Vuong Nguyen

Metaanalysis of real-world outcomes of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration

Purpose: To report the efficacy and safety of intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD) in real-world practice. Methods: Metaanalysis of ∼26,360 patients from 42 real-world observational studies reporting outcomes of intravitreal ranibizumab for nAMD published between 2007 and 2015. Baseline demographics, lesion type, and visual acuity (VA) were recorded. The weighted mean was calculated for change in VA and frequency of injections and visits during year 1, year 2, and ≥3 years. Local and systemic adverse events were recorded. Results: The mean change in VA for patients receiving a treat-and-extend regimen was +8.8 (95% confidence interval [CI]: 5.8 to 11.8), +6.7 (95% CI: 3.2 to 10.1), and +5.4 (95% CI: −4.1 to 14.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 1 year (n = 1,539), 2 years (n = 2,521), and ≥3 years (n = 1,298), in comparison with +3.5 (95% CI: 2.0 to 5.0), +1.3 (95% CI: −1.6 to 4.2), and −1.9 (95% CI: −9.8 to 6.0) ETDRS letters for pro re nata at 1 year (n = 20,247), 2 years (n = 14,408), and ≥3 years (n = 11,714). Treat-and-extend patients received on average more injections (6.9 vs. 4.7) but had fewer visits (7.6 vs. 9.2) in the first year. Baseline characteristics were similar between the regimens. The reported rate of endophthalmitis was 17 of 66,176 intravitreal injections (0.026%). Conclusion: Intravitreal ranibizumab for nAMD prevents severe visual loss in real-world practice. Patients can achieve visual gain from baseline, but the extent to which these are maintained in the long term may depend on the frequency of injections.

On the validity of visual cover estimates for time series analyses: a case study of hummock grasslands

Changes in vegetation cover are strongly linked to important ecological and environmental drivers such as fire, herbivory, temperature, water availability and altered land use. Reliable means of estimating vegetation cover are therefore essential for detecting and effectively managing ecosystem changes, and visual estimation methods are often used to achieve this. However, the repeatability and reliability of such monitoring is uncertain due to biases and errors in the measurements collected by observers. Here, we use two primary long-term monitoring datasets on spinifex grasslands, each established with different motivations and methods of data collection, to assess the validity of visual estimates in detecting meaningful trends. The first dataset is characterised by high spatial and temporal coverage but has limited detail and resolution, while the second is characterised by more intensive sampling but at fewer sites and over a shorter time. Using multivariate auto-regressive state-space models, we assess consistency between these datasets to analyse long-term temporal and spatial trends in spinifex cover whilst accounting for observation error. The relative sizes of these observation errors generally outweighed process, or non-observational errors, which included environmental stochasticity. Despite this, trends in the spatial dynamics of spinifex cover were consistent between the two datasets, with population dynamics being driven primarily by time since last fire rather than spatial location. Models based on our datasets also showed clear and consistent population traces. We conclude that visual cover estimates, in spite of their potential uncertainty, can be reliable provided that observation errors are accounted for.

Two Year Outcomes Of “treat And Extend” Intravitreal Therapy Using Aflibercept Preferentially For Neovascular Age-related Macular Degeneration

Purpose: To report 24-month outcomes of a treat and extend (T&E) regimen using aflibercept in eyes with neovascular age-related macular degeneration. Methods: This was a database observational study that included treatment-naive eyes with neovascular age-related macular degeneration tracked by the Fight Retinal Blindness! outcome registry completing 24 months of sole monotherapy with aflibercept treatment under a T&E regimen between November 1, 2012 and January 31, 2014. Locally weighted scatterplot smoothing curves were used to display visual acuity outcomes. Main outcome measures were change in visual acuity at 24 months and number of injections and visits during the study period. Results: The study population, identified by reviewing the database, consisted of 136 eyes from 123 patients completing 24 months of follow-up on aflibercept. Mean (SD) age was 77.2 (7.0) years, 59% were female. Mean visual acuity increased from 61.4 (∼20/60; SD 17.4) letters at baseline to 67.4 (∼20/45; SD 17.7) letters at 24 months (+6.0 letters [95% confidence interval: 3.3–8.5]; P < 0.001). From baseline to 24 months, the proportion of eyes with visual acuity ≥70 letters (20/40) increased (40%–58%, P < 0.001) and the proportion of eyes with visual acuity ⩽35 letters (20/200) remained the same (10%; P = 0.547). Ninety-eight per cent of eyes starting with visual acuity ≥70 letters (20/40) were able to maintain this up to 24 months. From the first to the second year of treatment, the mean number of injections (7.8 [2.1] vs. 5.7 [2.6]; P < 0.001) and visits (8.7 [1.7] vs. 6.5 [2.4]; P < 0.001) decreased for eyes completing 24 months of treatment. When data from 60 eligible eyes that did not complete 2 years follow-up, along with 14 eyes that switched to ranibizumab, were included using last observation carried forward, the mean change in visual acuity from baseline was +5.6 letters (95% confidence interval: 3.3–7.7). Conclusion: These data indicate that eyes treated with aflibercept, as a sole therapy, in routine clinical practice with a T&E regimen can achieve good visual outcomes while decreasing the burden of treatments and clinic visits.

Short-term vision gains at 12 weeks correlate with long-term vision gains at 2 years: results from the BEVORDEX randomised clinical trial of bevacizumab versus dexamethasone implants for diabetic macular oedema

Aim To determine whether early vision gains predict long-term visual outcomes in the BEVORDEX randomised clinical trial of bevacizumab or dexamethasone implants for diabetic macular oedema. Methods Post hoc analysis of 68 study eyes (77%) that completed 2 years follow-up of the BEVORDEX multicentre randomised clinical trial set in Australia (ClinicalTrials.gov identifier: NCT01298076). Study eyes from both groups were combined and stratified by visual acuity (VA) change in the first 12 weeks in to three groups: (a) suboptimal gain: <5 letters gain (includes VA loss), (b) moderate gain: 5–9 letters gain, (c) pronounced gain: ≥10 letters gain. This was correlated with VA outcome at 104 weeks taking into account treatment allocation and baseline lens status. Results The change in VA in the first 12 weeks was significantly correlated with VA change at 104 weeks (p<0.001). This was independent of treatment allocation (p=0.353) and lens status at baseline (p=0.593). The change in central macular thickness at 12 weeks did not correlate with VA gain at 104 weeks (p=0.847). Conclusion Short-term visual gain at 12 weeks was strongly correlated with long-term vision improvement independent of treatment allocation or baseline lens status. Early improvement in central macular thickness was not predictive of long-term visual outcomes. Trial registration number NCT01298076, Post-results.

Real-world visual outcomes in patients with neovascular age-related macular degeneration receiving aflibercept at fixed intervals as per UK licence

To assess the impact of injection frequency on visual outcomes in patients with neovascular age‐related macular degeneration (nAMD) treated with intravitreal aflibercept.

Relationship between reticular pseudodrusen and choroidal thickness in intermediate age-related macular degeneration: comment: Letter to the Editor

Dear Editor, we read with interest the study by Dr. Ho et al.1 about the relationship between reticular pseudodrusen (RPD) and choroidal thickness in intermediate age related macular degeneration and would like to comment on their results and conclusions.

Re: Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group, et al.: Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials (Ophthalmology 2016;123:1751-1761)

REPLY: We thank Dr Galvis and colleagues for their correspondence. The European Society of Cataract and Refractive Surgeons reported in 2007 the only randomized clinical trial (RCT) evaluating the use of intracameral antibiotics for endophthalmitis prophylaxis during cataract surgery. However, this study was limited by the relatively high rates of endophthalmitis in eyes not randomized to receive intracameral cefuroxime, the use of topical levofloxacin, and the use of multiple surgical techniques. The US Food and Drug Administration requires 2 consistent trials for good reason. In this case, the totality of evidence is far from clear, with other observational studies reporting very low rates of endophthalmitis without intracameral antibiotics and an unclear risk-benefit ratio associated with these very low rates. Many cataract surgeons, especially in the United States, do not find the results of the European Society of Cataract and Refractive Surgeons study sufficiently compelling to change their practice patterns. We agree with the conclusion of the Cochrane Review, cited by Galvis and colleagues, that it seems unlikely that another major RCT will be conducted in the near future to address this very important topic. Therefore, the practicing cataract surgeon must make clinical decisions based on the best available evidence. What is the best available evidence? Clearly, RCTs represent the highest level of evidence. “Big data” retrospective series and meta-analyses are also beneficial, but largely because of uncontrolled confounding they are not considered to provide the same level of evidence as RCTs. The widespread availability of electronic medical records has led to many observational series. One such recent study, including 3 351 401 surgeries, reported a significant negative association between intracameral cefuroxime and endophthalmitis rates yet concluded, “in the absence of a randomized clinical trial, [these data] cannot prove a direct cause-and-effect relationship.” Even if the clinical trial results are correct, they do not answer the question of whether the balance of risks and benefits is in favor of the treatment. These important considerations include both medical risks (immediate risk to individuals and risk to the population) and cost of treatment. Intracameral antibiotics are associated with risks to the patient to whom they are administered (including cystoid macular edema, toxic anterior segment syndrome, hemorrhagic occlusive retinal vasculitis, and others) and risks to the population at large by selecting for drug-resistant organisms. Antibiotic stewardship programs seek to reduce the unnecessary and inappropriate use of these agents. In the absence of definitive RCTs, the practicing clinician must consider these issues. “Standard of care” is a legal concept, not a medical one. Standards of care vary by geographic location and change over time. Intracameral antibiotics are not the universal standard of care, even in Europe. Evidence-based management emphasizes that clinical decisions should be guided by scientific data, preferably from RCTs. In our opinion, with only 1 RCT, conflicting results from observational studies and no clear risk-benefit ratio, cataract surgeons in the United States should not feel compelled to use intracameral antibiotics. STEPHEN G. SCHWARTZ, MD, MBA HARRY W. FLYNN, Jr., MD ANDRZEJ GRZYBOWSKI, MD, PHD NIDHI RELHAN, MD FREDERICK L. FERRIS, III, MD

Making the most of incomplete long-term datasets: the MARSS solution

ABSTRACT Long-term field-based monitoring is essential to develop a deep understanding of how ecosystems function and to identify species at risk of decline. However, conducting long-term field-based research poses some unique challenges due to the harsh environmental conditions or extreme weather events that may be encountered. Such conditions are especially likely to occur in arid environments. Fieldwork issues can arise from vehicle breakdowns, wildfires and heavy rainfall events, all of which can delay or even cancel data collection. In addition, long-term monitoring typically requires multiple observers, which may add observation bias to estimates of measured parameters. Thus there is an increasing need to develop new statistical techniques that take advantage of the power of long time-series datasets that also are incomplete. Here we discuss multivariate autoregressive state-space (MARSS) modelling; a relatively new statistical technique for modelling long-term time-series data. MARSS models allow u...

Dexamethasone implant for the treatment of persistent diabetic macular oedema despite long-term treatment with bevacizumab: Letter to the Editor

We conducted a prospective study to assess the benefit of switching from bevacizumab to dexamethasone 0.7mg intravitreal implant (DEX-implant) (Ozurdex, Allergan) in eyes with persistent diabetic macular oedema (DMO). This article is protected by copyright. All rights reserved.

No association between sleep apnoea and macular telangiectasia type 2 and its markers of severity and progression: a case-control study and retrospective cohort study: SAMTel study

Idiopathic Macular Telangiectasia Type 2 (MacTel) is an uncommon, progressive retinal disease usually affecting both eyes. Currently there is no know treatment however with similar comorbidities to Obstructive Sleep Apnoea (OSA) there is plausibility of an association which may accelerate disease progression.