spatial Distribution of Retinal Nonperfusion in Retinal Vascular Diseases

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