RETINAL NONPERFUSION IN THE EARLY TREATMENT DIABETIC RETINOPATHY STUDY SEVEN FIELDS COMPARED WITH WIDEFIELD FLUORESCEIN ANGIOGRAPHY: Correlation and Use of Extrapolation Factor.

BACKGROUND: In previous landmark studies on central retinal vein occlusion, retinal nonperfusion assessments were obtained using 7-field (7F) angiography. The widespread current use of widefield imaging allows better visualization of the peripheral retina and more comprehensive estimation of the total area of nonperfusion. The relationship between nonperfusion measurement of 7F and widefield angiography (WFA) in central retinal vein occlusion has not been studied. We aim to identify the correlation of retinal nonperfusion measured within the 7F and on WFA in eyes with central retinal vein occlusion. METHODS: Retinal nonperfusion in participants with central retinal vein occlusion was determined using a 7F Early Treatment Diabetic Retinopathy Study template and the concentric rings method. RESULTS: A total of 153 eyes were included. Pearson correlation test showed a near-perfect positive, linear correlation between the nonperfusion found in the 7F and total retinal nonperfusion on WFA (0.985 95% CI [0.793, 0.999]) The regression line equation for nonperfusion on 7F and WFA was y = 37 + 3.2x. Eyes with 0 disk areas (DA), >0 DA to 10 DA and >10 DA of nonperfusion on 7-fields had on average 23 DA 95% CI (19.20, 27.06), 45 DA 95% CI (35.75, 55.18), and 115 DA 95% CI (88.89, 142.05) on widefield respectively. CONCLUSION: There is a positive and linear relationship between nonperfusion measured by 7F and WFA in central retinal vein occlusion with more than 3-times the amount of nonperfusion identified on WFA. Despite <10 DA no areas of nonperfusion on 7F, there is typically at least 35 DA of nonperfusion on WFA whereas eyes with >10 DA of nonperfusion on 7F had at least 88 DA on WFA.

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.

Individualizing Therapy for Neovascular Age-Related Macular Degeneration with Aflibercept (VITAL): A Two-Year Prospective, Interventional Single-Centre Trial.

AIMS: To report the mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and reading performance (reading acuity and maximum reading speed (MRS) using the MNREAD test) between baseline and 24 months in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept injections. METHODS: A prospective, open-label, interventional non-randomised case series with 24 months' duration. Patients were recruited to the study from medical retina clinics at Moorfields Eye Hospital. Intravitreal injections of 2.0 mg aflibercept in the study eye were administered using a fixed dosing regimen during the first year and a treat-and-extend treatment regimen during the second year of treatment. RESULTS: Fifty patients were enrolled with a mean age (SD) of 78.7 (7.6) years; a mean BCVA of 62.8 ETDRS letters; mean reading acuity of 0.52 logMAR; mean maximum reading speed (MRS) of 141.3 words per minute and a central macular thickness of 322.6 µm at baseline. The mean improvement in BCVA was 6.4 letters for the 44 patients (88%) for whom data was available at 2 years. The mean improvement in reading acuity was 0.13 logMAR with an improvement in MRS of 2.9 words per minute. The mean reduction in CRT from baseline was 104.8 µm. CONCLUSIONS: Aflibercept treatment of nAMD using fixed dosing in year 1 and treat and extend in year 2 leads to improvements in reading ability, visual acuity and retinal morphology which were maintained to 2 years of treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02441816, the VITAL study.

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.

Swept-Source OCT and Near-Infrared Reflectance Patterns in Choroidal Nevi.

PURPOSE: To describe the 3 distinct patterns of choroidal nevi in swept-source (SS) OCT and apply that classification to a cohort of consecutive choroidal nevi. Also, we aim to describe the findings of these lesions in near-infrared reflectance (NIR) at different wavelengths (820 and 1050 nm). DESIGN: Single-center, retrospective, observational study. PARTICIPANTS: One hundred four consecutive patients with choroidal nevi. METHODS: Retrospective analysis of choroidal nevi imaged with SS OCT and NIR. MAIN OUTCOME MEASURES: Lesions were classified according to OCT patterns as type A (high reflectivity with optical shadowing), type B (medium reflectivity with partial visualization of the scleral boundary), and type C (hyporeflective with complete visualization of the scleral boundary). RESULTS: Of 104 choroidal nevi, 97 lesions (93.3%) could be classified into 1 of the SS OCT patterns. Forty-nine percent corresponded to type A, 26% corresponded to type C, and 18.3% corresponded to type B. In NIR (n = 820), 76% of lesions were hyperreflective, whereas in NIR (n = 1050), most of the lesions were hyporeflective (59.6%; inverse reflectance). CONCLUSIONS: Choroidal nevi present distinct patterns according to SS OCT features. Clinical implications are yet to be determined. In NIR, inverse reflectance may be a consequence of the confocality of the device, rather than a property of the lesions.

INCIDENCE AND LONG-TERM VISUAL ACUITY OUTCOMES OF RETINAL PIGMENT EPITHELIUM TEARS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To report the incidence of retinal pigment epithelium tears in eyes treated with aflibercept for neovascular age-related macular degeneration and compare it with ranibizumab, and to describe long-term visual outcomes of retinal pigment epithelium tears after intensive anti-vascular endothelial growth factor treatment. METHODS: Retrospective analysis of clinical charts, spectral domain optical coherence tomography and fundus fluorescein angiography imaging of consecutive naive patients treated with intravitreal aflibercept or ranibizumab for neovascular age-related macular degeneration. RESULTS: Eight hundred consecutive eyes were included in the study (300 treated with ranibizumab and 500 with aflibercept) with 34.0 ± 9.1 months of follow-up. The incidence of tears in the aflibercept group was 3.2% and 2.3% after ranibizumab (P = 0.52). Twenty-nine eyes with retinal pigment epithelium tears were followed for a mean of 30.76 months. Visual acuity at baseline was 20/100 (50.7 ± 19.3 Early Treatment Diabetic Retinopathy Study letters) and 20/200 (36.1 ± 26.1 Early Treatment Diabetic Retinopathy Study letters) at the end of follow-up. The mean number of injection was 7.3 at 12 months and 13.9 ± 8.1 at the end of the study. The number of injections positively correlated with the final visual outcome. CONCLUSION: There was a low rate of retinal pigment epithelium tears after aflibercept injections, similar to ranibizumab. The correlation between the number of anti-vascular endothelial growth factors received and visual outcomes supports the need for continuing anti-vascular endothelial growth factor therapy.

MULTIMODALITY IMAGING OF TORPEDO MACULOPATHY WITH SWEPT-SOURCE, EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Multimodality image analysis of two cases of torpedo maculopathy. METHODS: Imaging with fundus photography, autofluorescence (AF), swept-source optical coherence tomography (OCT), en face OCT, and OCT angiography. RESULTS: The basal diameter of the torpedo lesions was 1 mm × 2 mm. One case had a satellite lesion. Autofluorescence indicated variable loss of signal. Swept-source OCT and en face OCT demonstrated fundus excavation, attenuation of nuclear layers and disruption of the outer plexiform layer, loss of photoreceptors and a subretinal cleft. In one case, Sattler layer appeared extended at the cleft. Optical coherence tomography angiography indicated loss of flow in deep retinal vessels and increased flow in choroidal vessels surrounding the cleft. CONCLUSION: Multimodal imaging findings of torpedo maculopathy include disruption of the deep retinal capillary network, expansion of Sattler layer, and increased signal around the subretinal cleft.

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.

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.

Long-Term Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration in a Clinical Setting.

PURPOSE: To report 2-year treatment outcomes with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) in routine clinical practice. DESIGN: Retrospective, nonrandomized, interventional case series. METHODS: Retrospective analysis of electronic medical record (EMR) notes (OpenEyes) and paper case notes and review of spectral-domain optical coherence tomography (SDOCT) imaging of patients with consecutively treated eyes with previously untreated nAMD. Patients were commenced on aflibercept injections in 1 or both eyes from October 1, 2013 to December 31, 2013. Data including age, sex, visual acuity (VA) measured on Early Treatment Diabetic Retinopathy Study charts, injection episodes, and complications were recorded. Additionally, SDOCT data, including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1 and 2, were recorded. RESULTS: Of the 109 eyes of 102 patients treated, data from 94 eyes of 88 patients were available at 2-year follow-up (86% of patients). In the analysis of 2-year outcomes, there were 58 women (65.9%); the mean (± standard deviation) age was 77.5 ± 8 years. Over the 2 years, these eyes received a median of 12 (mean, 11.4 ± 4) injections at a median of 100 (mean, 99.3 ± 5.3) weeks of follow-up. The mean VA changed from 55.9 ± 15 letters at baseline to 61.3 ± 16.9 letters (VA gain 5.4 letters) at 1 year and to 61 ± 17.1 letters (VA gain 5.1 ± 14.9 letters) at 2 years. The reduction in CSMT was 79 µm with absence of macular fluid in 72.7% of the 88 eyes with SDOCT data available at 2-year follow-up. CONCLUSIONS: The VA and SDOCT results compare favorably with outcomes seen in randomized controlled trials. The results suggest that good long-term outcomes can be achieved using aflibercept for nAMD in clinical settings.

Posterior Segment Distortion in Ultra-Widefield Imaging Compared to Conventional Modalities.

BACKGROUND AND OBJECTIVES: To describe posterior segment distortions in Optos ultra-widefield images (Optos 200TX; Optos, Dunfermline, United Kingdom) compared to Topcon retinal camera images (Topcon, Tokyo, Japan) using optic disc dimensions and exploring a proposed method for correcting these distortions. PATIENTS AND METHODS: Comparative image analysis study on 20 eyes with color fundus images from Optos and Topcon. A model eye with vertical and horizontal grids imaged with Optos in the conventional position and rotated 90° was analyzed. RESULTS: Mean vertical-to-horizontal disc diameter ratios were 0.956 [95% CI, 0.919-0.993] for Optos and 1.083 [95% CI, 1.045-1.121] for Topcon (P < .001). This was 0.910 in the conventional position and 1.072 with the object rotated 90° for the model eye with Optos and 1.008 and 0.999, respectively, using Topcon. The average of the measurements taken using both images from Optos yielded a ratio of 0.987. CONCLUSION: Optos incorporates a consistent horizontal stretch to images. Combining images taken at right angles reduces the distortion. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:644-651.].

X-Linked retinoschisis associated to a novel intragenic microdeletion: case report.

BACKGROUND: X-linked retinoschisis is a recessively inherited retinal degeneration. Clinical diagnosis can be challenging due to the highly variable phenotypic presentation. Also, clinical diagnostic tests may be normal at early stages of this condition. Therefore, genetic diagnosis has become a priceless tool in the management of this disease. CASE PRESENTATION: We present a case of a 17-year-old caucasian male with foveal and peripheral schisis, along with Mizuo-Nakamura phenomenon. RS1 sequencing led to the discovery of an in-frame deletion not previously described in the literature. CONCLUSIONS: Genetic deletions causative of X-linked retinoschisis are quite rare, since more than 80 % are caused by misssense mutations. In this particular case, its pathological effect comes from affecting a key element of the retinoschisin, the discoidin domain.

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.