Outcome of combined trabeculectomy with cataract surgery in patients on prostaglandin analogs and aqueous suppressants.

PURPOSE: To compare the effect of prostaglandin analogs (PGA) against other glaucoma medications (non-PGA) on the intraocular pressure (IOP) outcomes of combined trabeculectomy with phacoemulsification, and the conjunctival cell profile in persons with primary open-angle (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS: A prospective cohort study was conducted among 116 patients with POAG or PXFG on glaucoma medications for a minimum of 3 months undergoing glaucoma triple procedure. Patients were divided into two groups (PGA and non-PGA) based on preoperative exposure to PGA. IOP outcomes were assessed for up to 2 years. Conjunctival biopsy specimens were obtained at the time of surgery, and histopathological analysis was performed. RESULTS: Forty-two patients were in the PGA group, 67 were in the non-PGA group, and seven were lost to follow-up. The non-PGA group had lesser mean postoperative IOP and needed fewer postoperative medications compared to the PGA group in all visits up to 2 years. The non-PGA group had better complete success rate (50.7% vs. 14.3%, P < 0.001). Kaplan-Meier survival estimates showed a significant difference in cumulative complete success rate between non-PGA (67%) and PGA (26%) by 24 months ( P < 0.001). The Cox proportional model showed the type of drug to be significantly associated with surgical failure. Histopathological analysis revealed that the PGA group had higher numbers for each type of inflammatory cell (except mast cells) compared to the non-PGA group. CONCLUSION: Patients on PGA are likely to have a higher postoperative IOP and may need more medications for IOP control after a glaucoma triple procedure.

How latanoprost changed glaucoma management.

Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone. Since then, due mainly to their efficacy, limited systemic side effects and once daily dosing, prostaglandin analogues (PGAs) have become as the first-choice treatment for primary open-angle glaucoma. PGAs are in general terms well tolerated, although they are associated with several mild to moderate ocular and periocular adverse events. Among them, conjunctival hyperemia, eyelash changes, eyelid pigmentation, iris pigmentation and hypertrichosis around the eyes are the most prevalent. The objective of this paper is to review the role of PGAs in the treatment of glaucoma over the 25 years since the launch of Latanoprost and their impact on clinical practice outcomes.

Currently available prostanoids for the treatment of glaucoma and ocular hypertension: A review.

Recent advancements in prostaglandin analogs (PGAs) have reinforced their role in managing intraocular pressure (IOP). Latanoprost excels in 24-h IOP control, while various PGAs offer similar effectiveness and side effects, generic PGAs perform as well as branded ones, and a notable IOP rise observed upon PGA discontinuation. Formulations with or without preservatives show comparable IOP reduction and adherence, often surpassing benzalkonium chloride (BAK)-preserved options. Emergent PGAs, such as latanoprostene bunod, fixed-dose netarsudil combined with latanoprost, and omidenepag Isopropyl, offer enhanced or non-inferior IOP reduction. The bimatoprost implant introduces a novel administration method with effective IOP reduction. These developments underscore ongoing progress in PGA-focused ophthalmological research. This article offers a comprehensive review of available prostanoid analogs and explores new developments.

Additive effects of brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination in prostaglandin analog-treated Japanese glaucoma patients.

PURPOSE: A brimonidine tartrate 0.1%/brinzolamide 1% fixed-dose combination (BBFC) was recently approved for glaucoma and ocular hypertension treatment in Japan. We investigated the efficacy and safety of BBFC used concomitantly with prostaglandin analogs (PG) or a PG/beta-blocker fixed-dose combination (PG/beta FC). STUDY DESIGN: This was a prospective, open-label, multicenter study. PATIENTS AND METHODS: We enrolled Japanese patients with open-angle glaucoma. BBFC (Ailamide) was concomitantly administered to either the PG or the PG/beta FC group, and intraocular pressure (IOP) and safety were evaluated at 4 and 12 weeks. The groups were stratified into low and high IOP baseline groups based on the median baseline IOP. RESULTS: We enrolled 100 patients, 91 of whom completed the 12-week follow-up. The mean ages were 67.1 and 65.7 years in the PG group (n = 45, baseline IOP of 15.7 ± 2.3 mmHg) and the PG/beta FC group (n = 46, baseline IOP of 16.3 ± 2.3 mmHg), respectively. After BBFC administration, IOPs at 4 and 12 weeks were 13.0 ± 2.0 and 13.0 ± 2.6 mmHg (P < 0.0001) in the PG group, respectively, and 13.7 ± 2.4 and 13.7 ± 2.2 mmHg (P < 0.0001) in the PG/beta FC group, respectively. IOP decreased by - 2.0 ± 1.8 mmHg (P < 0.0001) and -1.9 ± 1.4 mmHg (P < 0.0001) in the low baseline PG group (14.1 mmHg) and low baseline PG/beta FC group (14.8 mmHg) at 12 weeks, respectively. Sixteen adverse events were identified, all of which were common and did not affect visual acuity. CONCLUSIONS: BBFC can be used concomitantly with PG or PG/beta FC to reduce IOP without serious complications.

Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.

INTRODUCTION: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. METHODS: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. RESULTS: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. CONCLUSION: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. TRIAL REGISTRATION NUMBER: jRCTs051190125.

Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC­prostaglandin analogue combination therapy.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

Genotype and Phenotype Influence the Personal Response to Prostaglandin Analogues and Beta-Blockers in Spanish Glaucoma and Ocular Hypertension Patients.

Analysis of the genotype that predicts the phenotypic characteristics of a cohort of glaucoma and ocular hypertension patients, and the correlation with their personal pharmacological response to beta-blockers (BB) and prostaglandin analogues (PGA). Prospective study that included 139 eyes from 72 patients under BB and/or PGA treatment, and in some cases other types of ocular hypotensive treatments. Five single-nucleotide polymorphisms were genotyped by real-time PCR assays: prostaglandin-F2α receptor (rs3766355, rs3753380); cytochrome-P450 2D6 (rs16947, rs769258); and beta-2-adrenergic receptor (rs1042714). Other studied variables were mean deviation (MD) of visual field, previous ocular interventions, medical treatment, baseline (bIOP), and treated intraocular pressure (tIOP). From a total of 139 eyes, 71 (51.1%) were left eyes. The main diagnosis was primary open angle glaucoma (66.2%). A total of 57 (41%) eyes were under three or more medications (PGA + BB + other) and, additionally, 57 eyes (41%) had had some kind of glaucoma surgery. The mean bIOP and tIOP were 26.55 ± 8.19 and 21.01 ± 5.54 mmHg, respectively. Significant differences in tIOP were found between heterozygous (HT) (21.07 ± 0.607 mmHg) and homozygous (HM) (20.98 ± 0.639 mmHg) rs3766355 with respect to wildtype individuals (16 ± 1.08 mmHg) (p = 0.031). The MD values presented significant differences between wildtype rs3766355 (-2 ± 2.2 dB), HT (-3.87 ± 4 dB), and HM carriers (-9.37 ± 9.51 dB) (p = 0.009). Significant differences were also observed between the MD in wildtype rs3753380 (-6.1 ± 8.67 dB), HT (-9.02 ± 8.63 dB), and HM carriers (-9.51 ± 7.44 dB) (p = 0.017). Patients carrying the variant rs3766355 in HM or HT presented clinically-significantly higher tIOP than wildtype patients. Additionally, some differences in MD were found in rs3766355 and rs3753380 carriers, and the more alleles that were affected, the worse the MD value, meaning greater severity of the glaucoma. Poor response to treatment and more visual field damage may be associated with being a carrier of these mutated alleles.

Selective laser trabeculoplasty is safe and effective in patients previously treated with prostaglandin analogs: An evidence-based review.

PURPOSE: Prostaglandin analogs (PGAs) are first-line treatments for ocular hypertension (OHT) and open-angle glaucoma (OAG). However, frequent side effects and high costs hinder patient's compliance resulting in disease progression. Evidence suggests selective laser trabeculoplasty (SLT) may be considered a first-line treatment for OHT and OAG due to its safety profile, minor side effects, and reduced costs. Considering that PGAs and SLT share action mechanisms, it is hypothesized that previous PGA therapy may affect subsequent SLT efficacy. Therefore, we analyzed if PGAs reduce SLT efficacy. METHODS: An evidence-based review was performed to assess the safety and efficacy of SLT in patients previously treated with PGAs. For this purpose, we performed an extensive literature search using the National Library of Medicine's PubMed and Google Scholar database for all English language articles published until May 2021. RESULTS: There is evidence of non-superiority of PGAs therapy versus SLT for OHT and OAG. A multicenter, randomized, observer-masked clinical trial (RCT) of untreated OHT and OAG patients concluded that SLT should be offered as the first-line treatment for these patients. This study was supported by a meta-analysis of RCTs, comparing SLT efficacy versus antiglaucoma drugs only, with the advantage of an SLT lower rate of adverse effects. CONCLUSIONS: Cost-effectiveness, patient compliance, and antiglaucoma drugs' side effects, including higher surgical failure, favor consideration of SLT as first-line therapy for OAG and OHT. Furthermore, SLT efficacy does not seem to be affected by prior PGA administration; however, larger cohort, comparative, multicenter RCTs are necessary to answer this question.

[Changes in the types and daily treatment costs of anti-glaucoma eye drops in China in recent 15 years].

Objective: To investigate the changes in the types of anti-glaucoma eye drops and daily treatment costs in 2021 compared with 2006 in China. Methods: The information of the main anti-glaucoma eye drops in 2021 was obtained from the database of Yaozhi.com. The daily cost of each eye drop was calculated by recording the number of drops in a single bottle and pricing in the national market, and the corresponding information of anti-glaucoma eye drops collected in 2006 was compared. Based on the income of Chinese residents in 2006 and 2021, the proportion of the daily cost of anti-glaucoma eye drops in the annual income of residents was analyzed. Results There were 32 kinds of anti-glaucoma eye drops in 2021, and the daily cost was 0.34 to 16.00 yuan. The daily cost is 0.34 to 6.77 yuan after removing the single-dose package. The number of drugs in 2021 was significantly higher than that in 2006 (16). In 2021, prostaglandins accounted for the highest proportion of 31.25%. There was a significant increase in the number of generic drugs, fixed formulations and preservative-free single-dose packages. In 2021, the price of imported drugs was significantly reduced, with the daily cost falling by 29.28% to 53.78% compared with 2006. In 2021, the daily cost of the most expensive drugs accounted for 12.32% and 30.85% of the daily income of urban and rural residents, respectively (5.21% and 13.05% after removing single-dose packaged drugs), which were significantly lower than 37.46% and 122.79% in 2006. Conclusions Compared with 2006, the variety of anti-glaucoma eye drops increased significantly in 2021, and the daily treatment cost and the proportion of daily income were significantly reduced.

Effect of prostaglandin analogues on the biomechanical corneal properties in patients with open-angle glaucoma and ocular hypertension measured with dynamic scheimpflug analyzer.

PURPOSE: The aim of the study is to evaluate the effect of topical prostaglandin (PG) treatment on the corneal biomechanical properties in treatment-naïve patients with either primary open-angle glaucoma (POAG) or ocular hypertension (OHT) using the Corvis ST device. METHODS: This is an observational study. We analyzed the Corvis ST dynamic corneal response parameters of our database using the newest software available. Thirty-four eyes of 34 patients were included. They were all newly diagnosed and treatment-naïve. Patients were evaluated at baseline and after 6 months of treatment with prostaglandin analogues. Ultrasound pachymetry, Optical Coherence Tomography (OCT) and a 24-2 visual field test were performed in baseline visit. Goldman Applanation Tonometry (GAT-IOP) and Corvis ST dynamic corneal response parameters were registered at baseline and at the 6-month visit. RESULTS: After 6 months of treatment, the IOP decrease (Δ) values obtained with the different tonometers were ΔGAT -6.5 ± 3.7, ΔIOPnct -4.4 ± 5.7 and ΔbIOP -3.8 ± 5.4. The differences between ΔGAT vs ΔIOPnct, ΔGAT vs ΔbIOP, and ΔIOPnct vs ΔbIOP, were statistically significant (p < 0.05 for all comparisons). Statistically significant lower values of the stress-strain index (SSI) (1.77 ± 0.3 at baseline vs 1.54 ± 0.27 at the 6-month visit) were found (p = 0.0002). CONCLUSION: The SSI provided by the Corvis ST seems to decrease significantly after topical prostaglandin therapy. We believe that our results support the hypothesis that topical PG therapy does decrease the corneal stiffness and thus, that the ocular hypotensive effect of these drugs is overestimated if GAT is used for IOP measurement.

Effect of prostaglandin analogues on central corneal thickness in patients with glaucoma: A systematic review and meta-analysis with trial sequential analysis.

The objective of this meta-analysis was to evaluate the effect of prostaglandin analogues (PGA) on central corneal thickness (CCT) in patients with glaucoma. Key electronic databases were searched for randomized controlled trials (RCTs) involving the CCT effects of prostaglandin use for glaucoma. Primary outcome measures were the mean difference in the CCT measurement from baseline to the last available assessment. Intraocular pressure and other corneal changes were recorded as secondary. Efficacy estimates were measured by their weighted mean difference (WMD) with 95% confidence intervals (CI's) by using the random-effects model for primary and secondary outcomes Trial sequential analysis was used to determine if the current evidence was sufficient and conclusive. Eight RCTs met our inclusion criteria. A total of 879 patients were included. The overall effect showed that PGA's had a significant CCT lowering effect (WMD = -7.04, 95%CI: -10.07 to -4.00, P < 0.00001). We pooled results of 5 RCT's on Travoprost (WMD = -10.44, 95%CI: -16.80 to -4.08, P = 0.001), seven trials on Latanoprost (WMD = -4.73, 95% CI: -9.70 to 0.25, P = 0.06), and three trials on Bimatoprost (WMD = -11.88, 95%CI: -21.03 to -2.73, P = 0.01). The WMD across groups in >6 months of PGA use was -11.37 (95%CI: -17.17 to -5.58, P = 0.0001), and in <6 months of PGAs group was -8.35 (95% CI: -12.01 to -4.69, P < 0.00001), suggesting a longitudinal effect of PGAs on CCT. In conclusion, Bimatoprost and Travoprost caused a statistically significant reduction in the thickness of central cornea. Though only a few studies were included, the narrow confidence intervals and adequate sample size suggest that these findings are valid.

[Prostaglandins in ophthalmology]. / Prostaglandiny v oftal'mologii.

Prostaglandins are widely used in medicine as active physiological agents that form a new class of drugs for treatment of cardiovascular diseases, some forms of bronchial asthma, as well as in gynecology and ophthalmology. Development of aseptic inflammation is an example of intracellular process, in which the produced prostaglandins are able to and do cause vasodilatation, increased vascular permeability, pain and fever. These effects of prostaglandins and leukotrienes characterize the classic picture of inflammation, including the aseptic one. The use of non-steroidal anti-inflammatory drugs (NSAIDs) can provide therapeutic effect via inhibition of prostaglandin secretion. Prostaglandins play a special role in glaucoma treatment. Prostaglandin analogues are powerful agents that decrease IOP by 20-40% with a unique mechanism of action. Prostaglandin analogues have a well-balanced safety profile, which is why they are considered as a first line of therapy. However, patients with inflammatory diseases in anamnesis, such as uveitis, herpes, keratitis, as well as patients with planned cataract extraction should be careful when using prostaglandin analogues.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: Results from the VISIONARY Study Population in Spain.

Purpose: Data are presented from ophthalmology clinics in Spain participating in the VISIONARY study, examining the effectiveness, tolerability, and safety of the preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in the treatment of OAG and OHT. Methods: An observational, multicenter prospective study examined treatment outcomes following a switch to PF tafluprost/timolol FC in adult OAG/OHT patients demonstrating insufficient response to beta-blocker or prostaglandin analog (PGA) monotherapy. Primary end point was mean change in intraocular pressure (IOP) from baseline at month 6. Changes in the severity of ocular signs and symptoms were also assessed. Results: Overall, 92 patients (51.1% female) were included. Mean (standard deviation) age was 68.3 (12.1) years. Mean IOP was reduced from 21.9 mmHg at baseline to 16.7 mmHg at month 6 (22.3% decrease; P < 0.0001). Significant IOP reductions were observed at weeks 4 and 12 (P < 0.0001). Baseline PGA and beta-blocker users demonstrated mean month 6 IOP reductions of 5.5 mmHg (23.5%; P < 0.001) and 3.5 mmHg (14.6%; P = 0.029), respectively. Severity of conjunctival hyperemia, dry eye, irritation, itching, foreign body sensation, and eye pain was significantly reduced. Three treatment-related adverse events were reported, all were nonserious and mild/moderate in severity. Conclusion: In real-world clinical practice, PF tafluprost/timolol FC treatment provided significant IOP reductions over 6 months and was well tolerated among OAG/OHT patients showing poor response to PGA or beta-blocker monotherapy. IOP-lowering efficacy and improvements in ocular signs and symptoms were evident from week 4 and maintained over the 6-month study period. Trial Registration: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number EUPAS22204.

Glaucoma: diagnosis and management. Last updated: 26 January 2022

This guideline covers diagnosing and managing glaucoma in people aged 18 and over. It includes recommendations on testing and referral (case-finding) for chronic open-angle glaucoma and ocular hypertension and on effective diagnosis, treatment and reassessment to stop these conditions progressing. We have produced a large print version of this guideline, which is available to download in tools and resources. In January 2022, we reviewed the evidence and updated the recommendations on treatment for ocular hypertension and chronic open-angle glaucoma and organisation of care. For more information, see update information.

Guía de práctica clínica para el manejo de glaucoma de ángulo abierto: guía en versión extensa / Clinical Practice Guideline for the Management of Open-Angle Glaucoma: Comprehensive Version Guide

El tratamiento oportuno de personas con glaucoma primario de ángulo abierto busca minimizar el número de complicaciones por esta enfermedad. Por ello, el Seguro Social de Salud del Perú (EsSalud) priorizó la realización de la presente guía de práctica clínica (GPC) con la finalidad de establecer recomendaciones basadas en evidencia para gestionar de la mejor manera los procesos y procedimientos asistenciales relacionados a esta condición clínica. Esta GPC fue realizada por la Dirección de Guías de Práctica Clínica, Farmacovigilancia y Tecnovigilancia del Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) de EsSalud.

Effect of prostaglandin analogues on anterior scleral thickness and corneal thickness in patients with primary open-angle glaucoma.

Prostaglandin (PG) analogues are usually prescribed as a first-line therapy in patients with glaucoma because of its once-daily dosing benefit and effective intraocular pressure (IOP) reduction. However, the mechanism of PG analogues is not completely understood. In this study, we investigated the effect of PG analogues on the anterior scleral thickness (AST) in treatment-naïve eyes with primary open-angle glaucoma using anterior segment optical coherence tomography. The AST was measured at the location of the scleral spur, 1000 µm, and 2000 µm posterior to the scleral spur and was compared before and after using the medications for 3 months and 1 year. Among 54 patients enrolled in this study, 31 patients used prostaglandin analogues and 23 patients used dorzolamide/timolol fixed combination (DTFC) drugs. There was no significant difference in untreated IOP, glaucoma severity, and baseline AST values between the two groups. While there was no significant changes in AST after using the DTFC drugs, the AST at all 3 locations showed a significant reduction in both the nasal and temporal sectors after using PG analogues for 1 year (all, P < 0.05). These findings suggest that the AST reduction after using PG analogues might be related with the increased uveoscleral outflow.

High Correlation between Glaucoma Treatment with Topical Prostaglandin Analogs and BDNF Immunoreactivity in Human Retina.

PURPOSE: To examine the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin-related kinase receptor-B (TrkB), in normal and glaucomatous human retinas. METHODS: Human retinas were collected from 8 donors who had been clinically diagnosed and treated for glaucoma, and from 9 control donors. Immunohistochemical analysis for BDNF and TrkB was performed. The percent of each retina expressing BDNF and TrkB was quantified for the total retinal thickness, and separately for the retinal ganglion cell (RGC) complex + retinal nerve fiber layer (RNFL). The expression of each protein was correlated with clinical outcomes obtained from the subject's ocular histories. RESULTS: There was no significant difference in BDNF or TrkB expression when comparing glaucomatous and control retinas. Correlation analysis revealed a significant relationship between BDNF expression and the use of prostaglandin analogs. TrkB expression was highly correlated with the last-measured intraocular pressure (IOP), the use of carbonic anhydrase inhibitors, the use of beta blockers, and the total number of drugs used for the treatment of glaucoma. CONCLUSION: Topical drugs used to treat glaucoma were associated with an increase in retinal BDNF and TrkB expression in human retina, independent of IOP, which may represent molecular evidence of neuroprotective pathway activation.

Medical anti-glaucoma therapy: Beyond the drop.

Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti-glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti-glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta™ Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose™ , Ocular Therapeutix's OTX-TIC travoprost implant, and Santen's polycaprolactone implant with PGE2-derivative DE-117. Other prostaglandin-based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX-TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856-isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus® NT-501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals.

The influence of topical non-steroidal anti-inflammatory drugs on the intraocular pressure lowering effect of topical prostaglandin analogues-A systemic review and meta-analysis.

PURPOSE: This study aimed to review previous articles and evaluate the influence of topical non-steroidal anti-inflammatory drugs (NSAIDs) on intraocular pressure (IOP) in glaucoma patients who were treated with prostaglandin analogues (PGs). METHOD: The presenting study was designed as a meta-analysis of previous research. Databases include PubMed, Web of science, Cochrane library, and Embase were searched with keywords of "intraocular pressure, prostaglandin analogues, NSAIDs, latanoprost, travoprost, bimatoprost, tafluprost, unoprostone, latanoprostene bunod, ketorolac, diclofenac, nepafenac, bromfenac, flurbiprofen". Inclusion criteria were: 1. Study population were glaucoma patients; 2. Comparison between PGs monotherapy and PGs in combination with topical NSAIDs; 3. Changes of IOP as final outcomes. Studies with non-randomized design, treatments combining other anti-glaucomatous drugs, or unavailable absolute IOP were excluded from the analysis. Estimated difference in IOP were calculated using STATA 14.0. RESULT: Seven studies were retrieved for this meta-analysis. Since there is a significant heterogeneity (I2 = 94%) in these studies, random-effect model was used to calculate pooled standardized mean differences (SMD). Our results showed a significantly favorable IOP lowering effect in glaucoma patients treated with combination of topical NSAIDs and PGEs (SMD: 1.3 and -0.03, 95% CI: 0.29 to 2.38 and -0.32 to 0.26, Z = 2.50 and 0.23, p = 0.013 and 0.820, respectively). CONCLUSION: Results of our meta-analysis suggested that topical NSAIDs may enhance the IOP lowering effect of topical PGs in glaucoma patients.