[Cell cultures - model object for experimental studies in ophthalmology]. / Kletochnye kul'tury ­ model'nyi ob"ekt dlya eksperimental'nykh issledovanii v oftal'mologii.

The article presents results obtained on several types of model cultures. Primary cultures of corneal epithelial cells and fibroblast-like cells from the limbus were obtained from the tissues of the anterior eye segment. Tests were performed on these cultures to determine the cytotoxicity of antiglaucoma drugs and to trial a protection method. In addition, a comparative analysis of the regenerative potential of various blood derivatives was carried out. An in vitro culture of endotheliocytes showed a correlation between the degree of damaging effects of antiglaucoma drugs of various groups and the content of the preservative benzalkonium chloride in their composition. Corneal keratocytes were used to create a cell sheet reflecting the main structural features of the stroma and suitable for biomechanical tests. The antifibrotic activity of the drugs was tested on the culture of fibroblasts from the nasolacrimal duct. The conducted studies demonstrate that cell cultures can be used as an informative model object for researching the pathogenesis of ophthalmic diseases and for testing drugs.

Adherence to topical anti-glaucoma medications in Sidama regional state, Southern Ethiopia.

PURPOSE: To assess the proportion of adherence to topical anti-glaucoma medications and associated factors among glaucoma patients in Sidama regional state, Ethiopia. METHODS: An institution based cross-sectional study was conducted from May 30 to July 15, 2022 at Hawassa University comprehensive specialized and Yirgalem General Hospitals in Sidama regional state, Ethiopia. A systematic random sampling method was used to select 410 study participants. An adapted eight-item self-reported questionnaire was used to assess adherence. Binary logistic regression was used to identify factors associated with adherence to topical anti-glaucoma medications. Variables with a p-value of <0.05 under multivariable analysis were taken as statistically significant factors for adherence. The strength of the association was measured by using an adjusted odds ratio with 95% confidence interval. RESULTS: A total of 410 participants were included giving a response rate of 98.3%. Those who were adherent to their medications were 221(53.9%) (95% CI: 48.8-58.5). Urban residence (AOR = 2.81: 95% CI = 1.34-5.87), higher educational level (AOR = 3.17: 95% CI = 1.24-8.09), monthly follow-up frequency (AOR = 3.30: 95% CI = 1.79-6.11) and normal vision (AOR = 6.58: 95% CI = 3.03-10.84) were significantly associated with adherence. CONCLUSION: More than half of glaucoma patients attending at Hawassa University comprehensive specialized and Yirgalem general hospitals were adherent to their topical anti-glaucoma medications. Urban residence, educational level, follow-up frequency, and normal vision were associated with adherence.

Evaluation of the ocular surface in asymptomatic glaucoma patients on topical medications and following trabeculectomy - A cross-sectional study.

Purpose: This present prospective, cross-sectional study aims to comprehensively evaluate the ocular surface in asymptomatic patients with diffuse blebs after trabeculectomy versus chronic anti-glaucoma medication use and compare it with the age-matched normal population. Methods: Objective clinical evaluation was done by tear film break-up time (TBUT) and Schirmer's test (ST) in the three groups-trabeculectomy >6 months with a diffuse bleb (Wurzburg bleb classification score ≧10), chronic anti-glaucoma medication (AGM >6 months) group, and normal population. In all groups, tear film osmolarity was checked with the TearLab® device (TearLab Corp., CA, USA), and subjective evaluation was performed by administering Ocular Surface Disease Index (OSDI) questionnaire. Patients already on chronic lubricants or any other drug for the treatment of dry eyes (viz. steroids, cyclosporin) or having symptoms suggestive of an abnormal ocular surface, who had undergone refractive or intraocular surgery, and contact lens users were excluded. Results: In total, 104 subjects/eyes were recruited over 6 weeks. Thirty-six eyes recruited in the trab group were compared with 33 eyes studied in the AGM group, and both these groups were compared to 35 normal eyes. When compared to normals, TBUT and ST were significantly lower (P = 0.003 and 0.014) and osmolarity and OSDI were statistically significantly higher (P = 0.007 and 0.003) in the AGM group, whereas only TBUT was statistically significantly different (P = 0.009) when the trab group was compared to normals. Also, when the trab group was compared to the AGM group, ST was found to be higher (P = 0.003) and osmolarity was lower (P = 0.034). Conclusion: To conclude, ocular surface is affected even in asymptomatic patients on AGM but near normalcy is possible following trabeculectomy when blebs are diffuse.

Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55-MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin.

Polymorphisms rs2472493 near ABCA1, rs7636836 in FNDC3B, and rs61275591 near the ANKRD55-MAP3K1 genes were previously reported to exhibit genome-wide significance in primary open-angle glaucoma (POAG). Since these polymorphisms have not been investigated in the Arab population of Saudi Arabia, we examined their association with POAG in a Saudi cohort. Genotyping was performed in 152 POAG cases and 246 controls using Taqman real-time assays and their associations with POAG and clinical markers, such as intraocular pressure, cup/disc ratio, and the number of antiglaucoma medications, were tested by statistical methods. There was no association observed between POAG and the minor allele frequencies of rs2472493[G], rs7636836[T], or rs61275591[A]. None of the genetic models such as co-dominant, dominant, recessive, over-dominant, and log-additive demonstrated any genotype link. The Rs2472493 genotype showed a modest association (p = 0.044) with the number of antiglaucoma medications in the POAG group, but no significant genotype effect on post hoc analysis. In addition, a G-T allelic haplotype of rs2472493 (ABCA1) and rs7636836 (FNDC3B) did show an over two-fold increased risk of POAG (odds ratio = 2.18), albeit non-significantly (p = 0.092). Similarly, no other allelic haplotype of the three variants showed any significant association with POAG. Our study did not replicate the genetic association of rs2472493 (ABCA1), rs763683 (FNDC3B), and rs61275591 (ANKRD55-MAP3K1) in POAG and related clinical phenotypes, suggesting that these polymorphisms are not associated with POAG in a Saudi cohort of Arab ethnicity. However, large population-based multicenter studies are needed to validate these results.

Phacoemulsification versus Phacoemulsification/Trabeculectomy for the Treatment of Primary Open-Angle Glaucoma Coexistent with Cataract: A Comparative Study.

Background: The purpose of this study was to evaluate the clinical outcomes in patients with primary open-angle glaucoma (POAG) and coexistent cataract treated with phacoemulsification cataract surgery, either alone or in combination with trabeculectomy. Methods: Participants in this retrospective study were 52 patients diagnosed with previously controlled POAG and coexistent cataract, who underwent either uneventful phacoemulsification cataract surgery (Group I, n = 27) or combined uneventful phacoemulsification cataract surgery and trabeculectomy (Group II, n = 25), with at least a 24-month postoperative follow-up. We recorded the changes in intraocular pressure (IOP) and in the need of anti-glaucoma medications before and after surgical procedures. Results: There was a statistically significant decrease in IOP at postoperative day 7 in both groups (p < 0.001), which remained until the end of the 24-month follow-up. At month 24, the two groups did not differ significantly in terms of IOP (14.3 ± 1.4 vs. 13.1 ± 1.2 for Group I and Group II, respectively; p = 0.447). In addition, there was a statistically significant decrease in the number of anti-glaucoma medications needed at postoperative day 7 in both groups (p < 0.001 for both groups compared to baseline). At month 24, patients in both groups needed about one additional anti-glaucoma medication to control their IOP. Of note, during the first month after surgery, 20% of patients in Group II needed 0.1 mL 5-FU injections to the bleb, although antimetabolites were not used in the primary surgery. Conclusions: Both surgical interventions, namely phacoemulsification cataract surgery alone and phacoemulsification/trabeculectomy, were found to be effective in the management of POAG with coexistent cataract, presenting a significant decrease in IOP and in the need of anti-glaucoma medications postoperatively at a long-term follow-up period of 24 months.

Outcomes of Ultrasound Cyclo Plasty in Primary Angle Closure Glaucoma.

PRCIS: Ultrasound cyclo plasty (UCP) can be useful in decreasing the intraocular pressure (IOP) and burden of antiglaucoma medications in eyes with primary angle closure glaucoma (PACG). Nevertheless, baselines IOP was an important determinant for failure. PURPOSE: To evaluate the intermediate-term outcomes of UCP in PACG. METHODS: This retrospective cohort study included patients with PACG who underwent UCP. The main outcome measures were IOP, number of antiglaucoma medications, visual acuity, and presence of complications. The surgical outcomes of each eye were classified as a complete success, qualified success, or failure based on the main outcome measures. Cox regression analysis was performed to identify possible predictors for failure. RESULTS: Sixty-two eyes of 56 patients were included in the study. The mean follow-up period was 28.81 months (±18.2). The IOP and number of antiglaucoma medications decreased from a mean of 23.03 (±6.4) mmHg and 3.42 (±0.9) to 15.57 (±6.4) mmHg and 2.04 (±1.3), respectively, in the 12 th month and to 14.22 (±5.0) mmHg and 1.91 (±1.5) in the 24 th month ( P <0.01 for all). The cumulative probabilities of overall success were 72.6±5.7% and 54.8±6.3% at 12 and 24 months, respectively. A high baseline IOP was associated with a higher risk of failure (hazard ratio=1.10, P =0.03). The most common complications were cataract development or progression (30.6%), rebound or prolonged anterior chamber reaction (8.1%), hypotony with choroidal detachment (3.2%), and phthisis bulbi (3.2%). CONCLUSIONS: UCP offers reasonable 2-year IOP control and reduction of the antiglaucoma medication burden. However, counseling on possible postoperative complications is needed.

Advances in innovative delivery systems for antiglaucoma drugs.

PURPOSE OF REVIEW: Currently, glaucoma treatment drugs are facing problems such as low bioavailability, poor patient compliance, discontinuous administration affecting the efficacy of intraocular pressure (IOP) lowering and chronic damage to the eye caused by side effects of drugs. In order to solve these problems and to better meet clinical needs, various new dosage forms have been developed and applied in the clinical setting. RECENT FINDINGS: A number of nano formulations and extended-release gels are in successive animal trials, some tear plugs, implants and contact lenses are in clinical trials, and it is believed that more new carrier materials and formulations to improve the bioavailability of drugs are being developed. SUMMARY: Novel delivery systems for antiglaucoma drugs offer patients more and better therapeutic options, and ongoing or completed studies are providing clear directions for subsequent research to improve clinical applications.

Safety and efficacy of iStent Inject trabecular micro-bypass stents in combination with phacoemulsification for chronic open angle glaucoma associated with cataract.

BACKGROUND: The goal of this study was to assess the efficacy and safety of phacoemulsification combined with iStent Inject® implantation for the treatment of chronic open-angle glaucoma controlled on topical anti-glaucoma medications and associated with cataract. METHODS: This study was a retrospective analysis of patients who underwent phacoemulsification and implantation of an iStent Inject® for chronic open-angle glaucoma associated with cataract. For all patients, pre- and postoperative characteristics, including number of glaucoma medications and intraocular pressure (IOP), were compared using Paired-sample t-tests and Wilcoxon signed-rank tests, respectively. Postoperative visits were scheduled at 7 days and 1, 3, 6, and 12 months after surgery. RESULTS: Forty-nine eyes of 39 patients were included in the study. Mean preoperative IOP at baseline was 16.3±4.3mmHg (range, 10-29mmHg) with a mean of 2.2±1.0mmHg antiglaucoma medications. At 1 month, the mean IOP reduction was 16% (P<0.05) along with an 18.7% reduction in the mean number of medications. At 6 months, the mean IOP was 12.8±2.6, with a mean of 1.1±0.9 antiglaucoma medications. The mean IOP reduction at 6 months was 22% (P<0.05) along with a 49% reduction in the mean number of medications. At 12 months, the mean IOP was 13.8±2.5 with a mean of 1.1±1.2 medications. The mean IOP reduction at 12 months was 15% (P<0.05) along with a 47% reduction in the mean number of medications. No severe device-related side effects were observed. CONCLUSIONS: iStent Inject® implantation combined with phacoemulsification resulted in effective IOP reduction and medication burden in patients with mild to advanced chronic open-angle glaucoma and preoperative IOP well controlled with topical hypotensive medications.

Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors.

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H2S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H2S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H2S donors. The H2S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H2S by antiglaucoma H2S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.

Perceived Stress Levels and Associated Factors in Adult Patients with Primary Open-angle Glaucoma: A Prospective Survey Study.

PURPOSE: To investigate adult primary open-angle glaucoma (POAG) patients' perceived stress levels and to examine the associations with their clinical characteristics. METHODS: Sixty-seven POAG patients, excluding those meeting the exclusion criteria (retinal or neurological disease diagnoses) comprised the study population. A validated questionnaire, namely Perceived Stress Scale-10 (PSS-10), was used to assess stress level. Additional data on glaucoma surgery history, medical benefit receipt, comorbidities, and daily antiglaucoma medication number were collected. The clinical characteristics of high (PSS-10 ≥15) and low stress (PSS-10 <15) patients and the risk factors associated with high stress level were subjected to a multivariable logistic regression analysis. RESULTS: The patients were 56.8 ± 12.6 years of age on average, and 29 (43.3%) were female. The mean PSS-10 level was 13.5 ± 5.3 (range, 1-27) for the entire patient group; 31 patients (46.3%) were in the high stress group. In the high stress group relative to the low stress group, best-corrected visual acuity in the better eye was lower (p = 0.044) and the visual field defects, in both eyes, were more severe (better eye, p = 0.005; worse eye, p = 0.026). A logistic regression analysis indicated that severe visual field defect in the better eye (odds ratio, 1.159; 95% confidence interval, 1.016-1.323; p = 0.028) and lower best-corrected visual acuity in the better eye (odds ratio, 4.707; 95% confidence interval, 0.580-6.189; p = 0.072) were both likely to associated with high stress level in patients with POAG. CONCLUSIONS: These findings suggest an association between severe visual function loss and higher mental stress level in POAG patients. Stress level, therefore, might be an important consideration in POAG patient management.

Efficacy and safety of subliminal transscleral cyclophotocoagulation in uncontrolled glaucoma.

Purpose: To determine the efficacy of subliminal cyclophotocoagulation in reducing intraocular pressure (IOP) and to assess the safety profile of the procedure. Methods: We reviewed the charts of all patients who underwent subliminal cyclophotocoagulation between August 2019 and August 2020. The IOP, number of antiglaucoma medications, and visual acuity were compared at baseline and at 6 months. The post-laser complications were noted. Paired t-test, Wilcoxon rank-sum test, and McNemar test were used for analysis. Results: This study included 40 eyes of 40 patients. The most frequent diagnosis was neovascular glaucoma (55%), followed by primary open-angle glaucoma (17.5%). The mean IOP reduced from 32 to 21 mmHg (mean IOP reduction: 32%, 95% confidence interval [CI]: 27%-37%, P < 0.001). Mean number of antiglaucoma medications declined from 3.2 to 1.9 (P < 0.001). Use of oral acetazolamide decreased from 62% to 5% (P < 0.001). The success rate of the procedure at 6 months was 55%. One patient had unexplained visual acuity decline after the procedure. Conclusion: Subliminal sub-cyclophotocoagulation is effective in treating refractory glaucoma in the Indian population. It decreases the medication burden. However, subliminal lasers can also cause vision-threatening complications such as hypotony, uveitis, and optic nerve hypoperfusion. So, clinicians should be cautious when using sub-cyclophotocoagulation in patients with good vision.

Anti-glaucoma medications lowered decorin and altered profibrotic proteins in human tenon's fibroblasts.

Long term exposure to anti-glaucoma medications (AGMs) leads to an increase in extracellular matrix (ECM) accumulation in primary glaucoma patients. This study aims to evaluate the effect of topical AGMs in primary human tenon's fibroblasts (HTFs) and analyze the expression of profibrotic and anti-fibrotic proteins. Primary HTFs were cultured from patients undergoing cataract (control) and trabeculectomy. The different types of AGMs in single/multiple combinations (BB, PG, AA, CAI, CH, combinations of 3- PG + AA + CAI, 4A- BB + PG + AA + CAI, 4B- BB + PG + CAI + CH and 5- BB + PG + AA + CAI + CH) on chronic exposure were tested for cell viability using MTT assay and morphological alterations. Profibrotic proteins mainly SPARC, LOXL2, COL1A1 and anti-fibrotic DCN were analyzed in treated HTFs using q-PCR and ELISA. Sirius red staining and collagen gel contraction (CGC) assay were performed to assess collagen synthesis and the contractility of HTFs, respectively. Except for AA and CH, the other AGMs at a higher concentration were found to decrease the cell viability of HTFs. The morphology of HTFs were altered on exposure to BB, CH and AA; Profibrotic proteins i.e., SPARC, LOXL2 and COL1A1 were significantly increased (p < 0.05) on exposure to a combination of AGMs with TGF-ß1, whereas the anti-fibrotic DCN expression was significantly lowered (p < 0.05) in single/multiple AGM exposure. Sirius red staining showed increased collagen synthesis with combinations of AGMs with TGF-ß1. Meanwhile, HTFs showed increased collagen gel contraction with TGF-ß1, CAI and CH. This study reveals that altered profibrotic proteins, with significantly lowered DCN on chronic exposure of AGMs in HTFs.

Achieving Inner Aqueous Drain in Glaucoma Secondary to Iridocorneal Endothelial Syndrome: One Year Results of Penetrating Canaloplasty.

PURPOSES: To report the efficacy of a bleb-independent penetrating canaloplasty in the management of glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE). DESIGN: Prospective, non-comparative clinical study. METHODS: Penetrating canaloplasty was performed on 35 eyes from 35 patients with GS-ICE and medically uncontrolled intraocular pressure (IOP) between January 2018 and April 2020. Patients were followed up at 1 week, months 1, 3, 6, 12 postoperatively, and semi-annually thereafter. The IOP, anti-glaucoma medication, and surgery-related complications were recorded. Surgical success was defined as IOP ≥ 5 mmHg and ≤ 21 mmHg without (complete success) or with/without (qualified success) IOP-lowering medication. RESULTS: A total of 29 eyes (82.9%) had 360° catheterization and successfully received penetrating canaloplasty. Of these eyes, 24 (82.8%) achieved qualified success and 22 (75.9%) achieved qualified success at 12 months after surgery. The mean IOP decreased from 39.5 ± 11.8 mmHg on 2.9 ± 1.0 medications before surgery to 16.6 ± 5.3 mmHg (P < .001) on 0.2 ± 0.6 medications (P < .001) at 12 months postoperatively, respectively. Hyphema (37.9%), transient hypotony (34.5%), and transient postoperative IOP elevation (≥ 30 mmHg, 17.9%) were the most commonly observed early complications at the 1 week and 1 month visits. From 1 month and beyond, all treated eyes showed no obvious bleb at the operation quadrant. CONCLUSIONS: Penetrating canaloplasty rescued the inner aqueous outflow in ICE eyes and demonstrated acceptable success in IOP control with few complications, providing a new option for the management of GS-ICE.

Ultrasound Cyclo Plasty in Glaucoma: 2-Year Outcomes.

PRCIS: UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden. PURPOSE: The purpose of this study is to evaluate the 2-year outcomes of Ultrasound Cyclo Plasty (UCP) in uncontrolled glaucoma. MATERIALS AND METHODS: A retrospective cohort study included patients with uncontrolled primary or secondary glaucoma who underwent UCP at King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, between 2016 and 2021. The main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, and presence of vision-threatening complications. The surgical outcome of each eye was classified as complete success, qualified success, or failure based on the main outcome measures. RESULTS: One hundred and eighty-two eyes of 158 patients were included in the study. The mean follow-up period was 29.71 months (±18.1). The IOP and the number of antiglaucoma medications decreased significantly from a mean of 23.46 mm Hg (±6.3) and 3.33 (±0.9) to 17.33 (±7.1) and 2.14 (±1.4), and 16.24 (±6.3) and 1.90 (±1.5) on the 12th and 24 months, respectively. The overall success rates were 78.0% (143/182) and 85.6% (95/111), and the failure rates were 21.4% (39/182) and 14.4% (16/111) on the 12th and 24th months, respectively. The most common complications were cataract development/progression and anterior chamber reaction. CONCLUSIONS: UCP offers reasonable IOP control and reduction of the antiglaucoma medication burden.

Changes in ocular surface after withdrawal of anti-glaucoma medications following non-penetrating deep sclerectomy.

Purpose: : To analyze the ocular surface changes in eyes after the withdrawal of anti-glaucomatous drugs when non-penetrating deep sclerectomy (NPDS) is performed. Methods: Thirty-one patients (33 eyes) diagnosed with glaucoma that underwent NPDS were included in this prospective study. The control group included 33 eyes. Four variables were studied using Keratograph 5M (K5M): ocular hyperemia (OH), non-invasive tear film break-up time (NI-BUT), lower tear meniscus height (LTMH), and meibography. LTMH was also measured using the anterior segment module of a Spectralis Fourier-domain optical coherence tomography (FD-OCT) instrument. Moreover, an evaluation of corneal and conjunctival staining was performed. In the glaucoma group, five visits were carried out: pre-surgery, 1 week after surgery, and 1 month, 3 months, and 6 months after surgery. In control groups, examinations were performed in only one visit. In addition, patients were asked to answer two questionnaires: Ocular Surface Disease Index (OSDI) and National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) before and 6 months after surgery. Results: Before NPDS, eyes showed worse objective data than healthy control subjects (P ≤ 0.049). In this group, a significant improvement was observed in questionnaire responses (P < 0.001), LTMH-FD-OCT (P = 0.037), LTMH-K5M (P = 0.025), K5M-OH (P = 0.003), NI-BUT (P = 0.022), and conjunctival and corneal staining (P < 0.001). No significant differences were observed between groups in FD-OCT and K5M LTMH, NI-BUT, corneal-conjunctival staining, nor in the most OH sector values at 6 months (P ≥ 0.62). Conclusion: A significant improvement in the ocular surface was observed 6 months after NPDS, suggesting that the withdrawal of the topical anti-glaucomatous treatment had a beneficial effect on the subjects.

Topical ophthalmic beta-blockers are associated with ocular pseudopemphigoid: A pharmacovigilance study of antiglaucoma medications utilising the FDA adverse event reporting system.

BACKGROUND/OBJECTIVE: The association between antiglaucoma medications and the development of ocular pseudopemphigoid (OPP) has been described; however, the independent risk of each medication has not been quantified. METHODS: Case/non-case analyses were performed in the FDA Adverse Events Reporting System (FAERS) using data from 2010-2020 to examine the reporting odds ratio (ROR) signal for OPP for all classes of antiglaucoma medications under multiple conditions: (i) comparison to all other drugs in FAERs, (ii) comparison to other antiglaucoma medications, (iii) comparison to vehicle/hydrating eye drops with cases of OPP and (iv) comparison to vehicle/hydrating eyedrops with and without cases of OPP to control for topical irritant and preservative effects. RESULTS: A statistically significant ROR for OPP was found for aggregate antiglaucoma medications under the first condition but not the third or fourth (i.96.97 (95% CI 52.54-178.98). The largest signal for OPP when compared to other glaucoma drugs and eye drops was seen with unoprostone (ii.68.96 (95% CI 8.35-569.50, iii.39.85 (95% CI 4.14-383.33), iv.581.67 (95% CI 49.38-6851.57) followed by carteolol (ii.32.51(95% CI 9.02-117.67), iii.10.67 (95% CI 1.77-64.13), iv.77.84 (95% CI 12.95-467.78) and betaxolol (ii.23.38 (95% CI 7.28-74.46), iii.6.94 (95% CI 1.27-38.01), iv.50.67 (95% CI 9.26-277.25). A statistically significant ROR was noted only for the beta-blockers class aggregate under conditions ii and iv. CONCLUSIONS: Our findings support an association between OPP and antiglaucoma medications; under the most stringent control for topical irritant/preservative effect by of comparison to topical eye drops, unoprostone, carteolol, betaxolol and timolol all had a significant ROR for OPP.

Reasons for choice of glaucoma surgery in eyes not treated with anti-glaucoma medications.

BACKGROUND: In the real world, some glaucoma patients can undergo an incisional glaucoma surgery without using medication. The rate of cases with no medication treatment at the time of surgery among those that underwent incisional glaucoma surgeries performed in our department was reported. METHODS: The department database of Shimane University Hospital for eyes that underwent incisional surgeries to manage glaucoma at the hospital between April 2018 and September 2020 were searched. By reviewing the medical charts of 1,417 consecutive eyes listed, 90 (6.4%) eyes of 67 subjects (mean age of 72 ± 16 years; 22 men, 29 eyes; 45 women, 61 eyes) who underwent a surgery without use of antiglaucoma medication were identified. The types of glaucoma, glaucoma procedures, and reasons for choosing the glaucoma surgeries rather than medical therapy were collected for the 90 eyes. RESULTS: Among the 90 eyes, primary angle-closure disease (PACD) (60%) was the most frequent type of glaucoma followed by EXG (17%), POAG (16%), and others (8%). Among the reasons for the choice of incisional surgery, relief of angle closure (64%) was the most frequent, the second most frequent was the incidental diagnosis of glaucoma during the ocular examinations both for that eye's cataract surgery or the contralateral glaucoma surgery (13%). Other reasons included poor medication adherence (10%), dementia (6%), multiple medication allergy (3%), and acute IOP elevation other than PACD (3%). Cataract extraction (CE) alone (33%) was the most frequent glaucoma procedures performed in these eyes, followed by CE combined with goniosynechialysis (27%), CE + iStent (16%), CE + goniotomy by Tanito microhook ab interno trabeculotomy or using the Kahook Dual Blade (11%), Ahmed Glaucoma valve implantation (11%), and trabeculectomy (2%). CONCLUSION: In the real-world, 6.4% of incisional glaucoma surgeries were performed in the absence of medication use; of them, 32 eyes (2.3%) were with open angle glaucoma. In open angle glaucoma, the reasons can be classified into; 1) patients' inability to instill the medication, 2) incidental diagnosis of glaucoma during the pre-surgical examinations, and 3) the eyes with acute IOP rise.

Phase 2b, Randomized, 3-Month, Dose-Finding Study of Sepetaprost in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: The ANGEL Study.

Purpose: This phase 2b, randomized, observer-masked, placebo- and active-controlled, parallel-group, multinational (USA and Japan), multicenter study (NCT03216902) assessed the optimal dose of sepetaprost ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension. Methods: After washout, patients ≥18 years (USA) or ≥20 years of age (Japan) received once-daily sepetaprost for 3 months [0.0005% (n = 43); 0.001% (n = 43); 0.002% (n = 44); and 0.003% (n = 45)], latanoprost 0.005% (n = 44) or placebo until week 6, followed by sepetaprost 0.003% until month 3 (n = 22). Safety assessments included adverse event (AE) occurrence. Results: Baseline mean diurnal intraocular pressure (IOP) was 24.3 mmHg for latanoprost and ranged between 24.1 and 24.5 mmHg for the sepetaprost groups. Sepetaprost 0.002% had the lowest IOP at each month 3 time point (9:00 AM; 1:00 PM; 5:00 PM) of all sepetaprost concentrations (mean ± standard error: 17.6 ± 0.5; 17.4 ± 0.4; 16.7 ± 0.4 mmHg); similar values were observed with latanoprost (18.1 ± 0.6; 17.3 ± 0.5; 17.2 ± 0.5 mmHg). A positive dose-response relationship was observed with the 3 lower sepetaprost doses; sepetaprost 0.002% had numerically greater IOP-lowering effects than sepetaprost 0.003%. All sepetaprost doses had statistically significantly greater IOP reductions from baseline versus placebo at week 6 (P < 0.0001). This IOP-lowering effect was consistent between Japan- and USA-based patients. Most AEs were mild and occurred numerically less frequently with sepetaprost 0.002% (34.1%) versus latanoprost (50.0%). The most frequently reported AE was conjunctival hyperemia. Conclusion: In this study, sepetaprost 0.002% was the optimal concentration, showing comparable IOP-lowering efficacy and safety with latanoprost 0.005%. Most AEs were mild; occurrence was numerically lower with sepetaprost 0.002% than latanoprost 0.005%.

Association of the prolonged use of anti-glaucoma medications with the surgical failure of ab interno microhook trabeculotomy.

PURPOSE: This study examined the perioperative factors affecting surgical success in ab interno microhook trabeculotomy (µTLO). METHODS: A total of 146 consecutive patients who underwent µTLO were included in this retrospective study. We performed Cox proportional hazard modelling by setting surgical success at 1 year as an objective variable. The explanatory variables included age, sex, glaucoma type, preoperative intraocular pressure (IOP), glaucoma drug score, mean deviation (MD) of the Humphrey visual field test, duration of glaucoma drug use, antithrombotic drug use, combined cataract surgery, incision range and diabetes mellitus. Additionally, we performed 1:1 matching using propensity score analysis and compared the perioperative parameters between durations of glaucoma drug use of <4.5 years and ≥ 4.5 years (50 patients each). We defined surgical success as satisfaction of all three criteria: IOP 5-21 mmHg, IOP reduction of ≥20% from the preoperative IOP and no additional glaucoma surgery. RESULTS: The Cox proportional hazard model revealed that a longer duration of anti-glaucoma medication was significantly associated with surgical failure. Propensity score matching analysis showed that the <4.5-year users of anti-glaucoma drugs had significantly higher success rates than the ≥4.5-year users (72% versus 52%; p = 0.04). CONCLUSIONS: The prolonged use of multiple glaucoma drugs adversely affected the outcome of µTLO at least at 1 year postoperatively.

Wide Corneal Epithelial Thickness Mapping in Eyes With Topical Antiglaucoma Therapy Using Optical Coherence Tomography.

Purpose: The purpose of this study was to assess the corneal epithelial thickness (CET) of the 9-mm diameter zone in patients treated using topical antiglaucoma medications and to evaluate the factors associated with CET changes. Methods: Seventy-five patients treated using topical antiglaucoma medications and 65 healthy subjects were included in this cross-sectional study. Each patient completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent examinations including the Schirmer I test, tear breakup time (TBUT), and fluorescein staining. CET mapping of the 9-mm diameter zone was performed using RTVue XR. The CET of the different analyzed zones was compared between groups. The relationship between CET and confounding factors was investigated. Results: The patient group had a significantly shorter TBUT, shorter Schirmer I test, and greater fluorescein staining than those of the control group (all P < 0.05). The mean CET of patients with glaucoma was significantly lower than that of controls in the central, paracentral, mid-peripheral, and peripheral zones (all P < 0.001). Age affected the CET in the paracentral, mid-peripheral, and peripheral zones (all P < 0.01). The number of medications affected the CET in the central, paracentral, and mid-peripheral zones (all P < 0.05). The duration of treatment affected the CET in the central and peripheral zones (all P < 0.05). Conclusions: Use of topical IOP-lowering medications leads to epithelial thinning in the 9-mm diameter zone in glaucomatous eyes. Epithelial protection should be considered in older patients and patients treated with multiple medications from the early stages of long-term topical antiglaucoma therapy. Translational Relevance: The 9-mm diameter CET mapping by using widefield optical coherence tomography (OCT) can be a valuable and convenient method to assess the ocular surface damage in patients with topical antiglaucoma therapy.