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The Low-Pressure Glaucoma Treatment Study is a double-masked, randomized trial comparing the visual outcomes of 190 low-pressure glaucoma patients randomized to intraocular pressure reduction with brimonidine tartrate or timolol maleate. Baseline characteristics of participants are compared to published studies.Eye (2007) 21, S51–S54; doi:10.1038/sj.eye.6702890 [ABSTRACT FROM AUTHOR]

Background: Lens-induced glaucomas (LIGs) occur due to the lens's size, position, or inflammation, causing either open-angle or angle-closure mechanisms. These conditions vary clinically, and understanding their effect on post-operative cataract surgery outcomes is crucial for achieving better visual results. Aims and Objectives: The aim of the study was to evaluate the characteristics, risk factors, and their consequences in LIG on postoperative visual outcome, intraocular pressure, inflammation, and optic disc changes. Materials and Methods: Patients diagnosed with LIG between December 2019 and April 2021 underwent cataract surgery and were assessed pre-and postoperatively for visual outcomes, intraocular pressure (IOP), inflammation, and optic disc changes. Results: During the 18-month study, 2700 cataract cases attended the outpatient department at Oxford Medical College, Bangalore. Among them, 50 cases (1.85%) were diagnosed with LIG. The age range was 37-75 years, with a mean of 60.02 (61.70 years for females, 58.04 years for males). Best-corrected visual acuity (BCVA) of 6/12 or better was achieved in 48% of cases, while severe inflammation resulted in BCVA below 6/60 in 69.23%. Elevated IOP was noted in cases with symptoms lasting 2-4 weeks (39.67 mmHg). Glaucomatous disc damage affected 36% of cases, more common in phacomorphic glaucoma (54%) than phacolytic (28%), and significantly correlated with symptom duration over 2 weeks (P<0.01). Conclusions: Planned small incision cataract surgery with intraocular lens implantation along with minimal tissue handling and a good follow-up protocol with efficient management of complications and inflammation play a major role in management and allow for good visual outcome and fewer complications post-surgery. [ABSTRACT FROM AUTHOR]

Background: As the intracapsular cataract extaraction has been the prefered mode of surgery for the lens induced glaucomas since long time, although there is a perceptible shift towards extracapsular cataract in the recent times with reports of safety with posterior chamber intraocular lens implantation aiming to the prognosis of good postoperative visual recovery. Thus this study was planned to study the visual outcome in Phacolytic and Phacomorphic glaucomas with posterior chamber intraocular lens implantation in our set up. Research Question: What is the visual outcome in Phacolytic and Phacomorphic glaucoma after correction with posterior chamber intraocular lens implantation in our set up? The setting of the study was at department of Ophthalmology, Government Medical College, Machilipatnam. A one year observational study was conducted during the period from October 2022 to September 2023 on about 65 Phacolytic and Phacomorphic glaucoma patients admitted during the above period with an indication of surgical intervention in the department of Ophthalmology by studying their socio-demographic profiles, assessing the visual outcome by comparing the IOP range befor and after correction with posterior chamber intraocular lens implantation and also by visual acuity with assessing the impact of the risk factors on visual acuity postoperativrly etc ;. Results: Among the total study subjects about 40% were male and 60% were female. It was observed that the burden of the disease was more between 51-70 years of age group (66%) with the Mean age was 52 years. And also, it was noticed that the disease burden was more among females when compared to males significantly. It was observed that the visual acuity was poor among the study subjects > 60 years of age and when compared to males’ visual acuity was improved better among females in this study. And also, it was noticed that visual acuity was improved significantly among the study subjects who have > 35 mm of IOP at the time of presentation and with reference to type of glaucoma there was no difference observed related to visual acuity between the two. types. Further it was found that the visual acuity was significantly improved among the study subjects who´s preoperative IOP was raised within 1 week when compared to > 1week. About 13.8% of study group have IOP of < 30 mm Hg initially at the time admission followe by 20% have between 30 - 40 mm of Hg and remaining about 66.2% have > 40 mm of Hg. It was observed that about 10.8% of study subjects have IOP of < 10 mm of Hg at the time of last follow up visit after surgical intervention followed by 53.8% between 10-15 mm of Hg, 32.3% between 15-21 mm of Hg,1.5% have > 21 mm of Hg and about 1.5% that was for one study subject it was not recorded and nearly all the study subject´s IOP was come to near normal which statistically highly significant (P<0.005) and also it was noticed that the improvement of IOP between these two groups of Phacolytic & Phacomorphic glaucoma was same (P>0.05). There was no significant difference between Phacolytic and Phacomorphic glaucoma regarding distribution of visual acuity after correction [ABSTRACT FROM AUTHOR]

Most retinal and optic nerve diseases pose significant threats to vision, primarily due to irreversible retinal neuronal cell death, a permanent change, which is a critical factor in their pathogenesis. Conditions such as glaucoma, retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration are the top four leading causes of blindness among the elderly in Japan. While standard treatments—including reduction in intraocular pressure, anti-vascular endothelial growth factor therapies, and retinal photocoagulation—can partially delay disease progression, their therapeutic effects remain limited. To address these shortcomings, a range of neuroprotective and regenerative therapies, aimed at preventing retinal neuronal cell loss, have been extensively studied and increasingly integrated into clinical practice over the last two decades. Several of these neuroprotective therapies have achieved on-label usage worldwide. This narrative review introduces several neuroprotective and regenerative therapies for retinal and optic nerve diseases that have been successfully translated into clinical practice, providing foundational knowledge and success stories that serve as valuable references for researchers in the field. [ABSTRACT FROM AUTHOR]

Glaucoma is a major global health concern and the leading cause of irreversible blindness worldwide, characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons. This review focuses on the need for neuroprotective strategies in glaucoma management, addressing the limitations of current treatments that primarily target intraocular pressure (IOP) reduction. Despite effective IOP management, many patients continue to experience RGC degeneration, leading to irreversible blindness. This review provides an overview of both pharmacological interventions and emerging technologies aimed at directly protecting RGCs and the optic nerve, independent of IOP reduction. Pharmacological agents such as brimonidine, neurotrophic factors, memantine, Ginkgo biloba extract, citicoline, nicotinamide, insulin, and resveratrol show promise in preclinical and early clinical studies for their neuroprotective properties. Emerging technologies, including stem cell therapy, gene therapy, mitochondrial-targeted therapies, and nanotechnologies, offer innovative approaches for neuroprotection and regeneration of damaged RGCs. While these interventions hold significant potential, further research and clinical trials are necessary to confirm their efficacy and establish their role in clinical practice. This review highlights the multifaceted nature of neuroprotection in glaucoma, aiming to guide future research and clinical practice toward more effective management of glaucoma-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Background/Objectives: We aimed to investigate the genetic loci related to disc hemorrhage (DH) and the relationship of causation between DH and primary open-angle glaucoma (POAG) using a genome-wide association study (GWAS) in East Asian individuals. Methods: The GWAS included 8488 Koreans who underwent ocular examination including fundus photography to determine the presence of DH and POAG. We performed a GWAS to identify significant single-nucleotide polymorphisms (SNPs) associated with DH and analyzed the heritability of DH and genetic correlation between DH and POAG. The identified SNPs were utilized as instrumental variables (IVs) for two-sample Mendelian randomization (MR) analysis. The POAG outcome dataset was adopted from Biobank Japan data (n = 179,351). Results: We found that the rs62463744 (TMEM270;ELN), rs11658281 (CCDC42), and rs77127203 (PDE10A;LINC00473) SNPs were associated with DH. The SNP heritability of DH was estimated to be 6.7%, with an absence of a genetic correlation with POAG. MR analysis did not reveal a causal association between DH and POAG for East Asian individuals. Conclusions: The novel loci underlying DH in the Korean cohort revealed SNPs in the ELN, CCDC41, and LINC00473 genes. The absence of a causal association between DH and POAG implies that DH is a shared risk factor, rather than an independent culprit factor, and warrants further investigation. [ABSTRACT FROM AUTHOR]

Glaucoma is identified by the loss of retinal ganglion cells (RGCs). The primary approach to managing glaucoma is to control intraocular pressure (IOP). Lately, there has been an increasing focus on neuroprotective therapies for glaucoma because of the limited effectiveness of standard methods in reducing IOP and preventing ongoing vision deterioration in certain glaucoma patients. Various drug-based techniques with neuroprotective properties have demonstrated the ability to decrease the mortality of retinal ganglion cells. This study will analyze the currently recommended drug-based techniques for neuroprotection in the prospective treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of a new binocular infrared computerized pupillometer in the quantitative measurement of the relative afferent pupillary response in patients with glaucoma by assessing the correlation of the intereye difference in visual function as measured by standard automated perimetry (SAP) with the intereye difference in the afferent pupillary response., Methods: Twenty-three patients with glaucoma underwent examination with a prototype, automated, binocular pupillometer. Correlation between the intereye difference in the afferent pupillary response and the intereye difference in mean deviation (MD) was explored., Results: Within 7 months of pupillography, all patients underwent SAP using the Humphrey Field Analyzer IIi, 24-2, Swedish Interactive Threshold Algorithm. The intereye differential pupillary response was 0.69±0.59 (log units, mean±SD). The intereye difference in MD was 5.67±5.29 dB (mean±SD). There was a strong correlation between the intereye difference in the afferent pupillary response and the intereye difference in MD (Spearman correlation coefficient, r = -0.77; P<0.001)., Conclusions: A new, binocular computerized pupillometer provides an automated method for the quantitative assessment of the afferent pupillary response. The intereye asymmetry in the pupil response correlates strongly with asymmetry in visual function, as measured by SAP, in patients with glaucoma.

Purpose: To investigate risk factors for disc hemorrhage detection in the Low-Pressure Glaucoma Treatment Study., Design: Cohort of a randomized, double-masked, multicenter clinical trial., Methods: Low-Pressure Glaucoma Treatment Study patients with at least 16 months of follow-up were included. Exclusion criteria included untreated intraocular pressure (IOP) of more than 21 mm Hg, visual field mean deviation worse than -16 dB, or contraindications to study medications. Patients were randomized to topical treatment with timolol 0.5% or brimonidine 0.2%. Stereophotographs were reviewed independently by 2 masked graders searching for disc hemorrhages. The main outcomes investigated were the detection of disc hemorrhage at any time during follow-up and their recurrence. Ocular and systemic risk factors for disc hemorrhage detection were analyzed using the Cox proportional hazards model and were tested further for independence in a multivariate model., Results: Two hundred fifty-three eyes of 127 subjects (mean age, 64.7 ± 10.9 years; women, 58%; European ancestry, 71%) followed up for an average ± standard deviation of 40.6 ± 12 months were included. In the multivariate analysis, history of migraine (hazard ratio [HR], 5.737; P = .012), narrower neuroretinal rim width at baseline (HR, 2.91; P = .048), use of systemic β-blockers (HR, 5.585; P = .036), low mean systolic blood pressure (HR, 1.06; P = .02), and low mean arterial ocular perfusion pressure during follow-up (HR, 1.172; P = .007) were significant and independent risk factors for disc hemorrhage detection. Treatment randomization was not associated with either the occurrence or recurrence of disc hemorrhages., Conclusions: In this cohort of Low-Pressure Glaucoma Treatment Study patients, migraine, baseline narrower neuroretinal rim width, low systolic blood pressure and mean arterial ocular perfusion pressure, and use of systemic β-blockers were risk factors for disc hemorrhage detection. Randomization assignment did not influence the frequency of disc hemorrhage detection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Purpose: To investigate risk factors associated with visual field progression in the Low-pressure Glaucoma Treatment Study, a prospective trial designed to compare the effects of the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% on visual function in low-pressure glaucoma., Design: Prospective cohort study., Methods: Low-pressure Glaucoma Treatment Study patients with ≥5 visual field tests during follow-up were included. Progression was determined using pointwise linear regression analysis, defined as the same 3 or more visual field locations with a slope more negative than -1.0 dB/year at P < 5%, on 3 consecutive tests. Ocular and systemic risk factors were analyzed using Cox proportional hazards model and further tested for independence in a multivariate model., Results: A total of 253 eyes of 127 subjects (mean age, 64.7 ± 10.9 years; mean follow-up, 40.6 ± 12 months) were analyzed. Eyes randomized to timolol progressed faster than those randomized to brimonidine (mean rates of progression, -0.38 ± 0.9 vs 0.02 ± 0.7 dB/y, P < .01). In the final multivariate model adjusting for all tested covariates, older age (hazard ratio [HR] = 1.41/decade older, 95% confidence interval [CI] = 1.05 to 1.90, P = .022), use of systemic antihypertensives (HR = 2.53, 95% CI = 1.32 to 4.87, P = .005), and mean ocular perfusion pressure (HR = 1.21/mm Hg lower, 95% CI = 1.12 to 1.31, P < .001) were associated with progression whereas randomization to brimonidine revealed a protective effect (HR = 0.26, 95% CI = 0.12 to 0.55, P < .001)., Conclusions: While randomization to brimonidine 0.2% was protective compared to timolol 0.5%, lower mean ocular perfusion pressure increased the risk for reaching a progression outcome in the Low-pressure Glaucoma Treatment Study. This suggests that the beneficial effect of randomization to the brimonidine arm was independent of possible differences in ocular perfusion pressures between the 2 treatment arms. The current results and large number of drop-outs in the brimonidine 0.2% arm suggest that more research is necessary before altering clinical practice paradigms., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma., Design: Randomized, double-masked, multicenter clinical trial., Methods: Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope ≥-1 dB/year at P<5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression., Results: Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P=.001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method., Conclusion: Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Objective: To compare agreement of automated alternation flicker and serial stereophotograph inspection for detection of progressive glaucoma., Patients and Methods: Serial photographs of patients with glaucoma with at least 36 months of follow-up and perimetry every 4 months were assessed by four graders using predefined criteria with both flicker and stereophotography. The main outcome measure was progressive neuroretinal rim deterioration as identified by each technique., Results: Forty eyes (20 patients) were included and 12 eyes progressed with perimetry. Using stereophotography, the overall agreement (kappa ± standard error) was 0.19 ± 0.06 for rim change, 0.78 ± 0.06 for disc hemorrhage, and -0.04 ± 0.06 for vessel movement. Using flicker, the overall agreement was similar for rim change (0.28 ± 0.06; P = .29), worse for disc hemorrhage (0.43 ± 0.06; P < .001), and better for vessel movement (0.22 ± 0.06; P = .002). The agreement between perimetric and disc progression was similar using stereophotography (0.10 ± 0.05) and flicker (0.19 ± 0.05; P = .20)., Conclusion: Agreement between flicker and stereophotography was similar., (Copyright 2010, SLACK Incorporated.)

Background: To assess the effectiveness of OloGen (also named iGen), a porous, bioengineered, biodegradable, collagen-glycoaminoglycan matrix implant, in preventing poor bleb formation and early failure after trabeculectomy in eyes with a surgical wound defect., Methods: The right eyes of 30 female New Zealand albino rabbits underwent trabeculectomy with OloGen implanted subconjunctivally on top of the scleral flap, while six right eyes received trabeculectomy without the implant to serve as a control group. A 1-2 mm diameter circular conjunctival defect was created in all eyes. Six rabbits in the group receiving the implant were sacrificed on days 3, 5, 7, 21, and 28. Rabbits in the control group were sacrificed on day 28. Perkins applanation tonometry, Seidel test and measurement of both the extent of the conjunctival defect and the anterior chamber depth were performed. Enucleated eyes were fixed in 4% formaldehyde and stained with hematoxylin and eosin (H&E) for general histological observation, and with Sirius and Fast-green stains to assess collagen deposition and cell migration., Results: Seidel tests were negative for all operated and control eyes. No flat anterior chamber occurred in either group. With the exception of days 5 and 7, post-operative mean IOP difference is significant in both groups, (P>0.05 for day 5, 7 and P<0.05 for day 3, 14, 21 and 28). In the implant group, the mean IOP was reduced by between 42% and 35% at days 14, 21, and 28, whereas the mean IOP in the control group was reduced by between only 12% and 2%. In the implant group, histology showed randomized collagen deposition and microcyst formation in the bleb after the matrix had degraded completely at day 28. In the control group, histology showed dense collagen deposition subconjunctivally at day 28., Conclusions: OloGen successfully serves as a 3-dimensional scaffold for cell migration and proliferation, and can prevent failure by maintaining the size of the bleb in the presence of a large wound defect. It might also be successful at repairing postoperative bleb leaks.

Low-pressure (low-tension) glaucoma is reviewed in relation to neuroprotection, that is, the therapeutic strategy to keep neurons living and functionally connected to targets within the brain. Baseline results of the Low-Pressure Glaucoma Treatment Study (LoGTS) are reviewed.

Objective: To explore the relationship between asymmetric baseline intraocular pressure (IOP) and asymmetric visual field (VF) loss in the Low-Pressure Glaucoma Treatment Study., Design: Randomized, multicenter, controlled clinical trial., Participants: Low-pressure glaucoma (LPG) patients 30 years or older were identified. Exclusion criteria included an untreated pressure > 21 mmHg, advanced VF loss, and contraindications to study medications., Interventions: A baseline VF was created using the average of 2 reliable Humphrey full-threshold examinations. A baseline diurnal IOP curve was performed without IOP-lowering medication., Main Outcome Measures: Mean diurnal, peak, trough, IOP range (peak - trough), and standard deviation (SD) of IOP measurements, and mean deviation (MD) and corrected pattern SD (CPSD) of VF examinations., Results: One hundred ninety patients were enrolled (mean age, 64.9+/-10.7 years). Mean deviation and CPSD were not correlated with mean, peak, trough, or peak minus trough (P - T) IOP (Ps = 0.2-0.9). Among patients with unilateral VF loss (n = 53 [27.9%]), there were no differences (Ps = 0.3-0.9) in any IOP parameter between the normal VF eye and fellow glaucomatous eyes. Among patients with bilateral VF loss (n = 137 [72.1%]), mean, peak, trough, and P - T IOPs were similar in eyes with a better VF MD compared with eyes with a worse VF MD (Ps = 0.2-0.7). Cross-classified contingency tables demonstrated no relationship (Ps = 0.1-0.3) between IOP and VF MD or CPSD using chi-square analysis., Conclusions: Intraocular pressure asymmetry is unrelated to VF asymmetry in the Low-Pressure Glaucoma Treatment Study, suggesting an unclear pathogenic relationship between IOP and glaucomatous damage in eyes with LPG.

Glaucoma is a multifactorial optic neuropathy that primarily affecting retinal ganglion cells (RGC). Brimonidine is an intraocular pressure-lowering drug with reported neuroprotective properties. This study aimed to compare the neuroprotective effects of topical and intraperitoneal (IP) brimonidine on RGCs from different retinal segments in a murine optic nerve crush (ONC) model. Methods: forty-one Balb/c mice underwent unilateral ONC and were divided into three study groups: fifteen animals received saline drops twice per day and two additional IP injections of saline; fourteen mice received brimonidine drops twice per day; and 12 mice received brimonidine eye drops twice per day and two additional IP brimonidine injections. Animals were sacrificed seven days post-ONC, and immunohistochemical staining of retinal whole mounts was performed using neuronal NeuN and GFAP staining. Microscopic pictures of the central, middle, and peripheral regions of the retina were taken. The density of the retinal cells was assessed. Results: The total RGC density after ONC and RGC densities in all retinal eccentricities were significantly higher in the brimonidine eye drop and IP combination treatment group than in the saline drop + saline IP, and brimonidine drop treatment groups. Conclusions: brimonidine eye drops supplemented with IP brimonidine injections improved RGC survival in a preclinical model of ONC. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the prevalence and characteristics of pigmentary glaucoma (PG) and pigment dispersion syndrome (PDS) in patients diagnosed at a tertiary center eye clinic in Türkiye. Methods: This retrospective, single-center study was conducted at the glaucoma clinic of Haydarpaşa Numune Training and Research Hospital. The files of patients with glaucoma diagnoses between 2015 and 2023 were retrospectively reviewed. The prevalence of PG and PDS, characteristics of the patients, surgical requirements, applied surgical procedures, and risk factors for PG were analyzed. Results: Of the 7,800 files that were reviewed, 50 (0.64%) belonged to patients with PDS or PG. The mean follow-up time was 41.45±34.56 months, and the mean age of the patients was 48.9±12.86 years. Twenty-five (50%) patients were male. Of the 100 eyes reviewed initially, 56 had PDS, 44 had PG, and 17 (30.3%) with PDS progressed to PG during the follow-up period. The mean spherical equivalent (SE) was --1.03±1.62 diopter. In the comparison of eyes with PDS and PG, there were no significant differences with regard to age, sex, SE, central corneal thickness, or best-corrected visual acuity. A median intraocular pressure (IOP) of 17.5 mmHg was achieved on two median glaucoma medications at the last visit. Overall, 10 eyes with PG required surgical and laser interventions for IOP control. Laser peripheral iridotomy (LPI) was performed on nine of these eyes, trabeculectomy with antimetabolite augmentation on two (which had previously undergone LPI), and XEN® gel stent implantation on one. Conclusion: Among the glaucoma patients, the detected frequency of PDS and PG was 0.64%. We did not detect male dominance. The median SE was -1.03±1.62 diopter, indicating mild myopia, which is consistent with the literature. [ABSTRACT FROM AUTHOR]

Background To examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma. Methods This retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races. Results There were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) pm and 1.42 (1.34, 1.50) pm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p<0.05). In both races, intervening CE was most strongly correlated with higher RNFLT variability (0: 0.24-0.92, p<0.05). After excluding eyes with intervening CE, RNFLT variability was reduced and the small racial difference was no longer significant (AD: 1.40 (1.31, 1.48) pm vs ED: 1.34 (1.27, 1.40) pm; p=0.280). Conclusions Although some predictors were identified, long-term RNFLT variability appeared small for both AD and ED eyes. Moreover, the racial difference did not remain once intervening CE, the strongest predictor of variability, was eliminated. Our findings inform on strategies to optimise structural assessment and suggest that, when accounting for relevant factors, RNFLT is reliable across races. [ABSTRACT FROM AUTHOR]

Age‐related vision loss caused by retinal neurodegenerative pathologies is becoming more prevalent in our ageing society. To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short‐lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single‐cell RNA‐sequencing (scRNAseq) of three age groups (6‐, 12‐, and 18‐week‐old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age‐related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age‐matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast‐ageing killifish in elucidating molecular signatures in age‐associated retinal disease and vision decline. This study contributes to the understanding of how age‐related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age‐related pathologies. [ABSTRACT FROM AUTHOR]

The aim of the study is to assess the lacrimal gland tear production, using the Schirmer Tear Test (STT), in healthy sheep under general anesthesia and to explore the effects of applying 1% hyaluronic acid ophthalmic gel during general anesthesia. While STT values during anesthesia have been well documented in small animals such as cats and dogs, there seems to be a lack of information available for ruminants like sheep. This gap in the literature highlights the need for further research and exploration into tear production in sheep under anesthesia. The experimental research conducted on twelve adults female sheep provided valuable insights into tear production under anesthesia. By assessing tear production at various key time points the study was able to capture the changes in tear production throughout anesthesia and revealed a significant decrease in Schirmer Tear Test values in all sheep, following general anesthesia. The results showed that closing and taping the eye yielded determined better outcomes compared to administering a 1% lubricant ophthalmic gel. This finding suggests that eye care during anesthesia can impact tear production in sheep. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether phakia affects the outcome of XEN-45 gel stent implantation in the treatment of pseudoexfoliative glaucoma (PXG). Methods: A retrospective, comparative cohort study of 30 phakic and 55 pseudophakic PXG patients who received the XEN-45 gel stent at a tertiary centre. The primary outcome measure was two-year success defined as a ≥20% lowering of intraocular pressure (IOP) and a target IOP of 6–21 mmHg. Success was complete without and qualified irrespective of antiglaucoma medication use. Further glaucoma surgery other than needling was regarded as a failure. The secondary outcome measures included changes in IOP, revision and complication rates. Results: The complete two-year success rates were 70% and 59% in the phakic and pseudophakic groups, respectively (p = 0.75, log-rank test), and the qualified rates were 80% and 72%, respectively (p = 0.89). The median IOP reduction from baseline was 54% in phakic, and 46% in pseudophakic eyes. While needling rates were similar, the incidence of early incisional bleb revisions was significantly higher in the phakic eyes (13% vs. 0% within 3 months; p = 0.0098, chi-square). Increasing after a year, significantly more pseudophakic eyes failed due to secondary glaucoma surgery (16% vs. 0%; p = 0.0191). Conclusions: The XEN-45 gel stent offers equally effective IOP control for both phakic and pseudophakic patients. However, the onset of bleb revisions and the necessity for secondary glaucoma surgery differed significantly between the groups. [ABSTRACT FROM AUTHOR]

Background/Aim: Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy. Materials and Methods: Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot. Results: Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho-protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in antiapoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05). Conclusion: These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication. [ABSTRACT FROM AUTHOR]

Progressive loss of retinal ganglionic cells (RGC) causes degeneration of optic nerve axons, which leads to blindness in glaucoma. Elevated intraocular pressure (IOP) is the most important, treatable risk factor. Currently, the management of glaucoma is centred on reducing the IOP, and drugs in the form of topical drops are the first line of management. Drugs reduce IOP either by suppressing aqueous humour secretion or improving the aqueous humour outflow. Newer drugs added during the past three decades to the armamentarium of glaucoma treatment have targeted the aqueous outflow. With an evolving understanding of the pathogenesis of glaucoma, the role of 24-h IOP control and other IOP-independent risk factors affecting ocular blood flow and RGC toxicity is also being actively studied in clinical and pre-clinical models of glaucoma. The role of available drugs in controlling IOP over 24 h is being evaluated. Improvement of ocular blood flow and neuroprotection are seen as potential drug targets for preventing the loss of RGC. In this article, we review the pharmacotherapy of glaucoma based on current therapeutic principles. [ABSTRACT FROM AUTHOR]

Purpose: To devise a means of providing controlled resistance between the anterior chamber and the subconjunctival space after trabeculectomy by implantation of a biodegradable, porous collagen matrix., Methods: Matrices were implanted in the right eyes of 17 rabbits after trabeculectomy, while left eyes served as surgical controls. The scleral flap was sutured loosely, and the implant provided pressure on the scleral flap to reduce overfiltration. Trabeculectomy in the control eyes was performed with tight sutures using standard methodology. Intraocular pressure (IOP) was measured before surgery and on days 3, 7, 14, 21, and 28 after surgery. Masson trichrome and alpha-smooth muscle actin stains were used for histologic study of the filtering blebs., Results: The initial postoperative IOP reduction was approximately equal, at 14% to 16%, for both groups. In the implanted group, the IOP continued to decrease to 55% below baseline at day 28 as the implant gradually degraded. In the control group, IOP had returned to the preoperative level by day 21. Histologic examination with Masson trichrome and alpha-smooth muscle actin stains showed a prominent bleb in the implanted group compared with scar formation and limited bleb formation in the control group., Conclusions: Implantation of a biodegradable, porous collagen matrix in the subconjunctival space offers the potential for a new means of avoiding early scar formation and maintaining long-term IOP control by creating a loosely structured filtering bleb.

Objective: The Low-Pressure Glaucoma Treatment Study (LoGTS) seeks to evaluate visual field stability in low-pressure glaucoma patients randomized to intraocular pressure reduction in both eyes with topical twice daily brimonidine tartrate 0.2% versus twice daily timolol maleate 0.5%. This article describes the LoGTS design and presents baseline characteristics of the subjects., Design: Randomized, multicenter, double-masked clinical trial., Participants: Low-pressure glaucoma patients 30 years of age or older were identified. Exclusion criteria included an untreated pressure of more than 21 mmHg, advanced visual field loss, and contraindications to study medications., Interventions: Randomization of both eyes to double-masked monotherapy with brimonidine or timolol. Follow-up visits included Humphrey 24-2 full-threshold perimetry, tonometry every 4 months, and annual optic disc photography., Main Outcome Measure: Progression of visual field loss., Results: One hundred ninety patients were randomized between 1998 and 2000. Mean age (+/-standard deviation) was 64.9+/-10.7 years. Women comprised 59.5% of the patients. Fifty-three patients (27.9%) had unilateral field loss. The 137 patients with bilateral field loss were older than those with unilateral field loss: 65.7 versus 62.3 years of age (P<0.05). Mean untreated diurnal intraocular pressures were similar between the eyes of the bilateral patients (mean, 15.5 mmHg in both eyes) and unilateral patients (mean, 16.0 mmHg in field loss vs. 15.6 mmHg in fellow eyes). Visual field mean deviation for all eyes was -5.4+/-4.7 decibels. Central corneal thickness in 168 phakic patients was 543 +/- 35 microm (range, 435-655 microm); thickness was less than 500 microm in 15 eyes and was more than 600 microm in 11 eyes. Mean vertical cup-to-disc ratio for all eyes was 0.67+/-0.15. Unilateral field loss patients had a larger cup-to-disc ratio in the field loss eye (0.75+/-0.12) than the fellow eye with a normal field (0.60+/-0.17, P<0.0001). Disc hemorrhage was present at baseline in 29 patients (32 eyes)., Conclusions: The LoGTS was successfully able to recruit and enroll patients with open-angle glaucoma and statistically normal intraocular pressure into a longitudinal, prospective clinical trial comparing 2 different glaucoma medications. Baseline characteristics of note were a preponderance of females, unilateral field loss in 27.9% of participants, and frequent optic disc hemorrhage. Central corneal thickness had a normal distribution and did not account for false low-pressure measurements in LoGTS patients.

Purpose: Adrenergic agents decrease intraocular pressure by reducing aqueous humor secretion from ciliary epithelial cells. Since the ionic concentration of aqueous humor contributes to intraocular pressure, we have investigated the effect of (-)-isoproterenol, a beta-adrenergic agonist on the maxi-K( +) channel in rabbit nonpigmented ciliary epithelial (NPE) cells., Methods: Single-channel currents were recorded from the basolateral surface of acutely isolated NPE cells using patch clamp techniques., Results: A calcium dependent maxi-K(+) channel was identified in 31% of cell-attached patches. In the excised condition the channel was activated in presence of calcium. In symmetrical K(+) solution a linear current-voltage relationship and unitary conductance of 158 +/- 15 pS was observed. Replacing K(+) with Na(+) the current-voltage curve shifted to the right and approached a reversal potential for K( +) ( approximately -80 mV). Barium (2 mM) from the intracellular side or iberiotoxin (50 nM) from the extracellular side blocked the channel activity. In cell-attached patches, the beta-receptor agonist (-)-isoproterenol (2.5 microM) increased channel open probability (P(o)) only when applied directly through the patch pipette. beta(2)-adrenoceptor antagonists (ICI-118, 551, l-timolol) blocked the channel activity more efficiently than the beta(1)-adrenoceptor antagonist betaxolol. In excised patches, (-)-isoproterenol increased baseline P(o) 5-fold (0.5 +/- 0.13) when GTP (100 microM) and GTPgammaS (100 microM) were present at the cytosolic surface of the pipette (control; P(o), 0.12 +/- 0.006). GTP augmented baseline channel activity (0.1 +/- 0.004) 7-fold (0.7 +/- 0.03) when (-)-isoproterenol was included in patch pipette., Conclusions: Rabbit NPE cells expressed maxi-K(+) channels on their basolateral surface. The adrenergic agonist (-)-isoproterenol activated these channels via a beta(2)-adrenoceptor that was modulated by a direct G-protein gated pathway.

Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.