The unmet need for better risk stratification of non-proliferative diabetic retinopathy.

Diabetic retinopathy is a common microvascular complication of diabetes and remains one of the leading causes of preventable blindness in working-age people. Non-proliferative diabetic retinopathy is the earliest stage of diabetic retinopathy and is typically asymptomatic. Currently, the severity of diabetic retinopathy is assessed using semi-quantitative grading systems based on the presence or absence of retinal lesions. These methods are well validated, but do not predict those at high risk of rapid progression to sight-threatening diabetic retinopathy; therefore, new approaches for identifying these people are a current unmet need. We evaluated published data reporting the lesion characteristics associated with different progression profiles in people with non-proliferative diabetic retinopathy. Based on these findings, we propose that additional assessments of features of non-proliferative diabetic retinopathy lesions may help to stratify people based on the likelihood of rapid progression. In addition to the current classification, the following measurements should be considered: the shape and size of lesions; whether lesions are angiogenic in origin; the location of lesions, including predominantly peripheral lesions; and lesion turnover and dynamics. For lesions commonly seen in hypertensive retinopathy, a detailed assessment of potential concomitant diseases is also recommended. We believe that natural history studies of these changes will help characterize these non-proliferative diabetic retinopathy progression profiles and advance our understanding of the pathogenesis of diabetic retinopathy in order to individualize management of people with diabetic retinopathy.

The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D).

AIMS/HYPOTHESIS: This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi-ethnic cohort. METHODS: A population-based cross-sectional design was used. People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner-city boroughs of South London, serving a population in which 20% of residents are of black African or Caribbean ethnicity. Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records. Multiple logistic regression methods were used to report associations between ethnicity and diabetes-complication status. RESULTS: From 96 general practices, 1,506 patients were recruited. Their mean age was 55.6 (± 11.07) years, 55% were men, 60% were asymptomatic at diagnosis and 51%, 38% and 11% were of white, black and South Asian/other ethnicity, respectively. Compared with white participants, black and South Asian/other participants were: younger (mean age 58.9 [± 10.09], 52.4 [± 11.19] and 51.5 [± 10.42] years, respectively; p < 0.0001); less likely to have neuropathy (10.1%, 3.6% and 4.4%; p < 0.0001) or report coronary artery disease (12.7%, 4.8% and 7.3%; p < 0.0001). In logistic regression, compared with white participants, black participants had lower levels of macrovascular complications (OR 0.52, 95% CI 0.32, 0.84; p = 0.01). Male sex was independently associated with microvascular disease (OR 1.69, 95% CI 1.26, 2.28; p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of complications at time of diagnosis was lower than expected, especially in black and South Asian/other ethnic groups. However, in multi-ethnic inner-city populations, onset of type 2 diabetes occurred almost 10 years earlier in non-white populations than in white participants, predicating a prolonged morbidity.

Diabetic retinopathy: pathogenesis, clinical grading, management and future developments.

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.

The pathogenesis of early retinal changes of diabetic retinopathy.

Recent successful trials of antibodies to vascular endothelial growth factor (VEGF) in diabetic retinopathy implicate this cytokine as a major cause of diabetic retinopathy (DR) and diabetic macular oedema (DME). The mechanisms which cause VEGF to be over-expressed to cause the vasculopathy are not entirely clear. This review explores the earliest changes to the retina in DR and the factors that predispose or prevent DR, including sleep apnoea, receptor degenerations laser treatment and VEGF polymorphism. The review also presents the evidence that retinal hypoxia, existing in the earliest stages, causes DR. This hypoxia is much increased by dark adaptation, indicating a new and possibly superior therapy.

A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

AIM: To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). METHODS: Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 µg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 µm. RESULTS: Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 µm (±75). CONCLUSION: This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD.

Socio-economic and ethnic inequalities in diabetes retinal screening.

OBJECTIVE: We aimed to quantify socio-economic and ethnic inequalities in diabetes retinal screening. METHODS: Data were analysed for the retinal screening programme for three South London boroughs for the 18-month period to February 2009. Sight-threatening diabetic retinopathy (STDR) was defined as the occurrence of diabetic maculopathy, severe non-proliferative or proliferative diabetic retinopathy. Odds ratios were adjusted for sex, age group, duration and type of diabetes, self-reported ethnicity and deprivation quintile by participant postal code. RESULTS: There were 76 351 records obtained but, after excluding duplicate and ineligible records, data were analysed for 59 495 records from 31 484 subjects. There were 7026 (22%) subjects called for appointments who were not screened in the period, with 24 458 (78%) having one or more screening episodes. Non-attendance for screening was highest in young adults aged 18-34 years (32%) and in those aged 85 years or greater (28%). In the most deprived quintile, non-attendance was 23% compared with 21% in the least deprived quintile [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.16-1.61, P < 0.001]. There were 2819 (11.5%) participants with STDR, including 10.8% in the least deprived quintile and 12.2% in the most deprived quintile (OR 1.10, 95% CI 0.95-1.16, P = 0.196). Compared with white Europeans (9.4%), STDR was higher in Africans (15.2%) and African Caribbeans (14.7%), resulting from a higher frequency of diabetic maculopathy. CONCLUSION: Socio-economic inequality in diabetes retinal screening may be smaller than reported in earlier studies. This study suggested an increased frequency of diabetic maculopathy among participants of African origins.

Loss of chromatic sensitivity in AMD and diabetes: a comparative study.

BACKGROUND: Abnormalities in rod and cone photoreceptor morphology have been reported in normal aging retinas in the absence of known pathology and have been taken as an indicator of susceptibility to retinal disease. Some loss of visual performance may therefore precede retinal structural changes that can be detected reliably using conventional fundus imaging techniques. Red/green (RG) and yellow/blue (YB) colour discrimination thresholds are sensitive measures of normal retinal function and poor YB discrimination is often taken as an indicator of retinal disease, though it is generally acknowledged that RG loss is also present in most cases of acquired deficiency. Although structural changes in age-related macular degeneration (AMD) and diabetes share some similarities, significant differences remain and this may result in different patterns of RG and YB loss. AIM: The aim of this study was to quantify and compare the severity of RG and YB loss of chromatic sensitivity in patients with AMD and diabetes. METHODS: Patients with varying severity of AMD and diabetes and normal subjects of similar age were recruited for the study. RG and YB colour detection thresholds were measured in the two groups of patients and the control group, using the Colour Assessment and Diagnosis (CAD) test. RESULTS: Each AMD subject investigated showed significant, but unequal loss of YB and RG chromatic sensitivity, with YB discrimination showing the greatest loss. Diabetic subjects also exhibited reduced chromatic sensitivity, but with almost equal and highly correlated RG and YB thresholds (R(2) = 0.99). The severity of colour vision loss measured with the CAD test also correlates well with a clinical classification index of disease progression in AMD, and with the level of hyperglycaemic control in diabetes. CONCLUSIONS: These findings suggest that accurate measurements of RG and YB colour thresholds can provide a sensitive measure of functional change in diseases of the retina with patterns of loss that differ significantly in AMD and diabetes.

The ORNATE India Project: United Kingdom-India Research Collaboration to tackle visual impairment due to diabetic retinopathy.

INTRODUCTION: The ORNATE India project is funded by the UK Research and Innovation (UKRI) through the Global Challenges Research Fund. The aim is to build research capacity and capability in India and the UK to tackle global burden of diabetes-related visual impairment. As there are over 77 million people with diabetes in India, it is challenging to screen every person with diabetes annually for sight-threatening diabetic retinopathy (DR). Therefore, alternate safe approaches need to be developed so that those at-risk of visual impairment due to DR is identified promptly and treated. METHODS: The project team utilised diverse global health strategies and research methods to co-design work packages to build research capacity and capability to ensure effective, affordable and efficient DR services are made available for the population. The strategies and methods employed included health system strengthening; implementation science; establishing care pathways; co-designing collaborative studies on affordable technologies, developing quality standards and guidelines to decrease variations in care; economic analysis; risk modelling and stratification. Five integrated work packages have been developed to deal with all aspects of DR care. These included implementation of a DR screening programme in the public health system in a district in Kerala, evaluating regional prevalence of diabetes and DR and assessing ideal tests for holistic screening for diabetes and its complications in 20 areas in India, utilising artificial intelligence on retinal images to facilitate DR screening, exploring biomarker and biosensor research to detect people at risk of diabetes complications, estimating cost of blindness in India and risk modelling to develop risk-based screening models for diabetes and its complications. A large collaborative network will be formed to propagate research, promote shared learning and bilateral exchanges between high- and middle-income countries to tackle diabetes-related blindness.

IDF Diabetes Atlas: A review of studies utilising retinal photography on the global prevalence of diabetes related retinopathy between 2015 and 2018.

AIMS: The purpose of this study is to assess the prevalence of diabetic retinopathy (DR) world-wide from articles published since 2015 where the assessment of the presence and severity of DR was based on retinal images. METHODS: A total of 4 databases were searched for the MESH terms diabetic retinopathy and prevalence. Of 112 publications 32 studies were included and individual data pooled for analysis. The presence of any DR or diabetic macular edema (DME) was recorded and severity as mild, moderate or severe non-proliferative DR (NPDR), proliferative DR (PDR) and DME and/or clinically significant macular edema (CSME). The level of severity of DR reported refer to persons with diabetes and not individual eyes. RESULTS: The global prevalence of DR and DME, for the period 2015 to 2019 were 27.0% for any DR comprising of 25.2%, NPDR, 1.4% PDR and 4.6% DME. The lowest prevalence was in Europe at 20.6% and South East Asia at 12.5% and highest in Africa at 33.8%, Middle East and North Africa 33.8%, and the Western Pacific region at 36.2%. CONCLUSIONS: This study illustrated difficulties in deriving a meaningful global prevalence rate for DR and DME due to the lack of uniformity in defining the study populations, methodological differences, retinal image capture and grading criteria. Therefore, international consensus is required using a minimal data set for future studies.

Appropriateness of quality standards for meaningful intercentre comparisons of aflibercept service provision for neovascular age-related macular degeneration.

PurposeReal-world data give different information on health-care delivery compared with randomised controlled trials. We aimed to evaluate the appropriateness of possible quality standards for intersite comparisons of outcomes of providing Aflibercept for neovascular age-related macular degeneration (nAMD) in clinical practice.Patients and methodsRetrospective data analysis from an electronic medical record. A consecutive series of treatment-naive patients initiated on aflibercept for nAMD, in the UK from March 2013 to October 2015. Age, visual acuity (VA) at baseline and 1 year, and injection episodes were remotely extracted in an anonymised format.ResultsThe mean baseline VA was 54.3 letters, ranging from 51.3 to 58.1 between different centres, in 5620 eyes taken from 12 centres. Out of these, 3360 were initiated on treatment more than a year before. The percentage with <35 letters at baseline was 19.9-3% and that with >70 letters was 24.8-10.7%. Eyes with ≥70 letters at 1 year ranged from 20.2 to 42.9% and those with <35 ranged from 4.5 to 21.6% across different sites. Injection rates in 1 year varied from 5.5 to 8.6, and data available at 1 year also varied from 82.3 to 46.4%.ConclusionsSignificant variation was found between sites attempting to provide the same therapeutic regime. For fair comparisons between sites, we recommend that both VA measures and process measures, such as injection numbers, retention rates, and discharge policies, are used. More work is required to explain the differences. Such real-world data are not generated in the same way as a randomised clinical trial, and maybe best used to help improve service provision.

Identification of time point to best define 'sub-optimal response' following intravitreal ranibizumab therapy for diabetic macular edema based on real-life data.

PurposeTo determine the average time-point at which it is best to define 'sub-optimal response' after ranibizumab treatment for diabetic macular edema (DME) based on the data obtained from real-life clinical practice.MethodsIn this retrospective observational study, 322 consecutive treatment naïve eyes with DME were treated with three loading doses of intravitreal ranibizumab followed by re-treatment based on decision of the treating physician on a case-by-case basis. The demographic data, clinic-based visual acuity measurements and central subfield thickness (CST) assessed on spectral domain optical coherence tomography (OCT) were evaluated at baseline (month 0), 1, 2, 3, 6, and 12 months.ResultsOn an average, the improvement in visual acuity and CST was first seen after the loading dose. However, the maximal response in terms of proportion of patients with improvement in visual acuity and/ or CST in this cohort was observed at 12 months. Patients who presented with low visual acuity at baseline (<37 ETDRS letters) were unlikely to attain driving vision with ranibizumab therapy.ConclusionsOn an average, a 'sub-optimal response' after ranibizumab therapy is best defined at month 12 as patients may continue to improve with treatment.

Influence of baseline diabetic retinopathy status on initial anatomical response of intravitreal ranibizumab therapy for diabetic macular oedema.

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.

Spare the rods and spoil the retina: revisited.

Visual function improves with oxygen inhalation in people with diabetes even in the absence of visible retinopathy. Rods consume the most oxygen in the retina due to the high metabolic activity required to maintain the dark current. Therefore, Arden hypothesized that in diabetes where oxygen supply may also be affected due to the changes in retinal vasculature, prevention of dark adaptation may be a viable option to prevent or decrease the rate of progression of diabetic retinopathy. Animal experiments have proven that the absence of rods decreases the development of retinal neovascularisation. The same principle applies to panretinal photocoagulation, an established treatment for proliferative diabetic retinopathy. Recently, a few clinical studies have also shown that preventing dark adaptation by suppressing rods with 500-nm light source at night decreases the rate of progression of early diabetic retinopathy and maculopathy in the short-term. We await the results of a large two-year multi-centre trial (CLEOPATRA trial) to evaluate the long-term effects of decreasing dark adaptation by applying a 500nm light source as a mask over eyes with non-central diabetic macular oedema.

Determinants of visual acuity outcomes in eyes with neovascular AMD treated with anti-VEGF agents: an instrumental variable analysis of the AURA study.

PurposeTo 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.MethodsAURA 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.ResultsData 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.ConclusionsThese 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.

Non-steroidal anti-inflammatory agents for cystoid macular oedema following cataract surgery: a systematic review.

AIM: To examine the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular oedema (CMO) following cataract surgery. METHODS: Systematic literature review of randomised controlled trials (RCTs) that evaluated the effects of NSAIDs in the treatment of CMO following cataract surgery was done according to the Cochrane Collaboration methodology. RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three trials examined the effect of NSAIDs in acute CMO. Little evidence of effectiveness was found for oral indomethacin and topical fenoprofen for chronic CMO in two small trials. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials. Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of a NSAID to placebo, prednisolone or another NSAID. Because of considerable heterogeneity between these study designs, their results were not combined in a meta-analysis. CONCLUSION: A positive effect of topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) on chronic CMO was noted. However, there is not enough evidence to show the effectiveness of NSAIDs in acute CMO following cataract surgery.

Non-steroidal anti-inflammatory agents for treating cystoid macular oedema following cataract surgery.

BACKGROUND: Cystoid macular oedema (CMO) is the accumulation of fluid in the central retina (the macula) due to leakage from dilated capillaries. It is the most common cause of poor visual outcome following cataract surgery. The exact cause is unclear. Acute CMO, defined as oedema of less than four months duration, often resolve spontaneously. CMO that persists for four months or more is termed chronic CMO. Different types of non-steroidal anti-inflammatory agents (NSAIDs) are used in the treatment of CMO which may be delivered topically or systemically. OBJECTIVES: To examine the effectiveness of NSAIDs in the treatment of CMO following cataract surgery. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 2 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to May 2004), LILACS (April 2004) and the reference lists of identified trials. We searched conference abstracts (sessions related to cataract) in ARVO 1975 to 2003. We contacted experts in the field and NSAIDs manufacturers for details on published and unpublished trials. SELECTION CRITERIA: Randomised controlled trials evaluating the effects of NSAIDs in the treatment of CMO following cataract surgery. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data. Since considerable heterogeneity was observed between studies we did not conduct meta-analyses. MAIN RESULTS: Seven trials involving a total of 266 participants were included. Four trials studied the effects of NSAIDs in chronic CMO while the other three examined the effect of NSAIDs in acute CMO. Of the studies examining chronic CMO, one study enrolled 120 participants, but the remainder had 34 or fewer participants. Four different NSAIDs were used and administered in different ways. Indomethacin was used orally and was found to be ineffective for chronic CMO in one trial. Topical fenoprofen was also found to be ineffective for chronic CMO in another small trial. Treatment with topical 0.5% ketorolac for chronic CMO was found to be effective in two trials. Three trials examined the effect of topical NSAIDs on acute CMO. The comparisons among these studies were of an NSAID to placebo, prednisolone or another NSAID. The study design differed between the studies in other important aspects thus they could not be combined in a meta-analysis. AUTHORS' CONCLUSIONS: This review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO. However, the effects of NSAIDs in acute CMO remains unclear and needs further investigation.

Myopic foveoschisis: a clinical review.

To review the literature on epidemiology, clinical features, diagnostic imaging, natural history, management, therapeutic approaches, and prognosis of myopic foveoschisis. A systematic Pubmed search was conducted using search terms: myopia, myopic, staphyloma, foveoschisis, and myopic foveoschisis. The evidence base for each section was organised and reviewed. Where possible an authors' interpretation or conclusion is provided for each section. The term myopic foveoschisis was first coined in 1999. It is associated with posterior staphyloma in high myopia, and is often asymptomatic initially but progresses slowly, leading to loss of central vision from foveal detachment or macular hole formation. Optical coherence tomography is used to diagnose the splitting of the neural retina into a thicker inner layer and a thinner outer layer, but compound variants of the splits have been identified. Vitrectomy with an internal limiting membrane peel and gas tamponade is the preferred approach for eyes with vision decline. There has been a surge of new information on myopic foveoschisis. Advances in optical coherence tomography will continually improve our understanding of the pathogenesis of retinal splitting, and the mechanisms that lead to macular damage and visual loss. Currently, there is a good level of consensus that surgical intervention should be considered when there is progressive visual decline from myopic foveoschisis.

A randomized clinical trial comparing fixed vs pro-re-nata dosing of Ozurdex in refractory diabetic macular oedema (OZDRY study).

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

Aflibercept in wet AMD beyond the first year of treatment: recommendations by an expert roundtable panel.

This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.

Defining response to anti-VEGF therapies in neovascular AMD.

The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there is resolution of fluid (intraretinal fluid; IRF, subretinal fluid; SRF and retinal thickening), and/or improvement of >5 letters, subject to the ceiling effect of good starting VA. Poor response is defined as <25% reduction from the baseline in the central retinal thickness (CRT), with persistent or new IRF, SRF or minimal or change in VA (that is, change in VA of 0+4 letters). Non-response is defined as an increase in fluid (IRF, SRF and CRT), or increasing haemorrhage compared with the baseline and/or loss of >5 letters compared with the baseline or best corrected vision subsequently. Poor or non-response to anti-VEGF may be due to clinical factors including suboptimal dosing than that required by a particular patient, increased dosing intervals, treatment initiation when disease is already at an advanced or chronic stage), cellular mechanisms, lesion type, genetic variation and potential tachyphylaxis); non-clinical factors including poor access to clinics or delayed appointments may also result in poor treatment outcomes. In eyes classified as good responders, treatment should be continued with the same agent when disease activity is present or reactivation occurs following temporary dose holding. In eyes that show partial response, treatment may be continued, although re-evaluation with further imaging may be required to exclude confounding factors. Where there is persistent, unchanging accumulated fluid following three consecutive injections at monthly intervals, treatment may be withheld temporarily, but recommenced with the same or alternative anti-VEGF if the fluid subsequently increases (lesion considered active). Poor or non-response to anti-VEGF treatments requires re-evaluation of diagnosis and if necessary switch to alternative therapies including other anti-VEGF agents and/or with photodynamic therapy (PDT). Idiopathic polypoidal choroidopathy may require treatment with PDT monotherapy or combination with anti-VEGF. A committee comprised of retinal specialists with experience of managing patients with n-AMD similar to that which developed the Royal College of Ophthalmologists Guidelines to Ranibizumab was assembled. Individual aspects of the guidelines were proposed by the committee lead (WMA) based on relevant reference to published evidence base following a search of Medline and circulated to all committee members for discussion before approval or modification. Each draft was modified according to feedback from committee members until unanimous approval was obtained in the final draft. A system for categorising the range of responsiveness of n-AMD lesions to anti-VEGF therapy is proposed. The proposal is based primarily on morphological criteria but functional criteria have been included. Recommendations have been made on when to consider discontinuation of therapy either because of success or futility. These guidelines should help clinical decision-making and may prevent over and/or undertreatment with anti-VEGF therapy.