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Anastasiya Vinokurtseva,1 Matthew Fung,1 Erica Ai Li,2 Richard Zhang,1 James J Armstrong,1,2 Cindy ML Hutnik1– 3 1Department of Ophthalmology, Schulich School of Medicine and Dentistry, London, Ontario, Canada; 2Department of Pathology, Schulich School of Medicine and Dentistry, London, Ontario, Canada; 3Ivey Eye Institute, St Joseph’s Healthcare, London, Ontario, CanadaCorrespondence: Anastasiya Vinokurtseva, Department of Ophthalmology, Schulich School of Medicine and Dentistry, 268 Grosvenor St., London, ON, N6A 4V2, Canada, Tel +1 519.646.6100 x.66272, Fax +1 519.646.6410, Email avinokurtseva2022@meds.uwo.caPurpose: 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.Keywords: corticosteroids, asthma, glaucoma, intranasal, inhalation

Michael T Kryshtalskyj,1 Matthew J Novello,2 Monali S Malvankar-Mehta,3,4 Marcelo T Nicolela,5 Cindy ML Hutnik3,6 1Department of Surgery (Section of Ophthalmology), University of Calgary, Calgary, Alberta, Canada; 2Department of Physiology and Pharmacology, Western University, London, Ontario, Canada; 3Department of Ophthalmology, Western University, London, Ontario, Canada; 4Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; 5Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada; 6Department of Pathology, Western University, London, Ontario, CanadaCorrespondence: Michael T KryshtalskyjDepartment of Surgery (Section of Ophthalmology), University of Calgary, Eye Clinic, Rockyview General Hospital, Main (Fourth) Floor, Fisher Building, 7007 14th Street SW, Calgary, T2V1P9, Alberta, CanadaTel +1-(647)-938-4450Email michael.kryshtalskyj@ucalgary.caObjective: 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.Keywords: bibliometrics, h-index, m-quotient, scholarly impact, research, ophthalmology

Charles B Trelford,1 James T Denstedt,2 James J Armstrong,2,3 Cindy ML Hutnik2–4 1Schulich School of Medicine and Dentistry, Department of Physiology and Pharmacology, Western University, London, Ontario, Canada; 2Schulich School of Medicine and Dentistry, Department of Ophthalmology, Western University, London, Ontario, Canada; 3Schulich School of Medicine and Dentistry, Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; 4Ivey Eye Institute, St. Joseph’s Healthcare, London, Ontario, CanadaCorrespondence: Charles B Trelford N6A 3K7 Tel +1 226-668-5778Email ctrelfor@uwo.caPurpose: 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.Keywords: fibrosis, tenon’s capsule, bioartificial tissue, glaucoma, human Tenon’s capsule fibroblasts

Vinay Kansal,1 James J Armstrong,2,3 Cindy ML Hutnik2– 4 1University of Saskatchewan, Department of Ophthalmology, Saskatoon, SK, Canada; 2Western University Canada, Schulich School of Medicine, Department of Pathology and Laboratory Medicine, London, ON, Canada; 3Western University Canada, Schulich School of Medicine, Department of Ophthalmology, London, ON, Canada; 4Ivey Eye Institute, St. Joseph’s Hospital, London, ON, CanadaCorrespondence: Cindy ML HutnikIvey Eye Institute, St. Joseph’s Hospital, 268 Grosvenor Street, London, ON N6A 4V2, CanadaTel +1 519-646-6100 Ext 66272Fax +1 519-646-6410Email cindy.hutnik@sjhc.london.on.caBackground: Glaucoma surgical management has evolved significantly with the introduction of minimally invasive glaucoma surgery. Our aim was to evaluate trends in Canadian glaucoma surgery billing code usage as a surrogate index of the current impact of this new technology in Canada’s publicly funded health-care system.Methods: Retrospective administrative health records analysis of all patients who underwent a publicly funded glaucoma filtration procedure from January 2003 to December 2016 in the 6 largest Canadian provinces. The frequency of glaucoma-related procedures was adjusted against primary open-angle glaucoma prevalence data. Frequency of all glaucoma filtration procedures with and without implantation of a drainage device in each province per year is reported.Results: Nationwide, glaucoma filtration procedures per 1000 primary open-angle glaucoma patients per year remained constant, with increased drainage device implantation over time (P< 0.0001). Ontario and Nova Scotia mirrored the overall population. British Columbia and Saskatchewan showed increased rates of glaucoma filtration surgery, with increased drainage device implantations. In Quebec, overall filtration surgery decreased, while the rate of device implantation increased (p< 0.0001). Alberta showed a decline in filtration surgery and device implantations from 2003 to 2008, and then increased thereafter.Conclusion: Over the study period, there was a distinct trend towards billing code usage for implanted devices. Challenges encountered during this investigation highlight the need for identifiers in provincial health databases to accommodate the introduction of novel technologies. The absence of specific billing codes for newer technologies prevents accurate analyses of impact, utilization, efficacy and cost implications in contemporary patient management.Keywords: glaucoma, minimally invasive glaucoma surgery, MIGS, glaucoma filtration surgery, population analysis

Monali S Malvankar-Mehta,1,2 Lucy Feng,3 Cindy ML Hutnik1,4 1Department of Ophthalmology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 4V2, Canada; 2Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario N6A 5C1, Canada; 3School of Pharmacy, University of Waterloo, Kitchener, Ontario N2G 2B2, Canada; 4Department of Pathology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, CanadaCorrespondence: Monali S Malvankar-MehtaDepartment of Ophthalmology, St. Joseph’s Hospital, 268 Grosvenor Street, London, Ontario N6A 4V2, CanadaTel +1 519 685 8500 Ext 61288Fax +1 519 661 3766Email Monali.Malvankar@schulich.uwo.caBackground: According to the World Health Organization, glaucoma is a leading cause of irreversible blindness worldwide. By 2020, 80 million people will be affected by glaucoma in the world, which represents a significant financial burden to society. Glaucoma medications alone make up 38–52% of the total direct cost. The purpose of this research is to conduct a cost-minimization analysis to evaluate brand-name medications versus generic medications for treating glaucoma patients.Methods: The per-bottle cost (in Canadian dollars) of brand-name drugs for glaucoma was obtained from the wholesaler, McKesson Canada, and, for generic drugs, from the Ontario Drug Benefit (ODB) Formulary. Further, a wastage adjustment fee, a pharmacy mark-up, and an ODB dispensing fee ($CAD) was added to the cost of both brand and generic. Previously published frequencies of medication prescription were utilized to calculate the average annual cost for each class of brand and generic. For each medication class and for mono-, bi-, and tri-drug therapy, the cost differential between brands and generics over a six-year period was computed and analyzed from third-party payer perspective.Results: In descending order, the average annual government-funded health care system costs were: combination drugs such as Cosopt® ($748.23) were the most expensive, followed by prostaglandin analogs ($246.36), carbonic anhydrase inhibitors (CAIs) ($45.04), α-agonist ($30.34), β-blockers ($29.29), and cholinergic agonists ($16.51). Brand-name mono-drugs are 34% more expensive compared to generics. Brand-generic percentage cost differential for various medication classes over a six-year period was the highest for prostaglandin analogous (44%), followed by β-blockers (35%), α-agonist (31%), cholinergic agonists (22%), combination drugs (10%), and CAIs (1%).Conclusion: Brand-name drugs are relatively more expensive than their generic counterparts, with variable cost differentials depending on drug class.Keywords: glaucoma, open-angle, cost analysis, generic drugs, branded drugs

Richard Filek,1 Phil Hooper2,3 Tom G Sheidow2,3 John Gonder2,3 Subrata Chakrabarti,1 Cindy ML Hutnik1–31Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; 2Department of Ophthalmology, Western University, London, ON, Canada; 3Ivey Eye Institute, St. Joseph’s Health Care London, London, ON, CanadaPurpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients.Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia.Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p

Richard Filek,1 Phil Hooper,2,3 Tom G Sheidow,2,3 Hong Liu,3 Subrata Chakrabarti,1 Cindy ML Hutnik1–31Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada; 2Department of Ophthalmology, Western University, London, ON, Canada; 3Ivey Eye Institute, St. Joseph’s Health Care London, London, ON, CanadaPurpose: To analyze the safety of different concentrations of anti-VEGF on retinal cells.Methods: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA).Results: Diabetic rats had a significant increase (p

Efstathia Kiatos,1 James J Armstrong,2,3 Cindy ML Hutnik,3,4 Stephen M Tsioros,5 Monali S Malvankar-Mehta,1,4 William G Hodge1,4 1Department of Epidemiology and Biostatistics, 2Department of Pathology, 3Department of Ophthalmology, Schulich School of Medicine and Dentistry, Western University, 4Department of Ophthalmology, Ivey Eye Institute, St Joseph’s Health Care London, 5Department of Kinesiology, Western University, London, ON, Canada Purpose: This study evaluated the performance of donor corneoscleral rim cultures for predicting infection after corneal transplantation, and determines if there is a correlation between positive corneoscleral rim cultures and postkeratoplasty infection.Design and data sources: This was a systematic review, prognostic accuracy analysis, and cost-effectiveness analysis. Databases searched were: Medline (Ovid), Embase (Ovid), CINAHL, Cochrane Library, Web of Science, and BioSis Previews. Grey literature was also explored.Materials and methods: A systematic review was conducted to locate published and unpublished studies. All studies examining corneal button contamination and its association with endophthalmitis and keratitis posttransplantation were included. Extracted data were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value. Cost data from the London Laboratory Services Group in London, ON were used to calculate the cost-effectiveness of culturing donor rim cultures.Results: Of 7,870 grafts, 954 had a positive rim culture (12.1%), with 12 patients going on to develop keratitis or endophthalmitis (1.3%). The prevalence of keratitis and endophthalmitis in this study was 0.15%, and the positive predictive value 1.5%. Of the 12 infections, nine were fungal and three bacterial. The estimated cost of a positive and negative test result was CAD$45.99 and $14.15, respectively. The cost to run all 7,870 tests was estimated to be $141,735.86, with an incremental cost-effectiveness ratio of $40,215.70.Conclusion: There was a significant divergence between bacterial and fungal rim-culture results. Bacterial cultures predicted clinical infection poorly, did not change management, and were expensive. Fungal cultures predicted clinical infection in over 10% of patients, had the potential to change management, and were 40% less expensive than full rim culturing (bacterial and fungal tests). Fungal rim cultures may be considered in areas where fungal infection rates are high. Keywords: corneoscleral rim cultures, eye infection, keratoplasty, culture techniques

Tony Lin,1,2,* Richard Filek,3,* Joy M Wang,4 Chong H Wu,4 Hong Liu,2 Cindy ML Hutnik1–3 1Department of Ophthalmology, Western University, 2Ivey Eye Institute, St Joseph’s Health Care, St Joseph’s Hospital, 3Department of Pathology and Laboratory Medicine, 4Department of Biology, Western University, London, ON, Canada *These authors contributed equally to this work Purpose: Impression cytology in combination with a cell autophagy marker was used to demonstrate the utility of a novel frozen section technique, to assess the health of the ocular surface, as well as to correlate autophagic cell death with the commonly used clinical tests for dry eye. Methods: Female patients over the age of 18 years who attended an outpatient ophthalmology clinic were invited to participate. Schirmer’s test, tear film break-up time and the ocular surface disease index questionnaire were used as objective and subjective clinical tests for dry eye. The cellular biomarker microtubule-associated protein light chain 3 (LC3) was used as a marker of autophagic cell death. Results: Low LC3 nuclear staining was positively correlated with Schirmer’s test

Yogesh Patodia,1 Elizabeth Golesic,2 Alex Mao,2 Cindy ML Hutnik2 1Department of Medicine, Ross University, Iselin, NJ, USA; 2Department of Ophthalmology, University of Western Ontario, London, ON, Canada Purpose: The aim of this trial is to study the effectiveness of currently available low-vision devices in glaucoma patients with moderate-to-severe vision loss. Design: This is a randomized pilot clinical trial. Participants: Sixteen low-vision glaucoma patients participated in this study. Methods: Patients with a best-corrected visual acuity between 20/70 and 20/400 in the better eye and a diagnosis of stable primary or secondary open-angle glaucoma were randomized to a low-vision treatment group or a nonintervention control group. A telephone interview was conducted before and after the 4-week testing period to assess functional vision. Patients placed in the treatment group received a low-vision examination and used various currently available low-vision aids. Patients placed in the control group received a low-vision examination only. Changes in patients’ reading ability and overall visual ability were chosen as the primary outcomes. Other visual functioning domains (mobility, visual information processing and visual motor skills) were considered as secondary outcomes. Results: Ten patients in the treatment group showed a significant improvement in reading ability and overall visual ability compared to the control group. The difference in mean score for reading ability was 2.52 logits (2.02; P

Prima Moinul,1 Cindy ML Hutnik2 1Faculty of Medicine, University of Calgary, Calgary, AB, Canada; 2Ivey Eye Institute, St Joseph’s Health Care, Department of Ophthalmology, University of Western Ontario, London, ON, Canada Objective: To report a case of an aqueous misdirection-like presentation in a pseudophakic patient.Design: Retrospective case review.Participant: An 84-year-old pseudophakic gentleman presented with bilateral blurred vision 8 years after cataract surgery. A refractive shift with shallow anterior chambers and elevated intraocular pressures were noted. No corneal edema was noted. Although aqueous suppression and topical atropine would relieve the signs and symptoms, the effect was temporary with fluctuating and variable changes in refraction, anterior chamber depth, and intraocular pressure. The presence of patent iridotomies had no effect on the fluctuations. A pars plana vitrectomy and surgical iridectomy were successful in preventing further fluctuations.Conclusion: Aqueous misdirection is a form of secondary angle closure glaucoma marked by elevated intraocular pressures, myopic shift in refraction, and central shallowing of the anterior chamber. Here, a case of a pseudophakic patient experiencing bilateral and fluctuating signs and symptoms resembling aqueous misdirection is presented. Surgical intervention with a pars plana vitrectomy and iridectomy prevented further fluctuations. Keywords: aqueous misdirection, glaucoma, pars plana vitrectomy, secondary angle closure

Andrew C Crichton,1 Donald R Nixon,2 Susan Simonyi,3 Meetu Bhogal,3 Christopher S Sigouin,4 Marino J Discepola,5 Cindy ML Hutnik,6 Darryl C Baptiste,3 David B Yan7 On behalf of the CLEAR Study Group 1Division of Ophthalmology, University of Calgary, Calgary, AB, Canada; 2Private practice, Barrie, ON, Canada; 3Medical Affairs, Allergan Inc., Markham, ON, Canada; 4CLINWest Research, Burlington, ON, Canada; 5Department of Ophthalmology, McGill University, Montreal, QC, Canada; 6Department of Ophthalmology and Pathology, Ivey Eye Institute, London, ON, Canada; 7Department of Ophthalmology, University of Toronto, Toronto, ON, Canada Purpose: To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. Subjects and methods: This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. Results: After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from –2.3%±17.3% to –26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. Conclusion: This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%–15% reduction in IOP. Keywords: glaucoma, intraocular pressure, hyperemia, bimatoprost

Donald R Nixon,1 Susan Simonyi,2 Meetu Bhogal,2 Christopher S Sigouin,3 Andrew C Crichton,4 Marino Discepola,5 Cindy ML Hutnik,6 David B Yan71Private Practice, Barrie, ON, 2Allergan Inc, Markham, ON, 3CLINWest Research, Burlington, ON, 4University of Calgary, Calgary, AB, 5McGill University, Montreal, QC, 6London Health Sciences Centre, London, ON, 7University of Toronto, Toronto, ON, CanadaBackground: This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting.Methods: This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study.Results: After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline.Conclusion: This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.Keywords: glaucoma, intraocular pressure, hyperemia, bimatoprost

Dov B Kagan, Hong Liu, Cindy ML HutnikIvey Eye Institute, St Joseph's Hospital, London, ON, CanadaBackground: Oxidative stress induced retinal pigment epithelium (RPE) dysfunction is hypothesized to be fundamental in the pathogenesis of age-related macular degeneration (AMD). This study investigated whether vitamin C, vitamin C phosphate, vitamin E, propofol, betaxolol, and N-acetyl cysteine (NAC) protect human RPE cells from oxidative stress.Methods: ARPE-19 cells were pretreated with the compounds under investigation. The chemical oxidant tert-butyl hydroperoxide (t-BOOH) was used to induce oxidative stress. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.Results: Exposure to t-BOOH resulted in a dose- and time-dependent reduction in ARPE-19 cell viability. Compared with cells given t-BOOH alone, vitamin E and NAC pretreated cells had significantly improved viability, propofol and betaxolol pretreated cells had no significant difference in viability, and vitamin C and vitamin C phosphate pretreated cells had significantly reduced viability.Conclusion: Of the compounds studied, only vitamin E and NAC significantly mitigated the effects of oxidative stress on RPE cells. Because of their potential therapeutic value for AMD patients, these and other RPE protective compounds continue to merit further investigation.Keywords: age-related macular degeneration, N-acetyl cysteine, vitamin C, vitamin E, propofol, betaxolol

Objective: Because of increased evidence for safety and increased demands, there appears to be a recent adoption and endorsement of immediate sequential bilateral cataract surgery (ISBCS). This study aims to determine whether a paradigm shift has occurred in the delivery of cataract surgery in the province of Ontario and its the extent, if any, and to analyze the current role of ISBCS., Design: Retrospective health records analysis., Methods: We analyzed aggregate Ontario Health Insurance Plan claim counts for cataract surgeries between 2016 and 2022, categorizing cases into unilateral, ISBCS, and delayed sequential bilateral cataract surgery (DSBCS) cases. We examined trends, compared wait times for second surgeries in the DSBCS cohort with wait times for first surgeries, and used previously published cost estimates for ISBCS to estimate annual savings in Ontario., Results: There were 1,122 ISBCS cases in 2016, which increased sixfold during the pandemic (2020-2021) and further increased to 11,876 cases in 2022. Unilateral and DSBCS cases decreased during the pandemic but rebounded in 2022 to 102% and 153% of baseline, respectively. ISBCS increased from 1% to 10%, unilateral cases decreased from 41% to 29% of total cases, and DSBCS increased from 58% to 61%. Median wait for patients' first and second surgeries increased from 65 to 87 days and 28 to 33 days, respectively. Using estimates, ISBCS saved approximately $19 million in 2022., Conclusion: Our study demonstrates a paradigm shift in Ontario in favour of ISBCS. ISBCS also may be a strategy to reduce increasing wait times while saving health care system dollars., (Copyright © 2024 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Post-operative increases in intraocular pressure (IOP) are a frequent complication following phacoemulsification cataract surgery. Assessment of IOP is an essential element in post-operative checks. Despite this, guidance regarding the optimal timing remains vague. The purpose of this meta-analysis was to determine the current status of evidence that may help guide best practice regarding the optimal time following phacoemulsification cataract surgery to measure IOP. A comprehensive literature search was performed on MEDLINE and EMBASE. In two stages, independent reviewers screened articles that reported IOP measurements following uncomplicated cataract surgery. Risk of Bias Assessment was conducted following data extraction. The meta-analysis incorporated 57 randomized clinical studies involving a total of 6318 participants and 7089 eyes. Post-operative hour one had a significant decrease in IOP from baseline, while hour two had a non-significant increase. Post-operative hours four, six, and eight were the only timepoints to have a significant increase in IOP. Finally, post-operative day one had no significant change in IOP, while day two had a non-significant decrease. These results suggest that the optimal time to measure IOP is within the first 4-8 h following phacoemulsification cataract extraction. Taking measurements too soon or too late could result in missed IOP spikes.

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., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

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., (Copyright © 2022 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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 TGFβ1 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 TGFβ1. 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 TGFβ1-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 TGFβ1 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.

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 TGFβ1 (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 TGFβ1-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 TGFβ1-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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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.

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., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Authors.)

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.

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)., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

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.

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.

PurposeTo evaluate long-term structural and functional changes to the retina and optic nerve following panretinal photocoagulation (PRP) in diabetic retinopathy (DR) patients.MethodsParticipants were patients with DR requiring PRP and control patients with DR not requiring PRP. The Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT) were performed to analyze the optic nerve and macula. Best-corrected visual acuity (BCVA) and visual field (VF) testing were done to measure central and peripheral vision. Wide-field fluorescein angiogram was performed to monitor the progression of diabetic ischemia. The primary outcome measure was to determine the degree of retinal and optic nerve changes before and after PRP.ResultsThere was a non-significant thickening of the macula and retinal nerve fiber layer at 6 months post laser that recovered by 24 months. Mean perfused ratio was significantly increased (P=0.02) at 12 and 24 months post laser. Independently grading patient stereophotographs, grader 1 indicated there was a non-significant increase in cup to disk ratio post laser, while grader 2 indicated a significant increase at 6 (P=0.04), 12 (P=0.02), and 24 months (P=0.005). There was a significant VF decrease (P≤0.02) at 12 and 24 months post laser with BCVA showing a non-significant trend of deteriorating results.ConclusionDespite an improvement in peripheral perfusion, there was a significant progressive decline of peripheral VF over the study period. Clinical grading of the optic nerve was more unreliable following PRP, despite the absence of significant morphological changes as detected by the OCT and HRT.

Purpose: For patients with comorbid cataract and primary open-angle glaucoma (POAG), guidance is lacking as to whether cataract extraction and traditional filtering surgery should be performed as a staged or combined procedure. Achieving this guidance requires an evidence-based understanding of the effects of phacoemulsification alone on intraocular pressure (IOP) in patients with POAG. For this reason, a systematic review and meta-analysis was undertaken to synthesize evidence quantifying the effect of phacoemulsification on IOP and the required number of topical glaucoma medications in patients with cataract and POAG., Materials and Methods: Database searches were last run on August 15, 2016 to identify potentially relevant studies. Identified articles were screened for relevance and meta-analysis was used to compute postoperative mean and percentage reduction in IOP (IOPR%) as well as mean difference in topical glaucoma medications., Results: The search strategy identified 1613 records. Thirty-two studies (1826 subjects) were included in quantitative synthesis. A 12%, 14%, 15%, and 9% reduction in IOP from baseline occurred 6, 12, 24, and 36 months after phacoemulsification. A mean reduction of 0.57, 0.47, 0.38, and 0.16 medications per patient of glaucoma medication occurred 6, 12, 24, and 36 months after phacoemulsification., Conclusions: Phacoemulsification as a solo procedure does lower IOP in patients with POAG, and reduces dependency on topical glaucoma medications. These effects appear to last at least 36 months with gradual loss of the initial effect noted after 2 years. Certain populations appear to experience much greater reductions in IOP than others and future work to identify these high responding patients is needed.

The purpose of this systematic review and meta-analysis was to examine the availability of evidence for one of the earliest available minimally invasive glaucoma surgery (MIGS) procedures, the Trabectome. Various databases were searched up to December 20, 2016, for any published studies assessing the use of the Trabectome as a solo procedure in patients with primary open-angle glaucoma (POAG). The standardized mean differences (SMD) were calculated for the change in intraocular pressure (IOP) and number of glaucoma mediations used at 1-month, 6-month, and 12-month follow-up. After screening, three studies and one abstract with analyzable data were included. The meta-analysis showed statistically significant reductions in IOP and number of glaucoma medications used at all time points. Though the Trabectome as a solo procedure appears to lower IOP and reduces the number of glaucoma medications, more high-quality studies are required to make definitive conclusions. The difficulty of obtaining evidence may be one of the many obstacles that limit a full understanding of the potential safety and/or efficacy benefits compared to standard treatments. The time has come for a thoughtful and integrated approach with stakeholders to determine optimal access to care strategies for our patients.

Wet lab and surgical simulation can reduce the learning curve of difficult surgical techniques, accelerate the rate for trainees to achieve surgical competency, and improve patient safety. To provide the most up-to-date information and hands-on experiences with novel ophthalmic surgical techniques and instruments, the Department of Ophthalmology at Western University has created a wet lab-based, multilevel microsurgery skills transfer course through collaboration with various industry partners. Several elements in the course goal and design differentiate this type of surgical course from typical wet labs: the format is multileveled surgical training, with a beginner level targeting undergraduate medical students, an intermediate level for ophthalmology residents, and an advanced level for trained ophthalmologist. In addition, the level of industry participation allows the development of true partnership and offers a method to introduce awareness and innovation in a cost-effective manner. This article presents the organization, course setup, and feedback from the pilot course., (Copyright © 2016 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)