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In previous landmark studies on central retinal vein occlusion, retinal nonperfusion assessments were obtained using 7-field (7F) angiography. The widespread current use of widefield imaging allows better visualization of the peripheral retina and more comprehensive estimation of the total area of nonperfusion. The relationship between nonperfusion measurement of 7F and widefield angiography (WFA) in central retinal vein occlusion has not been studied. We aim to identify the correlation of retinal nonperfusion measured within the 7F and on WFA in eyes with central retinal vein occlusion.Retinal nonperfusion in participants with central retinal vein occlusion was determined using a 7F Early Treatment Diabetic Retinopathy Study template and the concentric rings method.A total of 153 eyes were included. Pearson correlation test showed a near-perfect positive, linear correlation between the nonperfusion found in the 7F and total retinal nonperfusion on WFA (0.985 95% CI [0.793, 0.999]) The regression line equation for nonperfusion on 7F and WFA was y = 37 + 3.2x. Eyes with 0 disk areas (DA),0 DA to 10 DA and10 DA of nonperfusion on 7-fields had on average 23 DA 95% CI (19.20, 27.06), 45 DA 95% CI (35.75, 55.18), and 115 DA 95% CI (88.89, 142.05) on widefield respectively.There is a positive and linear relationship between nonperfusion measured by 7F and WFA in central retinal vein occlusion with more than 3-times the amount of nonperfusion identified on WFA. Despite10 DA no areas of nonperfusion on 7F, there is typically at least 35 DA of nonperfusion on WFA whereas eyes with10 DA of nonperfusion on 7F had at least 88 DA on WFA.

Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (TE) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start TE was noninferior to late-start TE.A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start TE (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104.Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-TE) and 61.3 (10.8; late-TE) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-TE vs. late-TE; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-TE or late-TE regimen after initial dosing, with one injection difference over 2 years.ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).

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.

Purpose Single center, noninterventional cohort study to assess 10-year visual and anatomical outcomes following initiation of treatment with antivascular endothelial growth factor (anti-VEGF) agents in neovascular age-related macular degeneration (AMD) patients. Neovascular AMD patients initiated on intravitreal anti-VEGF injections in 2008–2009 and continued to be followed up for at least 10 years were included in this study. Methods The Moorfields OpenEyes database was searched for all patients who were initiated on anti-VEGF therapy for neovascular AMD in 2008–2009 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records were analyzed for those who have had at least 10-year follow-up. The spectral-domain optical coherence tomography (SD-OCT) scans, color fundus photos, and fundus fluorescein angiography (FA) were graded by two retinal physicians. The outcomes were also compared between those with good and poor VA outcomes based on pre-defined criteria. The primary end point was change in VA at 10 years; secondary outcomes included percentage with VA of 20/40 or better, 20/70 or better, VA gains and losses, anatomic outcomes and number of injections. Results After a mean of 10.04 years after initiation of anti-VEGF therapy, the mean decline in VA from baseline was −2.1 ETDRS letters (SD 19.9, p = 0.65). One hundred eyes (67.1%) achieved a VA threshold of 20/70 or better, 33.5% achieved a VA of 20/40 or better, and 76.5% eyes maintained VA defined as a loss of less than 15 letters. Fourteen percent of study eyes had VA of 20/200 or worse and 23.5% declined by 15 letters or more. 87.5% of eyes were switched from ranibizumab to aflibercept during the course of 10 years and the eyes received a mean of 52.2 (SD 18.1) injections over 10 years. From this cohort, 87 (58.3%) eyes are having on-going treatment. On OCT, 34.9% had persistent fluid at the last visit, 6.7% patients showed new onset atrophy compared to baseline, and 43.7% had increased area of macular atrophy. The mean area of atrophy at the final visit was 4.15 mm2. Comparison between the good and worse visual outcome groups showed lower baseline VA, fovea-involving atrophy and final area of atrophy had a statistically significant negative effect on the final visual outcome (p

Purpose To evaluate whether baseline demographic, clinical, and OCT characteristics predict visual acuity (VA) outcomes in patients receiving anti–vascular endothelial growth factor (VEGF) therapy for macular edema (ME) due to central retinal vein occlusion (CRVO). Design Post hoc analysis of the randomized noninferiority trial (Lucentis, Eylea, Avastin in CRVO) LEAVO Study from December 12, 2014, to December 16, 2016, carried out across 44 UK National Health Service ophthalmology departments. Participants Data on 267 participants with a baseline best-corrected mean visual acuity (BCVA) range of 19 to 78 Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent, 20/32 to 20/320) who had central subfield thickness (CST) ≥ 320 μm on Spectralis OCT (Heidelberg Engineering) were analyzed. Methods Study participants were randomized to receive repeated intravitreal injections of ranibizumab (0.5 mg/50 μl), aflibercept (2.0 mg/50 μl), or bevacizumab (1.25 mg/50 μl), and a protocol-driven pro re nata re-treatment regimen at 4 to 8 weekly visits was followed up to week 100 after 4 mandated 4-weekly loading injections. Main Outcome Measures Change in BCVA and percentage of patients gaining ≥ 10 letters and achieving BCVA letter score > 70 letters at 52 and 100 weeks. Results The analysis was adjusted for treatment effects and confirmed by sensitivity analysis. Age ≥ 75 years is a poor predictor for all 3 visual outcomes. Lower baseline BCVA predicted 10-letter gainers and higher gains in BCVA, although it is a poor predictor of achieving > 70 Early Treatment Diabetic Retinopathy Study letters. None of the baseline OCT morphologic characteristics except ellipsoid zone (EZ) integrity influenced any visual outcomes. Both baseline CST and total macular volume showed a nonlinear relation to 10-letter gainers, with CST > 900 μm being a poor prognostic indicator. Baseline CST and macular volume did not predict mean change in BCVA or BCVA > 70 letters at 52 and 100 weeks. The sensitivity analysis conclusions after removing iCRVO were similar. Conclusions At presentation, younger age, higher baseline BCVA, and a definitely intact subfoveal EZ are predictors of BCVA score > 70 letters at 100 weeks.

Background/aims To assess structural and functional outcomes of treatment with intravitreal aflibercept (®Eylea) for diabetic macular oedema in treatment-naïve patients. Methods Sixty-four eyes receiving intravitreal anti-vascular endothelial growth factor therapy were included in the data analysis of this retrospective, real-life study which follow-up was 3 years. Each patient had corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters and optical coherence tomography central foveal thickness and macular volume performed at baseline, 12, 24 and 36 months. Patients were initiated on a loading phase of five 1-monthly intravitreal aflibercept injections, followed by injections if needed as per clinicians’ discretion. Results The mean number of aflibercept injections received over 3 years was 12.59. At baseline, the mean visual acuity (standard deviation) (Snellen) was 61.45 (16.30) (20/63) Early Treatment Diabetic Retinopathy Study letters, the mean central foveal thickness (standard deviation) was 422 (138) µm, while the mean macular volume (standard deviation) was 9.51 (2.01) mm3. At 36 months, the mean visual acuity (standard deviation) (Snellen) was 68.34 (13.66) (20/50) Early Treatment Diabetic Retinopathy Study letters (p = .0003). Mean central foveal thickness (standard deviation) was 303 (106) µm (p 3 (p = .0022) at 36 months. Sixteen (25%) eyes gained ≥15 ETDRS letters at month 36, and 33 (52%) eyes had a decrease in central foveal thickness of ≥ 100 µm at the same time. Conclusion There was a significant improvement in visual acuity and in anatomical outcomes in aflibercept-treated eyes at 36 months after commencing treatment for diabetic macular oedema in real-life settings. The good vision and anatomical outcomes were maintained over second and third year of treatment with mean 2.93 and 2.57 intravitreal injections, respectively.

Paracentral acute middle maculopathy (PAMM) refers to band-like hyperreflective lesions seen on spectral-domain optical coherence tomography, mostly confined to the inner nuclear layer. It has been previously demonstrated to involve the deep capillary plexus (DCP) using optical coherence tomography angiography (OCTA). A 29-year-old female presented with PAMM and was investigated using a new OCTA system that shows not just the superficial capillary plexus and DCP, but also the four vascular plexuses as previously demonstrated in histology. Using this system, involvement of the DCP was shown, but also of more superficial layers, including the intermediate capillary plexus. [ Ophthalmic Surg Lasers Imaging Retina . 2018;49:619–624.]

Purpose To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. Design A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. Participants One hundred seventy-eight eligible patients aged ≥18 years. Methods Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Main Outcome Measures Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. Results Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. Conclusions The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12.

PurposeIntraocular vascular endothelial growth factor (VEGF) levels increases with the severity of diabetic retinopathy. Response of diabetic macular oedema (DMO) to ranibizumab is driven by VEGF suppression. We hypothesised that the initial reduction of central macular thickness by ranibizumab should be maximum in severe diabetic retinopathy until the levels of VEGF decreases to the levels observed in eyes with mild retinopathy.MethodsConsecutive patients with centre-involving DMO (central subfield thickness (CSFT)300 μm) who had three consecutive monthly ranibizumab injections followed by as needed therapy were included. Retinopathy status was graded as mild non-proliferative diabetic retinopathy (NPDR) (G1), moderate to severe NPDR with no prior panretinal photocoagulation (G2), and treated PDR (G3).ResultsTwo hundred and thirty-nine eyes from 204 patients with a mean age of 64.9 years were included. The distribution was 31.4 G1, 32.2 G2, and 36.4% G3. Mean baseline CSFT for all eyes was 458.5±110.8 μm. Baseline CSFT for G1, G2, and G3, respectively, were 437.6±90.9, 472.3±109.8, and 464.7±124.9 μm (P=0.2155). Mean change in CSFT after three consecutive injections was 128.5±116.6 μm. The mean changes were 95.8±101.4 μm for G1, 137.2±112.9 μm for G2, and 148.9±126.9 μm for G3. The changes in CSFT between groups adjusted for baseline CSFT were statistically significant (P=0.0473). At 6 and 12 months after a mean of 4.5 and 7.7 injections, the changes between groups were no longer significant, P=0.4783 and P=0.8271, respectively.ConclusionsThe initial anatomical response of DMO with intravitreal ranibizumab injections was maximum in eyes with treated PDR, suggesting that the higher the VEGF levels, the better the response with ranibizumab.

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

Purpose To determine visual acuity (VA) and spectral-domain optical coherence tomography (OCT) outcomes with intravitreal ranibizumab for diabetic macular edema (DME) in a United Kingdom National Health Service clinical setting. Design Retrospective interventional case series. Participants Consecutive patients with DME, treated with the first ranibizumab injection between August 2013 and March 2014 across 4 sites of Moorfields Eye Hospital, London. Methods Two hundred eyes of 164 consecutive patients with center-involving DME and VA ≤79 ETDRS letters, central subfield macular thickness (CST) ≥350 μm on Topcon 3D OCT 2000, initiated on a loading phase of 3 intravitreal ranibizumab injections and who had at least 6 months follow-up were reviewed. Subsequent retreatment was guided by VA and OCT with the aim of treating to stability. VA, OCT CST, and macular volume (MV) were recorded at baseline and monthly to 12 months. Results The mean VA, mean CST, and mean MV at baseline were 54.4 (± 15.26) letters, 490.16 (± 116.54) μm, and 10.46 (± 2.28) mm 3 . The mean VA change at 12 months was +6.6 (± 13.35) letters ( P = .0003). A total of 40.3% of patients (n = 77) gained ≥10 letters and 25.1% (n = 48) gained ≥15 letters; 8.9% (n = 17) lost ≥10 letters and 6.3% (n = 12) lost ≥15 letters. At 12 months, the mean change in CST and MV were −133.9 (± 160.12) μm ( P = .0001) and −1.5 (± 1.96) mm 3 ( P = .0001), respectively. An average of 7.2 (± 2.3) injections were given over 12 months. Conclusions Outcomes with 3 loading injections of 0.5 mg ranibizumab given monthly followed by pro re nata retreatment in a clinical setting are comparable with outcomes from clinical trials.

Roxanne Crosby-Nwaobi, Philip Hykin, Tunde Peto, Sobha Sivaprasad NIHR Clinical Research Facility, NIHRMoorfields Biomedical Research Centre, London, UK Purpose: The aim of this study was to assess the impact of daily oral supplementation with Macushield (10mg/d meso-zeaxanthin, 10mg/d lutein, and 2mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Methods: Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. Results: A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P

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

PURPOSE: To develop a diagnostic algorithm in patients with pathologic myopia who present with typical symptoms or signs of myopic choroidal neovascularisation (mCNV). METHODS: Retrospective study. Patients with high myopia and suspected mCNV underwent fluorescein angiography (FFA), structural spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). Active mCNV on one imaging modality plus clinical features were considered as the benchmark reference for the other two tests. Sensitivity was calculated for each modality individually and in combination. Morphological features were noted on SD-OCT and OCTA. RESULTS: Twenty-seven eyes of 26 patients were analysed. Sensitivity of SD-OCT or FFA alone was 85.19% (23/27 eyes). Sensitivity of OCTA was 74.07% (20/27 eyes). The sensitivity for SD-OCT combined with OCTA was 96.16% and combined with FFA was 97.80%. On OCTA, a “tight net” appearance was seen in 16 eyes (80%); a core vessel was visible in seven eyes (35%), all with active lesions. A “perilesional halo” was visible in 11 eyes (55%) of which 10 had active lesions. CONCLUSION: When combined, OCTA and SD-OCT or SD-OCT and FFA showed similar higher sensitivities than each modality alone. A tight vascular net and the combination of a perilesional halo and a visible core on OCTA may serve as biomarkers of mCNV activity.

Introduction To report 3-year treatment outcomes with intravitreal aflibercept injections for neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods This was a retrospective, single-centre, non-randomized interventional case series analysis. Data from treatment-naïve patients with nAMD treated between 1 October 2013 and 31 February 2014 were included in the analysis. Data including age, gender, vision acuity (VA) measured on Early Treatment of Diabetic Retinopathy Study charts (ETDRS) and injection numbers were recorded. Spectral domain optical coherence tomography (SD-OCT) data including presence or absence of macular fluid and automated central subfield macular thickness (CSMT) at year 1, 2 and 3 were also recorded. Results Of the 157 eyes of 148 patients treated, data from 108 eyes of 102 patients were available at 3-year follow-up. The mean (± SD) age was 80.6 ± 8.3 years with a mean of 154.5 ± 5.4 weeks follow-up. The mean VA changed from 54.4 ± 16 letters at baseline to 60.3 ± 18.1 letters (VA gain 5.9 ± 13.8 letter gain) at 1 year, to 60.8 ± 17.4 letters (VA gain 6.4 ± 14.9 letters) at 2 years and to 61.0 ± 16.6 letters (VA gain 6.6 ± 15.4 letters) at 3 years. The reduction in CSMT was 77.9 ± 101.4 µm with absence of macular fluid in 71% of eyes. The total mean number of injections was 15.9 ± 6.1 at year 3. Conclusion The results suggest that good long-term morphological and functional treatment outcomes can be achieved using aflibercept for nAMD in a clinical setting. Electronic supplementary material The online version of this article (10.1007/s40123-018-0139-5) contains supplementary material, which is available to authorized users.

Background/aims To identify predictive markers for the outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD). Methods AURA was a retrospective, observational, multicentre study that monitored the 2-year outcomes following intravitreal ranibizumab treatment in patients with nAMD. Using stepwise regression analysis, we evaluated the association between visual acuity outcomes, baseline characteristics and resource utilisation in order to determine which variables are significantly linked to outcomes in AURA. We also examined the relationship between visual acuity outcomes and number of injections received. Results Analyses were performed using data from year 1 (n=1695) and year 2 completers (n=1184). Logistic analysis showed that baseline visual acuity score, age at start of therapy, number of ophthalmoscopies and optical coherence tomography (OCT) (combined) and number of injections (ranibizumab) were significant (p7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of

To evaluate the clinical efficacy and safety of combined repeated Ozurdex and macular laser therapy (MLT) compared with MLT monotherapy in participants with visual impairment due to centre-involving diabetic macular oedema (DMO).80 patients with best corrected visual acuity (BCVA) between 54 and 78 ETDRS letters due to centre-involving DMO were randomised to combination therapy with Ozurdex and MLT or MLT only. The combination arm received mandated Ozurdex injections at baseline and 16 weeks followed by retreatment criteria-guided pro-re-nata therapy at 32 and 48 weeks. Patients randomised to MLT only were treated every 16 weeks if clinically significant macular oedema was present. The primary outcome was the mean change from baseline in BCVA between arms at 56 weeks.The mean change in BCVA at 56 weeks was -0.3 (SD 11.4) ETDRS letters in the combination arm versus +0.4 (SD 9.6) ETDRS (Early Treatment Diabetic Retinopathy study) letters in the MLT arm (effect estimate 1.15 (95% CI -3.32 to 5.61)). However, at 56 weeks, a post hoc comparison of central subfield thickness (CST) showed a decrease of -113 μm (IQR -218, -64) (combination) versus -17 μm (-128, 12) (MLT arm) (p0.001). Elevated intraocular pressure requiring topical therapy was observed in 8 (20%) eyes in the combination versus 1 (2.5%) in the MLT arm. 33% (9/27) of phakic patients in the combination arm underwent cataract surgery.Visual outcome following combination therapy did not differ from MLT alone in the centre-involving DMO despite a significant decrease in CST likely due to an entry visual acuity-related ceiling effect and cataract development.EudraCT 2011-003339-74.

Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Background Disorganization of the retinal inner layers (DRIL) on optical coherence tomography (OCT) is thought to represent retinal capillary non-perfusion (CNP) in eyes with diabetic retinopathy. This study was designed to evaluate the ability of DRIL to accurately predict CNP. Design Retrospective masked reliability and diagnostic accuracy study performed in the National Institute for Health Research (NIHR) Moorfields Biomedical Research Centre, London, UK Samples Retinal images of patients with diabetic retinopathy Methods The OCT images from 90 separate areas of angiographically confirmed perfused and non-perfused areas of the macula from 37 eyes of 31 patients were anonymized and coded. Two masked graders independently graded these OCT scans for the presence or absence of DRIL to determine the intergrader reliability. The diagnostic accuracy of DRIL in identifying CNP was evaluated from the results obtained. Main Outcome Measures Sensitivity and specificity of DRIL in accurately detecting CNP Results The intergrader agreement was high with a Cohen's kappa of 0.909. DRIL was present in 84.4% (38/45) of non-perfused retina and none in perfused retina (0/45). The sensitivity and specificity of DRIL in detecting angiographic evidence of CNP was 84.4% and 100%, respectively. The positive predictive value was 100% and the negative predictive value was 86.5%. Conclusions The presence of DRIL is a reliable predictor of areas of macular CNP. However, DRIL is not a universal finding of non-perfusion, with some cases exhibiting absence of DRIL despite angiographic CNP.

In the 12-month MINERVA study, a subgroup of 5 adolescent patients aged 13–17 years received open-label ranibizumab 0.5 mg at baseline, followed by individualized pro re nata regimen based on disease activity, for the treatment of choroidal neovascularization. Visual and anatomical outcomes were improved, and no new safety findings were observed with ranibizumab., Purpose: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adolescent patients with any choroidal neovascularization etiology enrolled in the 12-month MINERVA study. Methods: In the open-label, non-randomized study arm, ranibizumab 0.5 mg was administered to five adolescents (aged 13–17 years). The findings were assessed descriptively as individual case reports at Month 12. Best-corrected visual acuity changes, central subfield thickness, treatment exposure, and safety were described over 12 months. Results: Baseline choroidal neovascularization etiologies of the study eye included choroidal neovascularization secondary to Best disease (n = 2), idiopathic chorioretinopathy (n = 2), and optic disk drusen (n = 1). At Months 2, 6, and 12, the observed mean best-corrected visual acuity changes in the study eye from baseline were +9.2, +16.6, and +16.6 letters, respectively, and the observed mean central subfield thickness change from baseline was −31.4, −87.6, and −116.4 μm, respectively. Adolescent patients received a mean of three (range, 2–5) ranibizumab injections in the study eye. No adverse events or serious adverse events related to ranibizumab were reported. Conclusion: Ranibizumab 0.5 mg treatment was beneficial in improving visual acuity and stabilizing or reducing central subfield thickness in five adolescents with differing choroidal neovascularization etiologies requiring infrequent injection. No new safety findings were observed over 12 months.

To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration.A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study.One hundred seventy-eight eligible patients aged ≥18 years.Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous).Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months.Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab.The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12.

Supplemental Digital Content is Available in the Text. Ranibizumab was effective in treating choroidal neovascularization of various etiologies, with a treatment effect of +9.9 letters versus sham at Month 2 and a mean gain of 11.0 letters from baseline to Month 12. The beneficial effects of ranibizumab were observed across all etiology subgroups., Purpose: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with choroidal neovascularization because of an uncommon cause enrolled in the 12-month MINERVA study. Methods: In this Phase III, double-masked study, adult (≥18 years) patients (N = 178) were randomized 2:1 to receive either ranibizumab (n = 119) or sham (n = 59) at baseline and, if needed, at Month 1 and open-label individualized ranibizumab from Month 2. Best-corrected visual acuity change from baseline to Month 2 (primary endpoint) and Month 12, treatment exposure, and safety over 12 months were reported. Subgroup analysis was conducted on five predefined choroidal neovascularization etiologies (angioid streak, postinflammatory, central serous chorioretinopathy, idiopathic, and miscellaneous). Results: Ranibizumab showed superior efficacy versus sham from baseline to Month 2 (adjusted least-squares mean best-corrected visual acuity: +9.5 vs. −0.4 letters; P < 0.001). At Month 12, the mean best-corrected visual acuity change was +11.0 letters (ranibizumab) and +9.3 letters (sham). Across the 5 subgroups, the treatment effect ranged from +5.0 to +14.6 letters. The mean number of ranibizumab injections was 5.8 (ranibizumab arm) with no new ocular or nonocular adverse events. Conclusion: Ranibizumab 0.5 mg resulted in clinically significant treatment effect versus sham at Month 2. Overall, ranibizumab was effective in treating choroidal neovascularization of various etiologies with no new safety findings.

Contains fulltext : 153434.pdf (Publisher’s version ) (Open Access) BACKGROUND/AIMS: Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. METHODS: Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. RESULTS: 2227 patients who received >/=1 anti-VEGF injection with a baseline visual acuity assessment and >/=1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSIONS: In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. TRIAL REGISTRATION NUMBER: NCT01447043.

Purpose of review Three long-acting corticosteroid implants are now available for the treatment of retinal disease, offering control of macular edema and inflammation for between 6 months and up to 3 years. This review evaluates their efficacy and side-effect profile in comparison with the antivascular endothelial growth factor agent ranibizumab in diabetic macular edema, retinal vein occlusion, pseudophakic macular edema, and uveitis. Recent findings Trials of ranibizumab in diabetic macular edema have demonstrated excellent efficacy without serious safety concerns to date. Fluocinolone acetonide implants can be considered, but have a high risk of cataract and sequelae from intraocular pressure rise. In retinal vein occlusion, both ranibizumab and Ozurdex have been shown to be effective, although their relative efficacy has not been determined in head-to-head clinical trials. In pseudophakic and uveitic macular edema, steroid implants are probably the first choice therapy, although there is evidence that ranibizumab is effective. For choroidal neovascularization secondary to inflammatory disease, ranibizumab is indicated, whereas Retisert has been shown to reduce the risk of uveitis relapse. Summary In diabetic macular edema, ranibizumab has shown greater efficacy with fewer side-effects than steroid implants. Both ranibizumab and steroid implants can be considered in retinal vein occlusion, but trials are awaited to determine their relative efficacy.

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

To assess the efficacy and safety profile of an individualized, stabilization criteria-driven regimen of ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO).A 24-month, prospective, open-label, single-arm, multicenter study.A total of 357 patients.Patients received monthly ranibizumab 0.5 mg injections (minimum, 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg injections were administered if monitoring indicated a loss of VA due to disease activity. The primary outcome results have been published previously.Mean change from baseline at months 1 through 24 in best-corrected VA (BCVA) in the overall population and in subgroups categorized according to baseline BCVA, CRVO duration, or presence of macular ischemia.The baseline mean BCVA was 53.0 letters and baseline mean CRVO duration was 8.9 months (median, 2.4 months). The mean (standard deviation) gain in BCVA from baseline with ranibizumab 0.5 mg at month 24 was 12.1 (18.60) letters (P0.0001). Best-corrected VA gains at month 24 were similar in patients with or without baseline macular ischemia (mean change, 11.1 and 12.9 letters, respectively). The mean BCVA gain at month 24 was higher in patients with CRVO duration3 months (13.2 letters) compared with that in those with CRVO duration9 months (10.5 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 24 (≤39 letters; 18.5 letters) than those with higher baseline BCVA (40-59/≥60 letters; 13.9/7.2 letters), although the absolute BCVA values at month 24 were higher in patients with higher baseline BCVA. The mean (standard deviation) and median number of ranibizumab injections up to month 23 were 13.1 (6.39) and 15.0 injections, respectively. No new ocular or nonocular safety events were reported.An individualized, stabilization criteria-driven dosing regimen of ranibizumab 0.5 mg led to sustained BCVA gains for up to 24 months in patients with CRVO. The presence of macular ischemia at baseline did not influence VA gains. Shorter duration of CRVO at baseline was associated with better VA gains. Safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

Objective: AURA was an observational study that monitored visual acuity outcomes following ranibizumab use in neovascular age-related macular degeneration patients over 2 years. The aim of this analysis was to identify factors that were predictive of visual acuity outcomes in AURA. Methods: The correlation between the baseline characteristics, the use of resources and the visual acuity outcomes in AURA was explored using principal component analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA). The response variables analysed were mean change in visual acuity over 2 years (analysed via PCA) and no decline in visual acuity at 2 years compared with baseline (analysed via PLS-DA). Results: The AURA dataset comprised 2,227 patients and 132 variables. Using PCA and PLS-DA, we found that the number of ranibizumab injections, clinic and monitoring visits, number of optical coherence tomography scans and ophthalmoscopies correlated with a change in visual acuity at Years 1 and 2, and are therefore key drivers of treatment success. Conclusion: This is a novel approach to graphically explore relationships between multiple correlated covariates and outcomes in real-life ophthalmology studies. It identified a number of variables that are positively linked with treatment outcomes.

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

Purpose To evaluate interobserver agreement for the detection of spectral-domain optical coherence tomography (SDOCT) features of diabetic macular edema (DME). Method Cross-sectional study in which 2 retinal specialists evaluated SDOCT scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39 patients were graded for features of DME including intra-retinal fluid (IRF), diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as present or absent at zones involving the fovea, 1mm from the fovea and the whole scan of 49 line scans. Analysis was performed using cross-tabulations for percentage concordance and kappa values (κ). Results In the 2950 line scans analysed, there was an increase in percentage concordance for DRE and HRF when moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88% vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with κ ranging from substantial to almost perfect. Percentage concordance for SRF was 96% at all 3 regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line-scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and whole scan with almost perfect and substantial κ respectively. κ agreement was substantial for VMT at all regions analysed. Conclusion We report a high level of interobserver agreement in the detection of SDOCT features of DME. This finding is important as detection of macular fluid is used to guide retreatment with anti-angiogenic agents.

Retinal vein occlusion (RVO) is a common retinal vascular disorder, affecting visual acuity and quality of life. Macular edema (ME) and retinal ischemia are the main causes for visual impairment in RVO. Although several modalities have been evaluated for the treatment of ME secondary to RVO in clinical trials, various questions need to be clarified when translating clinical trials into real-world practice.Intravitreal steroids and anti-VEGF agents are now widely used for the treatment of ME due to RVO. Herein, evidence from randomized controlled trials regarding the use of steroids and anti-VEGF agents in ME related to RVO are presented. In addition, an approach regarding the optimal treatment regimen, the most suitable time for initiating treatment and monitoring patients, as well as the potential role of ischemia in the response to treatment and the impact of treatment on the natural course of the disease was made.A comprehensive presentation of randomized clinical trials evaluating intravitreal steroids and anti-VEGF treatment for RVO indicates that both are effective and safe. However, the comparative effectiveness of the various anti-VEGF agents, the most suitable dosing regimen and the effect of these agents on retinal ischemia remains unclear.

Objective To determine the characteristic features of indocyanine green videoangiography (ICG-V) of circumscribed choroidal hemangioma. Design Prospective, observational case series. Participants Twenty-five eyes of 25 consecutive patients with circumscribed choroidal hemangioma. Intervention Indocyanine green videoangiography and intravenous fluorescein angiography (IVFA) were prospectively performed and reviewed. The specific features on ICG-V were compared with features of IVFA. Main outcome measures The behavior of circumscribed choroidal hemangioma cases was observed with ICG-V and IVFA. Results On ICG-V, earliest hyperfluorescence of circumscribed choroidal hemangioma was achieved at a mean of 27.6 seconds (range, 13–62 seconds), whereas maximum hyperfluorescence occurred at 222 seconds (range, 33–707 seconds). In the late frames, all eyes demonstrated a relative decrease in fluorescence, including 18 eyes (72%) that demonstrated "washout" of the dye. Other findings on ICG-V included intrinsic vessels in 19 eyes (76%), a late hyperfluorescent rim in 19 eyes (76%), and late frame hot spots in 14 eyes (56%). On IVFA, the earliest hyperfluorescence was achieved at a mean of 24 seconds (range, 10–66 seconds), whereas maximum hyperfluorescence occurred at a mean of 76.3 seconds (range, 21–720 seconds). Increasing hyperfluorescence in the late frames was found in all cases. Other findings included intrinsic vessels in 12 eyes (48%) and hot spots in the late frames in 9 eyes (36%). Conclusions Circumscribed choroidal hemangioma have specific characteristics on ICG-V that are not visualized with IVFA. We believe that ICG-V may become an important noninvasive tool for the diagnosis of choroidal hemangioma.

PURPOSE Cataract surgery in the presence of active proliferative diabetic eye disease carries a high risk of progression of retinopathy and neovascular glaucoma. Lens opacities may prevent panretinal photocoagulation (PRP) before surgery, and applying PRP in the immediate post-operative period can be difficult. The purpose of this study is to report results of cataract extraction combined with per-operative indirect laser PRP in a group of these patients. METHODS Nine eyes of 9 diabetic patients with active retinal or iris neovascularisation in which lens opacities prevented adequate pre-operative PRP underwent cataract surgery combined with indirect laser PRP after cortex aspiration and before intraocular lens implantation. RESULTS Regression of neovascularisation with this combined procedure alone was achieved in 5 eyes, 3 responded to further PRP, and 1 developed neovascular glaucoma. Visual acuity improved in all eyes, 4 achieving > or = 6/12. Four patients developed increased post-operative uveitis. One developed clinically significant macular oedema. CONCLUSIONS The method described has definite practical advantages over PRP attempted in the immediate post-operative period, when many factors can prevent its application or reduce its effectiveness, and when neovascularisation may be progressing rapidly. In addition, adjunctive per-operative indirect laser PRP appears to improve the outcome of cataract surgery in eyes with active proliferative diabetic eye disease.

AIMS The aim of this prospective study was, firstly, to judge the effect of early aggressive treatment with a standardised regimen of high dose broad spectrum intraocular and systemic antibiotics on visual outcome and, secondly, to assess the sensitivity of isolated organisms to the treatment regimen utilised. METHODS Thirty two consecutive patients presenting with presumed bacterial endophthalmitis were treated and completed follow up. In every case, intraocular sampling was undertaken and treatment with intraocular vancomycin, amikacin, and systemic ciprofloxacin was commenced immediately, followed by systemic steroids 1 day later. RESULTS In 69% of patients vision improved with 47% achieving a final visual acuity of 6/36 or better and 31% achieving 6/12 or better. Of the intraocular samples taken from post-surgical and post-traumatic cases, 10/27 (37%) and 3/5 (60%) were culture positive, respectively. All the bacteria isolated were sensitive to at least one of the three antibiotics used. CONCLUSIONS The study demonstrated that the combination of vancomycin, amikacin, and ciprofloxacin is adequate as a standard regimen for the treatment of most patients with suspected bacterial endophthalmitis. The prognosis for a good visual outcome, however, remains poor with 15/27 (55%) post-surgical and 2/5 (40%) post-traumatic cases achieving a final acuity of 6/60 or less.

Purpose To identify the strongest variable(s) linked with the number of ranibizumab injections and outcomes in AURA, and to identify ways to improve outcomes using this association. Methods AURA was a large observational study that monitored visual acuity over a 2-year period in patients with neovascular age-related macular degeneration (AMD) who received ranibizumab injections. Baseline characteristics, resource use, and outcomes were analyzed using an instrumental variable approach and regression analysis. Results Data were analyzed from 2227 patients enrolled in AURA. Optical coherence tomography (OCT) and ophthalmoscopy were the most common diagnostic tests used, and this combination was the strongest instrumental variable. Use of OCT and ophthalmoscopy affected the number of injections given and resulted in an increase in visual acuity gains from baseline of 17.6 letters in year 1 and 2.5 letters in year 2. Regression models using the instrumental variable (OCT and ophthalmoscopy combined) showed that ≥5.1 (95% CI: 3.3–11.4) ranibizumab injections were needed to maintain visual acuity from baseline to year 1 and ≥8.3 (95% CI: 5.3–18.8) injections were needed to maintain visual acuity from year 1 to year 2. To gain ≥15 letters, ≥7.9 (95% CI: 5.1–17.5) ranibizumab injections would be needed in year 1 and ≥16.1 (95% CI: 10.3–36.4) injections would be needed over 2 years. Conclusions These findings highlight the role that regular monitoring plays in guiding neovascular AMD therapy and they showed that the number of ranibizumab injections needed to maintain visual acuity is higher than that administered in AURA.

Introduction or background: The hallmark of wet age-related macular degeneration (AMD) is choroidal neovascularization (CNV). The key cytokine involved in the pathogenesis of CNV is vascular endothelial growth factor (VEGF). Since 2005, antiVEGF therapy has revolutionized the management of this condition. Sources of data: A systematic computerized literature search was conducted on PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). Areas of agreement: AntiVEGF therapy has resulted in improvement in visual function and performance. Currently, practitioners are spoilt for choice of these agents. Areas of controversy: Bevacizumab is unlicensed for intraocular use but has a better market share than ranibizumab in the treatment of wet AMD as it is approximately 40 times cheaper than ranibizumab, if aliquoted into smaller doses for intraocular use. This has stirred up questions on indemnity, safety, dosing, treatment regimen and quality control, despite the fact that welldesigned clinical trials have shown that both drugs are equally effective. Another dilemma for the physicians is the choice of treatment regimens with antiVEGF agents that include fixed dosing, optical coherence tomography (OCT)guided re-treatment, treat and extend or a combination of proactive and reactive dosing. Real-life outcomes of physician-dependent OCT-guided retreatment with these agents are inferior to outcomes reported in clinical trials. Growing points: A recently food and drug administration-approved antiVEGF agent, aflibercept, is rapidly becoming a popular choice as well-designed randomized clinical trials indicate that eight weekly fixed dosing of aflibercept is non-inferior to monthly ranibizumab. Areas timely for developing research: Options for reducing the frequency of repeated intravitreal injections are being explored. Combination therapy with photodynamic therapy and epimacular brachytherapy seem scientifically plausible due to their synergistic effects. However, so far the results on these combinations have not shown any superior visual outcomes to antiVEGF monotherapy, and the practicalities of delivering these therapies are formidable. So, research into other novel therapeutic approaches such as pigment

Although pre-operative retinopathy severity appears to be a major factor in determining the visual outcome of diabetic extracapsular cataract extraction, its precise relationship to post-operative visual acuity is ill defined. A meta-analysis was therefore carried out, and studies were included if pre-operative maculopathy and retinopathy status was sufficiently defined to permit discrimination of visual outcome between subgroups. Weighted mean proportions of eyes achieving a post-operative visual acuity > or = 6/12 were as follows: no retinopathy, 87%; non-proliferative retinopathy with no maculopathy, 80%; quiescent proliferative retinopathy with no maculopathy, 57%; non-proliferative retinopathy with maculopathy, 41%; quiescent proliferative retinopathy with maculopathy, 11%; active proliferative retinopathy, 0. Differences in visual outcome between groups were significant (chi 2 = 119.9, p < 0.0005), attributable mostly to the trend across groups (chi 2 for trend = 115.4, p < 0.0005). Logistic regression indicated that maculopathy was a more potent predictor of post-operative visual acuity < or = 6/12 (odds ratio 6.4, 95% CI 4.13-9.94, p < 0.0005) than quiescent proliferative retinopathy (odds ratio 3.33, 95% CI 2.04-5.42, p < 0.0005). The severity of retinopathy and maculopathy prior to cataract surgery in diabetics are the major determinants of post-operative visual acuity. Further study of the relationship between pre-operative retinopathy severity and the incidence of post-operative complications, progression of retinopathy and maculopathy is required to optimise the management of cataract in diabetes.

Reduced visual acuity following standard ETDRS macular laser for clinically significant macular oedema

Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working-age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti-vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity.

We estimated coefficients of repeatability for Spectralis optical coherence tomography (OCT)-derived automated retinal thickness and volume measurements in subjects with center-involving diabetic macular edema (DME).A total of 50 eyes of 50 consecutive patients with center-involving DME underwent four consecutive "fast" volume scans at a single session using one OCT device operated by one of two experienced operators. Bland-Altman coefficients of repeatability (CR) were calculated for automated retinal thickness measurements in the nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields, center point thickness, and total macular volume. Scans were evaluated for significant automated retinal boundary detection error and revised estimates for CR calculated with these scans excluded.CR in the central subfield was 8.03 μm (95% confidence interval [CI] 7.70-8.35 μm). In other subfields, CR ranged from 6.54 to 18.25 μm. Scan sets from 13 subjects had significant boundary detection error; reanalysis with these excluded yielded a CR for the central subfield of 7.44 μm with CR for all other subfields8 μm.Retinal thickness measurements in subjects with DME obtained using Spectralis OCT are considerably less variable than has been reported with other devices. Changes in central subfield thickness8 μm can be considered more indicative of true clinical change rather than measurement variability. This finding informs clinical practice and clinical trial design.

Objective To report the 2-year outcomes of the BOLT study, a prospective randomized controlled trial evaluating intravitreous bevacizumab and modified Early Treatment Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant macular edema (CSME). Methods In a 2-year, single-center, randomized controlled trial, 80 patients with center-involving CSME and visual acuity of 20/40 to 20/320 were randomized to receive either bevacizumab or MLT. Main Outcome Measures Primary outcome: difference in ETDRS best-corrected visual acuity (BCVA) between arms. Secondary outcomes: mean change in BCVA, proportion gaining at least 15 and at least 10 ETDRS letters, losing fewer than 15 and at least 30 letters, change in central macular thickness, ETDRS retinopathy severity, and safety outcomes. Results At 2 years, mean (SD) ETDRS BCVA was 64.4 (13.3) (ETDRS equivalent Snellen fraction: 20/50) in the bevacizumab arm and 54.8 (12.6) (20/80) in the MLT arm (P = .005). The bevacizumab arm gained a median of 9 ETDRS letters vs 2.5 letters for MLT (P = .005), with a mean gain of 8.6 letters for bevacizumab vs a mean loss of 0.5 letters for MLT. Forty-nine percent of patients gained 10 or more letters (P = .001) and 32% gained at least 15 letters (P = .004) for bevacizumab vs 7% and 4% for MLT. Percentage who lost fewer than 15 letters in the MLT arm was 86% vs 100% for bevacizumab (P = .03). Mean reduction in central macular thickness was 146 μm in the bevacizumab arm vs 118 μm in the MLT arm. The median number of treatments over 24 months was 13 for bevacizumab and 4 for MLT. Conclusions This study provides evidence supporting longer-term use of intravitreous bevacizumab for persistent center-involving CSME. Application to Clinical Practice Improvements in BCVA and central macular thickness seen with bevacizumab at 1 year were maintained over the second year with a mean of 4 injections. Trial Registration eudract.ema.europa.eu Identifier: 2007-000847-89

One hundred and seventeen patients with a history of recurrent corneal erosion were recruited at initial hospital presentation. Seventy-five cases had a history of shallow corneal injury, 23 had epithelial basement membrane dystrophy (EBMD), 8 had both and 11 had neither. Mean age at presentation was 38 years and follow-up ranged from 6 to 16 months (mean 10.6 months). Sixty-one patients presented with a first acute corneal erosion, 21 with a subsequent acute corneal erosion and 35 with chronic symptoms. Patients with EBMD or a trauma-related focal epithelial basement membrane abnormality were more likely to present with chronic recurrent symptoms than trauma-related cases with no abnormality on examination. Both EBMD and trauma-related cases typically recurred in the lower half of the cornea, frequently in the midline (z = 7.3, p < 0.0001), suggesting an intrinsic or acquired abnormality of the epithelial basement membrane at this site. Only four of 82 acute episodes did not resolve by 5 days with simple patching, cycloplegia and topical antibiotic ointment. In the vast majority of patients presenting with an acute erosion, simple management measures only are required. Of 117 cases started on prophylactic ointment at night, further therapy due to prophylaxis failure was required in only 5. EBMD was a risk factor for failure (relative risk 10.77). There was no difference in efficacy between once daily prophylactic paraffin and hypertonic saline ointments (p = 0.17), suggesting they both have only a lubricant action.

To identify and quantify risk factors for posterior capsule rupture or vitreous loss or both (PCR or VL or both) during cataract surgery and provide a method of composite risk assessment for individual operations.The Cataract National Dataset was extracted on 55,567 operations from 12 National Health Service (NHS) Trusts using an electronic patient record (EPR) system between November 2001 and July 2006. Risk indicators for variations in the rate of 'PCR or VL or both' were identified by univariate and multivariate analyses. Adjusted odds ratios (ORs) were used to formulate a composite 'bespoke' risk for individual cases.Overall 'PCR or VL or both' rate was 1.92% (95% CI=1.81-2.04%). Risk indicators for this complication were increasing age, male gender, presence of glaucoma, diabetic retinopathy, brunescent/white cataract, no fundal view/vitreous opacities, pseudo-exfoliation/phacodonesis, reducing pupil size, axial lengthor = 26.0 mm, the use of the alpha-blocker doxazosin, inability to lie flat and trainee surgeons performing operations. Adjusted ORs for these variables are used to estimate overall composite risk across multiple risk indicators in the form of a predicted probability of PCR or VL or both. Predicted probability for this complication ranged from less than 0.75% to more than 75%, depending on risk profile of individual operations.Higher-risk cases can be predicted, thus better informing the consent process and allowing surgeons to take appropriate precautions. Case-mix is a major determinant of the probability of an intraoperative complication. A simple composite risk estimation system has been developed.

Objectives: (1) To assess the safety of administration of a sub-Tenon fluid bolus directly contacting the globe, and compare it to posterior delivery by retrobulbar injection. (2) To assess the effect of differing volumes of anaesthetic solution administration upon intraocular pressure for sub-Tenon, retrobulbar and peribulbar administration. Study Design: (1) Intraocular pressure assessment by Perkins applanation tonometry, immediately prior to and after administration of sub-Tenon and retrobulbar anaesthesia. (2) Intraocular pressure comparison of sub-Tenon, retrobulbar and peribulbar administration. Setting: Seventy-eight routine scheduled local anaesthetic administrations for cataract surgery at Moorfields Eye Hospital. Patients: Twenty-eight patients had sub-Tenon administration, 23 retrobulbar injection and 27 peribulbar administration. Main Outcome Measures: Volume administered and change in intraocular pressure. Results: The mean volume used was 3.2 ml for sub-Tenon, 3.6 ml for retrobulbar and 6.4 ml for peribulbar administration. After sub-Tenon delivery there was mean rise in intraocular pressure of 0.9 mmHg and after retrobulbar injection a mean rise of 1.4 mmHg. These rises did not reach statistical significance. Peribulbar injection involved a larger mean volume of administration than the sub-Tenon or retrobulbar techniques, with a mean rise of intraocular pressure of 4.9 mmHg, which is statistically significant ( P Conclusions: Retrobulbar and sub-Tenon administration have only a marginal effect upon intraocular pressure for small volumes (3–4 ml) and sub-Tenon administration of this volume load appears to be safe with regard to intraocular pressure. Where a significant volume of local anaesthetic agent is administered, as with peribulbar injection, this is likely to be associated with a significant rise in intraocular pressure and consideration should be given to use of a pressure lowering device.