Alan Berger

Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration

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.

Key drivers of visual acuity gains in neovascular age-related macular degeneration in real life: findings from the AURA study

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 (p<0.05) prognostic factors for vision maintenance (loss <15 letters) or vision gain (≥15 letters). Patients who received >7 injections (in 1 year) or >14 injections (over 2 years) gained more letters and demonstrated greater vision maintenance (loss of <15 letters) than patients who received fewer injections. There was a significant (p<0.05) association between number of injections and national reimbursement schemes and OCT. Conclusions A number of factors that are predictive of treatment outcomes in a real-life setting were identified. Notably, the decline of treatment benefits may be linked to number of injections and a failure to visit clinicians and receive OCT as required. These findings may be helpful in guiding ophthalmologist treatment decisions under limited time and financial constraints. Trial registration number NCT01447043.

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.

Subconjunctival Lidocaine before Laser Treatment : A Randomized Trial

PURPOSE The aim of the study was to determine whether subconjunctival anesthesia is effective at reducing pain associated with laser retinopexy. DESIGN This was a single-center, prospective, patient-masked, randomized, controlled trial. PARTICIPANTS In the primary study group, 65 patients were recruited. Thirty-two patients (32 eyes) received anesthetic injection, and 33 patients (33 eyes) received the sham injection. The crossover study group consisted of 28 patients (56 eyes). METHODS Between February 2008 and April 2008, all patients who were consecutively booked to undergo panretinal photocoagulation (PRP) or peripheral laser retinopexy (PLR) were invited to participate in the study. Patients were randomized to receive subconjunctival lidocaine injection or a sham injection before their intended laser retinal treatment. These patients were defined as our primary study group. Patients who required a second laser treatment received the opposite injection in a masked fashion before laser retinal treatment. These patients were defined as our crossover group. Patients in both the primary study group and the crossover group were masked to the treatment given. After the laser treatment, patients completed a pain questionnaire. MAIN OUTCOME MEASURES The primary outcome was incidence of pain. The secondary outcome was severity of pain. RESULTS Primary study group: In the anesthetic treatment group, 19 patients (59%) experienced pain compared with 32 patients (97%) in the sham treatment group (P<0.001). Among the patients who did experience pain, the average pain score was 3.6 in the anesthetic treatment group and 4.1 in the sham treatment group (P=0.55). Crossover study group: In the anesthetic treatment group, 12 patients (43%) experienced pain compared with 28 patients (100%) in the sham treatment group (P<0.001). In patients who did experience pain, the average pain score was 3.3 in the anesthetic treatment group and 4.6 in the sham treatment group. Twenty patients (71%) preferred anesthetic to sham treatments, 1 patient (4%) preferred sham over anesthetic, and 7 patients (25%) thought both laser treatments were the same. CONCLUSIONS Subconjunctival 2% lidocaine significantly reduces the incidence of pain in patients who receive PRP or PLR.

Efficacy/safety of ranibizumab monotherapy or with laser versus laser monotherapy in DME

OBJECTIVE To compare the efficacy and safety of ranibizumab 0.5 mg intravitreal injection, as monotherapy or in combination with laser, with laser monotherapy in patients with visual impairment caused by diabetic macular edema. DESIGN Twelve-month, multicentre, open-label, parallel-group, randomized, active-control study. PARTICIPANTS A total of 220 (ranibizumab monotherapy: n = 75, ranibizumab + laser: n = 73, laser monotherapy: n = 72) patients with a diagnosis of type I or II diabetes and visual impairment caused by macular edema were included in the efficacy analysis. METHODS Ranibizumab was initiated with a fixed loading phase of 3 monthly injections followed by as needed therapy until stable vision achievement. Efficacy end points were the change in best corrected visual acuity (BCVA), change in central retinal thickness (CRT) measured by optical coherence tomography, proportion achieving a 15-letter BCVA gain, and 12-month Visual Function Questionnaire-25 (VFQ-25) score. Safety was assessed with the incidence and severity of adverse events. RESULTS At 12 months, significant (p < 0.001) mean BCVA improvements were observed for both the ranibizumab monotherapy (+8.9 [95% confidence interval (CI) 7.0-10.7] letters) and the ranibizumab + laser (+8.2 [95% CI 6.0-10.4] letters) groups compared with the laser monotherapy group (+0.3 [95% CI -2.9 to 3.5] letters). Similarly, a better response in terms of CRT improvement, BCVA letter gain, and VFQ-25 was observed in both ranibizumab groups compared with laser monotherapy. The safety profile was comparable in the 2 ranibizumab groups. CONCLUSIONS Ranibizumab as monotherapy or combined with laser resulted in significantly higher improvements in visual acuity and vision-related quality of life at month 12 as compared with laser monotherapy.

Optical coherence tomography angiography in chorioretinal disorders

Optical coherence tomography angiography (OCTA) is a novel imaging modality that incorporates blood motion contrast to create angiograms of the retinal vasculature in a noninvasive manner, without the use of dye. It is a safe procedure and can be repeated as frequently as desired. The use of OCTA for delineation of choroidal neovascular membranes, for the study of microvascular abnormalities in diabetic patients, to assess nonperfused areas in retinal occlusions and vascular changes in macular telangiectasia are some of the potential OCTA applications. However, it is not free of drawbacks. Major limitations include the small field of view and its great sensitivity to movement. As a result, it is prone to motion artifacts, leading to poor-quality images. The scope of the body literature regarding this new modality rapidly increases as we learn how to better use this technology. Our objective is to point overall aspects of OCTA, including its limitations and review some of its initial reports on chorioretinal diseases.

Identifying Predictors of Anti-VEGF Treatment Response in Patients with Neovascular Age-Related Macular Degeneration through Discriminant and Principal Component Analysis

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.

Low-glycaemic index diet to improve glycaemic control and cardiovascular disease in type 2 diabetes: design and methods for a randomised, controlled, clinical trial

Introduction Type 2 diabetes (T2DM) produces macrovascular and microvascular damage, significantly increasing the risk of cardiovascular disease (CVD), renal failure and blindness. As rates of T2DM rise, the need for effective dietary and other lifestyle changes to improve diabetes management become more urgent. Low-glycaemic index (GI) diets may improve glycaemic control in diabetes in the short term; however, there is a lack of evidence on the long-term adherence to low-GI diets, as well as on the association with surrogate markers of CVD beyond traditional risk factors. Recently, advances have been made in measures of subclinical arterial disease through the use of MRI, which, along with standard measures from carotid ultrasound (CUS) scanning, have been associated with CVD events. We therefore designed a randomised, controlled, clinical trial to assess whether low-GI dietary advice can significantly improve surrogate markers of CVD and long-term glycaemic control in T2DM. Methods and analysis 169 otherwise healthy individuals with T2DM were recruited to receive intensive counselling on a low-GI or high-cereal fibre diet for 3 years. To assess macrovascular disease, MRI and CUS are used, and to assess microvascular disease, retinal photography and 24-hour urinary collections are taken at baseline and years 1 and 3. Risk factors for CVD are assessed every 3 months. Ethics and dissemination The study protocol and consent form have been approved by the research ethics board of St. Michaels Hospital. If the study shows a benefit, these data will support the use of low-GI and/or high-fibre foods in the management of T2DM and its complications. Trial Registration number NCT01063374; Pre-results.

Unmet eye care needs among a homeless youth population

OBJECTIVE To assess the rate of visual impairment and quantify the unmet eye care needs within Torontos homeless youth community. DESIGN Prospective and cross sectional. PARTICIPANTS Ninety randomly selected homeless youth aged 16-24 years. METHODS From each of 9 participating homeless youth shelters and drop-in centres in Toronto, 10 English-speaking youths between ages 16 and 24 were randomly recruited. Information regarding sociodemographics, medical history, subjective visual acuity, and access to eye care was collected. Comprehensive visual screening and undilated direct fundoscopy were also performed. RESULTS The median age of participants was 21 years (interquartile range = 19-23 years), and 62.2% were male. Most participants were homeless for less than 5 years (90%) and earning less than

Surgical management of submacular hemorrhage: experience at an academic Canadian centre

500 monthly (57.8%). Despite 51.1% of participants having previously owned corrective lenses, only 20% of participants currently owned them when assessed/at study time. When analyzing the better-seeing eye, presenting visual acuity was 20/50 or worse in 18.9% (95% CI 10.8%-27.0%) of participants. Pinhole occlusion decreased the number to 2.2% (95% CI 0%-5.3%). The most common cause of visual impairment was uncorrected refractive error. Ocular pathology was observed in 8 participants. Compared to adults, youth have similar functional visual impairment (adults 24.0%, youth 18.9%) but less impairment uncorrectable by pinhole occlusion (adults 11.0%, youth 2.2%) and are less dissatisfied with their vision (adults 70.0%, youths 36.7%). Although a higher proportion of homeless youths have visited an eye specialist in the past year (adults 14.0%; youths 17.8%), neither group is visiting as frequently as the Canadian average (41%) (p < 0.01). CONCLUSIONS Homeless youth have a high prevalence of visual impairment, even when living within a system of universal health insurance. Ongoing vision-screening programs, readily accessible free eye clinics, and particularly low-cost glasses may help address this need.