Pentosan Polysulfate Maculopathy With 13 Years of Follow-up Imaging.

Purpose: To describe a case of pentosan polysulfate maculopathy progression with 13 years of follow-up imaging. Methods: A case was analyzed and a literature review performed. Results: A 65-year-old woman was referred to the retina service for a second opinion of a bilateral progressive pigmentary maculopathy. Her medical history was significant for interstitial cystitis that was actively treated with daily pentosan polysulfate since 2003. Multimodal imaging and fundus examination were consistent with pentosan polysulfate maculopathy. A review of records showed previous fundus imaging dating back 13 years that permitted longitudinal assessment of the disease course. Imaging findings were more prominent than the fundus examination findings. There was a 5-year period from the onset of parafoveal atrophy to foveal involvement. A pseudopodial pattern of disease expansion was seen on fundus autofluorescence. Conclusions: To our knowledge, this case represents the longest documented follow-up imaging of the progression of pentosan polysulfate maculopathy in the literature.

Bilateral non-arteritic posterior ischaemic optic neuropathy following COVID-19 vaccination.

We report a case of bilateral posterior ischaemic optic neuropathy, which followed vaccination with ChAdOx1 nCoV-19 for COVID-19 prophylaxis. A man in his early 60s was initially assessed for bilateral acute vision loss following 3 days of frontal headaches. The patient denied any other preceding visual concerns or symptoms of giant cell arteritis. The patient received his first dose of the ChAdOx1 nCoV-19 vaccination 10 days before the onset of his symptoms.At initial presentation, visual acuity was counting fingers bilaterally. Blood work found normal erythrocyte sedimentation rate (6 mm/hour) and C reactive protein (<5 mg/L) as well as a negative infectious and autoimmune serology. He was negative for COVID-19 with PCR testing. Diffusion-weighted MRI showed restricted diffusion along both optic nerves. After 5 months, the patient's visual acuity remained counting fingers bilaterally with pale optic nerves. Isolated bilateral posterior ischaemic optic neuropathy has not been reported in association with the ChAdOx1 nCoV-19 vaccine.

Association Between Indication for Descemet Stripping Automated Endothelial Keratoplasty and Rural Residency.

PURPOSE: Residing in rural locations can be a barrier to health care access. This study investigated the impact of residing in rural and small town (RST) areas on Descemet stripping automated endothelial keratoplasty (DSAEK) indications and outcomes in Atlantic Canada. METHODS: A retrospective cohort analysis examined consecutive DSAEKs performed in Nova Scotia between 2017 and 2020. Patient rurality was determined by the Statistical Area Classification system developed by Statistics Canada. Univariate and multivariate logistic regression models were used to assess for factors associated with DSAEK indication, including repeat keratoplasty, RST residence status, and travel time. RESULTS: Of 271 DSAEKs during the study period, 87 (32.1%) were performed on the eyes of RST residents. The median postoperative follow-up time was 1.6 years. Undergoing DSAEK for a previous failed keratoplasty was not associated with a higher odds of RST residency (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.19-1.16; P = 0.13) but was associated with travel time (OR, 0.78 for each increasing hour of travel; 95% CI, 0.61-0.99; P = 0.044). RST residency was not associated with the occurrence of graft failure (OR, 0.48; 95% CI, 0.17-1.17; P = 0.13). CONCLUSIONS: Residing in a rural area in Atlantic Canada was not associated with DSAEK graft failure. Repeat endothelial keratoplasty was associated with shorter travel time for corneal surgery but not rural residency status. Further research in this field could inform regional health strategies aimed at improving equity and accessibility to ophthalmology subspecialist care.

Pars Plana Vitrectomy for Vitreomacular Traction Resulting in Persistent Postoperative Loculated Foveal Subretinal Fluid.

Purpose: To describe a case of postoperative persistent loculated subretinal fluid (SRF) that developed after pars plana vitrectomy (PPV) for vitreomacular traction (VMT) syndrome. Methods: A case was analyzed and a literature review performed. Results: A healthy 64-year-old man with no significant ocular history presented with persistent, symptomatic VMT. Combined phacoemulsification and PPV, epiretinal membrane and internal limiting membrane peeling, and gas-fluid exchange were performed. Postoperative spectral-domain optical coherence tomography imaging showed loculated foveal SRF. The SRF persisted for 8 months, with minimal change in size and little best-corrected visual acuity improvement. Conclusions: Although persistent loculated SRF has been reported after vitrectomy for rhegmatogenous retinal detachment (RD) in high myopia and tractional RD in diabetes, it has not yet been reported postoperatively after PPV for VMT. Studies of the pathophysiology and long-term course of persistent SRF after PPV for VMT are needed to inform management decisions for this rare complication.

Compliance With Cannabis Act Regulations Regarding Online Promotion Among Canadian Commercial Cannabis-Licensed Firms.

Importance: As global jurisdictions shift toward cannabis legalization, 2 areas of public health importance relate to exposure to youth and to truthful promotion. Although Canada's Cannabis Act specifies many prohibitions related to cannabis promotion, no systematic monitoring or enforcement among licensed firms exists. Compliance with marketing regulations has effects beyond Canadian citizens because of the global outreach of websites and social media. Objectives: To evaluate compliance among licensed firms with the Cannabis Act and analyze trends among violations regarding promotional material. Design, Setting, and Participants: This cross-sectional study evaluated cannabis-licensed firms after cannabis legalization. Data were extracted from online public platforms, including company websites, Facebook, Instagram, and Twitter, from October 1, 2019, to March 31, 2020. Descriptive statistics, Poisson regression, and logistic regression were used to analyze the associations of covariates with promotion violations. Main Outcomes and Measures: The primary outcome was characterization of type and prevalence of promotion violations. Secondary outcomes were the role of various covariates (namely, licensed firm characteristics and online platforms) in the frequency and probability of violations. Hypotheses were formulated before data collection. Results: Among 261 licensed firms, 211 (80.8%) had an online platform, including 204 (96.7%) with websites, 128 (60.7%) with Facebook, 123 (58.3%) with Instagram, and 123 (58.3%) with Twitter. Of all licensed firms with an online platform, 182 (86.3%) had at least 1 violation. Compared with websites, the risk of violations was significantly higher on Facebook (rate ratio [RR], 1.24; 95% CI, 1.11-1.39) and Instagram (RR, 1.19; 95% CI, 1.05-1.34). The most common violations included lack of age restrictions, brand glamorization, and omission of risk information. With websites as the reference group, lack of age restrictions was approximately 15 times more likely to occur on Facebook (odds ratio [OR], 14.76; 95% CI, 8.06-27.05); the odds of an age restriction violation were also higher on Instagram (OR, 2.48; 95% CI, 1.43-4.32) and Twitter (OR, 4.03; 95% CI, 2.29-7.09). For unsubstantiated claims, the odds of violations were significantly decreased on Facebook (OR, 0.23; 95% CI, 0.11-0.48) and Instagram (OR, 0.28; 95% CI, 0.14-0.57). The odds of glamorization were associated with an increase on Instagram (OR, 2.90; 95% CI, 1.72-4.88). Conclusions and Relevance: In this cross-sectional study, widespread violations were observed in online Canadian cannabis promotion. To protect public health and safety amid legalization, decision-makers should make explicit federal regulation and enforcement regarding promotional activities of cannabis retailers. These results suggest that policy and enforcement of cannabis promotion in Canada would have an international impact, from ease of access to online media and downstream consequences of unregulated promotion.

Drug Advertising Violations: A Longitudinal Trend Analysis of FDA Enforcement Letters from 2005 to 2019.

INTRODUCTION: In the United States, all pharmaceutical promotional activities must comply with regulatory standards set by the Food and Drug Administration (FDA); failure to comply may lead to receiving an FDA enforcement letter. Letters include details of the specific advertisement in violation, as well as the action that is required by the company to rectify the non-compliant promotion. OBJECTIVES: The aim of this study was to determine trends in enforcement letters from the FDA to parties responsible for pharmaceutical promotion violations from 2005 to 2019. METHODS: A longitudinal trend analysis was conducted of FDA enforcement letters sent to pharmaceutical companies from 2005 to 2019 (n = 318). Publicly available enforcement letters released by the Office of Prescription Drug Promotion were accessed and analysed online through the Center for Drug Evaluation and Research, a part of the FDA. Variables analysed included number of letters by year, violation categories, venues, intended audience, drug age and company revenues. Publicly available revenue was the major source for company revenue information. RESULTS: The total number of enforcement letters significantly decreased over time. Violations concerning risk information were significantly more prevalent than all other violation categories. Online promotional materials were most frequently cited. Proportionally, larger companies received the majority of letters in earlier years of observation, and smaller companies in later years (2013-2019). CONCLUSIONS: These trends are of value for industry and regulators alike in refining policy to ensure fair, balanced and meaningful information in pharmaceutical promotion. The frequency of violation letters has decreased in recent years; however, smaller companies have increasingly received the majority of letters. Small firms must increase their compliance around informing drug risk potential with balanced safety information across all promotional venues. Specifically, these findings are useful for pharmaceutical companies to direct educational efforts to promotional staff and their advertising agencies, especially regarding online advertising.

The Impact of Bariatric Surgery on Diabetic Retinopathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: While bariatric surgery induces remission of type 2 diabetes mellitus and reduces other microvascular complications, its impact on diabetic retinopathy (DR) is unclear. Some trials suggest early worsening of DR postsurgery because of rapid improvements in hyperglycemia. This meta-analysis sought to estimate the impact of bariatric surgery on DR for obese patients compared with medical treatment. DESIGN: Systematic review and meta-analysis. METHODS: The Medline, Embase, and PubMed Central databases were searched to March 2020. Primary studies comparing DR in patients undergoing bariatric surgery with those undergoing medical management were included. Results were meta-analyzed using a random-effects model. Primary outcomes included prevalence of all DR and sight-threatening DR after surgery. Secondary outcomes included worsening of DR within and beyond 12 months. RESULTS: Overall, 14 studies comprised of 110,300 surgical patients and 252,289 control subjects were included. Surgical patients had a statistically significantly lower postoperative prevalence of all DR (relative risk [RR] 0.17 [95% confidence interval {CI} 0.13-0.22]) and sight-threatening DR (RR 0.47 [95% CI 0.27-0.82]). Early worsening of DR and progression to sight-threatening DR had occurred more often in those with more severe DR initially. However, beyond 12 months, bariatric surgery resulted in significantly fewer patients with worsened DR (RR 0.29 [95% CI 0.16-0.54]). The overall risk of bias was low; estimates of relative effects had low to moderate certainty of evidence. CONCLUSION: While bariatric surgery was associated with fewer cases of all and sight-threatening DR, early worsening was more severe in patients with existing sight-threatening DR. These findings argue for frequent monitoring during the first postoperative year.

Association Between the Use of Surrogate Measures in Pivotal Trials and Health Technology Assessment Decisions: A Retrospective Analysis of NICE and CADTH Reviews of Cancer Drugs.

OBJECTIVE: To assess whether using surrogate versus patient-relevant endpoints in pivotal trials of cancer drugs was associated with health technology assessment recommendations in England (National Institute for Health and Care Excellence [NICE]) and Canada (Canadian Agency for Drugs and Technologies in Health [CADTH]). METHODS: Cancer drug approvals from 2012 to 2016 were categorized by demonstrating benefit on overall survival (OS), progression-free survival, disease response, or having no comparator. Approvals were analyzed by benefit category and health technology assessment recommendation. The association between benefit (surrogate vs OS) and recommending a drug was examined using descriptive statistics and linear probability models controlling for unmet need, orphan designation, and cost-effectiveness. RESULTS: Of 42 cancer indications that NICE recommended, 15 (36%) demonstrated OS benefit. Cancer indications with OS benefit were less likely to receive a recommendation from NICE than those without (P = .04). In linear probability models, availability of OS benefit was no longer associated with a recommendation from NICE (P = .32). Cost-effective cancer drugs had a 55.6% (95% CI: 38.9%-72.3%) higher probability of receiving a recommendation from NICE than those that were not. In Canada, 15 of 37 (41%) cancer indications that were recommended showed OS benefit. There was no detectable association between surrogate measures and CADTH recommendations based on descriptive statistics (P = .62) or in linear probability models (P = .73). CONCLUSION: When cost-effectiveness was considered, pivotal trial endpoints were not associated with NICE recommendations. Pivotal trial endpoints, unmet need, orphan status, and cost-effectiveness did not explain CADTH recommendations.

Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13.

Objective To determine the availability of data on overall survival and quality of life benefits of cancer drugs approved in Europe.Design Retrospective cohort study.Setting Publicly accessible regulatory and scientific reports on cancer approvals by the European Medicines Agency (EMA) from 2009 to 2013.Main outcome measures Pivotal and postmarketing trials of cancer drugs according to their design features (randomisation, crossover, blinding), comparators, and endpoints. Availability and magnitude of benefit on overall survival or quality of life determined at time of approval and after market entry. Validated European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) used to assess the clinical value of the reported gains in published studies of cancer drugs.Results From 2009 to 2013, the EMA approved the use of 48 cancer drugs for 68 indications. Of these, eight indications (12%) were approved on the basis of a single arm study. At the time of market approval, there was significant prolongation of survival in 24 of the 68 (35%). The magnitude of the benefit on overall survival ranged from 1.0 to 5.8 months (median 2.7 months). At the time of market approval, there was an improvement in quality of life in seven of 68 indications (10%). Out of 44 indications for which there was no evidence of a survival gain at the time of market authorisation, in the subsequent postmarketing period there was evidence for extension of life in three (7%) and reported benefit on quality of life in five (11%). Of the 68 cancer indications with EMA approval, and with a median of 5.4 years' follow-up (minimum 3.3 years, maximum 8.1 years), only 35 (51%) had shown a significant improvement in survival or quality of life, while 33 (49%) remained uncertain. Of 23 indications associated with a survival benefit that could be scored with the ESMO-MCBS tool, the benefit was judged to be clinically meaningful in less than half (11/23, 48%).Conclusions This systematic evaluation of oncology approvals by the EMA in 2009-13 shows that most drugs entered the market without evidence of benefit on survival or quality of life. At a minimum of 3.3 years after market entry, there was still no conclusive evidence that these drugs either extended or improved life for most cancer indications. When there were survival gains over existing treatment options or placebo, they were often marginal.