Search

PURPOSE: Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and different medications. This study describes the treatment patterns and, importantly, visual outcomes over ten years in a large cohort of patients. DESIGN: Retrospective analysis of electronic health records from 27 National Health Service (NHS) secondary care healthcare providers in the UK. PARTICIPANTS: Treatment-naïve patients receiving at least three intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first six months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 were excluded. METHODS: Eyes with at least three years of follow-up were grouped by years of treatment initiation, and three-year outcomes were compared between the groups. Data were generated during routine clinical care between 09/2008 and 12/2018. MAIN OUTCOME MEASURES: Visual acuity, number of injections, number of visits. RESULTS: A total of 15,810 eyes of 13,705 patients receiving 194,904 injections were included. Visual acuity (VA) improved from baseline during the first year, but dropped thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting visual acuities over the decade. The number of injections dropped substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at three years. CONCLUSION: Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest that these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.

Purpose The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient's evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR. Design Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists). Main Outcome Measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings. Results The new pathway showed sensitivity of 97% (95% confidence interval [CI], 92%–99%) and specificity of 31% (95% CI, 23%–40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images (85% [95% CI, 77%–91%] and 48% [95% CI, 41%–56%], respectively) or UWF images (83% [95% CI, 75%–89%] and 54% [95% CI, 46%–61%], respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images (87% [95% CI, 78%–93%] and 49% [95% CI, 42%–56%], respectively, for UWF versus 80% [95% CI, 69–88%] and 40% [95% CI, 34%–47%], respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1390 per 100 DME visits and between £461 and £1189 per 100 PDR visits. Conclusions The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

The aim of this study is to report on didanosine-associated retinal toxicity (DART) in four adult patients with human immunodeficiency virus (HIV) identified incidentally during routine diabetic eye screening and review all reported cases to date. This study is a retrospective, observational, case series from two health institutions with a review of published literature. DART is often asymptomatic, and patients have good vision (mean visual acuity 6/9), but in advanced cases, severe visual field defects can occur. Fundal changes range from mild granular pigmentary mottling to patches of mid-peripheral chorioretinal atrophy. Continuous expansion of chorioretinal degenerative changes posteriorly may lead to significant macular involvement as demonstrated in two of our cases. Despite cessation of therapy, DART was progressive in approximately 25% of reported cases. Our cases were incidentally discovered during routine diabetic eye screening and did not report any ocular symptoms prior to referral. Given the initial asymptomatic nature of DART, we believe that the true prevalence of the disease may be higher than previously thought. It may be prudent to screen and follow-up patients with a history of DDI use. We demonstrate the utility of multimodal imaging, optical coherence tomography, electrodiagnostic testing and visual fields in evaluating the effects of DART.

Determine clinical-effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT)400μ.Pragmatic, multicenter, allocation-concealed, double-masked, randomized, non-inferiority trial.Adults with400μ center-involved DME and best-corrected visual acuity (BCVA)24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes.Randomisation 1:1 to 577nm SML or SL; retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if10 ETDRS-letter-loss and/or CRT increased400μ.Primary: Mean change in BCVA in the study eye at 24 months (non-inferiority margin 5 ETDRS-letters). Secondary: mean change from baseline to month-24 in binocular BCVA; CRT and mean deviation (MD) of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL (EQ-5D-5L), National Eye Institute-Visual Function Questionnaire (NEI-VFQ25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life year (QALY) gained; adverse effects; number of laser and rescue treatments.DIAMONDS recruited fully (n=266); 87% SML and 86% SL had primary outcome data. Mean BCVA change from baseline to month-24 was -2.43 (Standard Deviation [SD] 8.20) and -0.45 (SD 6.72) in SML and SL, respectively. SML was deemed not only non-inferior but also equivalent to SL as the 95% confidence interval (CI) (-3.9 to -0.04) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS-letters). There was no statistically significant difference in binocular BCVA (0.32 ETDRS letters; 95% CI -0.99, 1.64; p = 0.63), CRT (-0.64 microns; 95% CI -14.25, 12.98; p = 0.93), MD (0.39 dB; 95% CI -0.23, 1.02; p = 0.21), meeting driving standards (% point difference 1.6, 95% CI -25.3, 28.5; p=0.91), adverse effects (Risk Ratio 0.28, 95% CI 0.06, 1.34; p=0.11), rescue treatments (% point difference -2.8, 95% CI -13.1, 7.5; p=0.59) or EQ-5D/VFQ-25/VisQoL scores. Number of laser treatments was higher in SML (0.48; 95% CI 0.18, 0.79; p = 0.002). Base-case analysis indicated no differences in costs or QALYs.SML was equivalent to SL, requiring slightly higher laser treatments.

Background: Diabetic macular oedema (DMO) is effectively treated with ranibizumab but multiple injections are required. Where there is also peripheral ischaemia, it has been promoted that targeted panretinal photocoagulation (PRP) may reduce the number of injections. Method: Patients with optical coherence tomography confirmed DMO and Ultra-widefield Fundus Fluorescein Angiography confirmed peripheral retinal ischaemia were randomised to PRP plus ranibizumab or ranibizumab monotherapy. After three injections, repeat injections were given until the visual acuity was stable and the macula was dry. Re-treatment was given if there was a drop of visual acuity and/or a recurrence of intra-retinal fluid. The primary outcome was the number of repeat injections required after the first 6 months up until 1 year. Results: There were 49 patients, 25 in the ranibizumab only group and 24 in the ranibizumab + PRP group recruited at seven UK sites. The average number of injections in the ranibizumab-only arm was 6.84 over 1 year and 2.52 between months 6 and 12. The average number of injections in the combined arm was 6.67, with the number of injections in the second 6 months 1.92. For the primary outcome, comparing the number of 6- to 12-month injections, the result was not statistically significant (p = 0.33). Conclusion: The addition of targeted PRP to areas of non-perfusion in a patient with DMO does not reduce the number of injections required in the first year. It seems most likely that local VEGF at the macula is the main cause of DMO.

It is a global challenge to provide regular retinal screening for all people with diabetes to detect sight-threatening diabetic retinopathy (STDR).To determine if circulating biomarkers could be used to prioritize people with type 2 diabetes for retinal screening to detect STDR.This cross-sectional study collected data from October 22, 2018, to December 31, 2021. All laboratory staff were masked to the clinical diagnosis, assigned a study cohort, and provided with the database containing the clinical data. This was a multicenter study conducted in parallel in 3 outpatient ophthalmology clinics in the UK and 2 centers in India. Adults 40 years and older were categorized into 4 groups: (1) no history of diabetes, (2) type 2 diabetes of at least 5 years' duration with no evidence of DR, (3) nonproliferative DR with diabetic macular edema (DME), or (4) proliferative DR. STDR comprised groups 3 and 4.Thirteen previously verified biomarkers were measured using enzyme-linked immunosorbent assay.Severity of DR and presence of DME were diagnosed using fundus photographs and optical coherence tomography. Weighted logistic regression and receiver operating characteristic curve analysis (ROC) were performed to identify biomarkers that discriminate STDR from no DR beyond the standard clinical parameters of age, disease duration, ethnicity (in the UK) and hemoglobin A1c.A total of 538 participants (mean [SD] age, 60.8 [9.8] years; 319 men [59.3%]) were recruited into the study. A total of 264 participants (49.1%) were from India (group 1, 54 [20.5%]; group 2, 53 [20.1%]; group 3, 52 [19.7%]; group 4, 105 [39.8%]), and 274 participants (50.9%) were from the UK (group 1, 50 [18.2%]; group 2, 70 [25.5%]; group 3, 55 [20.1%]; group 4, 99 [36.1%]). ROC analysis (no DR vs STDR) showed that in addition to age, disease duration, ethnicity (in the UK) and hemoglobin A1c, inclusion of cystatin C had near-acceptable discrimination power in both countries (area under the receiver operating characteristic curve [AUC], 0.779; 95% CI, 0.700-0.857 in 215 patients in the UK with complete data; AUC, 0.696; 95% CI, 0.602-0.791 in 208 patients in India with complete data).Results of this cross-sectional study suggest that serum cystatin C had good discrimination power in the UK and India. Circulating cystatin-C levels may be considered as a test to identify those who require prioritization for retinal screening for STDR.

ObjectivesTo report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at 1 year.DesignRetrospective clinical audit and simulation model.SettingMultiple UK National Health Service (NHS) ophthalmology centres.ParticipantsData on the reduction in new nAMD referrals were obtained from four NHS Trusts comparing April 2020 with April 2019. To estimate the potential impact on 1-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20 825 nAMD eyes from 27 NHS Trusts.Main outcome measuresSimulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at 1 year under four hypothetical scenarios: 0-month, 3-month, 6-month and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at 1 year nationally.ResultsThe number of nAMD referrals dropped on average by 72% (range 65%–87%). Simulated 1-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2%–17.9%) to 23.3% (20.7%–25.9%), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1%–38.1%) to 26.4% (23.8%–29.2%). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level for 1 month nationally, these simulated results suggest an additional 186–365 eyes with vision ≤6/60 at 1 year.ConclusionsWe report a large decrease in nAMD referrals during the COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at 1 year.

ObjectivesTo report the reduction in new neovascular age-related macular degeneration (nAMD) referrals during the COVID-19 pandemic and estimate the impact of delayed treatment on visual outcomes at one year.DesignRetrospective clinical audit and simulation model.SettingMultiple UK NHS ophthalmology centres.ParticipantsData on the reduction in new nAMD referrals was obtained from four NHS Trusts in England comparing April 2020 to April 2019. To estimate the potential impact on one-year visual outcomes, a stratified bootstrap simulation model was developed drawing on an electronic medical records dataset of 20,825 nAMD eyes from 27 NHS Trusts.Main outcome measuresSimulated mean visual acuity and proportions of eyes with vision ≤6/60, ≤6/24 and ≥6/12 at one year under four hypothetical scenarios: no treatment delay, 3, 6 and 9-month treatment delays. Estimated additional number of eyes with vision ≤6/60 at one year nationally.ResultsThe number of nAMD referrals at four major eye treatment hospital groups based in England dropped on average by 72% (range 65 to 87%) in April 2020 compared to April 2019. Simulated one-year visual outcomes for 1000 nAMD eyes with a 3-month treatment delay suggested an increase in the proportion of eyes with vision ≤6/60 from 15.5% (13.2 to 17.9) to 23.3% (20.7 to25.9), and a decrease in the proportion of eyes with vision ≥6/12 (driving vision) from 35.1% (32.1 to 38.1) to 26.4% (23.8 to29.2). Outcomes worsened incrementally with longer modelled delays. Assuming nAMD referrals are reduced to this level at the national level for only one month, these simulated results suggest an additional 186-365 eyes with vision ≤6/60 at one-year with even a short treatment delay.ConclusionsWe report a large decrease in nAMD referrals during the first month of COVID-19 lockdown and provide an important public health message regarding the risk of delayed treatment. As a conservative estimate, a treatment delay of 3 months could lead to a >50% relative increase in the number of eyes with vision ≤6/60 and 25% relative decrease in the number of eyes with driving vision at one year.

Optical coherence tomography angiography is one of the latest noninvasive imaging modalities for visualizing the vasculature of retina and choroid. We describe its application in the diagnosis, treatment, and monitoring of a patient with peripapillary choroidal neovascular membrane in the setting of idiopathic intracranial hypertension, who responded well to a course of ranibizumab intravitreal injections.

Supplemental material available at www.aaojournal.org.; International audience; PURPOSE: Comparison of the efficacy of ranibizumab (RBZ) 0.5 mg intravitreal injections plus panretinal photocoagulation (PRP) versus PRP alone in the regression of the neovascularization (NV) area in subjects with high-risk proliferative diabetic retinopathy (HR-PDR) over a 12-month period. DESIGN: Prospective, randomized, multicenter, open-label, phase II/III study. PARTICIPANTS: Eighty-seven participants (aged >/=18 years) with type 1/2 diabetes and HR-PDR (mean age, 55.2 years; 37% were female). METHODS: Participants were randomized (1:1) to receive RBZ+PRP (n = 41) or PRP monotherapy (n = 46). The RBZ+PRP group received 3 monthly RBZ injections along with standard PRP. The PRP monotherapy group received standard PRP between day 1 and month 2; thereafter, re-treatments in both groups were at the investigators' discretion. MAIN OUTCOME MEASURES: The primary outcome was regression of NV total, on the disc (NVD) plus elsewhere (NVE), defined as any decrease in the area of NV from the baseline to month 12. Secondary outcomes included best-corrected visual acuity (BCVA) changes from baseline to month 12, time to complete NV regression, recurrence of NV, macular retinal thickness changes from baseline to month 12, need for treatment for diabetic macular edema, need for vitrectomy because of occurrence of vitreous hemorrhage, tractional retinal detachment or other complications of DR, and adverse events (AEs) related to treatments. RESULTS: Seventy-seven participants (88.5%) completed the study. Overall baseline demographics were similar for both groups, except for age. At month 12, 92.7% of participants in the RBZ+PRP group presented NV total reduction versus 70.5% of the PRP monotherapy participants (P = 0.009). The number of participants with NVD and NVE reductions was higher with RBZ+PRP (93.3% and 91.4%, respectively) versus PRP (68.8% and 73.7%, respectively), significant only for NVE (P = 0.048). Complete NV total regression was observed in 43.9% in the RBZ+PRP group versus 25.0% in the PRP monotherapy group (P = 0.066). At month 12, the mean BCVA was 75.2 letters (20/32) in the RBZ+PRP group versus 69.2 letters (20/40) in the PRP monotherapy group (P = 0.104). In the RBZ+PRP group, the mean number of PRP treatments over month 12 was 3.5+/-1.3, whereas in the PRP monotherapy group, it was 4.6+/-1.5 (P = 0.001). No deaths or unexpected AEs were reported. CONCLUSIONS: Treatment with RBZ+PRP was more effective than PRP monotherapy for NV regression in HR-PDR participants over 12 months.

BackgroundIn chronic central serous chorioretinopathy (CSCR), fluid accumulates in the subretinal space. CSCR is a common visually disabling condition that develops in individuals up to 60 years of age, and there is no definitive treatment. Previous research suggests the mineralocorticoid receptor antagonist, eplerenone, is effective for treating CSCR; however, this drug is not licensed for the treatment of patients with CSCR. We aimed to evaluate whether eplerenone was superior to placebo in terms of improving visual acuity in patients with chronic CSCR.MethodsThis randomised, double-blind, parallel-group, multicentre placebo-controlled trial was done at 22 hospitals in the UK. Participants were eligible if they were aged 18–60 years and had had treatment-naive CSCR for 4 months or more. Patients were randomly assigned (1:1) to either the eplerenone or the placebo group by a trial statistician through a password-protected system online. Allocation was stratified by best-corrected visual acuity (BCVA) and hospital. Patients were given either oral eplerenone (25 mg/day for 1 week, increasing to 50 mg/day for up to 12 months) plus usual care or placebo plus usual care for up to 12 months. All participants, care teams, outcome assessors, pharmacists, and members of the trial management group were masked to the treatment allocation. The primary outcome was BCVA, measured as letters read, at 12 months. All outcomes apart from safety were analysed on a modified intention-to-treat basis (participants who withdrew consent without contributing a post-randomisation BCVA measurement were excluded from the primary analysis population and from most secondary analysis populations). The trial is registered with ISRCTN, ISRCTN92746680, and is completed.FindingsBetween Jan 11, 2017, and Feb 22, 2018, we enrolled and randomly assigned 114 patients to receive either eplerenone (n=57) or placebo (n=57). Three participants in the placebo group withdrew consent without contributing a post-randomisation BCVA measurement and were excluded from the primary outcome analysis population. All patients from the eplerenone group and 54 patients from the placebo group were included in the primary outcome. Modelled mean BCVA at 12 months was 79·5 letters (SD 4·5) in the placebo group and 80·4 letters (4·6) in the eplerenone group, with an adjusted estimated mean difference of 1·73 letters (95% CI −1·12 to 4·57; p=0·24) at 12 months. Hyperkalaemia occurred in eight (14%) patients in each group. No serious adverse events were reported in the eplerenone group and three unrelated serious adverse events were reported in the placebo group (myocardial infarction [anticipated], diverticulitis [unanticipated], and metabolic surgery [unanticipated]).InterpretationEplerenone was not superior to placebo for improving BCVA in people with chronic CSCR after 12 months of treatment. Ophthalmologists who currently prescribe eplerenone for CSCR should discontinue this practice.FundingEfficacy and Mechanism Evaluation Programme, and National Institute for Health Research and Social Care.

Background/AimsProspective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity.MethodsSAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed.ResultsOne hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of −30.75 µm (95% CI −59.50,–20.50; pConclusionSwitching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Roles and responsibilities of the Trial Steering Committee (TSC) and Data monitoring and Ethics Committee (DMEC). (PDF 434 kb)

BACKGROUND: We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema.METHODS: CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558.FINDINGS: Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change -9·2 μm [SE 2·5] for the light mask vs -12·9 μm [SE 2·9] for the sham mask; adjusted mean difference -0·65 μm, 95% CI -6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9-51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one).INTERPRETATION: The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication.FUNDING: The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Purpose: The purpose of this study was to evaluate the role of inflammatory/lipid markers and potential risk factors for diabetic retinopathy (DR) development in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Methods: Participants in this study were 1062 patients with newly diagnosed T2DM. Demographic and clinical data of patients were collected. Assessment of DR status was performed using digital two-field photography. In addition, HbA1c (%), lipid profile, and urinary albumin were measured at recruitment. The following inflammatory markers were also measured: serum C-reactive protein, white blood cells, platelet, adiponectin, IL-4, IL-6, IL-10, vascular endothelial growth factor, tumor necrosis factor-a (TNF-a), IL-1b, IL-1 receptor antagonist (IL-1RA), and monocyte chemotactic protein-1. Univariate and multivariate analyses of the association of various potential risk factors and DR were conducted.Results: Univariate analysis showed that male sex, any cardiovascular event, and HbA1c were positively associated with DR, while IL-1RA, IL-1b, IL-6, and TNF-a were significantly negatively associated with presence of DR in the cohort. Risk factors that remained significantly associated with DR presence at the multivariate analysis were male sex, any cardiovascular event, HbA1c, and IL-1RA. Conclusions: Our study demonstrated that HbA1c levels, male sex, and previous cardiovascular events were risk factors for presence of DR in people with newly diagnosed T2DM, while IL-1RA seemed to have a protective role. The prevalence of DR in our population was 20.2%, reflecting current practice. Our findings may contribute to future risk-based modelling of screening for DR.

PURPOSE To describe the anterior chamber migration of a fluocinolone acetonide (Iluvien) implant in the context of previous vitrectomy and complicated cataract surgery. METHODS Retrospective observational case series. Two patients with a history of vitrectomy and complicated phacoemulsification surgery, one of whom had pseudoexfoliation. RESULTS The implant migrated to the anterior chamber shortly after implantation. One patient had the implant removed after one recurrence; the other used pilocarpine 2% eye drops to reduce the risk of further migration. CONCLUSION Complicated cataract surgery and vitrectomy can be associated with migration of fluocinolone acetonide implants into the anterior chamber.

Introduction: The inadvertent intra-ocular administration of benzalkonium chloride-preserved hydroxypropyl methylcellulose during cataract surgery at another hospital in 1999 resulted in toxic corneal endothelial injury and profound postoperative corneal oedema as a result of endothelial decompensation. The long-term effect of this adverse event was assessed. Methods: All 19 patients were invited to return for examination including corneal endothelial specular microscopy and pachymetry seven years after the incident. Results were compared with data from one year after the incident. Results: Five patients attended for examination, one had received a penetrating keratoplasty and was, therefore, excluded. Ten patients had died and four had moved out of the region and were unable to attend. All four study patients were pain free and achieved 6/12 or better. Mean central corneal thickness reduced by 13% from 652.6 μm at one year to 563.4 μm. Mean central corneal endothelial cell density (n = 3) increased 28% from 663.7 cells/mm 2 at one year to 835.7 cells/mm 2 (p Conclusions: After toxic injury, corneal endothelial function may have a remarkable capacity for recovery even after the first postoperative year. The rise in central endothelial cell density may represent cell migration from less affected areas or cellular proliferation. Should this unfortunate event recur, clinicians may expect continued recovery beyond one year.

OBJECTIVE: To report the anatomical and functional results of intravitreal injections of aflibercept (Eylea) (A-IVI) for the treatment of naïve eyes with neovascular age-related macular degeneration (nv-AMD). SUBJECTS AND METHODS: This retrospective, one-center, non-comparative chart review included 26 treatment naïve eyes with nv-AMD of 26 patients (14 male) with a mean age of 80.5 (range 63-91) who had a complete follow-up of 14 months. The morphological analysis included spectral domain optical coherence tomography and fundus fluorescein angiography, while the functional assessment included logarithm of the minimum angle of resolution (LogMAR) best correct visual acuity (BCVA). The timing of the follow-up was: baseline, 3, 6, and 14 months. All patients received 8 A-IVI according to the protocol (first 3 consecutive monthly A-IVI, followed by bi-monthly retreatment for the first year, regardless of disease activity as per local guidelines). Statistical analysis was performed using ANOVA. Improvement of visual acuity more than 15 letters was considered as "improvement", less than 5 letters as "stable" and any letter loss as "worsening". RESULTS: Mean±standard deviation LogMAR visual acuity improved from 0.26±0.15 at presentation to 0.14±0.20 at the final follow-up of 14 months (P=0.02). BCVA was stable in 23.1%, improved in 61.5% (16 eyes) worsened in 15.4%. A mean pretreatment central macular thickness of 409μm reduced significantly to 229μm at month 14 (P

A 36-year-old woman with high myopia had uneventful implantation of a phakic refractive lens (PRL) bilaterally. Two months postoperatively, the best corrected visual acuity (BCVA) in the right eye decreased to the preoperative level and the posterior chamber PRL disappeared from the anterior segment and was found lying in the vitreous cavity inferiorly. After lensectomy and pars plana vitrectomy, the PRL was removed through the initial clear corneal incision, improving the BCVA to 1.0. A zonular defect associated with high myopia, previously forgotten and unrecognized ocular trauma, or intraoperative manipulations may have resulted in the spontaneous dislocation of the PRL.

Objective Superior conjunctival graft is commonly used in pterygium surgery, which may adversely affect the outcome of future filtration surgery. We retrospectively studied the success rate of inferior conjunctival autografting for primary pterygia in our unit. Design A noncomparative, retrospective, interventional case series. Participants Thirty eyes of 27 patients treated between August 1996 and February 2001 with primary pterygia. Intervention Excision of pterygium followed by conjunctival autograft harvested from the inferior bulbar conjunctiva. Surgeries were performed by an experienced surgeon (CL) in 23 patients and by trainees in the remaining four cases. Main outcome measures Recurrence of the pterygium and complications. Results Mean follow-up was 27 months (range, 8–53). Recurrence occurred in one eye (3.3%). This was a white female in her early fifties, with recurrence detected 3 months after the surgery. Conjunctival scarring at the donor site was observed in 11 eyes (36.66%). There was no symblepharon formation. There was no restriction of up gaze. Hemorrhage under the conjunctival graft developed in three eyes, corneal dellen near the limbus developed in four eyes, and epithelial inclusion cysts at the recipient site developed in two eyes. Conclusions Inferior conjunctival autografting is an effective technique with a low recurrence rate. This is a useful technique in cases in which it is not possible or desirable to use the superior conjunctiva as a donor source.

A 66-year-old man developed an unexplained corneal decompensation 7 years after extracapsular cataract extraction and implantation of a single-piece poly(methyl methacrylate) (PMMA) posterior chamber intraocular lens (IOL). He had penetrating keratoplasty (PKP). Two years later, he developed corneal graft failure secondary to an IOL haptic fragment in the anterior chamber angle. The patient had a repeat corneal graft and IOL exchange. The broken haptic was examined with scanning electron microscopy. The findings were consistent with late fracture of the haptic within the capsular bag, which was presumably weakened by an improper implantation technique. Fracture of a PMMA haptic should be suspected as a cause of corneal decompensation and corneal graft failure after cataract surgery. This case emphasizes the importance of safe implantation techniques.

BACKGROUND/AIMS Interlenticular opacification (ILO) is a recognised complication of piggyback intraocular lenses (IOLs). The aetiology, histopathology, and treatment are not clearly defined, however. METHODS Two pairs of AcrySof IOLs were explanted from a patient with bilateral ILO. The explantation technique and surgical challenges of IOL exchanges are described. The explanted IOL complexes and a sample of the anterior capsule were examined by phase, polarising, and immunofluorescence microscopy. RESULTS A 50 year old man developed ILO bilaterally after piggyback AcrySof IOL implantation. A central contact zone was surrounded by a homogeneous paracentral opacity possibly consisting of extracellular matrix previously laid down by proliferating lens epithelial cells (LECs). These opacities were in turn surrounded by interlenticular Elschnig pearl-type opacities contiguous with the same material filling the periphery of the capsular bag. The IOL complexes were very adherent to the capsular bag and they had to be separated with the help of high viscosity viscoelastic before a single one piece PMMA IOL implantation via large limbal incisions. The sample of anterior capsule showed a ridge configuration from the piling of LECs in the site of apposition with the anterior capsule and cells showing different characteristics on either side of the ridge. CONCLUSION Cellular proliferation, deposition of ECM from proliferating LECs, and capsular changes induced by cell metaplasia may lead to ILO formation in piggyback AcrySof IOLs. Careful separation of the AcrySof IOL complex from the capsule, meticulous clean up of the proliferating material, and implantation of single or dual in the bag PMMA IOLs through a large incision with capsulorrhexis enlargement may help in the prevention of recurrence of interface opacification.

Background: The single optical cylinders used in the osteo-odonto-keratoprosthesis (OOKP) are known to produce very small visual fields. Values of 40° are typically quoted. The purpose of this paper is to present designs for new optical cylinders that significantly increase the field of view and therefore improve the visual rehabilitation of patients having an OOKP. Methods: Computer ray-tracing techniques were used to design and analyse improved one- and two-piece optical cylinders made from polymethyl methacrylate. All designs were required to have a potential visual acuity of 6/6 before consideration was given to the visual field and optimising off-axis image quality. Aspheric surfaces were used where this significantly improved off-axis image quality. Results: Single optical cylinders, with increased posterior cylinder (intraocular) diameters, gave an increase in the theoretical visual field of 18% (from 76° to 90°) over current designs. Two-piece designs based on an inverted telephoto principle gave theoretical field angles over 120°. Aspheric surfaces were shown to improve the off-axis image quality while maintaining a potential visual acuity of at least 6/6. This may well increase the measu-red visual field by improving the retinal illuminance off-axis. Conclusions: Results demonstrate that it is possible to significantly increase the theoretical maximum visual field through OOKP optical cylinders. Such designs will improve the visual rehabilitation of patients undergoing this procedure.

To report the anatomical and functional results of intravitreal injections of aflibercept (Eylea) (A-IVI) for the treatment of naïve eyes with neovascular age-related macular degeneration (nv-AMD).This retrospective, one-center, non-comparative chart review included 26 treatment naïve eyes with nv-AMD of 26 patients (14 male) with a mean age of 80.5 (range 63-91) who had a complete follow-up of 14 months. The morphological analysis included spectral domain optical coherence tomography and fundus fluorescein angiography, while the functional assessment included logarithm of the minimum angle of resolution (LogMAR) best correct visual acuity (BCVA). The timing of the follow-up was: baseline, 3, 6, and 14 months. All patients received 8 A-IVI according to the protocol (first 3 consecutive monthly A-IVI, followed by bi-monthly retreatment for the first year, regardless of disease activity as per local guidelines). Statistical analysis was performed using ANOVA. Improvement of visual acuity more than 15 letters was considered as "improvement", less than 5 letters as "stable" and any letter loss as "worsening".Mean±standard deviation LogMAR visual acuity improved from 0.26±0.15 at presentation to 0.14±0.20 at the final follow-up of 14 months (P=0.02). BCVA was stable in 23.1%, improved in 61.5% (16 eyes) worsened in 15.4%. A mean pretreatment central macular thickness of 409μm reduced significantly to 229μm at month 14 (P0.02). The OCT of eyes with worsened BCVA showed resolution of retinal fluid but presence of subretinal fibrosis. No adverse events were attributed to aflibercept.Patients who had a worsening in visual acuity were found to have longer duration of symptoms prior to treatment and presence of geographic atrophy, and/or subretinal haemorrhage and/or subretinal fibrosis at baseline. From our experience, with 14 months follow-up, A-IVI is an effective treatment for treatment naïve patients with nv-AMD. Our real world results were similar to pivotal trials.

To study real world outcomes of ranibizumab (Lucentis) intravitreal injection in diabetic macular oedema (DMO).We included 100 patients with DMO. Those who had optical coherence tomography central retinal thickness (CRT) of 400μm or more (Group 1) underwent combination treatment with ranibizumab and macular LASER, while those with CRT less than 400μm (Group 2) had LASER monotherapy. The primary outcome measure was change in best corrected visual acuity (BCVA) from baseline. Secondary outcomes were change of CRT from baseline, the number of intravitreal injections in group one during the first and second year of follow-up and the proportion of LASER sessions in both groups at 2 years follow-up. Patients' lipid profile was compared to the presence and extent of macular hard exudates, quantified using masked readers and image analysis software.Group 1 showed better outcomes in terms of BCVA and CRT compared to Group 2 during the two-year follow-up period. The mean number of ranibizumab intravitreal injections in Group 1 was reduced from 3.86 (standard deviation±1.37) in the first year to 2.02 in the second year. At 2 years, Group 1 had a higher proportion of individuals that had undergone 3 macular LASER treatments (4% Group 1, 28% Group 2). The presence of hard exudates was associated with higher total cholesterol (P=0.004 and P=0.041 group 1 and 2 respectively) and with higher low density lipoprotein (LDL) cholesterol (P=0.01 and P=0.045 respectively). The size of hard exudates was associated with higher total cholesterol (P=0.02 and P=0.03 respectively) and with higher LDL cholesterol (P=0.003 and P=0.01 respectively). Neither high density lipoprotein (HDL) cholesterol, nor triglycerides were related to the presence or size of hard exudates. No serious adverse events were attributed to either LASER or ranibizumab.Combination treatment of intravitreal ranibizumab injections and macular LASER appears safe and effective over two years. The need for injection declines over time. There is an association between higher levels of serum total and LDL cholesterol and the presence and the extent of hard exudates.

Acute macular neuroretinopathy (AMNR) is a rare disorder characterised by acute onset of unilateral or bilateral visual impairment associated with reddish-brown wedge-shaped outer macular lesions. It is more frequently reported in young females and though the pathophysiology remains unclear, factors reported in association with its onset include post-viral illness and vasoconstrictor use. We report a case of AMNR in an 18-year old female patient presenting with a 2-day history of acute painless blurring of central vision bilaterally, following 1 month of preceding flu-like illness. For 1 week prior to presentation, the patient had taken large doses of oral preparations containing phenylephrine hydrochloride. In addition to demonstrating characteristic optical coherence tomography findings seen in AMNR, we illustrate some rarely seen acute ophthalmoscopic features. Based on associations from this case, we add further insight into the pathophysiology of this condition which remains poorly understood.

A 64-year-old woman with zonular weakness in the left eye and a 79-year-old man with bilateral pseudoexfoliation and intraoperative zonular dehiscence had phacoemulsification with in-the-bag implantation of a single-piece poly(methyl methacrylate) intraocular lens (IOL) and a capsular tension ring. Ten to 12 weeks postoperatively, all 3 eyes developed significant visual loss secondary to capsule shrinkage and occlusion of the capsulorhexis opening. All eyes had a neodymium:YAG laser radial anterior capsulotomy, anterior capsulectomy, or both. Visual acuity was restored in all eyes despite slight IOL decentration.

Aim—To determine the long term visual and refractive results, and stability and complications of primary polypseudophakia using poly(methylmethacrylate) (PMMA) intraocular lenses (IOLs) for cataract surgery in hypermetropic eyes. Methods—Prospective study of 15 short or hypermetropic eyes undergoing phacoemulsification with primary polypseudophakia with two PMMA IOLs implanted within the capsular bag. Results—The spherical equivalent was reduced from a mean +4.87 (SD 3.00) dioptres (D) to ˛0.12 (1.40 D), and the deviation from the intended refraction was +0.005 (1.30) D, 23.6 (12.36) months post-implantation. The deviation from intended refraction was not statistically significant (p = 0.989; paired t test). Postoperative best corrected visual acuity (BCVA) was 6/12 or better in all eyes without macular or optic nerve co-morbidity. Interlenticular opacification (ILO) in the form of peripheral Elschnig pearls was seen in four (26.67%) eyes. A new type of ILO in the form of usually pigmented deposits in the central interface developed in five (33.33%) eyes and resulted in the appearance of Newton’s rings in three. None of the eyes with ILO had any loss of BCVA or hyperopic shift. Six (40%) eyes were within 1 D from the intended refraction and 14 (93.33%) within 2 D. There was no statistically significant diVerence in the accuracy of the two intraocular lens calculation formulas used (SRK II and SRK/T). Conclusion—Peripheral Elschnig pearltype ILO can occur as a late complication of primary in the bag implantation of two PMMA IOLs. A new type of ILO is described. Both types of ILO have not to date resulted in deterioration of visual acuity in our cohort. Use of appropriate biometry techniques and IOL calculation formulas may yield more accurate refractive results. (Br J Ophthalmol 2001;85:1198‐1202)