Association of pre-residency publications with research productivity in residency, fellowship, and academic career choice among Canadian ophthalmologists.

OBJECTIVE: This study aimed to assess whether the research output of medical students who matched into a Canadian ophthalmology residency program influences their subsequent research productivity during residency, decision to pursue a fellowship, or engagement in academic practice. DESIGN: Retrospective database review. PARTICIPANTS: A total of 369 trainees commencing ophthalmology residency from 2004 to 2015 at 15 residency programs. METHODS: Each trainee's publication record was queried in Scopus before and after the date they started residency. Multiple public sources were searched to identify fellowship placement and the type of subsequent practice (i.e., academic or community). Predictors of research productivity during residency, fellowship, and practice setting were assessed using multivariable regression analyses. RESULTS: Trainees with pre-residency publications (n = 187) demonstrated significantly higher research productivity during residency than those without pre-residency publications (n = 182), with a mean of 5.17 ± 5.97 versus 1.60 ± 2.38 publications on any topic (p < 0.001). Pre-residency research output was a predictor of research productivity during residency (relative risk = 1.17; 95% CI, 1.09-1.27; p < 0.001), pursuing fellowship (odds ratio, 2.9; 95% CI, 1.74-4.83), and an academic career (odds ratio = 1.85; 95% CI, 1.07-3.2). CONCLUSION: Pre-residency research output is a significant predictor of research productivity during residency and subsequent career choices, suggesting that pre-residency publishing reflects a propensity toward an academic trajectory. Residency publication count moderates this association, underscoring the role of the residency program environment in fostering research productivity. Addressing barriers such as mentorship, funding, and curriculum may be key to incentivizing trainees to pursue academic medicine.

Prophylaxis against intraocular pressure spikes following uncomplicated phacoemulsification: a systematic-review and meta-analysis.

BACKGROUND: To investigate the effect of perioperative intraocular pressure (IOP) lowering medications on controlling postoperative IOP following uncomplicated phacoemulsification. METHODS: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched up until November 2022. Randomised controlled trials (RCTs) that assessed IOP change via applanation tonometry in medicated and control arms following uncomplicated cataract surgery in healthy eyes were included. The primary outcome was the weighted mean difference (WMD) of IOP at 2-8 h, 12-24 h, and 1-7 days postoperatively within each medication class or common fixed-combination formulations. Risk of bias was assessed using the revised risk of bias in randomised trials (RoB-2). Level of evidence was rated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) RESULTS: From 702 screened articles, 30 RCTs involving 2986 eyes were included. There was a statistically significant reduction in IOP favouring treatment arms at 2-8 h (WMD = -3.87 mmHg; 95% CI [-4.75, -3.00]; p < 0.001) and 12-24 h (WMD = -2.69 mmHg; 95% CI [-3.36, -2.02]; p < 0.001), with the effect wearing off beyond 1 day (p = 0.18). Between medication classes, the largest effect at both 2-8 h and 12-24 h was observed with intracameral cholinergics or fixed-combination carbonic anhydrase inhibitor-beta-blocker (FCCB) formulations. Conversely, the smallest effect was observed with prostaglandin analogues, alpha-agonists, and topical carbonic anhydrase inhibitors (CAIs). CONCLUSION: Prophylaxis against acute IOP elevations following uncomplicated cataract surgery is effective. FCCB and intracameral cholinergics are the most effective ocular antihypertensive agents, while alpha-agonists, prostaglandin analogues, and topical CAIs were found to be the least effective. These findings may inform future surgical guidelines.

Evaluating Measurement Properties of Patient-Reported Outcome Measures in Glaucoma: A Systematic Review.

TOPIC: The purpose of the current study was to systematically identify and evaluate existing patient-reported outcome measures (PROMs) for clinical glaucoma practice. CLINICAL RELEVANCE: Understanding and incorporating patient preferences into decision-making is now recognized as critical for optimal resource allocation, especially in technologically advancing areas, such as minimally invasive surgeries. Patient-reported outcome measures are instruments designed to evaluate the health outcomes that are most important to patients. Despite their recognized importance, especially in the era of patient-centered care, their routine use in clinical settings remains low. METHODS: A systematic literature search was conducted in 6 databases (EMBASE, MEDLINE, PsycINFO, Scopus, BIOSIS, and Web of Science) from the date of inception. Studies were included in the qualitative review if they reported measurement properties of PROMs in adult patients with glaucoma. COnsensus-based Standards for the selection of health Measurement INstruments guidelines were used to assess the included PROMs. The study protocol is registered with PROSPERO (registration number: CRD42020176064). RESULTS: The literature search yielded 2661 records. After deduplication, 1259 studies entered level 1 screening, and based on title and abstract review, 164 records proceeded to full-text screening. In 48 included studies, 70 instrument reports discuss 43 distinct instruments in 3 major categories: glaucoma-specific, vision-specific, and general health-related quality of life. Most used measures were glaucoma-specific (Glaucoma Quality of Life [GQL] and Glaucoma Symptom Scale [GSS]) and vision-specific (National Eye Institute Visual Function Questionnaire [NEI VFQ-25]). All 3 have sufficient validity (especially construct), with GQL and GSS having sufficient internal consistency, cross-cultural validity, and reliability, with reports suggesting high methodological quality. CONCLUSION: The GQL, GSS, and NEI VFQ-25 are the 3 most used questionnaires in a research setting, having considerable validation in a patient population with glaucoma. Limited reports on interpretability, responsiveness, and feasibility in all 43 identified instruments make identifying a single optimal questionnaire for clinical use challenging and highlight the need for further studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ALK5 Inhibition of Subconjunctival Scarring From Glaucoma Surgery: Effects of SB-431542 Compared to Mitomycin C in Human Tenon's Capsule Fibroblasts.

Purpose: The gold standard for managing postoperative ocular fibrosis in glaucoma surgery is the chemotherapeutic mitomycin C (MMC) despite its association with significant adverse effects. This study compares in vitro the antifibrotic efficacy and cytotoxicity of the small-molecule TGFß1 inhibitor SB-431542 (SB) to MMC. Methods: To measure collagen contraction, human Tenon's capsule fibroblasts (HTCFs) embedded in a three-dimensional collagen lattice were exposed to 0.2 mg/mL MMC or 20 µM SB followed by incubation with 2 ng/mL TGFß1. Total protein extracted from experimentally treated HTCFs underwent immunoblotting for α-smooth muscle actin (α-SMA), matrix metallopeptidase 9 (MMP-9), and EDA splice-variant fibronectin (EDA-FN) expression. Cytotoxicity and cell metabolism were assessed using LIVE/DEAD staining, lactate dehydrogenase (LDH) assay, and methylthiazole tetrazolium (MTT) assay. Results: Collagen lattice contraction in TGFß1-induced HTCFs was significantly lowered by SB and MMC. Pretreatment with SB and MMC significantly lowered protein expression of α-SMA, MMP-9, and EDA-FN in HTCFs relative to TGFß1 alone. HTCF viability in collagen lattices was significantly reduced with MMC pretreatment but not SB pretreatment. MMC-pretreated HTCFs had a significant increase in LDH release after 3 hours and a decrease in MTT activity after 20 minutes, while SB-pretreated HTCFs showed no significant changes via MTT or LDH assay during the same treatment period. Conclusions: SB shows comparable efficacy to MMC in reducing expression of fibrosis-promoting proteins in HTCFs and in vitro scarring activity. SB distinguishes itself from MMC by exhibiting less cytotoxicity in both two-dimensional and three-dimensional in vitro assays. Translational Relevance: This study demonstrates in vitro the potential of SB as a safer alternative ocular antifibrotic agent.

Deep Ensemble Learning for Retinal Image Classification.

Purpose: Vision impairment affects 2.2 billion people worldwide, half of which is preventable with early detection and treatment. Currently, automatic screening of ocular pathologies using convolutional neural networks (CNNs) on retinal fundus photographs is limited to a few pathologies. Simultaneous detection of multiple ophthalmic pathologies would increase clinical usability and uptake. Methods: Two thousand five hundred sixty images were used from the Retinal Fundus Multi-Disease Image Dataset (RFMiD). Models were trained (n = 1920) and validated (n = 640). Five selected CNN architectures were trained to predict the presence of any pathology and categorize the 28 pathologies. All models were trained to minimize asymmetric loss, a modified form of binary cross-entropy. Individual model predictions were averaged to obtain a final ensembled model and assessed for mean area under the receiver-operator characteristic curve (AUROC) for disease screening (healthy versus pathologic image) and classification (AUROC for each class). Results: The ensemble network achieved a disease screening (healthy versus pathologic) AUROC score of 0.9613. The highest single network score was 0.9586 using the SE-ResNeXt architecture. For individual disease classification, the average AUROC score for each class was 0.9295. Conclusions: Retinal fundus images analyzed by an ensemble of CNNs trained to minimize asymmetric loss were effective in detection and classification of ocular pathologies than individual models. External validation is needed to translate machine learning models to diverse clinical contexts. Translational Relevance: This study demonstrates the potential benefit of ensemble-based deep learning methods on improving automatic screening and diagnosis of multiple ocular pathologies from fundoscopy imaging.

Research productivity of ophthalmology residents and its relationship to academic career outcomes.

OBJECTIVE: To assess the impact of ophthalmology resident research and its relationship to subsequent practice. DESIGN: Cross-sectional study. PARTICIPANTS: Three hundred and twenty residents of Canadian ophthalmology programs graduating between 2009 and 2020. METHODS: Bibliometric data were obtained for each resident from Scopus. Indices of scholarly productivity included number of publications, h-index, m-quotient, and total citations. Demographic and career data were obtained from faculty listings and professional and regulatory web sites. Career outcomes included location and subspecialty of fellowship training and type of ultimate practice (academic vs community). RESULTS: In total, 208 of 320 graduates (65%) published at least 1 peer-reviewed article during residency. Bibliometric indices, including numbers of papers, h-index, and total citations, were significantly higher for male residents and residents who pursued academic and subspecialized practices. No significant trends were seen regarding scholarly productivity and fellowship match outcomes (e.g., location and subspecialty of fellowship). The bulk of resident research projects was of lower tiers of evidence, including retrospective studies (n = 111) and case reports (n = 108). Five-year scholarly impact of resident research decreased over time (h-index, m = -0.14; p < 0.01) despite stable publication volumes. CONCLUSIONS: Greater scholarly activity in residency corresponds to more academic and subspecialized practices but is not associated with type of fellowship. The impact of resident research declined between 2009 and 2020. Sex-based disparities exist.

Differential effects of acetylsalicylic acid and mitomycin C on cytokine-induced Tenon's capsule myofibroblast transdifferentiation and activity: Implications for glaucoma surgery.

Inflammation-driven scarring is a major contributor to surgical failure after subconjunctival bleb forming glaucoma surgery. The current gold standard anti-scarring adjuvant mitomycin C (MMC) has variable effectiveness and is associated with significant risks. Acetylsalicylic acid (ASA), when delivered locally, repurposes the typically pro-inflammatory cyclooxygenase (COX-2) signaling for the resolution of inflammation and mitigating inflammation-mediated fibrosis. The aim of this study is to compare the effects of ASA and MMC in an in vitro model of subconjunctival scarring. Glaucoma patient-derived Tenon's capsule fibroblasts (HTCFs) were treated with TGFß1 (2 ng/mL) plus or minus ASA (1600 µg/ml), or MMC (0.05, 0.1, 0.2 mg/mL). In vitro collagen contraction, MTT, LDH, immunofluorescence, and Western blot assays were performed. To elucidate the mechanistic effects of ASA in TGFß1-induced HTCFs, liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to identify and measure pro-inflammatory and pro-resolving lipid mediator secretion. ASA was at least as effective as MMC in reducing TGFß1-induced HTCF-mediated collagen contraction, metabolic activity, and pro-fibrotic protein expression, with less cytotoxicity. Within cytokine-activated HTCFs, ASA significantly impaired secretion of pro-inflammatory lipid mediators prostaglandin E2 and 6-keto-prostaglandin F1α and significantly increased secretion of the pro-resolving mediators 5-hydroxyeicosatetraenoic acid (HETE), 15-HETE and 18-hydroxyeicosapentaenoic acid (HEPE). ASA reduces cytokine-induced myofibroblast transdifferentiation in HTCFs, being non-inferior to MMC in vitro. ASA's effects are associated with a unique lipid mediator expression profile, suggesting that the ASA-induced resolution of inflammation may be a promising strategy to mitigate inflammation-mediated scarring and could offer a novel alternative as a surgical adjuvant.

Impact of Inhaled and Intranasal Corticosteroids Exposure on the Risk of Ocular Hypertension and Glaucoma: A Systematic Review and Meta-Analysis.

Purpose: Starting in 2019, the Global Initiative for Asthma recommended the use of inhaled corticosteroids (ICS) as part of reliever combination therapy in patients 12 years of age and older, thus dramatically increasing the population exposure to ICS. ICS and intranasal corticosteroids (INS) are commonly used for a variety of respiratory diseases. Chronic steroid use is a well-known risk factor for elevated intraocular pressure (IOP) and glaucoma regardless of route of administration. This study aimed to determine the reported risk of glaucoma, ocular hypertension (OHT) and IOP elevation associated with ICS and INS use. Materials and Methods: Systematic literature search in MEDLINE, EMBASE, Cochrane, CINAHL, BIOSIS, and Web of Science databases from the date of inception identified studies that assess ocular outcomes related to glaucoma in ICS and INS users. Study selection, risk of bias assessment and data extraction were done independently in duplicate. Meta-analysis assessed glaucoma incidence, OHT incidence and IOP changes in patients using ICS and INS. Study adhered to PRISMA guidelines. Study protocol was registered with PROSPERO: CRD42020190241. Results: Qualitative and quantitative analyses included 65 and 41 studies, respectively. Incidence of glaucoma was not significantly different in either ICS or INS users compared to control over 45,457 person-years of follow-up. Similarly, no significant difference in OHT incidence over 4431 person-years was detected. In studies reporting IOP, a significantly higher IOP was observed (0.69 mmHg) in 857 ICS or INS users compared to 615 controls. However, no significant increase in IOP was observed within ICS or INS users when compared to pre-treatment baseline. Conclusion: Overall, use of ICS or INS does not significantly increase the incidence of glaucoma or OHT. However, ICS and INS patients had significantly higher IOPs compared to untreated patients. Awareness of these findings is significant in care of patients with additional risk factors for glaucoma.

Scholarly Impact of Academic Ophthalmologists and Vision Scientists in Canada.

OBJECTIVE: To outline the current impact of Canadian ophthalmology and vision science research as measured by novel research metrics. DESIGN: Cross-sectional survey. PARTICIPANTS: All Canadian ophthalmologists (n = 687) and vision scientists (n = 119) with an online bibliometric profile and academic appointment at a major ophthalmology training centre were included. METHODS: Faculty lists of Canada's 15 major academic ophthalmology departments were obtained. Faculty names, appointments, sex, and educational background were recorded. Elsevier's Scopus database was used to calculate H-index, m-quotient, and total citations for each faculty member. Details around grant funding were obtained through the Canadian Institutes of Health Research (CIHR) Funding Decisions Database. RESULTS: Average H-indices were 7.42 ± 7.98 for ophthalmologists and 23.78 ± 15.25 for vision scientists. Higher academic appointment was correlated with higher h-indices and m-quotients (p <0.0001 for both). Most academic departments had significantly more males than females (avg. 71% male, 29% female); however, more equal ratios were seen in faculties in Quebec. No significant differences in research impact were identified between male and female ophthalmologists when controlled for academic appointment and career stage (p > 0.05). In clinical ophthalmology research, the top three departments with the highest average H-indices were Western University, the University of Toronto, and Dalhousie University. The University of British Columbia, Université de Montréal, and McGill University received the most funding from the CIHR in the last 10 years. CONCLUSION: This study highlights the current scope of ophthalmology and vision science research in Canada. Important trends were identified in research productivity across academic rank, sex, and clinical subspecialty.

Rapid visual field progression in a patient with glaucoma as the presenting manifestation of sarcoidosis.

PURPOSE: To report a case of accelerated visual field progression secondary to a new orbital apex lesion in a patient with a longstanding history of fatigue and cough. OBSERVATIONS: A 73-year-old myopic female with known open angle glaucoma presented with accelerated unilateral visual field progression. Maximally tolerated medical therapy was instituted over a period of 1-2 years with imminent discussions of surgical intervention. Around this time the patient reported worsening cough and fatigue, which were initially attributed to glaucoma medication side effects. Consideration of the patient's remote history of melanoma and the current asymmetry of the visual field progression triggered a computerized tomography (CT) scan of the orbits as part of the management. An orbital apex lesion was discovered, raising suspicion for metastatic melanoma, and restaging CT imaging uncovered renal, hepatic, and mediastinal masses. Unexpectedly, biopsies revealed non-necrotizing granulomatous inflammatory processes consistent with a diagnosis of sarcoidosis. It is perhaps noteworthy that the patient had received interferon therapy for management of her melanoma; previous reports have associated interferon exposure with subsequent sarcoid disease, regardless of duration of therapy or elapsed time since exposure. CONCLUSIONS AND IMPORTANCE: Although rare, sarcoidosis can occur virtually anywhere in the body, including the orbital apex. Its common early symptoms, fatigue and cough, are insidious and seen frequently in this patient's age group and medication side effect profile. It is important to maintain an appropriate index of suspicion when monitoring atypical visual field progression in a patient with glaucoma. In this case, imaging, subsequent biopsy, and a multi-specialty team were integral to this patient's diagnosis and management.

Dorzolamide/Timolol Fixed Combination: Learning from the Past and Looking Toward the Future.

The key clinical attributes of preserved dorzolamide/timolol fixed combination (DTFC) and the emerging potential of preservative-free (PF) DTFC are reviewed with published evidence and clinical experience. The indications and role of DTFC in current glaucoma management are critically discussed. Preserved DTFC became the first intraocular pressure (IOP)-lowering fixed combination (FC) approved by the US Food and Drug Administration (FDA) and remains one of most commonly used medications worldwide. The pharmacological properties of DTFC reflect those of its two time-tested constituents, i.e., the carbonic anhydrase inhibitor dorzolamide and the non-selective beta-blocker timolol. In regulatory studies DTFC lowers IOP on average by 9 mmHg (32.7%) at peak and by 7.7 mmHg (27%) at trough. In trials DTFC shows equivalence to unfixed concomitant therapy, but in real-life practice it may prove superior owing to enhanced convenience, elimination of the washout effect from the second drop, improved tolerability, and better adherence. PF DTFC became the first PF FC approved, first in unit-dose pipettes, and more recently in a multidose format. Cumulative evidence has confirmed that PF DTFC is at least equivalent in efficacy to preserved DTFC and provides a tangible clinical benefit to patients with glaucoma suffering from ocular surface disease by improving tolerability and adherence. Finally, we identify areas that warrant further investigation with preserved and PF DTFC.

The Pro-Fibrotic Behavior of Human Tenon's Capsule Fibroblasts in Medically Treated Glaucoma Patients.

PURPOSE: The aim of this study was to compare human Tenon's capsule fibroblasts (HTCFs) obtained from patients who received medical therapy for glaucoma (glaucomatous patients) and patients not treated for glaucoma (non-glaucomatous patients) in terms of wound healing and fibrosis. PATIENTS AND METHODS: Bioartificial tissues (BATs) were generated using primary HTCF-populated collagen lattices. Pro-fibrotic gene expression within HTCFs was compared between glaucomatous patients and non-glaucomatous patients after BAT culture. The BATs were also assessed regarding fibroblast-myofibroblast transition, collagen remodeling and collagen contraction using alpha-smooth muscle actin immunohistochemistry, picrosirius red staining and collagen contraction assays, respectively. RESULTS: Pro-fibrotic gene expression in BAT-cultured HTCFs derived from glaucomatous patients was significantly increased compared to non-glaucomatous patients. BATs imbued with HTCFs collected from glaucomatous patients exhibited a greater proportion of myofibroblasts as well as increased collagen contraction/remodeling compared to HTCFs isolated from non-glaucomatous patients. CONCLUSION: HTCFs from glaucomatous and non-glaucomatous patients differ in the expression of genes involved in fibrosis, proportion of fibroblasts undergoing transdifferentiation into myofibroblasts, contractile properties and collagen remodeling. These results suggest that for any number of reasons, at a cellular level, patients who received medical therapy for glaucoma have eyes primed for fibrosis.

Estimating patient-reported outcomes for glaucoma management: A cross-sectional study.

AIM: To identify important explanatory variables of four patient-reported outcomes (PROs): vision-related quality of life (VRQoL), preference-based health-related quality of life (HRQoL), social support and community integration and depressive symptoms. METHODS: Cross-sectional study conducted at one ophthalmic practice in a hospital setting. Patients with a diagnosis of glaucoma or glaucoma suspect (n = 250) were sequentially recruited. Patients with language restrictions were excluded. Data were collected through medical chart reviews and face-to-face interviews. The PROs were measured using validated tools. Candidate models for predicting PROs from explanatory variables were constructed using linear and logistic regression, as well as classification and regression trees. Through leave-one-out cross-validation, the performance of each model was assessed in terms of mean absolute error. RESULTS: Use of mobility aids, best corrected visual acuity (BCVA), income, and living arrangements were most predictive of VRQoL, social support, and community integration. Use of mobility aids was also most predictive of the presence of depressive symptoms, and BCVA with preference-based HRQoL. CONCLUSION: Although promising associations were discovered, the models based on commonly collected clinical variables had limited ability to accurately predict individual patient PROs. Thus, although this study identifies clinical and demographic variables that are most predictive of PROs, routine collection of PROs in clinical practice may be necessary to obtain a complete picture of the quality of life of glaucoma patients.

Effect of 6-week washout period on intraocular pressure following chronic prostaglandin analogue treatment: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of a 6-week washout period on intraocular pressure (IOP) following long-term monotherapy prostaglandin use. DESIGN: Prospective, randomized, controlled, single-centre, single-blinded, parallel-group clinical study. PARTICIPANTS: Subjects aged >18 years diagnosed with open-angle glaucoma or open-angle glaucoma suspects based on elevated IOP in one or both eyes, using monotherapy topical latanoprost, bimatoprost, or travoprost once daily. METHODS: Subjects were prospectively randomized to continue prostaglandin analogue (PGA) monotherapy (control group) or discontinue PGA monotherapy (washout group) for 42 days. IOP was measured at day 0 (day of randomization), 7, 21, and 42. MAIN OUTCOME MEASURE: Mean IOP (mm Hg) ± standard deviation. RESULTS: 154 eyes (87 participants) completed the study, with 69 eyes (39 participants) in the control group and 85 eyes (48 participants) in the washout group. In the control group, day 0 IOP (14.64 ± 2.68 mm Hg) did not significantly differ from IOP at days 7 (14.25 ± 3.01 mm Hg), 21 (14.57 ± 2.61 mm Hg), and 42 (14.78 ± 2.30 mm Hg) (all p > 0.30). In the washout group, mean IOP values at days 7 (16.19 ± 3.80 mm Hg), 21 (17.28 ± 3.55 mm Hg), and 42 (17.84 ± 3.31 mm Hg) were significantly greater than those at day 0 (14.48 ± 1.94 mm Hg) and day-matched control group values (all p < 0.002). In the washout group, 24.7% of eyes had a day 42 IOP ≥21 mm Hg. No eyes in the control group had a day 42 IOP ≥21 mm Hg. CONCLUSIONS: Six weeks of PGA washout after long-term monotherapy resulted in a small but statistically significant IOP increase. Majority of washout group participants maintained an IOP lower than 21 mm Hg after the 6-week washout duration. (https://clinicaltrials.gov/ identifier, NCT03534882).

Secondary surgical intervention after primary glaucoma filtration surgery: an Ontario population-based study.

OBJECTIVE: To identify factors associated with secondary surgical intervention after glaucoma filtration surgery. DESIGN: Population-based retrospective cohort. METHODS: Patient records with billing claims for a primary glaucoma filtration surgery occurring between April 2003 and March 2015 were identified. Each identified record was examined for instances of secondary glaucoma surgeries within the patient's first postoperative year. Baseline characteristics of patients who required secondary surgical intervention were compared with those who did not. A multivariable Cox proportional hazards model was used to calculate hazard ratios. RESULTS: Within a cohort of 10,097 patients, 349 (3.46%) underwent a secondary surgical intervention within the first postoperative year. Interventions were less frequent after surgeries that included an indwelling drainage device (HR=0.58 95% CI, 0.37-0.89), phacoemulsification (HR=0.33, 0.21-0.52), or both (HR=0.09, 0.03-0.31). Patients with preoperative aminoglycoside and mydriatic exposure had significantly increased risk of secondary surgical intervention (HR=3.19, 1.89-5.36) and (HR=2.32, 1.49-3.61). Patients who underwent surgery on their contralateral eye experienced secondary surgical interventions more frequently: 7.44 per 10,000 person-days (versus 1.18 per 10,000 person-days, p < 0.0001). No significant differences in the rates of secondary surgical intervention were observed for patients taking different classes of glaucoma medications or those exposed to higher amounts of benzalkonium chloride. CONCLUSIONS: In Ontario, the overall rates of secondary surgical interventions in the first postoperative year are low but significantly higher in certain patient populations. Further work is required to address the higher rate of secondary surgical intervention in patients with a history of certain perioperative eye drop medications and those who require sequential-bilateral procedures.

Trends in low vision care provided by ophthalmologists in Ontario between 2009 and 2015.

OBJECTIVE: Little is known about how low vision services by ophthalmologists are being provided. Here, we analyze the patterns of provision and utilization of vision rehabilitation services in Ontario, Canada. DESIGN: Retrospective population-based study between 2009 and 2015. PARTICIPANTS: Ophthalmologists (n = 92) who billed for vision rehabilitation services through the Ontario Health Insurance Plan in Ontario and the patients (n = 8949) who received these services. METHODS: Billing data for low vision services (2009-2015) was received from Ontario Health Insurance Plan. Data were analyzed to describe patient demographics (age, sex, geographic distribution, number, and type of visits) and service provider information (geographic location, number of years providing services, and number of services per year). RESULTS: It is estimated that ≤ 5% of patients with low vision in Ontario accessed these vision rehabilitation services by ophthalmologists. The majority of these patients were females (61%) and > 60 years old (79%). While patient and provider geographic distributions overlapped in the areas with largest patient populations, many regions lacked services. The majority of patients (71%) made only one vision rehabilitation visit. Nine providers practiced low vision for 7 years, while 43 provided services for only 1 year. In 2015, the most common diagnostic service provided to low vision patients was Optical Coherence Tomography of the retina and the most common therapeutic service was intravitreal for wet age-related macular degeneration. CONCLUSION: Although low vision services increased between 2009 and 2015, there were differences in ability to access care based on age, sex, and geographic location.

Differential effects of dexamethasone and indomethacin on Tenon's capsule fibroblasts: Implications for glaucoma surgery.

Dysregulated wound healing and subsequent fibrosis represents the most common cause of failure in glaucoma filtration surgery. Primary means to prevent this outcome are the anti-metabolite surgical adjuvants, however, topical corticosteroids are commonly used postoperatively to permit further control of wound healing and development of the filtration bleb. Unfortunately, they carry important side effects such as raised intraocular pressure, cataract and increased infection risk. Non-steroidal anti-inflammatory drugs (NSAIDs) show promising results in clinical trials as an alternative wound modulatory drug. NSAIDs exhibit non-inferiority to steroids in terms of post-operative intraocular pressure control and secondary IOP lowering interventions, however there is little known about the differing effects these drugs exert on human Tenon's capsule fibroblast (HTCF) mediated wound healing. The purpose of this study was to assess the individual effects of dexamethasone and indomethacin on the extracellular matrix modifying actions of HTCFs in vitro. To this end, HTCFs were cultured in 3D collagen matrices as well as in 2D monolayers and exposed to clinically relevant concentrations of dexamethasone or indomethacin for up to seven days. HTCF-mediated wound healing functions were assayed through collagen matrix contraction, extracellular matrix morphology, estimation of HCTF proliferation and differentiation into myofibroblasts within the collagen matrices, as well as western blot. Both drugs significantly reduced HTCF-mediated collagen contraction relative to control however there was a significant trend towards greater inhibition with indomethacin exposure compared to dexamethasone. Indomethacin exposure significantly reduced HTCF-mediated collagen remodelling activity compared vehicle control, whereas dexamethasone was unable to reduce remodelling activity at any of the studied exposures. Both drugs reduced myofibroblast differentiation, however indomethacin alone demonstrated an inhibitory effect on final cell number relative to control whereas dexamethasone had no significant effect at any studied exposure. These findings demonstrate that both steroidal and NSAID treatment can mitigate HTCF-mediated collagen contraction and αSMA expression. However, NSAIDs may function to better impede HTCF proliferation and remodelling activity. Taken in the context of previous glaucoma surgical trials, NSAIDs appear to be a viable alternative to steroids for post-operative wound modulation.

Administration of Nitric Oxide Through a Novel Copper-Chitosan Delivery System in Human Corneal and Limbal Epithelial Cell Injury.

Purpose: Nitric oxide (NO) has gained attention for its role in facilitating wound healing by promoting cell migration, while being cytoprotective in a variety of cell types. We determined the efficacy of NO, administered using a novel application of copper-chitosan treatments (Cu-Ch), in facilitating corneal epithelial wound healing using an in vitro model of corneal epithelial and limbal epithelial cell injury. Methods: Human corneal epithelial (HCE) and human limbal epithelial (HLE) cells were monitored under no-scratch (CON), untreated scratch (CS), scratch + plain chitosan composite (0%), scratch + 1% copper solution Cu-Ch (1%), and scratch + 2% copper solution Cu-Ch (2%) conditions. Cell migration, cytotoxicity, apoptosis, and total nitrate/nitrite concentrations were measured at 24, 48, and 72 hours after injury and treatment. iNOS expression in HLE cells also was determined using Western blot. Results: Wound closure significantly increased in HCE cells treated with Cu-Ch (1% and 2%) after 72 hours, while HLE cells showed a significant decrease in closure with Cu-Ch (1% and 2%) treatment compared to CS. Cytotoxic fragments decreased significantly with 1% and 2% Cu-Ch treatments in HCE cells. Nitrate/nitrite levels in HLE cells showed a significant increase with 2% Cu-Ch treatment compared to CS. This increase is complemented with an upregulation of iNOS. Conclusions: Overall, HCE wound healing was accelerated with administration of Cu-Ch treatment. Differences between HCE and HLE responses may be due to intrinsic differences in NO metabolism, as evidenced by differences in NO production, potentially caused by differences in iNOS expression with treatment.

Assessing the Methodological Quality of Glaucoma Clinical Practice Guidelines and Their Recommendations on Microinvasive Glaucoma Surgery: A Systematic Review.

INTRODUCTION: Clinical practice guidelines (CPG) are regarded by many as critical communications providing guidance within specific medical fields. Over a decade ago, the first microinvasive glaucoma surgical (MIGS) procedures were introduced. Since then, a number of these novel intraocular pressure controlling surgical options have been approved worldwide. Governing bodies and health care administration often utilize CPGs when considering funding for newer technologies. This highlights the importance of well-written, accurate, and up-to-date CPGs in the rapidly evolving field of MIGS. If CPGs are unable to fill this role, their use in treatment decision-making is doing a disservice to patients, who will be denied currently available and potentially superior care. To determine the overall value of a CPG, the methodological quality with which it was developed, in addition to the current relevance and appropriateness of its recommendations, should be evaluated. The objective of the present study was to assess the methodological quality of currently available international glaucoma CPGs, as well as their coverage of MIGS as a surrogate marker of relevance and appropriateness to policy-makers and ophthalmologists alike. MATERIALS AND METHODS: To identify potentially relevant CPGs, a predefined search strategy was used to search the following databases: Medline, EMBASE, BIOSIS, and Web of Science. All CPGs related to adult glaucoma and published in English were included. CPG methodological quality was assessed by 3 individuals using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Studies were then assessed for coverage of MIGS devices and procedures. RESULTS: Search strategy and subsequent screening identified 11 CPGs for analysis. Eight were of high quality according to the AGREE II criteria. Three included basic information on MIGS, but none provided specific recommendations regarding their indications or which patient populations would benefit most. CONCLUSIONS: Many international glaucoma CPGs are of high methodological quality. However, coverage of MIGS is sparse, nonspecific and in many instances, absent. This causes CPGs to be a suboptimal source in guiding physicians and health policy-makers in areas characterized by novel and/or rapidly evolving technologies. Mechanisms to incorporate updated evidence in CPGs would have to be considered before they can be used as a source of contemporary clinical decision-making.