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Objective: To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD)., Methods: Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated., Results: A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST) are considered, 90% will be eligible for interval extension., Conclusion: Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Importance: Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials., Objective: To analyze the association between pegcetacoplan and consensus GA SD-OCT end points., Design, Setting, and Participants: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023., Interventions: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month., Main Outcomes and Measures: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal)., Results: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month., Conclusions and Relevance: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors., Trial Registration: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

Purpose : To discuss the pathophysiology of metamorphopsia, its characterisation using retinal imaging and methods of assessment of patient symptoms and visual function. Methods : A literature search of electronic databases was performed Results : Metamorphopsia has commonly been associated with vitreomacular interface disorders (such as epiretinal membrane) and has also regularly been noted in diseases of the retina and choroid, particularly age-related macular degeneration and central serous chorioretinopathy. Developments in optical coherence tomography retinal imaging have enabled improved imaging of the foveal microstructure and have led to the localisation of the pathophysiology of metamorphopsia within the retinal layers of the macula. Alteration of alignment of inner and outer retinal layers at various retinal loci has been identified using multimodal imaging in patients with metamorphopsia in a range of conditions. Although the Amsler Grid assessment of metamorphopsia is a useful clinical indicator, new emerging methods of metamorphopsia assessment with psychophysical tests such as M-CHARTS and preferential hyperacuity perimetry, have been developed. Conclusions : It appears that there is a complex relationship between visual acuity and metamorphopsia symptoms that vary between retinal conditions. Although metamorphopsia has traditionally been challenging to measure in the clinic, advances in technology promise more robust, easy-to-use tests. It is possible that home assessment of metamorphopsia, particularly in conditions such as age-related macular degeneration, may help to guide the need for further clinic evaluation and consideration of treatment.

Purpose: To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti-vascular endothelial growth factor (VEGF) therapy., Design: Retrospective cohort study., Participants: Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy., Methods: Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed., Main Outcome Measures: Correlation coefficients (R 2 values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline)., Results: Visual acuity at distant time points could be predicted: R 2  = 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and R 2  = 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P < 0.001 for both), respectively. Best performing models included both baseline qOCT parameters and treatment response. Furthermore, we present proof-of-principle evidence that the incremental change in VA from an injection can be predicted: R 2  = 0.14 (MAE, 5.6 ETDRS letters) for injection 2 and R 2  = 0.11 (MAE, 5.0 ETDRS letters) for injection 3 (P < 0.001 for both)., Conclusions: Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

One-in-four ophthalmology trials are single-armed, which poses challenges to their interpretation. We demonstrate how real-world cohorts used as external/synthetic control arms can contextualize such trials. We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week 54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n = 65) was taken from the ABC randomized controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from electronic health records and synthetic control arms were created by emulating randomization conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 Early Treatment Diabetic Retinopathy (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to -15 ETDRS letters by week 54. The findings suggest off-label bevacizumab to be neither inferior nor superior to licensed aflibercept. Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed trials when analyzed in accord to the target trial framework. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? One-in-four randomized controlled trials in ophthalmology are single-armed, which poses challenges for interpreting their efficacy relative to standard of care. Recent conceptual advances in the methods of causal inference and in the emulation of target trials suggests that the standard-of-care arms representing the counterfactual intervention can be approximated with observational data. WHAT QUESTION DID THIS STUDY ADDRESS? How real-world cohorts representing the counterfactual intervention can aid the interpretation of single-armed ophthalmological trials. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our study highlights how real-world cohorts representing the counterfactual intervention could aid the interpretation of single-armed ophthalmological trials when undertaken in accord with the target trial framework. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? External counterfactual arms could reduce the time and cost to reach potential regulatory approval., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

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) mm 3 . 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) mm 3 (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.

Background/aims: Neovascular age-related macular degeneration (nAMD) is frequently bilateral, and previous reports on 'fellow eyes' have assumed sequential treatment after a period of treatment of the first eye only. The aim of our study was to analyse baseline characteristics and visual acuity (VA) outcomes of fellow eye involvement with nAMD, specifically differentiating between sequential and non-sequential (due to macular scarring in the first eye) antivascular endothelial growth factor treatment and timelines for fellow eye involvement., Methods: Retrospective, electronic medical record database study of the Moorfields AMD database of 6265 patients/120 286 single entries with data extracted between 21 October 2008 and 9 August 2018. The data set for analysis consisted of 1180 sequential, 807 non-sequential and 3410 unilateral eyes., Results: Mean VA (ETDRS letters±SD) of sequentially treated fellow eyes at baseline was significantly higher (63±13), VA gain over 2 years lower (0.37±14) and proportion of eyes with good VA (≥70 letters) higher (46%) than the respective first eyes (baseline VA 54±16, VA gain at 2 years 5.6±15, percentage of eyes with good VA 39%). Non-sequential fellow eyes showed baseline characteristics and VA outcomes similar to first eyes. Fellow eye involvement rate was 32% at 2 years, and median time interval to fellow eye involvement was 71 (IQR: 27-147) weeks., Conclusion: This report shows that sequentially treated nAMD fellow eyes have better baseline and final VA than non-sequentially treated eyes after 2 years of treatment. Sequentially treated eyes also had a greater proportion with good VA after 2 years., Competing Interests: Competing interests: KF has received fellowship support from Alfred Vogt Stipendium and Schweizerischer Fonds zur Verhütung und Bekämpfung der Blindheit. She has been an external consultant for DeepMind. SW is an academic clinical fellow funded by the National Institute of Health Research (NIHR). PAK has received speaker fees from Heidelberg Engineering, Topcon, Carl Zeiss Meditec, Haag-Streit, Allergan, Novartis and Bayer. He has served on advisory boards for Novartis and Bayer and has been an external consultant for DeepMind and Optos. PAK is supported by a UK NIHR Clinician Scientist Award (NIHR-CS-2014-12-023). RC received studentship support from the College of Optometrists and is a paid intern at DeepMind. PJP has received speaker fees from Novartis UK, Bayer UK and Roche UK and has received an advisory board honorarium from Novartis UK and Bayer UK. AYL has received research funding from Novartis, NVIDIA and Microsoft Corporation. He is supported by the National Institutes of Health (K23EY029246) and Research to Prevent Blindness., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To present the routine use of OCT and OCT angiography (OCTA) for the objective diagnosis and monitoring of proliferative diabetic retinopathy (PDR)., Design: Retrospective, observational case series., Participants: Patients with diabetic retinopathy imaged using a standardized PDR protocol., Methods: Patients routinely imaged with a standardized PDR protocol between March 2017 and January 2019 were included. This included a 12×9-mm structural OCT volume centered on the macula and a 6×6-mm OCTA scan centered on the optic nerve head obtained using a Topcon swept-source system (DRI OCT-1 Triton, Topcon, Tokyo, Japan). Ultra-widefield fluorescein angiography (FA) was also performed when clinically indicated. The ground truth for each case was determined by merging the findings from biomicroscopy and imaging modalities to generate the maximum level of detection for each finding., Main Outcome Measures: Detection rates of new-onset, regression, and reactivation of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE) using different modalities (biomicroscopy/color photography, structural OCT, B-scan OCTA, en face OCTA). Detection of progression of tractional retinal detachment (TRD)., Results: A total of 383 eyes of 204 patients were evaluated. After excluding patients without PDR or with insufficient image quality, 47 eyes of 35 patients were included. For the detection of new-onset NVD and NVE, structural OCT had the highest detection rate (100%) of all modalities. However, for the detection of regression or reactivation of neovascularization (NV), B-scan OCTA had the highest detection rate (100%). Structural OCT detected regression only in 45.5% of cases, resulting in a low detection rate of reactivation (12.5%). Among 10 eyes with TRD, OCT detected fovea-threatening TRD during follow-up in 7 eyes, resulting in vitrectomy., Conclusions: This study demonstrates the utility of novel multimodal imaging in the daily management of patients with PDR. Posterior pole structural OCT had the best detection rate for NV, and B-scan OCTA showed the most potential for objective monitoring of disease after treatment., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

Objectives: To report the prevalence and severity of metamorphopsia, estimate its impact on vision-related quality of life (VRQoL) and evaluate predictors of VRQoL in patients with vitreomacular traction (VMT)., Patients and Methods: A prospective, cross-sectional multi-centre study in the United Kingdom of 185 patients with VMT, with or without a full thickness macular hole (FTMH). Self-reported metamorphopsia was determined using the metamorphopsia questionnaire. VRQoL was assessed using the Visual Function Questionnaire (VFQ-25). Physicians recorded clinical and ocular characteristics in both eyes including a physician assessment of metamorphopsia. ANOVA and predicted least-squares means were used to estimate the impact of metamorphopsia on VRQoL. Predictors of VRQoL were assessed using ordinary-least-squares regression adjusting for clinically important variables., Results: The prevalence of self-reported metamorphopsia was 69.7% (95% CI 62.6-76.3%) and was higher in eyes with a concomitant FTMH vs. without FTMH (85.4% vs. 64.2%). Physician assessment of metamorphopsia was 53.0% (95% CI: 45.5-60.3%). Comparing eyes with metamorphopsia vs. without metamorphopsia, the VFQ-25 composite score was lower (82.3 vs. 91.4), and mean VA (LogMAR) was worse (0.44 vs. 0.33). The largest difference in VFQ-25 scores was observed for near activities (metamorphopsia: 75.3, No metamorphopsia: 90.2). The adjusted model showed that metamorphopsia severity and age were significantly associated with lower VFQ-25 scores., Conclusion: Metamorphopsia was highly prevalent in patients with VMT and associated with significantly lower VRQoL. Physician assessment of symptoms underestimated the self-reported presence of metamorphopsia. Metamorphopsia severity acts as a predictor of impaired VRQoL, over and above decrements due to reduced vision.

Background: The diagnosis of primary vitreoretinal lymphoma (PVRL) poses significant difficulties; presenting features are non-specific and confirmation usually necessitates invasive vitreoretinal biopsy. Diagnosis is often delayed, resulting in increased morbidity and mortality. Non-invasive imaging modalities such as spectral domain optical coherence tomography (SD-OCT) offer simple and rapid aids to diagnosis. We present characteristic SD-OCT images of patients with biopsy-positive PVRL and propose a number of typical features, which we believe are useful in identifying these lesions at an early stage., Methods: Medical records of all patients attending Moorfields Eye Hospital between April 2010 and April 2016 with biopsy-positive PVRL were reviewed. Pretreatment SD-OCT images were collected for all eyes and were reviewed independently by two researchers for features suggestive of PVRL., Results: Pretreatment SD-OCT images of 32 eyes of 22 patients with biopsy-proven PVRL were reviewed. Observed features included hyper-reflective subretinal infiltrates (17/32), hyper-reflective infiltration in inner retinal layers (6/32), retinal pigment epithelium (RPE) undulation (5/32), clumps of vitreous cells (5/32) and sub-RPE deposits (3/32). Of these, the hyper-reflective subretinal infiltrates have an appearance unique to PVRL, with features not seen in other diseases., Conclusion: We have identified a range of SD-OCT features, which we believe to be consistent with a diagnosis of PVRL. We propose that the observation of hyper-reflective subretinal infiltrates as described is highly suggestive of PVRL. This case series further demonstrates the utility of SD-OCT as a non-invasive and rapid aid to diagnosis, which may improve both visual outcomes and survival of patients with intraocular malignancies such as PVRL., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The cost utility of treatments of age-related macular degeneration (AMD) is commonly assessed using health state transition models defined by levels of visual acuity. However, there is evidence that another measure of visual function, contrast sensitivity, may be better associated with utility than visual acuity. This paper investigates the difference in cost effectiveness resulting from models based on visual acuity and contrast sensitivity using the example of bevacizumab (Avastin) for neovascular AMD. The implications of the choice of outcome on structural uncertainty in the model are investigated., Method: Health state transition Markov models based on levels of visual acuity and contrast sensitivity are used to represent the costs, health utilities and outcomes of the Avastin for choroidal neovascular age-related macular degeneration (ABC) trial. Health states are associated with costs and utilities based on literature values. Treatment outcomes from the ABC trial are used to predict transitions between states in both models. Total costs and quality-adjusted life-years (QALYs) are calculated for a cohort of patients treated over a defined number of model cycles., Results: Over a 5-year time horizon, a contrast sensitivity model predicts a statistically significant (p < 0.05) 25% greater QALY gain than the visual acuity model based on 10,000 Monte Carlo simulations. Bevacizumab is more effective and less costly than the comparator in the contrast sensitivity model and the visual acuity model., Conclusion: There is considerable structural uncertainty associated with the choice of outcome for modelling the cost effectiveness of AMD treatments. Bevacizumab has a higher incremental QALY gain and more favourable incremental cost-effectiveness ratio when cost effectiveness is assessed using contrast sensitivity outcomes compared with using visual acuity outcomes. Previous cost-effectiveness analyses may have underestimated the cost effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapy.

Purpose: To compare the functional and structural effects of ranibizumab versus macular laser therapy in patients with center-involving diabetic macular edema., Design: Prospective, randomized, single-masked clinical trial., Setting: Single center., Study Population: Thirty-three eyes of 33 patients with center-involving diabetic macular edema, with best corrected visual acuity of 55 to 79 Early Treatment Diabetic Retinopathy Study letters at baseline, completing the 48-week study period., Intervention: Subjects were randomized 2:1 to 3 loading doses of ranibizumab then retreatment every 4 weeks as required; or macular laser therapy at baseline, repeated as required every 12 weeks. Exploratory Outcome Measures: Structural imaging studies included greatest linear dimension and area of foveal avascular zone, perifoveal capillary dropout grade, and presence of morphologic features of diabetic macular edema on Spectralis optical coherence tomography (Heidelberg Engineering GmbH, Heidelberg, Germany). Functional measures: Visual acuity, retinal sensitivity in the central 4 and 12 degrees on microperimetry, color contrast sensitivity protan and tritan thresholds, pattern and full-field electroretinogram amplitudes and implicit times, and multifocal electroretinogram amplitude distribution. These were reported at 12, 24, and 48 weeks., Results: Ranibizumab-treated subjects gained 6.0 vs 0.9 letters lost for laser, demonstrated improved tritan and protan color contrast thresholds, and improved retinal sensitivity. Electrophysiologic function also improved after ranibizumab therapy. No safety issues were evident. Better retinal thickness reduction and structural improvement in optical coherence tomography features of diabetic macular edema were seen with ranibizumab therapy than in the laser group. There was no evidence of progressive ischemia with ranibizumab therapy., Conclusions: Ranibizumab therapy in the treatment of diabetic macular edema seems to improve retinal function and structure as demonstrated by this evaluation of different assessment methods., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To investigate the impact of diabetic macular ischemia (DMI) on visual acuity (VA), through the analysis of novel fluorescein angiography (FA) parameters., Methods: Data were retrospectively collected over a 6-month period. DMI severity was graded using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols. Custom software was used to quantify areas of the foveal avascular zone (FAZ), and of capillary nonperfusion over the papillo-macular nerve fiber layer bundle, and temporal macula, and associations tested with VA., Results: A total of 488 patients with type 2 diabetes mellitus and FAs of sufficient quality to allow detailed quantitative analyses were included. ETDRS-DMI SEVerity was graded as: none, 39.7%; questionable, 18.4%; mild, 25.2%; moderate, 11.0%; and severe, 5.6%. Median FAZ areas were 0.19 mm(2) (interquartile range [IQR], 0.13-0.25); 0.25 mm(2) (IQR, 0.18-0.32); 0.27 mm(2) (IQR, 0.19-0.38); 0.32 mm(2) (IQR, 0.25-0.54); and 0.78 mm(2) (IQR, 0.60-1.32), respectively, and were significantly different between all grades (P < 0.002), apart from "questionable" versus "mild" grades. Significant association of VA to FAZ area was observed only in the moderate (β = 0.406, SE = 0.101, P = 0.001) and severe (β = 0.299, SE = 0.108, P = 0.006) subgroups, but not in milder ETDRS-DMI grades. A strong association with VA was observed in cases with papillomacular ischemia (β = 1.123, SE = 0.355, P = 0.005), independent of FAZ size or the presence of macular edema., Conclusions: Diabetic macular ischemia is associated with reduced VA in eyes with moderate to severe ETDRS-DMI grades of ischemia but preserved in milder grades. In addition, we describe the independent association of papillomacular nerve fiber bundle ischemia with reduced VA.

Purpose: To investigate whether the Nidek MP1 microperimeter (NAVIS software Version 1.7; Nidek Technologies, Padua, Italy) can detect functional decline in progressive atrophic macular disease with stable visual acuity., Methods: Nine eyes of nine patients with stable acuity but progressive inherited or age-related atrophic macular disease evident on fundus autofluorescence imaging were reviewed. Each patient underwent 3 consecutive microperimetry tests at baseline, 6 months, and 12 months. Acuity, fixation, and microperimetry tests were performed at each visit. Changes in acuity, fixation stability, and macular sensitivity were analyzed. To detect regional change in retinal sensitivity, the test grid was divided into clusters based on either topographical or functional features. The mean sensitivities within each zone were also compared across the three visits., Results: In this cohort, there was no significant change in visual acuity, fixation stability, and macular sensitivity over 1 year. However, significant decline in mean sensitivity within the central macula and test loci adjacent to dense scotoma was found (P = 0.004 and 0.002, respectively). In contrast, mean sensitivity elsewhere remained stable., Conclusion: The MP1 can detect significant change in regional retinal sensitivity within 12 months in patients with progressive atrophic macular disease and stable acuity. Individualized analysis of regional sensitivity may be a useful method for quantifying microperimetry.

Purpose: To describe the intersession repeatability of visual acuity measures obtained with Early Treatment of Diabetic Retinopathy Study (ETDRS) charts in patients with age-related macular degeneration., Methods: Visual acuity was measured in four sessions over 12 weeks using a standardized protocol with ETDRS charts in 107 nontreated eyes of 107 patients with age-related macular degeneration enrolled in an ongoing clinical trial., Results: Data from 90 patients were included in the analysis. The 95% coefficient of repeatability (CR) was 12 ETDRS letters and ranged from 9 letters for 29 eyes with small to intermediate drusen only to 17 letters for 25 eyes with late AMD (macular scars or geographic atrophy). Ten (11%) eyes had a 5-letter reduction or more in visual acuity at the week 1 visit compared with baseline. Excluding seven eyes with visual acuity measurements potentially affected by measurement-related factors (a change in testing distance between visits) the revised CR was 10 letters for the cohort (n = 83) and 11 letters for the late-AMD subgroup (n = 18)., Conclusions: Intersession ETDRS visual acuity measurements are subject to considerable variability in patients with AMD. The variability may be due to both measurement- and disease-related factors. The variable readings have implications for AMD clinical trial design and for the assessment and treatment of patients with neovascular AMD. Further work is needed to determine both the sources of variability in visual acuity measurements and the optimal change criterion for visual acuity measurements in this important group of patients.

Praveen J Patel,1 Helen Devonport,2 Sobha Sivaprasad,1 Adam H Ross,3 Gavin Walters,4 Richard P Gale,5 Andrew J Lotery,6 Sajjad Mahmood,7 James S Talks,8 Jackie Napier9 1National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 2The Ophthalmology Department, Bradford Royal Infirmary, Bradford, UK; 3The Ophthalmology Department, Bristol Eye Hospital, Bristol, UK; 4Department of Ophthalmology, Harrogate District Hospital, Harrogate, UK; 5The Ophthalmology Department, The York Hospital and Department of Health Sciences, University of York, York, UK; 6Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; 7Manchester Royal Eye Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Newcastle Eye Centre, Royal Victoria Infirmary, Newcastle upon Tyne, UK; 9Medical Affairs, Bayer plc, Reading, Berkshire, UK Abstract: National recommendations on continued administration of aflibercept solution for injection after the first year of treatment for neovascular age-related macular degeneration (nAMD) have been developed by an expert panel of UK retina specialists, based on clinician experience and treatment outcomes seen in year 2. The 2017 update reiterates that the treatment goal is to maintain or improve the macular structural and functional gains achieved in year 1 while attempting to reduce or minimize the treatment burden, recognizing the need for ongoing treatment. At the end of year 1 (ie, the decision visit at month 11), two treatment options should be considered: do not extend the treatment interval and maintain fixed 8-weekly dosing, or extend the treatment interval using a treat-and-extend regimen up to a maximum 12 weeks. Criteria for considering not extending the treatment interval are persistent macular fluid with stable vision, recurrent fluid, decrease in vision in the presence of fluid, macular hemorrhage, new choroidal neovascularization or any other sign(s) of exudative disease activity considered vision threatening in the opinion of the treating clinician. Treatment extension is recommended for eyes with a dry macula (ie, without macular fluid) and stable vision. Under both options, the treatment interval may be shortened if visual and/or anatomic outcomes deteriorate. Monitoring without treatment may be considered for eyes with a fluid-free macula for a minimum duration of 48 weeks. A patient completing one full year of monitoring without requiring injections may be considered for discharge from clinic. The treatment algorithm incorporates return to fixed 8-weekly dosing for disease reactivation during treatment extension and reinstatement of treatment for disease recurrence following discontinuation or discharge. For bilateral nAMD, either the eye requiring the more intensive treatment or the eye with the better vision, guided by local clinical practice, should determine the retreatment schedule overall. Keywords: anti-vascular endothelial growth factor, maintenance therapy, treatment algorithm, treat-and-extend, visual acuity