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

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

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 = -0.103, P = 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 = -0.295, P = 0.029). This was not significant for the area of retinal nonperfusion in the periphery while controlling for posterior pole nonperfusion and age (R = 0.124, P = 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

Retinal non-perfusion 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: 42 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 non-perfusion (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 two 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 non-perfusion in total, to 14.3% in eyes with 10-30DA, 20.0% for 30-75DA and 80% risk with 75-150DA of non-perfusion. From 13 (31.0%) eyes with a perfused posterior pole (an area encompassing a five disc diameter radius centered at the fovea) and more than 10DA of non-perfusion isolated in the periphery (beyond the posterior pole), only one (7.7%) eye developed new vessels, OR 0.12 [95% CI:0.01,1.03]. Comparatively, for 13 (31.0%) eyes with more than 10DA of non-perfusion in the posterior pole, 11 (84.6%) developed new vessels, OR 74.25 [95% CI: 9.26, 595.30], p<0.001. CONCLUSION: With ultra-widefield angiography, we have ascertained that posterior pole non-perfusion of more than 10DA remains the key risk factor for new vessel development compared to areas of non-perfusion confined to the periphery

Quantifying Retinal Area in Ultra-Widefield Imaging Using a 3-Dimensional Printed Eye Model

Purpose: To study the effects of different axial lengths on ultra-widefield imaging to determine the presence of distortion in images despite software correction and calculate an enlargement factor based on angular location. / Design: Experimental image analysis study. / Study Objects: Three 3-dimensional printed model eyes simulating eyes with axial lengths of 22, 24, and 26 mm. Each model has a grid of rings 9° apart centered at the posterior pole. / Methods: Single-center study performed at the National Institute for Health Research Moorfields Biomedical Research Centre (London, UK). Each model was imaged using Optos 200TX (Optos, Dunfermline, UK). Two images for each model eye that were corrected using V2 Vantage Pro software (Optos) were used for analysis and the average values obtained. Each image inter-ring area was measured using ImageJ to obtain a measured image area in pixel and square millimeters. This was compared with the true calculated object inter-ring area and an enlargement factor was determined. / Main Outcome Measures: Measured image inter-ring area in pixels and square millimeters. True calculated object inter-ring area in square millimeters. / Results: The enlargement factor of the rings gradually increases toward the periphery with factors of 1.4 at 45° and 1.9 at the equator. The axial lengths did not affect the enlargement factor of the rings imaged in 3 different model eyes (P = 0.9512). The anterior equator exhibits a significant distortion despite the software correction. / Conclusion: The enlargement factor depends on angular location and not axial length. The enlargement factors can be used in clinical practice to more accurately measure area in ultra-widefield imaging

Mechanistic Evaluation of Panretinal Photocoagulation Versus Aflibercept in Proliferative Diabetic Retinopathy: CLARITY Substudy

PURPOSE: The purpose of this study was to study the effects of panretinal photocoagulation (PRP) and intravitreal aflibercept on retinal vessel oxygen saturations, area of retinal nonperfusion, and area of neovascularization in proliferative diabetic retinopathy. //METHODS: This is a prospective randomized single center study. Forty patients with proliferative diabetic retinopathy were randomized to PRP or intravitreal aflibercept treatment for 52 weeks. Retinal oximetry and ultra-widefield angiography were performed at baseline and week 52. Ultra-widefield color fundus imaging was performed at baseline, week 12, and week 52. The outcomes were retinal arterio-venous oximetry differences (AVD), area of retinal nonperfusion, and area of neovascularization in disc areas (DA). // RESULTS: The AVD in the PRP group increased from 36.7% at baseline to 39.7%, whereas it decreased from 33.4% to 32.5% in the aflibercept group. The difference in AVD between groups at week 52 was 4.0% (95% confidence interval, −0.08, 8.8; P = 0.10). The baseline mean area of retinal nonperfusion of 125.1 DA and 131.2 DA in the PRP and aflibercept groups increased to 156.1 DA and 158.4 DA, respectively, at week 52 (P = 0.46). The median baseline area of neovascularization decreased from 0.98 DA to 0.68 DA in the PRP group and from 0.70 DA to 0 DA in the aflibercept group at week 12 (P = 0.019). At week 52, this measured 0.24 DA in the PRP group and 0 DA in the aflibercept group (P = 0.45). // CONCLUSIONS: Intravitreal aflibercept achieved an earlier and complete regression of neovascularization in proliferative diabetic retinopathy compared with PRP. There were no significant differences in global change in intravascular oxygen saturation or areas of retinal nonperfusion between the two groups by 52 weeks

Intravitreal aflibercept for diabetic macular oedema: Moorfields’ real-world 12-month visual acuity and anatomical outcomes

OBJECTIVES:: To assess structural and functional outcomes of treatment with intravitreal aflibercept (Eylea®) for diabetic macular oedema in treatment-naive patients. DESIGN:: This is a retrospective, real-life, cohort study. PARTICIPANTS AND METHODS:: In all, 92 diabetic patients (102 eyes) receiving intravitreal anti-vascular endothelial growth factor therapy were included. A total of 99 aflibercept-treated eyes were included in the statistical analysis. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline and 12 months. Patients were initiated on a loading phase of five monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians' discretion. RESULTS:: The mean number of aflibercept injections received was 6.92. At baseline, the mean visual acuity (standard deviation; Snellen) was 59.7 (16.1) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 431 (129) µm, while the mean macular volume (standard deviation) was 9.53 (1.79) mm3. At 12 months, the mean visual acuity (standard deviation; Snellen) was 69.6 (15.2; 20/40) Early Treatment Diabetic Retinopathy Study letters (p < .0001). Mean central foveal thickness (standard deviation) was 306 (122) μm (p < .0001) and mean macular volume (standard deviation) was 8.43 (1.58) mm3 (p < .0001) at 12 months; 33 (33.67%) eyes gained ⩾15 Early Treatment Diabetic Retinopathy Study letters at month 12, and 50 (55.55%) eyes had a decrease in central foveal thickness of ⩾100 µm. CONCLUSION:: There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 12 months after commencing treatment for diabetic macular oedema in real-life settings

Radiation Retinopathy: Case report and review

BACKGROUND: Ocular damage from radiation treatment is a well established phenomenon. Many factors are now known to influence the incidence of radiation retinopathy, including total dosage and daily fraction size. Patients who are diabetic, hypertensive or received previous chemotherapy are more susceptible to radiation retinopathy. CASE PRESENTATION: A 55 year old male was referred from the oncology department with epiphora. His medical history included Type 2 Insulin treated Diabetes Mellitus and hypertension. One year prior to presentation he had undergone a total rhinectomy with a 4 week course of post-operative radiotherapy for an aggressive sqaumous cell carcinoma of the nose. On examination the visual acuity was noted to be 6/36 left eye and 6/9 right eye. Posterior segment examination revealed marked retinal ischaemia present in the posterior pole and macular region of both eyes. The appearance was not thought to be typical of diabetic changes, radiation retinopathy being the more likely diagnosis especially in view of his history. Over the next four months the vision in both eyes rapidly deteriorated to 3/60 left eye and 1/60 right eye. Bilateral pan retinal photocoagulation was thought to be appropriate treatment at this point. CONCLUSION: This case highlights the importance for ophthalmologists and oncologists to be aware of the close relationship between diabetes and radiation treatment and the profound rapid impact this combination of factors may have on visual function. Radiation is being used with increasing frequency for ocular and orbital disease, because of this more cases of radiation retinopathy may become prevalent. Factors which may potentiate radiation retinopathy should be well known including, increased radiation dosage, increased fraction size, concomitant systemic vascular disease and use of chemotherapy. Counselling should be offered in all cases at risk of visual loss. As no effective treatment currently exists to restore visual function, monitoring of visual acuity in all cases and early referral to the ophthalmologist as appropriate is warranted

The combination of intravitreal triamcinolone and phacoemulsification surgery in patients with diabeticfoveal oedema and cataract

BACKGROUND: The management of diabetic patients with refractory macular oedema or patients with no adequate pre-operative view to administer laser treatment provide a challenge to the ophthalmologist. We wished to assess the use, safety and effect of intravitreal triamcinolone injection at the time of cataract surgery in patients with diabetic foveal oedema and sight limiting lens opacities. METHOD: This was a longitudinal non-randomised prospective pilot study in 18 eyes (12 patients). All patients had visually significant lens opacities and either persistent diabetic foveal oedema unresponsive to laser treatment-group A, or foveal oedema with no adequate pre-operative view for laser treatment- group B. The cataract surgery was carried out under full aseptic technique using a self-sealing temporal incision and a foldable acrylic lens. Intravitreal triamcinolone was given infratemporally pars plana at the completion of the cataract surgery. The patients were reviewed at day 5, 2 weeks, 2 months and then every 3 months as required. The Wilcoxin matched-pairs test was used to assess the significance of the improvement in visual acuity at 2 months. RESULTS: Twelve patients with a total of 18 eyes were included in the study. There were 10 patients (15 eyes) in group A and 3 patients (3 eyes) in group B. Preoperatively 16 of the 18 eyes had a visual acuity of 6/24 or worse. Postoperatively 83% of patients had completely dry foveae at 2 weeks. Best-corrected visual acuities at two months review ranged from 6/6 to CF with 9 eyes (50%) achieving 6/12 or better (7 eyes (47%) in group A and 2 eyes (67%) in group B). Three eyes had no recorded improvement in visual acuity, but no eyes had deterioration in acuity. The improvement in visual acuity was significant at p = 0.001. There were no significant sight threatening complications. CONCLUSION: Intravitreal triamcinolone has been shown to lead to an improvement in macular oedema and visual improvement in diabetic patients not undergoing cataract surgery but has not, to our knowledge, been previously used in a study like this one. We suggest that intravitreal injection at the time of cataract surgery could be carried out safely with encouraging visual outcomes in patients with diabetic foveal oedema and cataract