Trends in immediate sequential bilateral cataract surgery in Ontario.

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.

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.

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.

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.

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.

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.

When Is Evidence Enough Evidence? A Systematic Review and Meta-Analysis of the Trabectome as a Solo Procedure in Patients with Primary Open-Angle Glaucoma.

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.

The Effects of Phacoemulsification on Intraocular Pressure and Topical Medication Use in Patients With Glaucoma: A Systematic Review and Meta-analysis of 3-Year Data.

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.

Surgical indications, outcomes, and complications with the use of a modified capsular tension ring during cataract surgery.

PURPOSE: To determine the surgical indications, outcomes, and complications with the use of modified capsular tension rings (CTRs) during cataract surgery. SETTING: Ivey Eye Institute, Western University, London, Ontario, Canada. DESIGN: Systematic review. METHODS: A systematic review of databases was conducted for studies related to the use of modified CTRs during cataract surgery that were published between 1992 and 2015. Primary research papers on human participants published in English were screened. The surgical indications, outcomes, and complications of modified CTR use during cataract surgery were compiled and analyzed. RESULTS: The search identified 6035 records from published and gray literature. After screening, 10 studies involving 320 eyes were included in the systematic review. The most common surgical indications for modified CTR use were Marfan syndrome (40.3%), idiopathic zonular insufficiency (27.2%), and previous ocular trauma (22.8%). The weighted average of indicated zonular insufficiency was 173 degrees, with 75.4% of eyes achieving visual acuity better than 20/40 postoperatively. The use of modified CTRs resulted in a reduction in intraocular lens (IOL) decentration and tilt. Vitrectomy during surgery was required in 19.8% of eyes. The rate of posterior capsule opacification (PCO) was 41.1%. Intraocular pressure (IOP) elevation, suture breakage, and uveitis were the most common postoperative complications. CONCLUSIONS: The use of modified CTRs during cataract surgery was associated with causes of large and progressive zonular insufficiency. Use of the CTR produced good postoperative visual outcome and reduced IOL decentration and/or tilt. The most common complications were PCO, IOP elevation, and suture breakage. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Canadian ophthalmic microsurgery course: an innovative spin on wet lab-based surgical education.

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.

Secretion of matrix metalloproteinase-3 by co-cultured pigmented and non-pigmented human trabecular meshwork cells following selective laser trabeculoplasty.

BACKGROUND: Matrix metalloproteinases (MMPs) are reported to contribute to the mechanism of argon laser trabeculoplasty, but it is unknown whether they are also secreted after selective laser trabeculoplasty (SLT). The aim of this study was to investigate whether human primary trabecular meshwork (HTM) cells secrete MMP-3 after stimulation by SLT. The relationship between SLT and the two principal forms of cell death, apoptosis and necrosis, was also examined. METHODS: Non-pigmented primary HTM cells were challenged with melanin granules to artificially introduce pigmentation. Isolated non-pigmented HTM cells and 1:1 co-cultures of pigmented and non-pigmented cells were treated with 0.5-1.5 mJ SLT. Cellular metabolic activity (CMA) was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and necrosis were measured using a cell death ELISA and a lactate dehydrogenase assay, respectively. MMP-3 secretion was measured by ELISA. RESULTS: Co-cultures exhibited a dose-dependent decline in CMA and a dose-dependent increase in necrosis 4 and 24 h after SLT. Non-pigmented cells did not undergo necrosis and displayed a trend towards increased CMA. Apoptosis was reduced in non-pigmented cells but elevated in co-cultures. Increased MMP-3 secretion was observed from co-cultures but not isolated non-pigmented cells. CONCLUSIONS: Pigmentation is necessary for both post-SLT cell death and MMP-3 secretion. SLT appears to have a hormetic effect on non-pigmented HTM cells.

iStent with Phacoemulsification versus Phacoemulsification Alone for Patients with Glaucoma and Cataract: A Meta-Analysis.

BACKGROUND: Minimally invasive glaucoma surgeries (MIGS) have attracted significant attention, as they have been reported to lower intra-ocular pressure (IOP) and have an excellent safety profile. The iStent is an example of a minimally invasive glaucoma device that has received particular attention due to its early and wide spread utilization. There is a growing body of evidence supporting its use at the time of phacoemulsification to help lower IOP. However, it is still not clear how much of the IOP lowering effect can be attributed to the iStent, the crystalline lens extraction or both when inserted concurrently at the time of phacoemulsification. This has been an important issue in understanding its potential role in the glaucoma management paradigm. PURPOSE: To conduct a systematic review and meta-analysis comparing the IOP lowering effect of iStent insertion at the time of phacoemulsification versus phacoemulsification alone for patients with glaucoma and cataracts. METHODS: A systematic review was conducted utilizing various databases. Studies examining the IOP lowering effect of iStent insertion in combination with phacoemulsification, as well as studies examining the IOP lowering effect of phacoemulsification alone were included. Thirty-seven studies, reporting on 2495 patients, met the inclusion criteria. The percentage reduction in IOP (IOPR%) and mean reduction in topical glaucoma medications after surgery were determined. The standardized mean difference (SMD) was computed as a measure of the treatment effect for continuous outcomes taking into account heterogeneity. Fixed-effect and random-effect models were applied. RESULTS: A 4% IOP reduction (IOPR%) from baseline occurred following phacoemulsification as a solo procedure compared to 9% following an iStent implant with phacoemulsification, and 27% following 2 iStents implants with phacoemulsification. Compared with cataract extraction alone, iStent with phacoemulsification resulted in significant reduction in the post-operative IOP (IOPR%) (SMD = -0.46, 95% CI: [-0.87, -0.06]). A weighted mean reduction in the number of glaucoma medications per patient was 1.01 following phacoemulsification alone compared to 1.33 after one iStent implant with phacoemulsification, and 1.1 after 2 iStent implants with phacoemulsification. Compared to cataract extraction alone, iStent with cataract extraction showed a significant decrease in the number of glaucoma medications (SMD = -0.65, 95% CI: [-1.18, -0.12]). Funnel plots suggested the absence of publication bias. CONCLUSION: Both iStent implantation with concurrent phacoemulsification and phacoemulsification alone result in a significant decrease in IOP and topical glaucoma medications. In terms of both reductions, iStent with phacoemulsification significantly outperforms phacoemulsification alone.

iStent as a Solo Procedure for Glaucoma Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Glaucoma is a leading cause of irreversible blindness. It is firmly entrenched in the traditional treatment paradigm to start with pharmacotherapy. However, pharmacotherapy is not benign and has been well documented to have a number of significant challenges. Minimally invasive glaucoma surgery (MIGS) that targets the outflow pathway with minimal to no scleral dissection has resulted in the need to reconsider the glaucoma treatment paradigm. PURPOSE: To perform a systematic review and meta-analysis to evaluate and quantify the effect on post-operative intraocular pressure (IOP) and number of topical glaucoma medications, in patients receiving the iStent MIGS device as the solo procedure without concurrent cataract surgery. METHODS: A systematic review was conducted by searching various databases between January 1, 2000, and June 30, 2014. Studies reporting up to a maximum follow-up period of 24 months were retrieved and screened using the EPPI-Reviewer 4 gateway. Percentage reduction in IOP (IOPR%), and mean reduction in topical glaucoma medications after surgery were computed. Meta-analysis was performed using STATA v. 13.0. The standardized mean difference (SMD) was calculated as the effect size for continuous scale outcomes. Heterogeneity was determined using the I2 statistics, Z-value, and χ2 statistics. Fixed-effect and random-effect models were developed based on heterogeneity. Sub-group analysis was performed based on the number of iStents implanted and the follow-up period. The outcome measures were changes in the IOP and number of glaucoma medications. RESULTS: The search strategy identified 105 records from published literature and 9 records from the grey literature. Five studies with 248 subjects were included for quantitative synthesis. A 22% IOP reduction (IOPR%) from baseline occurred at 18-months after one iStent implant, 30% at 6-months after two iStents implantations, and 40% at 6-months after implantation of three iStents. A mean reduction of 1.2 bottles per patient of topical glaucoma medications occurred at 18-months after one iStent implant, 1.45 bottles per patient at 6-months after two iStents, and one bottle of medication per patient was reduced at 6-months following placement of three iStents implants. Meta-analysis results showed a significant reduction in the IOP after one iStent (SMD = -1.68, 95% CI: [-2.7, -0.61]), two iStents (SMD = -1.88, 95% CI: [-2.2, -1.56]), and three iStents (SMD = -2, 95% CI: [-2.62, -1.38]) implantation. Results showed a significant drop in the topical glaucoma medications after one iStent (SMD = -2.11, CI: [-3.95, -0.27]), two iStent (SMD = -1.88, CI: [-2.20, -1.56]), and three iStents (SMD = -2.00, CI: [-2.62, -1.38]) implantation. The maximum reduction in IOP occurred at 12-months (SMD = -2.21, CI: [-2.53, -1.88]) and a significant reduction in post-operative topical glaucoma medications occurred even after 18-months of iStent implantation (SMD = -0.71, CI: [-1.15, -0.26]). CONCLUSION: iStent implantation as a solo procedure without concurrent cataract extraction does lower IOP, and reduces the dependency on glaucoma medications. This effect seems to last at least 18 months.

A randomized clinical trial of selective laser trabeculoplasty versus argon laser trabeculoplasty in patients with pseudoexfoliation.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) versus argon laser trabeculoplasty (ALT) in lowering the intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension secondary to pseudoexfoliation. DESIGN: Multicentered randomized clinical trial. PARTICIPANTS: A total of 76 eyes from 60 patients with pseudoexfoliation and uncontrolled IOP were recruited from 5 Canadian academic institutions. Patients with prior laser trabeculoplasty, ocular surgery within 6 months, previous glaucoma surgery, an advanced visual field defect, current steroid use, and monocular patients were excluded. METHODS: Eyes were randomized to receive either 180-degree SLT or 180-degree ALT by a nonblocked randomization schedule stratified by center. MAIN OUTCOME MEASUREMENT: The primary outcome was the change in IOP at 6 months versus baseline and secondary outcomes included change in number of glaucoma medications after laser. Baseline variables included age, sex, angle grade, angle pigmentation, and number of glaucoma medications. RESULTS: Of the 76 eyes, 45 eyes received SLT and 31 eyes received ALT. The overall age was 72.9 years (65% females). The baseline IOPs in the SLT and ALT groups were 23.1 and 25.2 mm Hg, respectively (P=0.03). The IOP reduction 6 months after SLT was -6.8 mm Hg and post-ALT was -7.7 mm Hg (P>0.05). The SLT group had reduced glaucoma medications by 0.16 medications at 6 months and the ALT group had no decrease in medications over the same time period (P=0.59). There were no postlaser IOP spikes in either group. DISCUSSION: ALT and SLT are equivalent in lowering IOP at 6 months posttreatment in patients with PXF.