Roxanne Crosby-Nwaobi

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

BACKGROUNDnCystoid 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.nnnOBJECTIVESnTo examine the effectiveness of NSAIDs in the treatment of CMO following cataract surgery.nnnSEARCH METHODSnWe searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 7), MEDLINE (January 1950 to August 2011), EMBASE (January 1980 to August 2011), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (August 2011) and ClinicalTrials.gov (www.clinicaltrials.gov) (August 2011). We searched the reference lists of identified trials. We searched conference abstracts (sessions related to cataract) in The Association for Research in Vision and Ophthalmology (ARVO) 1975 to 2011. We contacted experts in the field and NSAIDs manufacturers for details on published and unpublished trials.There were no language or date restrictions in the search for trials. The electronic databases were last searched on 5 August 2011.nnnSELECTION CRITERIAnWe included randomised controlled trials evaluating the effects of NSAIDs in the treatment of CMO following cataract surgery.nnnDATA COLLECTION AND ANALYSISnTwo review authors independently extracted data. Since considerable heterogeneity was observed between studies we did not conduct meta-analyses.nnnMAIN RESULTSnSeven 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 appeared effective but not statistically significantly so 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.nnnAUTHORS CONCLUSIONSnThis review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO and two trials which revealed no significant difference between comparative groups. As such, the effects of NSAIDs in acute and chronic CMO remain unclear and needs further investigation.

Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy

AIMSnWe previously showed that circulating mitochondrial DNA (MtDNA) levels are altered in diabetic nephropathy. The aim of the current study was to determine if circulating MtDNA levels are altered in patients with diabetic retinopathy.nnnMETHODSnPatients with diabetes (n=220) were studied in a clinical setting using a cross-sectional study design as the following groups: DR-0 (no retinopathy, n=53), DR-m (mild non-proliferative diabetic retinopathy NPDR, n=98) and DR-s (severe proliferative diabetic retinopathy, n=69). MtDNA content in peripheral blood DNA was measured as the mitochondrial to nuclear genome ratio using real time qPCR. Circulating cytokines were measured using the luminex assay and MtDNA damage was assessed using PCR. Differences were considered significant at P<0.05.nnnRESULTSnCirculating MtDNA values were higher in DR-m compared to DR-0 (P=0.02) and decreased in DR-s compared to DR-m (P=0.001). These changes remained significant after adjusting for associated parameters. In parallel there were increased levels of circulating cytokines IL-4 (P=0.005) and TNF-α (P=0.02) in the DR-s group and increased MtDNA damage in DR-m patients compared to DR-0 (P=0.03).nnnCONCLUSIONSnOur data show that circulating MtDNA levels are independently associated with diabetic retinopathy, showing an increase in DR-m and decrease in DR-s with a parallel increase in MtDNA damage and inflammation. Hyperglycemia-induced changes in MtDNA in early diabetes may contribute to inflammation and progression of diabetic retinopathy. Longitudinal studies should be carried out to determine a potential causality of MtDNA in diabetic retinopathy.

Caregiver Burden in Patients Receiving Ranibizumab Therapy for Neovascular Age Related Macular Degeneration

Purpose To assess the caregiver burden and factors determining the burden in patients receiving ranibizumab therapy for neovascular AMD (nAMD). Methods This is a cross-sectional questionnaire survey of 250 matched patient caregiver dyads across three large ophthalmic treatment centres in United Kingdom. The primary outcome was the subjective caregiver burden measured using caregiver reaction assessment scale (CRA). Objective caregiver burden was determined by the caregiver tasks and level of care provided. The factors that may predict the caregiver burden such as the patient’s visual acuity of the better eye and vision related quality of life, demographics, satisfaction and support provided by the healthcare and the health status of the dyads were also collected and assessed in a hierarchical regression model. Results The mean CRA score was 3.2±0.5, similar to the score reported by caregivers for atrial fibrillation who require regular hospital appointments for monitoring their thromboprophylaxis. Caregiver tasks including accompanying for hospital appointments for eye treatment and patient’s visual acuity in the better eye were the biggest contributors to the caregiver burden hierarchical model explaining 18% and 11% of the variance respectively. Conclusion Ranibizumab therapy for nAMD is associated with significant caregiver burden. Both disease impact and treatment frequency contributed to the overall burden.

Long-Term Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration in a Clinical Setting

PURPOSEnTo report 2-year treatment outcomes with intravitreal aflibercept for neovascular age-related macular degeneration (nAMD) in routine clinical practice.nnnDESIGNnRetrospective, nonrandomized, interventional case series.nnnMETHODSnRetrospective 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.nnnRESULTSnOf 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 79xa0μm with absence of macular fluid in 72.7% of the 88 eyes with SDOCT data available at 2-year follow-up.nnnCONCLUSIONSnThe 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.

A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study).

Background/aims 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). Methods 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 16u2005weeks followed by retreatment criteria-guided pro-re-nata therapy at 32 and 48u2005weeks. Patients randomised to MLT only were treated every 16u2005weeks if clinically significant macular oedema was present. The primary outcome was the mean change from baseline in BCVA between arms at 56u2005weeks. Results The mean change in BCVA at 56u2005weeks 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 56u2005weeks, a post hoc comparison of central subfield thickness (CST) showed a decrease of −113u2005μm (IQR −218, −64) (combination) versus −17u2005μm (−128, 12) (MLT arm) (p<0.001). 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. Conclusions 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. Trial registration number EudraCT 2011-003339-74

Treatment satisfaction of patients undergoing ranibizumab therapy for neovascular age-related macular degeneration in a real-life setting

Context Treatment satisfaction with a loading phase of monthly injections for 3 months followed by a pro-re-nata regimen of ranibizumab in neovascular age-related macular degeneration (nAMD) remains unclear. Aims The aim was to evaluate the treatment satisfaction of persons with nAMD treated with ranibizumab in a real-life setting. Settings and design A cross-sectional study was conducted across three eye clinics within the National Health Service in the UK, where treatment is provided free at point of contact. Materials and methods A total of 250 patients were selected randomly for the study. Treatment satisfaction was assessed using the Macular Treatment Satisfaction Questionnaire. Data were collected on satisfaction of the service provided (Client Service Questionnaire-8) and the patients’ demographic and quality of life and treatment history. Factors governing treatment questionnaire were determined. Results The most important factors that determined the satisfaction were the service provided at the clinic (Client Service Questionnaire-8), health-related quality of life (EQ-5D-3L), and duration of AMD. Visual acuity changes were rated as less important than one would have expected. Conclusion The study result suggested that treatment satisfaction for nAMD was governed by the perception of being reviewed and injected regularly over a long period of time than the actual change in visual acuity from the treatment.

A prospective randomized controlled study of a virtual clinic integrating primary and specialist care for patients with Type 2 diabetes mellitus.

To investigate the effectiveness of a diabetes virtual clinic to enhance diabetes in primary care by developing clinical management plans for patients with suboptimal metabolic control and/or case complexity.

Associations between Retinal Markers of Microvascular Disease and Cognitive Impairment in Newly Diagnosed Type 2 Diabetes Mellitus: A Case Control Study

Objective To investigate associations between retinal microvascular changes and cognitive impairment in newly diagnosed type 2 diabetes mellitus. Design Case control study. Setting A primary care cohort with newly diagnosed type 2 diabetes mellitus. Methods For this analysis, we compared 69 cases with lowest decile scores (for the cohort) on the Modified Telephone Interview for Cognitive Status and 68 controls randomly selected from the remainder of the cohort. Retinal images were rated and the following measures compared between cases and controls: retinal vessel calibre, arterio-venous ratio, retinal fractal dimension, and simple and curvature retinal vessel tortuosity. Results Total and venular (but not arteriolar) simple retinal vessel tortuosity levels were significantly higher in cases than controls (t = 2.45, p = 0.015; t = 2.53, p = 0.013 respectively). The associations persisted after adjustment for demographic factors, retinopathy, neuropathy, obesity and blood pressure. There were no other significant differences between cases and controls in retinal measures. Conclusions A novel association was found between higher venular tortuosity and cognitive impairment in newly diagnosed type 2 diabetes mellitus. This might be accounted for by factors such as hypoxia, thrombus formation, increased vasoendothelial growth factor release and inflammation affecting both the visible retinal and the unobserved cerebral microvasculature.

Model for Risk-Based Screening of Diabetic Retinopathy in People With Newly-Diagnosed Type 2 Diabetes Mellitus.

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

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

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