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To compare the visual outcomes and rates of intraoperative complications, in eyes that underwent combined cataract extraction (CE) and pars plana vitrectomy (PPV) (combined group) to those that underwent sequential surgery (sequential group).Multicenter study.A retrospective chart review.CE dataset pooled from 8 UK sites between 2000 and 2015. The main outcome measures were the mean postoperative visual acuity (VA) and the rate of intraoperative complications in both groups.The study included 2236 eyes in the combined group and 2270 eyes in the sequential group. Mean preoperative VA was 1.0 logMAR in both groups. The mean logMAR postoperative VA was worse in the combined group than in the sequential group (P0.0001) at all time points, however, the differences in visual improvement between both groups decreased with longer follow-up time; 1.0±0.7 vs. 0.6±0.6, 0.7±0.6 vs. 0.4±0.5 and 0.7±0.6 vs. 0.5±0.5 at 0-4 weeks, 4-12 weeks and 12-24 weeks, respectively. Proportions of eyes that gained3 logMAR units were 49% in the combined group and 66.2% in the sequential group (P0.0001). Logistic regression analysis showed that sequential surgery (OR = 2.1) was a predictor for reaching 20/40 vision by 6 months. In the combined group, there was a statistically significantly higher rate of posterior capsular rupture.Postoperative visual gain was less in the combined group with a higher rate of posterior capsular rupture as compared to sequential phacovitrectomy. However, we observed small differences in visual improvements between both groups by the 6-month.

Objective Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. Methods After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. Results A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: −202 µm vs. −145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. Conclusion In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Background The primary aim was to investigate outcome of the decision making on duration of injection intervals between injection visits over the first 2 years of a treat and extend regimen. Method Consecutive patients receiving Aflibercept for treatment naive neovascular age-related macular degeneration between 01.01.2016 and 15.07.2017 were identified from our departmental register. Retrospective data collected on all visits over 24 months were classified into three groups: (A) Without Interval Decision Events (IDE)" Injection only" (B) IDE resulting in injection intervals of 5 weeks. The primary outcome was number of successful IDE relative to the total visits in Group C. Successful decision making was defined as absence of worsening of visual acuity (>5 L) or central retinal thickness (>50 microns) at the subsequent visit. Secondary visual and anatomical outcomes at 24 months were also evaluated. Results Data from 56 eyes of 50 patients were included in the study. Visual acuity improved by +7.11 L at 24 months. Forty one patients with unilateral therapy made 721 visits: 280 visits (38.8%) were group A; 164 visits (22.8%) were group B and 277 visits (38.4%) were group C. Average interval in Group C was 8.9 weeks (range 5-15). The success rate of extension was 95.31% (264/277 visits). Conclusion These metrics for evaluating the decision making aspect of disease activity monitoring may be useful for monitoring performance and have given us a more realistic view and expectations of what can be achieved using this regime to optimise the timing of injections.

Background We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion. Methods We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually. Results Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection. Conclusions Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.

Background Neovascular age-related macular degeneration (nAMD) presents a significant treatment burden for patients, carers and medical retina services. However, significant debate remains regarding how best to manage nAMD when assessing disease activity by optical coherence tomography (OCT), and particularly the significance of different types of fluid and how the understanding of anatomical efficacy can influence treatment strategies. This article provides opinion on the practical implications of anatomical efficacy and significance of fluid in the management of nAMD and proposes recommendations for healthcare professionals (HCPs) to improve understanding and promote best practice to achieve disease control. Methods An evidence-based review was performed and an expert panel debate from the Retina Outcomes Group (ROG), a forum of retinal specialists, provided insights and recommendations on the definition, role and practical implications of anatomical efficacy and the significance of fluid at the macula in the management of nAMD. Results The ROG has developed recommendations for achieving disease control through a zero-tolerance approach to the presence of fluid in nAMD as patients who avoid fluctuations in fluid at the macula have better visual outcomes. Recommendations cover five key areas: service protocol, training, regimen, multidisciplinary teams and engagement. This approach facilitates more standardised protocol-based treatment strategies. Conclusions Targeting a fluid-free macula and aiming for disease control are essential to improve outcomes. As new therapies and technologies become available, drying the macula and maintaining disease control will become even more achievable. The outlined recommendations aim to promote best practice among HCPs and medical retina services to improve patient outcomes.

An aging population leads to increasing demand for medical retina services with chronic diseases being managed in long-term care pathways. Many hospital services struggle to deliver efficient and effective MR care due, at least in part, to infrastructure that does not expand responsively enough to meet the increased demand. A steering committee of retinal specialists from a variety of UK NHS hospital ophthalmology departments with experience of leading and managing NHS retinal services in the intravitreal era came together for the generation of this document to review and compile key aspects that should be considered when optimising intravitreal treatment capacity within MR services. This article aims to provide a useful collation and signposting of key published evidence, consensus and insights on aspects of delivering an intravitreal service, including treatment regimens, virtual clinics, staff training and governance, telemedicine and information technology, and data collection and key performance indicators. The objective is to equip ophthalmologic healthcare professionals with the necessary tools to develop and adapt their local service in the face of current and projected increased demand.

Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER.After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12.A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm.In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

We describe a patient who developed acute bilateral corneal decompensation following COVID-19 pneumonia and prolonged intensive care unit ventilation. SARS-CoV-2 uses human ACE2 as the receptor for entry with subsequent downregulation of ACE2. ACE2 receptors are found in human ocular surface cells including cornea. Mouse models of ACE2 deficiency result in corneal haze, oedema and ocular surface inflammation due to upregulation of the inflammatory cascades. We therefore hypothesise that the cause of this patient’s corneal decompensation was viral endotheliitis due to direct infection by the SARS-CoV-2 virus.

LUMINOUS study confirms the effectiveness of ranibizumab for the treatment of neovascular age-related macular degeneration in real-world clinical practice. Visual acuity gains were higher among patients receiving a greater number of ranibizumab injections, particularly with three loading doses and lower BLVA levels. No new safety signals with ranibizumab were identified. Supplemental Digital Content is Available in the Text., Purpose: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in treatment-naive patients with neovascular age-related macular degeneration enrolled in LUMINOUS study. Methods: This 5-year, prospective, multicenter, observational study recruited 30,138 adult patients (treatment-naive or previously treated with ranibizumab or other ocular treatments) who were treated according to the local ranibizumab label. Results: Six thousand two hundred and forty-one treatment-naive neovascular age-related macular degeneration patients were recruited. Baseline (BL) demographics were, mean (SD) age 75.0 (10.2) years, 54.9% females, and 66.5% Caucasian. The mean (SD) visual acuity (VA; letters) gain at 1 year was 3.1 (16.51) (n = 3,379; BLVA, 51.9 letters [Snellen: 20/92]) with a mean (SD) of 5.0 (2.7) injections and 8.8 (3.3) monitoring visits. Presented by injection frequencies 6 (n = 918), visual acuity gains were 1.6 (14.93), 3.3 (16.57), and 3.7 (17.21) letters, respectively. Stratified by BLVA

PURPOSE To compare the visual outcome and the rate of intraoperative complications in eyes with and without retinal vein occlusion (RVO) underwenting phacoemulsification over a period of 15 years in a real-world clinical setting. SETTING Eight independent United Kingdom National Health Service ophthalmology departments. DESIGN Retrospective, multicenter cohort study. METHODS Eyes were classified based on the presence or absence of RVO. For the visual acuity (VA) analysis and the incidence of postoperative cystoid macular edema (CME), eyes with any co-pathology, combined ocular surgical procedures, intraoperative complications, or diabetes were excluded. RESULTS Of 178,856 eyes, 1,796 eyes with RVO preoperatively and 177,060 eyes without RVO were allocated to the RVO group and reference group, respectively. Cataract surgery in eyes with RVO was associated with an improvement in mean VA of 0.35 LogMAR (3-4 Snellen lines) and a substantial gain (≥ 0.30 LogMAR units [3-Snellen lines]) in 55.10 % at the 4-12 weeks postoperatively. Mean postoperative VA was worse in eyes with RVO compared to eyes without RVO at 4-12 weeks (logMAR 0.40 vs. 0.12 [20/50 vs. 20/25]; p

Background Licensed ranibizumab (0.5 mg/0.05 ml Lucentis®; Novartis International AG, Basel, Switzerland) and aflibercept (2 mg/0.05 ml Eylea®; Bayer AG, Leverkusen, Germany) and unlicensed bevacizumab (1.25 mg/0.05 ml Avastin®; F. Hoffmann-La Roche AG, Basel, Switzerland) are used to treat macula oedema due to central retinal vein occlusion, but their relative clinical effectiveness, cost-effectiveness and impact on the UK NHS and Personal Social Services have never been directly compared over the typical disease treatment period. Objective The objective was to compare the clinical effectiveness and cost-effectiveness of three intravitreal antivascular endothelial growth factor agents for the management of macula oedema due to central retinal vein occlusion. Design This was a three-arm, double-masked, randomised controlled non-inferiority trial. Setting The trial was set in 44 UK NHS ophthalmology departments, between 2014 and 2018. Participants A total of 463 patients with visual impairment due to macula oedema secondary to central retinal vein occlusion were included in the trial. Interventions The participants were treated with repeated intravitreal injections of ranibizumab (n = 155), aflibercept (n = 154) or bevacizumab (n = 154). Main outcome measures The primary outcome was an increase in the best corrected visual acuity letter score from baseline to 100 weeks in the trial eye. The null hypothesis that aflibercept and bevacizumab are each inferior to ranibizumab was tested with a non-inferiority margin of –5 visual acuity letters over 100 weeks. Secondary outcomes included additional visual acuity, and imaging outcomes, Visual Function Questionnaire-25, EuroQol-5 Dimensions with and without a vision bolt-on, and drug side effects. Cost-effectiveness was estimated using treatment costs and Visual Function Questionnaire-Utility Index to measure quality-adjusted life-years. Results The adjusted mean changes at 100 weeks in the best corrected visual acuity letter scores were as follows – ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). Aflibercept was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval –2.17 to 6.63 letters; p = 0.0006), but not superior. The study was unable to demonstrate that bevacizumab was non-inferior to ranibizumab in the intention-to-treat population (adjusted mean best corrected visual acuity difference –1.73 letters, 95% confidence interval –6.12 to 2.67 letters; p = 0.071). A post hoc analysis was unable to demonstrate that bevacizumab was non-inferior to aflibercept in the intention-to-treat population (adjusted mean best corrected visual acuity difference was –3.96 letters, 95% confidence interval –8.34 to 0.42 letters; p = 0.32). All per-protocol population results were the same. Fewer injections were required with aflibercept (10.0) than with ranibizumab (11.8) (difference in means –1.8, 95% confidence interval –2.9 to –0.8). A post hoc analysis showed that more bevacizumab than aflibercept injections were required (difference in means 1.6, 95% confidence interval 0.5 to 2.7). There were no new safety concerns. The model- and trial-based cost-effectiveness analyses estimated that bevacizumab was the most cost-effective treatment at a threshold of £20,000–30,000 per quality-adjusted life-year. Limitations The comparison of aflibercept and bevacizumab was a post hoc analysis. Conclusion The study showed aflibercept to be non-inferior to ranibizumab. However, the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out. Bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered. Future work To obtain extensive patient feedback and discuss with all stakeholders future bevacizumab NHS use. Trial registration Current Controlled Trials ISRCTN13623634. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 38. See the NIHR Journals Library website for further project information.

Ageing presents adverse effects on the retina and is the primary risk factor for age‐related macular degeneration (AMD). We report the first RNA‐seq analysis of age‐related transcriptional changes in the human retinal pigment epithelium (RPE), the primary site of AMD pathogenesis. Whole transcriptome sequencing of RPE from human donors ranging in age from 31 to 93 reveals that ageing is associated with increasing transcription of main RPE‐associated visual cycle genes (including LRAT, RPE65, RDH5, RDH10, RDH11; pathway enrichment BH‐adjusted P = 4.6 × 10−6). This positive correlation is replicated in an independent set of 28 donors and a microarray dataset of 50 donors previously published. LRAT expression is positively regulated by retinoid by‐products of the visual cycle (A2E and all‐trans‐retinal) involving modulation by retinoic acid receptor alpha transcription factor. The results substantiate a novel age‐related positive feedback mechanism between accumulation of retinoid by‐products in the RPE and the up‐regulation of visual cycle genes.

To compare visual outcomes, incidence of cystoid macular edema (CME), and rate of repeat epiretinal membrane (ERM) surgery following phacovitrectomy for primary and secondary ERM.Retrospective review of 178,856 cataract surgeries from 2003 to 2015. Eyes that underwent cataract surgery combined with ERM peel were included (n = 708). Eyes were divided into primary (n = 538) and secondary (n = 170) ERM groups. Patient demographics, visual acuity (VA), and postoperative CME were recorded.Patients with secondary ERM had worse preoperative VA, 0.9 ± 0.6 logMAR (20/160 Snellen equivalent) as compared to patients with primary ERM, 0.6 ± 0.3 (20/80), respectively (p 0.0001). There was no difference between the secondary and primary ERM groups in postoperative vision (0.5 ± 0.4 logMAR vs. 0.5 ± 0.3; p = 0.9962) or proportion with VA ≥ 20/40 (46.4% vs. 43.1%; p = 0.6744) at 12-24 weeks. Postoperative CME was twice as likely in the secondary ERM group (16.5%) compared to the primary ERM group (7.8%) (p = 0.0018). There was no difference in the rate of repeat ERM surgery between the secondary ERM group (1.8%) and the primary ERM group (1.5%) (p = 0.7308).Eyes with secondary ERM had significant postoperative improvement in VA. They had worse preoperative VA and had a twofold increase in postoperative CME than primary ERM.

PURPOSE: To compare the visual outcome and the rate of intraoperative complications in eyes of diabetic and non-diabetic patients undergoing phacoemulsification over 15 years DESIGN: Retrospective clinical cohort study METHODS: Data of 179,159 eyes that underwent phacoemulsification at 8 centers were classified based on the presence or absence of diabetes mellitus. Visual acuity (VA) was defined as the best value of uncorrected or corrected distance measure available. For the VA analysis, eyes with co-pathologies, or combined surgical procedures were further excluded, leaving a subset of 90,729 eyes. Main outcome measures were logarithm of the minimum angle of resolution (logMAR) VA at 4-12 weeks postoperatively, and rate of intraoperative complications.RESULTS: Cataract surgery in eyes of diabetic patients was associated with an improvement in mean VA of 0.48 LogMAR (5 Snellen lines). Mean postoperative VA was slightly worse in diabetic compared to non-diabetic group (logMAR 0.23 vs. 0.13; Snellen 20/30 vs. 20/25; p < 0.0001) and the proportions of eyes achieving a visual gain of ≥3 Snellen lines (≥ 0.3 logMAR) was lower in the diabetic group (56.6% vs. 63.5%; p < 0.0001). There was a linear relationship between diabetic retinopathy severity and worse postoperative visual acuity (β coefficient 0.098 to 0.288; p < 0.0001). We observed higher rates of posterior capsule rupture (2.3% vs.1.6%; p CONCLUSIONS: Postoperative VA negatively correlated with diabetes and diabetic retinopathy severity. Eyes of diabetic subjects had higher risks of posterior capsular rupture.

Purpose: To analyze the visual outcomes and rate of intraoperative complications of phacoemulsification surgery after prior pars plana vitrectomy (PPV). Design: Retrospective, multicenter database study. Participants: Eyes that underwent phacoemulsification between June 2005 and March 2015 at 8 sites in the United Kingdom. Methods: Study eyes were classified as vitrectomized (prior PPV group) or nonvitrectomized (reference group) depending on the vitreous state at the time of cataract surgery. Eyes with multiple intraocular surgeries or history of ocular diseases known to cause cataract progression or increased risk of intraoperative complications during phacoemulsification were excluded. Main Outcome Measures: Logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), rate of intraoperative complications, and time interval to cataract surgery. Results: Eyes in the prior PPV group (n = 2221) had worse preoperative logMAR VA (0.96±0.60 vs. 0.62±0.52, P < 0.0001), were from younger patients, and had longer axial lengths than the nonvitrectomized group (n = 136 533). At all postoperative time points measured up to 24 weeks, mean vision was poorer in the prior PPV group (0.41±0.47 vs. 0.17±0.29 at 4–12 weeks, P < 0.0001) and a smaller proportion of eyes achieved postoperative VA ≤0.30 logMAR (Snellen, ≥20/40) (60.8% vs. 86.5% at 4–12 weeks, P < 0.0001). The rate of posterior capsular rupture was not different between the prior PPV (1.5%) and the nonvitrectomized (1.7%) groups, but the incidences of zonular dialysis (1.3% vs. 0.6%) and dropped nuclear fragments (0.6% vs. 0.2%) were higher in the prior PPV group (P < 0.0001). The mean time interval between PPV and cataract surgery was 399 days. Conclusions: We found a significant improvement in VA with postvitrectomy cataract surgery. However, compared with eyes without prior PPV, there was a worse mean postoperative vision of 0.2 logMAR units, a higher rate of zonular dialysis and dropped nuclear fragments, and a similar rate of posterior capsule rupture.

This paper identifies best practice recommendations for managing diabetes and sight-threatening diabetic eye disease. The authors provide an update for ophthalmologists and allied healthcare professionals on key aspects of diabetes management, supported by a review of the pertinent literature, and recommend practice principles for optimal patient management in treating visual impairment due to diabetic eye disease. In people with diabetes, early optimal glycaemic control reduces the long-term risk of both microvascular and macrovascular complications. The authors propose more can and should be done to maximise metabolic control, promote appropriate behavioural modifications and encourage timely treatment intensification when indicated to ameliorate diabetes-related complications. All people with diabetes should be screened for sight-threatening diabetic retinopathy promptly and regularly. It is shown that attitudes towards treatment adherence in diabetic macular oedema appear to mirror patients' views and health behaviours towards the management of their own diabetes. Awareness of diabetic macular oedema remains low among people with diabetes, who need access to education early in their disease about how to manage their diabetes to delay progression and possibly avoid eye-related complications. Ophthalmologists and allied healthcare professionals play a vital role in multidisciplinary diabetes management and establishment of dedicated diabetic macular oedema clinics is proposed. A broader understanding of the role of the diabetes specialist nurse may strengthen the case for comprehensive integrated care in ophthalmic practice. The recommendations are based on round table presentations and discussions held in London, UK, September 2016.

Objectives This paper describes recommendations from a panel of UK retina experts on aflibercept in diabetic macular oedema (DMO). Methods A roundtable meeting was held in London, UK in March 2018. The meeting was sponsored by Bayer. Results Recommendations are based on clinical experience and level 1 evidence. Clinical experience supports the evidence base, reinforcing that aflibercept should be initiated with intensive proactive dosing at 2 mg every 4 weeks. Most panel members use six initial 4-weekly doses as in Protocol T, rather than five initial monthly doses as recommended in the Summary of product characteristics (SmPC). After intensive proactive dosing, patients with a good response (meet Protocol T ‘improvement’ criteria ≥5-letter improvement in visual acuity [VA] and/or ≥10% improvement in central subfield thickness [CST] from baseline) but who are not yet stable should continue with 4-weekly aflibercept until stability is reached. Patients with a good response and stability should initiate monitor-and-extend (not in line with SmPC). Those with a sub-optimal response (meet ‘improvement’ criteria but with additional concerns e.g. fluid worsening on macular volume map) should continue with 4-weekly aflibercept but additional treatments should be considered (aflibercept is not licensed for combination treatment). For patients with no response (no change, or meeting Protocol T ‘worsening’ criteria [≥5-letter decrease in VA and/or ≥ 10% increase in CST] from baseline), switching to a non-anti-vascular endothelial growth factor treatment should be considered. Conclusions Clinical experience reinforces that, when using aflibercept in DMO, the licensed posology or Protocol T regimens achieve the best outcomes.

BACKGROUND/AIMS: Cataract is an important source of visual loss in patients with uveitis. Whether or not outcomes of cataract surgery in eyes with uveitis are worse compared with non-uveitic eyes have to date been compromised by lack of reliable estimates of benefit and harm, which require data from large cohorts.METHODS: Electronic medical record data were extracted from eight independent UK clinical sites for eyes undergoing cataract extraction between January 2010 and December 2014. 1173 eyes with a recorded diagnosis of uveitis were compared with a reference group of 95 573 eyes from the same dataset.RESULTS: Uveitic eyes represented 1.2% of all eyes undergoing cataract surgery. Eyes in the uveitic group had worse preoperative visual acuity (0.87 vs 0.65 logarithm of the minimum angle of resolution (logMAR) units), were from younger patients and had shorter axial lengths and a higher incidence of ocular copathology including glaucoma. A greater number had documented small pupils, required additional surgical procedures, developed more intraoperative complications and had poorer postoperative visual acuity at all time points measured up to 6 months (0.41 vs 0.27 logMAR units at 12-24 weeks).CONCLUSIONS: This large study cohort of eyes with a diagnosis of uveitis undergoing cataract surgery highlights more precisely the complex surgical demands, copathology and worse visual outcomes in this group. These data will allow more accurate preoperative counselling and planning. Although improvement in visual acuity is achieved in most cases, prognosis should be guarded, so that patient expectations are met. Compared with the non-uveitic population, the mean postoperative visual acuity is between one and two lines worse at all time points.

Purpose To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors. Design Retrospective database study of electronic medical records (EMRs). Participants A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites. Methods Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded. Main Outcome Measure Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery. Results Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57–4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45–9.07), uveitis (RR, 2.88; 95% CI, 1.50–5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56–5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60–5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36–2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12–7.58) and rose proportionately with increasing severity of DR. Conclusions Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs.

The retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age‐related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)—known to accumulate on the ageing RPE's underlying Bruch's membrane in situ—on both key lysosomal cathepsins and NF‐κB signalling in RPE. Cathepsin L activity and NF‐κB effector levels decreased significantly following 2‐week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE‐related change of NF‐κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE‐exposed cells had significantly higher ratio of phospho‐p65(Ser536)/total p65 compared to non‐AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE‐related activation of NF‐κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF‐κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para‐inflammatory) mechanism but renders them more responsive to pro‐inflammatory stimuli.

Winfried Amoaku,1 Konstantinos Balaskas,2,3 Tomas Cudrnak,4 Louise Downey,5 Markus Groppe,6 Sajjad Mahmood,7 Hemal Mehta,8 Quresh Mohamed,9 Bushra Mushtaq,10 Philip Severn,11 Athanasios Vardarinos,12 Yit Yang,13 Saad Younis14 1Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK; 2NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and University College of London Institute of Ophthalmology, London, UK; 3University of Manchester, Manchester, UK; 4Royal Eye Infirmary, University Hospitals Plymouth NHS Trust, Plymouth, UK; 5Hull and East Yorkshire Eye Hospital, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK; 6Ophthalmology, Stoke Mandeville, Buckinghamshire Healthcare NHS Trust, Aylesbury, UK; 7Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 8Royal Free London NHS Foundation Trust, London, UK; 9Gloucestershire Eye Unit, Cheltenham General Hospital, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK; 10Birmingham and Midland Eye Centre, Sandwell and West Birmingham NHS Trust, Birmingham, UK; 11South Tees Hospitals NHS Foundation Trust, Middlesbrough, UK; 12Eye Treatment Centre, West Suffolk Hospital, West Suffolk NHS Foundation Trust, Bury St Edmunds, UK; 13Wolverhampton Eye Infirmary, The Royal Wolverhampton NHS Trust, Wolverhampton, UK; 14Ophthalmology, Western Eye Hospital, Imperial College Healthcare NHS Trust, London, UK Abstract: The treatment of neovascular (wet) age-related macular degeneration (AMD) with ranibizumab is now very well established in terms of efficacy and safety. Recent clinical trials and real-world studies have demonstrated the advantages of a Treat-and-Extend (T&E) regimen, and many hospital departments are now in the process of adopting this new regimen in favor of the pro re nata regimen for initiating and continuing ranibizumab therapy for patients with wet AMD. The comprehensive spectrum of issues related to implementation of the regimen is covered qualitatively in ten didactic topics provided by a group of clinicians with direct experience of this regimen in their department. The topics include definition, new and previously treated eyes, management of high-frequency injections, maximum extensions, discontinuing T&E, bilateral cases, clerical, audit, and patient counseling. This article aims to provide a useful resource for the implementation of the T&E regimen. A quantitative summary of the visual outcomes in key publications is also provided in this article. This article should be a valuable resource for staff training. Keywords: ranibizumab, age-related macular degeneration, nAMD, Treat and Extend, anti-VEGF treatment

Purpose:To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema.Methods:Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the

To compare the clinical effectiveness and safety of 5-monthly fixed dosing vs pro-re-nata (PRN) Ozurdex treatment in patients with refractory diabetic macular oedema (DMO).Prospective, multicentre, randomized active-controlled non-inferiority clinical trial.Participants were 100 patients who attended Medical Retina Clinics for management of centre-involving refractory DMO.Participants were randomized 1 : 1 to either 5-monthly fixed dosing or optical coherence tomography (OCT)-guided PRN regimen of Ozurdex therapy for DMO. Data were collected on best-corrected visual acuity (BCVA), patient-reported outcome measures (PROM), macular thickness and morphology, diabetic retinopathy status, number of injections and adverse events from baseline for a period of 12 months.Main outcome measuresThe primary outcome was the difference between arms in change in BCVA from baseline to 12 months. The prespecified non-inferiority margin was five ETDRS letters. Key secondary outcomes included change in PROM scores, change in macular thickness, change in retinopathy and macular morphology, and safety profile.The mean change in BCVA was +1.48 (SD 14.8) in the fixed arm vs -0.17 (SD 13.1) in the PRN arm, with adjusted effect estimate +0.97, 90% confidence interval (-4.01, +5.95), P=0.02 (per protocol analysis). The conclusions of the ITT analysis were primarily supportive, -0.34 (-5.49, 4.81) P=0.07, but sensitive to an alternative assumption on missing data, +0.28 (-4.72, 5.27) P=0.04.The mean change in BCVA with 5-monthly fixed dosing of Ozurdex was non-inferior to OCT-guided PRN Ozurdex therapy for refractory DMO based on a per protocol analysis.

Age-related macular degeneration (AMD) and Alzheimer’s disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case–control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R2 = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele. Electronic supplementary material The online version of this article (doi:10.1007/s00439-015-1552-7) contains supplementary material, which is available to authorized users.

The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients.

Introduction Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study. Methods Two cohorts, those switching from a PRN to a T&E regimen (‘prior PRN’) and those initiating ranibizumab on the T&E regimen as their first anti-VEGF therapy (‘anti-VEGF-naïve’) were enrolled in TERRA. Retrospective clinical assessments were gathered from medical records, while resource use patterns were collected via an operating cost questionnaire completed by each study site. Results At the interim analysis cut-off date (15 November 2016), 11 sites had enrolled 145 patients (prior PRN: n = 110; anti-VEGF-naïve: n = 35). Mean change from baseline (date of first injection) in visual acuity and central subfield retinal thickness to 12 months was +7.6 Early Treatment Diabetic Retinopathy Study letters [95% confidence interval (CI) 2.8, 12.4; p = 0.003; n = 27] and −67.7 μm (95% CI −106.5, −28.9; p = 0.001, n = 29), respectively, in the anti-VEGF-naïve cohort. Most T&E clinics were run as one-stop services (same-day monitoring and injection), whereas 4/10 PRN clinics were run as two-stop services (monitoring and injection on different days). In general, one-stop clinics used less staff resources and were likely to be shorter in duration for healthcare providers than the cumulative time spent for two-stop clinics. Conclusion This is the first real-world observational study conducted in England and Wales demonstrating the effectiveness of the ranibizumab T&E regimen in anti-VEGF-naïve patients. T&E is compatible with one-stop clinic services, which these real-world data suggest to be less resource intensive than two-stop clinic services, possibly providing a dosing regimen beneficial to both patients and resource burden in UK clinical practice. Funding: Novartis Pharmaceuticals UK Limited. Electronic supplementary material The online version of this article (doi:10.1007/s40123-017-0091-9) contains supplementary material, which is available to authorized users.

Jayashree Ramu,1 Irini Chatziralli,1 Yit Yang,2 Geeta Menon,3 Clare Bailey,4 Michael Eckstein,5 Phil Hykin,1 Sobha Sivaprasad1 On behalf of the OZDRY Study Group 1NIHR Moorfields Biomedical Research Centre, London, 2The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, 3Frimley Health NHS Foundation Trust, Surrey, 4Bristol Eye Hospital, Bristol, 5Brighton and Sussex University Hospital, Brighton, UK Purpose: The aim of this study was to explore and describe quantitatively patient-reported outcome measures (PROMs), ie, health-related quality of life (QoL), visual function and treatment satisfaction, in patients with diabetic macular edema (DME) receiving two different regimens of Ozurdex (intravitreal dexamethasone implant). Methods: In this multicenter, prospective study, 100 patients with center-involving refractory DME were randomized 1:1 to either five monthly fixed dosing or optical coherence tomography (OCT)-guided pro re nata (PRN) regimen of dexamethasone intravitreal implant therapy. The primary outcome was the difference between arms in change in PROMs and health-related QoL from baseline to 12months, as measured by the Retinopathy-Dependent Quality of Life (RetDQoL) questionnaire, Visual Function Questionnaire-25 (VFQ-25) and Retinopathy Treatment Satisfaction Questionnaire (RetTSQ). Results: There was no statistically significant difference in the RetDQoL score and VFQ-25 score at month 12 compared to those at baseline, whereas the total mean RetTSQ score increased significantly at the exit visit. The two treatment arms did not differ significantly regarding the change in PROMs and health-related QoL questionnaires. Logistic regression analysis showed that visual acuity (VA) of ≥55 letters, central foveal thickness

As the disease duration increases, the multifactorial nature of diabetic macular edema becomes more prominent, and corticosteroid therapy represents an important treatment option for patients whose disease is multifactorial., Purpose: To report functional and morphologic outcomes, based on diabetic macular edema (DME) chronicity and baseline best-corrected visual acuity (BCVA), from a subanalysis of the fluocinolone acetonide for macular edema (FAME) trials. Methods: Patients were categorized by DME duration (nonchronic [ncDME] or chronic [cDME] DME) and three nonexclusive baseline vision strata. Anatomic and visual acuity VA outcomes of these cohorts were compared with treatment assignment. Results: For all patients with ncDME and cDME who received sham control, 27.8% and 13.4%, respectively, gained ≥15 BCVA letters, whereas 22.3% and 34.0% of 0.2 μg/day fluocinolone acetonide (FAc)-treated patients, respectively, gained ≥15 BCVA letters. Among patients with ncDME who received sham control, as baseline vision decreased, the percentage gaining ≥15 BCVA letters increased; however, among those with cDME, the percentage gaining ≥15 BCVA letters did not change as baseline vision decreased. Conversely, among 0.2 μg/day FAc-treated patients, the percentage gaining ≥15 BCVA letters increased with decreasing baseline vision, regardless of DME chronicity. Anatomical outcomes were similar within treatment arms, regardless of the DME duration. Conclusion: Patients with cDME and poor baseline vision who were exposed to low-dose FAc experienced BCVA improvements that were not observed in a similar group from the sham-control arm. These data support the multifactorial pathogenesis of cDME.

This randomized clinical trial compares the clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs bevacizumab for the management of macular edema secondary to central retinal vein occlusion., Key Points Question Does intravitreal aflibercept or bevacizumab result in a noninferior mean change in vision at 100 weeks compared with ranibizumab for eyes with central retinal vein occlusion–related macular edema? Findings In this randomized clinical trial of 463 individuals with central retinal vein occlusion–related macular edema from 44 UK National Health Service ophthalmology departments, aflibercept treatment was noninferior (no worse than) ranibizumab treatment at 100 weeks and the results for bevacizumab vs ranibizumab were not noninferior (ie, inconclusive compared with the ranibizumab group). Meaning This is important information for ophthalmologists to consider before treating such cases., Importance The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear. Objective To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema. Design, Setting, and Participants This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 μm or greater. Data were analyzed from March 4, 2019, to April 26, 2019. Interventions Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n = 155), aflibercept (2.0 mg/0.05 mL) (n = 154), or bevacizumab (1.25 mg/0.05 mL) (n = 154) for 100 weeks. Main Outcomes and Measures Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above –5 letters. Results Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, 2.23 letters; 95% CI, –2.17 to 6.63 letters; P

Capsular block syndrome (CBS) has been known to occur as a rare complication of cataract surgery with continuous curvilinear capsulorhexis and a posterior-chamber lens implant. Typically, it presents with reduced vision in the early postoperative period and is characterised by a forward displacement of the posterior-chamber intra-ocular lens and an accumulation of intra-capsular opaque material. Management of CBS is usually by Nd:YAG laser capsulotomy. In this report, we describe a unique case of very-delayed-onset CBS with good visual acuity, occurring 8 years after surgery. It was treated successfully with surgical removal of the opaque material.

To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD.Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness350 µm were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 µm (W). Group means were compared between eyes with SMD and eyes without SMD.SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 µm vs 550 µm, p0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011).There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO.

To determine whether a Pro Re Nata (PRN) regimen with three initial mandatory loading doses results in better functional and anatomical outcome compared with a PRN regimen without initial loading when using intravitreal bevacizumab in patients with minimal classic or occult choroidal neovascularisation secondary to age-related macular degeneration.Patients were randomised (1 : 1) to Loading (LD group) or No Loading (NLD group) and treated with open label intravitreal bevacizumab. In the LD group, patients received two mandatory doses after the baseline dose before entering the PRN phase and in the NLD group, patients did not receive mandatory doses after the baseline dose. Six-weekly evaluations were performed up to week 54 and retreatment was done based on OCT criteria. Visual stability and reduction in central retinal thickness were compared between groups.49 patients were in the NLD group and 50 patients were in the LD group. At the 12-month end point, 84% of the patients in the LD group achieved visual stability (15 letter loss) compared with 67% of the patients in the NLD group (P0.05). The mean reduction in central macular thickness was 105.35 μm in the LD group and 81.45 μm in the NLD group (P0.05). There was no significant difference in scores of VFQ-25 questionnaire testing between the two groups and no serious ocular or systemic side effects were observed.The results supported our hypothesis that a loading dose leads to slightly better visual stability in terms of proportions of patients experiencing moderate visual loss, but did not support the hypothesised difference in anatomical outcome.

The structural and functional integrity of the retinal pigment epithelium (RPE) is fundamental for maintaining the function of the neuroretina. These specialized cells form a polarized monolayer that acts as the retinal–blood barrier, separating two distinct environments with highly specialized functions: photoreceptors of the neuroretina at the apical side and Bruch's membrane/highly vascularized choriocapillaris at the basal side. The polarized nature of the RPE is essential for the health of these two regions, not only in nutrient and waste transport but also in the synthesis and directional secretion of proteins required in maintaining retinal homoeostasis and function. Although multiple malfunctions within the RPE cells have been associated with development of age-related macular degeneration (AMD), the leading cause of legal blindness, clear causative processes have not yet been conclusively characterized at the molecular and cellular level. This article focuses on the involvement of directionally secreted RPE proteins in normal functioning of the retina and on the potential association of incorrect RPE protein secretion with development of AMD. Understanding the importance of RPE polarity and the correct secretion of essential structural and regulatory components emerge as critical factors for the development of novel therapeutic strategies targeting AMD.

Purpose: This retrospective review examined visual acuity (VA) in subjects with neovascular age-related macular degeneration and identified early and delayed response to ranibizumab. Procedures: MARINA, ANCHOR, HARBOR, and CATT published data were examined for response with monthly versus individualized dosing and predictors of early versus delayed response. Results: Data were available for 1,631 subjects; 18-29% were early gainers and 15-16% were delayed gainers. Of the early gainers, 72-83% maintained their best-corrected VA gain at month 12 with monthly or individualized dosing. Delayed gainers in HARBOR almost reached the same level of response as early gainers by 12 months who were able to maintain their response. The main predictor of response was baseline VA. Conclusion: There are two distinct types of ranibizumab response; some responded by month 3, while others took up to 12 months. In delayed responders, this may have implications for switching or not switching therapies.

Purpose: To evaluate the use of Snellen and modified Early Treatment Diabetic Retinopathy Study (ETDRS) charts in estimating compliance with the UK Driver and Vehicle Licensing Agency visual acuity standard in patients with neovascular age-related macular degeneration. Methods: Patients with neovascular age-related macular degeneration in at least one eye underwent acuity test using 2m ETDRS chart, 6m Snellen chart and number plate test at 20m. The overlap zones between pass and fail in terms of ETDRS and Snellen charts were analyzed. The levels of descending acuity on the ETDRS chart that corresponded to varying percentages of patients passing or failing the number plate test were analyzed. Results: In total, 26 patients failed the number plate test and 24 patients passed. Fail acuities ranged from 6/36 to 6/6 on Snellen and from 49L to 79L on ETDRS chart. Pass acuities ranged from 6/12 to 6/5 on Snellen and from 67L to 85L on ETDRS chart. The overlap zone of acuities that contained patients who passed and failed was narrower with the ETDRS chart (69L–79L) compared to Snellen ( 6/6-6/12, which is equivalent to 85L-70L on ETDRS chart format). Conclusion: There are overlap zones of acuities in which patient’s presumptive eligibility to drive cannot be reliably estimated. An ETDRS cut-off of 77L provides a reasonable estimate of ability to pass the number plate test. These findings should provide a useful evidence base for advising patients of their compliance with the number plate test based on their logMAR acuity.

To describe the frequency of neovascular age-related macular degeneration (nAMD) in second eyes of patients undergoing ranibizumab therapy in their first eye and to evaluate the patterns of optical coherence tomography (OCT) abnormalities in fellow eyes before nAMD.Patients who developed choroidal neovascularization (CNV) in the second eye while on treatment for the first eye were identified. OCT scans of the second eyes, performed before the onset of CNV, were retrospectively examined and graded. Frequency of second eye involvement was estimated and patterns of progression of OCT abnormalities were described and classified.In all, 65 out of 749 consecutive patients required ranibizumab in their second eye for treatment-naïve nAMD over a 2-year period. The mean interval from commencement of ranibizumab in first eye to conversion in second eye was 12 months (2-35.5 months). There were three patterns of CNV development: group A (12%, n=8) had no OCT abnormalities in the second eye just before developing CNV; group B (38%, n=25) had no abnormalities at baseline but developed OCT changes more than one visit before conversion and group C (50%, n=32) had OCT changes from baseline, which did not progress until just before conversion.Patients with retinal pigment epithelial elevation without sub-retinal fluid on OCT in their fellow eyes have a high risk of progression to require therapy within a 2-year period. An anticipatory approach may be warranted, but a small group with completely normal OCT appearances can still develop lesions between visits.

Importance: Primary epiretinal membrane (ERM) is a common retinal disorder with a prevalence of 4% to 18.5%. Although ERM and cataracts commonly occur together, to our knowledge, no studies have investigated the outcome of cataract surgery alone in this setting.Objective: To analyze the visual outcome and cystoid macular edema risk with cataract surgery in eyes with primary ERM.Design, Setting, and Participants: In this retrospective clinical database study, data were collected from July 2003 to March 2015 from 8 locations in the United Kingdom. Cataract surgery data of 217 557 eyes were extracted from the electronic medical record of the UK National Health Service. After exclusion of 57 561 eyes with combined surgery, prior vitrectomy, copathology, and complications, 812 eyes with primary ERM and 159 184 reference eyes were analyzed.Main Outcomes and Measures: We report on visual acuity (VA), the incidence of cystoid macular edema, and the need for ERM surgery.Results: The mean (SD) age of patients in the ERM group was 73.7 (9.23) years, and 395 of 812 were men (46.8%). The mean (SD) age of patients in the reference group was 74.4 (12.19) years, and 65 265 of 159 184 were men (41%). Epiretinal membrane eyes assessed at 4 to 12 weeks postoperatively gained 0.27 (0.32) logMAR (approximately 3 Snellen lines), with 200 of 448 (44.6%) improving by 0.30 logMAR or more (≥3 Snellen lines) and 32 of 448 (7.1%) worsening by 0.30 logMAR or more. Reference eyes gained a mean (SD) of 0.44 (0.26) logMAR (approximately 4 Snellen lines), with 48 583 of 77 408 (62.8%) improving by 0.30 logMAR or more and 2125 of 77 408 (2.7%) worsening by 0.30 logMAR or more. Although all eyes with preoperative VA of 20/40 or less improved, only reference eyes with preoperative VA of more than 20/40 showed improvement. Cystoid macular edema developed in 57 of 663 ERM eyes (8.6%) (95% CI, 6.69-10.98) and 1731 of 125 435 reference eyes (1.38%) (95% CI, 1.32-1.45) (P Conclusions and Relevance: On average, VA improved 0.27 logMAR (approximately 3 Snellen lines) in eyes with ERM. Eyes with ERM and VA of 20/40 or less showed more benefit after cataract surgery than those with better preoperative vision. However, compared with eyes without ERM, higher rates of cystoid macular edema and a lower postoperative VA gain were noted.

To define the incidence of pseudophakic macular edema (PME) after cataract surgery and to identify contributory risk factors.Retrospective database study of electronic medical records (EMRs).A total of 81984 eyes undergoing cataract surgery between December 2010 and December 2014 from 8 independent United Kingdom clinical sites.Structured clinical data mandated by the EMR were anonymized and extracted for each eye undergoing cataract surgery including: perioperative visual acuity, copathologic features, simultaneous surgical procedures, and the presence or absence of a specified list of intraoperative complications. Diabetic status with matched Early Treatment Diabetic Retinopathy Study (ETDRS) grading also was mandated by the EMR. Eyes receiving prophylactic nonsteroidal anti-inflammatory drugs were excluded.Diagnosis of cystoid macular edema or new-onset macular edema in patients with diabetes, recorded by a healthcare professional within 90 days of surgery.Baseline incidence of PME in eyes without operative complications, diabetes, or risk factors was 1.17%. Eyes in which PME developed were more likely to be male, older, and to demonstrate risk factors. The relative risk (RR) was increased in eyes with capsule rupture with or without vitreous loss (RR, 2.61; 95% confidence interval [CI], 1.57-4.34), a previous diagnosis of epiretinal membrane (RR, 5.60; 95% CI, 3.45-9.07), uveitis (RR, 2.88; 95% CI, 1.50-5.51), retinal vein occlusion (RR, 4.47; 95% CI, 2.56-5.92), or retinal detachment repair (RR, 3.93; 95% CI, 2.60-5.92). High myopia, age-related macular degeneration, or prostaglandin analog use were not shown to increase risk. Eyes with PME on average had poorer postoperative visual acuity, which persisted to the latest time point assessed, up to 24 weeks. Eyes from patients with diabetes, even in the absence of retinopathy, had an increased RR (RR, 1.80; 95% CI, 1.36-2.36) of new macular edema after surgery. The risk was higher in the presence of any diabetic retinopathy (DR; RR, 6.23; 95% CI, 5.12-7.58) and rose proportionately with increasing severity of DR.Pseudophakic macular edema occurs commonly after phacoemulsification cataract surgery, even in the absence of complications and risk factors. This large retrospective study using structured EMR data quantified the RRs of PME and the risk with increasing ETDRS severity of DR. It highlights the need for prophylactic therapy, especially in those groups of eyes with the highest RRs.

Background and purpose Patients are increasingly well informed about the availability of antioxidant products and the claims made for their benefits in age-related macular degeneration (AMD). Consequently, their use is becoming widespread. The purpose of this study is to conduct a survey of the commonly encountered products, and to compare their ingredients with the current Age-Related Eye Disease Study (AREDS) recommendations. Methods A search was undertaken for products sold as ‘eye nutrients’ at local pharmacies and health food shops, and for products advertised via the Internet. Information about these products was collated and analysed. Results We identified 22 eye nutrient products. Analysis of their constituents showed that, although over 75% contained all the constituents used in AREDS, only two matched the dosage profiles recommended in the study. Conclusion The authors draw no conclusion on the efficacy of nutritional supplements in the prevention of AMD. In order to advise their patients, ophthalmologists should be familiar with these products. The compiled list in this paper should provide a useful reference for them.

Wet age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Verteporfin photodynamic therapy (PDT) is significantly effective in preventing visual loss in patients with subfoveal choroidal neovascularization caused by exudative AMD. This article reviews verteporfin PDT and discusses treatment and evolving appraisal guidance.

Posterior microphthalmos is a rare congenital malformation characterized by normal anterior segment dimensions with an abnormally small posterior segment resulting in high hyperopia. Reduced visual acuity in these cases is sometimes caused by the presence of papillomacular retinal folds. We report two cases of posterior microphthalmos in which the papillomacular folds could be visualized on spectral domain optical coherence tomography with sufficient detail to illustrate that only the layers of neural retina within the external limiting membrane were involved.

Purpose: To evaluate the visual outcome of patients with posteriorly dislocated lens fragments after phacoemulsification managed with pars plana vitrectomy (PPV) and identify risk factors for poor visual outcome. Setting: Vitreo-Retinal Service, St. Paul Eye Unit, Liverpool, United Kingdom. Methods: The medical records of all patients who had PPV for posteriorly dislocated lens fragments after phacoemulsification between March 1993 and August 1998 were retrospectively reviewed. Demographics, preexisting eye conditions, details of the previous cataract surgery, findings at presentation, details of the vitreoretinal procedure, final visual acuity, and complications observed during the follow-up were evaluated. Univariate and multiple regression analyses were used to determine the significance of these clinical variables as determinants of poor visual outcome (visual acuity 6/12 or worse). Results: Of the 106 patients identified, 89 had a full set of data and were included in the study. In 79 patients (89%), PPV was performed from 1 to 357 days (median 15 days) after cataract extraction. In 10 patients (11%), PPV was done on the same day as the cataract surgery. Sixty-two patients (69%) had a final visual acuity of 6/12 or better. Preexisting eye disease (P < .01), PPV delayed for more than 4 weeks (P < .03), occurrence of retinal detachment after vitrectomy (P < .01), and the use of ultrasound (US) fragmentation (P < .01) were statistically significantly correlated with a poor visual outcome. Conclusions: Posterior dislocated lens fragments after phacoemulsification were safely retrieved using PPV. It appears that intervening early (within 4 weeks) and avoiding the use of US fragmentation are associated with a better visual outcome and reduced rate of postoperative complications.