Glaucoma Research Articles

Efficacy of selective laser trabeculoplasty in primary open-angle glaucoma eyes with functional versus organic blockage of Schlemm’s canal

Efficacy of selective laser trabeculoplasty in primary open-angle glaucoma eyes with functional versus organic blockage of Schlemm’s canal

Distribution and Determinants of Anterior Chamber Angle and Anterior Chamber Volume in Young Chinese Adults

ABSTRACT Purpose Current study aimed to understand the distribution and determinants of anterior chamber angle (ACA) and anterior chamber volume (ACV) in Chinese young adults, which can help fill current data gaps and aid in early detection and intervention for high-risk population of primary angle closure glaucoma. Methods This cross-sectional study utilized data from 2014 participants who completed questionnaire and eye examination in September 2021. ACV and ACA were measured using a Pentacam tomographer. Spherical equivalent (SE) was evaluated by autorefractor without cycloplegia. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated using Corvis-ST. Axial length (AL), corneal radius (CR), anterior chamber depth (ACD), and white to white were assessed using the IOL Master. Results A total of 1635 students were included in the analysis. The mean ACV and AVA were 194.74 ± 32.30 μL and 38.81 ± 4.84°, respectively. Males have a larger ACV and wider ACA than females. ACV was positively correlated with ACA (r = 0.24, p < 0.001), and the correlation was stronger for non-myopic students than for myopic students. Multivariable linear regression model showed that AL (β = 2.41), CR (β = –4.12), CCT (β = –0.11), ACD (β = 97.93), and bIOP (β = 0.40) were associated with ACV, and CCT (β = –0.01), CR (β = 0.38), and ACD (β = 7.41) were associated with ACA (all p < 0.05). Random forest model indicated that ACD was the most critical predictor of both ACV and ACA. Conclusions This study reported the distribution and determinants of ACA and ACV. Deeper ACD was associated with larger ACV and wider ACA.

Comparison of ocular biometric parameters between two swept-source optical coherence tomography devices and Scheimpflug tomography in patients with cataract.

To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

Loss to Follow Up Among Glaucoma Patients: An IRIS® Registry (Intelligent Research in Sight) Retrospective Cohort Analysis

ABSTRACT Purpose To identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG). Methods This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period. Results Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36–1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38–1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17–1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18–1.20), and Black race (RR = 1.10; 95% CI: 1.09–1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78–0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32–1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08–1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32–1.38). Conclusion We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease.

No Evidence That Vitamin D Levels or Deficiency Are Associated with the Risk of Open-Angle Glaucoma in Individuals of European Ancestry: A Mendelian Randomisation Analysis.

Glaucoma is the second leading cause of blindness worldwide, with intraocular pressure as the only known modifiable risk factor. Vitamin D has been proposed to influence intraocular pressure and decrease retinal ganglion cell degeneration. Based on these findings, vitamin D has been suggested to prevent or reduce the severity of primary open-angle glaucoma (POAG), which is the most common form. We applied two-sample Mendelian randomisation (MR) analyses to data from the SUNLIGHT consortium and the UK Biobank to assess the causal effect of vitamin D levels and vitamin D deficiency on primary open-angle glaucoma (POAG). MR analysis, including sensitivity tests using other GWAS summary statistics from FinnGen, was also performed. We also investigated the association between single nucleotide polymorphisms (SNPs) on genes involved in vitamin D metabolic pathways and POAG. We found no statistical evidence that vitamin D levels (OR = 1.146, 95% CI 0.873 to 1.504, p = 0.326) or vitamin D deficiency (OR = 0.980 (95% CI 0.928 to 1.036, p = 0.471) causally affect the risk of developing POAG. Sensitivity analyses, including the use of a more relaxed p-value threshold, and use of winter-measured samples only, replication in the FinnGen dataset, and exploration of specific genetic markers also showed no evidence of association between SNPs for genes involved in key steps of vitamin D metabolism and POAG. These results indicate that vitamin D may not be a significant factor in modifying POAG risk, challenging the hypothesis that vitamin D supplementation could be effective in reducing POAG risk. Further research should focus on identifying other potential risk factors for POAG prevention strategies.

Efficacy and Safety of a Preservative-Free Latanoprost Cationic Emulsion in Patients with Open-Angle Glaucoma and Concurrent Ocular Surface Disease: A Randomized Phase 2 Study.

Purpose: To compare intraocular pressure (IOP), ocular surface disease (OSD) parameters, and safety in patients with open-angle glaucoma (OAG)/ocular hypertension (OH) and concurrent OSD treated with preservative-free latanoprost 0.005% cationic emulsion (PF-latanoprost-E) or travoprost-Z 0.004% ophthalmical solution containing a soft preservative system. Methods: Patients with OAG/OH and OSD were randomized to treatment with PF-latanoprost-E or travoprost-Z nightly for 3 months. Outcomes included mean diurnal IOP reduction; OSD endpoints, including symptom improvement, tear break-up time (TBUT), and corneal fluorescein staining (CFS) score; and safety after 1 and 3 months. Results: A total of 105 patients were randomized, 51 to PF-latanoprost-E and 54 to travoprost-Z. IOP reductions (LS mean differences) at 3 months were numerically greater in the PF-latanoprost-E than in the travoprost-Z group at 8AM (7.2 versus 6.0 mmHg), 10AM (6.7 versus 5.9 mmHg), and 4PM (6.0 versus 5.4 mmHg). LS mean changes in IOP from baseline in both groups at 1 and 3 months, however, were comparable. Mean ± SD CFS scores on the Ora scale at month 3 showed significantly greater reductions in the PF-latanoprost-E than in the travoprost-Z group (-1.07 ± 1.863 versus -0.16 ± 2.553 P = 0.0461). The mean TBUT at month 3 showed similar improvements in both groups (1.1 versus 1.0 s, P > 0.05). OSD symptoms improved but did not differ significantly in the two groups. Overall safety was comparable in both groups. Conclusion: PF-latanoprost-E effectively and safely lowered IOP and improved OSD parameters in patients with OAG/OH. These findings provide evidence for the beneficial effects of this new formulation of latanoprost in glaucoma patients with OSD.

Suspicious eyes - Elvis's glaucoma battle.

Elvis Presley (1935-1977) is an iconic figure in modern pop culture. Although many of his medical conditions have been the subject of extensive speculation, less is known about his ophthalmological problems, including steroid-induced glaucoma caused by a life-long use of steroids, both prescribed and self-administered, and secondary angle closure glaucoma most likely due to anterior uveitis. Further, he had an episode of acute angle closure glaucoma in 1971 that was treated with a subconjunctival injection of a mydriatic agent or, less likely, a paracentesis combined with an iridotomy. David Meyer, MD, was Presley's main ophthalmologist from 1971 until the latter's death in 1977.

Proteomic and Cytokine Profiling in Plasma from Patients with Normal-Tension Glaucoma and Ocular Hypertension

Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before (“baseline”), during (“hypoxia”), and after hypoxia (“recovery”). Proteomics based on liquid chromatography coupled with mass spectrometry (LC–MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1β (IL-1β) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP.Graphical

Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling

Deep learning has enabled breakthroughs in automated diagnosis from medical imaging, with many successful applications in ophthalmology. However, standard medical image classification approaches only assess disease presence at the time of acquisition, neglecting the common clinical setting of longitudinal imaging. For slow, progressive eye diseases like age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), patients undergo repeated imaging over time to track disease progression and forecasting the future risk of developing a disease is critical to properly plan treatment. Our proposed Longitudinal Transformer for Survival Analysis (LTSA) enables dynamic disease prognosis from longitudinal medical imaging, modeling the time to disease from sequences of fundus photography images captured over long, irregular time periods. Using longitudinal imaging data from the Age-Related Eye Disease Study (AREDS) and Ocular Hypertension Treatment Study (OHTS), LTSA significantly outperformed a single-image baseline in 19/20 head-to-head comparisons on late AMD prognosis and 18/20 comparisons on POAG prognosis. A temporal attention analysis also suggested that, while the most recent image is typically the most influential, prior imaging still provides additional prognostic value.

The predictive value of anterior segment optical coherence tomography for postoperative corneal edema in cataract patients.

To evaluate the predictive value of anterior segment optical coherence tomography (AS-OCT) for postoperative corneal edema in cataract patients. A retrospective cohort study of 144 cataract patients from December 2020 to December 2021 was conducted. Patients were divided into edema eyes (84 cases) and observation (60 cases) group based on postoperative corneal edema occurrence. Relevant indicators were compared between groups. Logistic regression identified risk factors for postoperative corneal edema. Receiver operating characteristic curves evaluated the predictive value. The edema eyes group had significantly higher postoperative central corneal thickness (CCT) and lower postoperative endothelial cell density (ECD) than the observation group (P < 0.05). The edema eyes group also had significantly lower preoperative ECD, anterior chamber depth (ACD), anterior chamber angle (ACA), and preoperative lens position (LP) than the observation group (P < 0.05). Logistic regression analysis showed that preoperative ECD, ACD, ACA, and LP were independent risk factors for postoperative corneal edema (P < 0.05), all of which also showed good predictive value for postoperative corneal edema, with areas under the curve (AUCs) of 0.854, 0.812, 0.791, and 0.778, respectively, under the ROC curve analysis. AS-OCT can provide useful information for predicting postoperative corneal edema in cataract patients. Preoperative ECD, preoperative ACD, preoperative ACA, and preoperative LP are important parameters that can be measured by AS-OCT and used as risk factors for postoperative corneal edema.

Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis.

The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO. We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (P-value < 5 × 10-8) leveraging data from a genome-wide association study (GWAS) (N = 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (P-value < 5 × 10-8) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association. MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26; p-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods. Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.

Long-term Visual Field Variability in Patients with Primary Open-angle Glaucoma

Purpose: To investigate factors associated with variability in the longitudinal visual field (VF) test in patients with primary open-angle glaucoma (POAG).Methods: This retrospective study enrolled POAG patients with VF ≥ 12 who were followed up for ≥ 6 years. First, 52 total deviation values of VF series for each eye were linearly regressed against time (years), and the root mean square error (RMSE) of the residuals was used to measure long-term pointwise VF variability. The mean deviation (MD) of the VF series for each eye was linearly regressed against time (years), and the RMSE of the residuals was used to measure long-term global VF variability. Using hierarchical clustering, variable clustering was performed to select variables and Spearman’s correlation was used as a similarity index. We fitted a mixed effect linear regression model and evaluated factors associated with the long-term VF variability in each regression model.Results: The study included 246 eyes of 157 patients with POAG. Worse baseline peripapillary retinal nerve fiber layer (RNFL) thickness, lower baseline intraocular pressure (IOP), lower mean IOP, greater IOP fluctuation, and a faster VF decay rate were associated with increased long-term pointwise VF variability in the RNFL thickness model (all &lt;i&gt;p&lt;/i&gt; ≤ 0.037). Worse baseline MD, lower baseline IOP, lower mean IOP, and faster VF decay rate were associated with increased long-term global VF variability in the MD model (all &lt;i&gt;p&lt;/i&gt; ≤ 0.035).Conclusions: Lower baseline and mean IOP, greater IOP fluctuation, worse glaucoma severity, and a faster VF decay rate were associated with greater long-term VF variability in patients with POAG. These factors should be considered when evaluating VF progression.

Evaluating the risk of new-onset glaucoma in chronic kidney disease patients: a nationwide cohort study

BackgroundA better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019.MethodThis retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan–Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported.ResultsSeven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26–1.32], p < 0.001). Kaplan–Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13–1.21] for females vs. aHR 1.39 [CI:1.35–1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37–1.62]; 50–59: aHR 1.48 [CI: 1.40–1.56]; 60–69: aHR 1.30 [CI: 1.25–1.6]; 70–79: aHR 1.21 [CI: 1.17–1.26]; > 80: aHR 1.29 [CI: 1.21–1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001).ConclusionsOur cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients.Trial registrationDue to the retrospective nature of the study, no registration was necessary.

Analysis of sociodemographic profile of glaucoma patients with risk factors, subtypes, and disease severity in a tertiary eye care facility in Northern India.

To study the different subtypes of glaucoma and to analyze the demographic and clinical profile of glaucoma patients along with associated risk factors in a multi-locational North Indian study. Newly diagnosed and known glaucoma patients on treatment were enrolled in the study. Complete history was taken, and clinical evaluation was done by senior glaucoma experts. Five hundred and eighty-six patients (1121 eyes) were included with 383 males (65.4%) and 203 females (34.6%). Of these, 508 (86.7%) had primary glaucoma and 78 (13.3%) had secondary glaucoma. Also, 263 (44.9%) patients had primary open angle glaucoma (POAG) and 172 (29.4%) had primary angle closure glaucoma. Four hundred and fifty-one (77%) were graduates or postgraduates and 293 (50%) were dependents on family income. One hundred and forty-one (24%) had a positive family history. Secondary glaucoma patients had a lower average age (52.6 ± 16.8 years) and higher average intraocular pressure (IOP; 34.23 ± 13 mm) compared to primary glaucoma patients (26.6 ± 9.7 mm) (P < 0.0001). Thirty-three (47.8%) out of 78 secondary glaucoma patients had advanced disease. Seventy-four (12.6%) were first-time diagnosed and 18 had advanced disease. In addition, 161 eyes had one or more glaucoma surgeries done (128 trabeculectomy and 28 phacotrabeculectomy). Ninety-five (16.2%) patients were advised surgery at our centers (46 trab, 26 phacotrab, 15 phaco, five Ahmed glaucoma valve implantation, and three pars plana vitrectomy). Disease progression was noted in 62 patients reporting good compliance to medicines. POAG was the most common variant in this study. Secondary glaucoma patients were youngest in age and had the highest IOP. Trabeculectomy was the most performed surgery. A good literacy rate did not prevent late presentations.

Assessment of silent reading ability among glaucoma patients using an eye tracking system with horizontally scrolling text.

There have been many reports suggesting that glaucoma patients with visual field defects may have decreased silent reading ability compared with individuals without glaucoma. This study used an eye tracking system to assess the ability of glaucoma patients to silently read horizontally scrolling text. Glaucoma patients who met the following criteria were recruited: age of ≤ 70 years, at least one eye with a 10 - 2 threshold on standard automated perimetry, a mean deviation value of n 4.0 dB or less, and corrected decimal visual acuity of 0.7 or better in both eyes. Using heat map images created from data from an eye tracking system operating during presentation of a video in which a sentence scrolled horizontally from right to left, reading time, average gaze position, and average fixation time (AFT) were compared between normal eyes (23 individuals, 46 eyes) and glaucomatous eyes (25 patients, 45 eyes). Four styles of sentences (large slow, large fast, small slow, and small fast) were scrolled in the top or bottom sections of the screen. Primary open-angle glaucoma was the most common type of glaucoma in 34 eyes (75.6%), followed by secondary glaucoma in six eyes (13.3%). In comparison with normal eyes, the reading time among right eyes was significantly longer in glaucomatous eyes when reading large fast text that was shown in the bottom area and left glaucomatous eyes showed a leftward shift in gaze position in the top, bottom, or both sections with all four sentence types. There was no significant difference in AFT between glaucomatous and normal eyes across the four sentence styles. In the left eye with inferior visual field loss, text presented at the top consistently showed a correlation with leftward shift of the gaze position across all scenarios. Glaucoma patients with central visual field defects in their left eyes may experience greater difficulty reading horizontally scrolling text than individuals with normal eyes.

Neuropeptide alpha-Melanocyte stimulating hormone preserves corneal endothelial morphology in a murine model of Fuchs dystrophy

Fuchs endothelial corneal dystrophy is a heterogenous disease with multifactorial etiology, and genetic, epigenetic, and exogenous factors contributing to its pathogenesis. DNA damage plays a significant role, with ultraviolet-A (UV-A) emerging as a key contributing factor. We investigate the potential application of neuropeptide α-melanocyte stimulating hormone (α-MSH) in mitigating oxidative stress induced endothelial damage. First, we examined the effects of α-MSH on a cultured human corneal endothelial cell line (HCEnC-21T) exposed to hydrogen peroxide (H2O2) induced oxidative DNA damage. We performed immunofluorescence and flow cytometry to assess DNA damage and cell death in the cultured cells. Additionally, we used an established mouse model that utilizes ultraviolet light to induce corneal endothelial cell damage resulting in decreased CEnC number, increased cell size variability, and decreased percentage of hexagonal cells. This endothelial decompensation leads to an increase in corneal thickness. Following UV-A exposure, the mice were systemically treated with α-MSH, either immediately after exposure (early treatment) or beginning two weeks post-exposure (delayed treatment). To evaluate treatment efficacy, we analyzed CEnC density and morphology using in vivo confocal microscopy, and central corneal thickness using anterior segment optical coherence tomography. Our findings demonstrated that α-MSH treatment effectively protects HCEnC-21T from free-radical induced oxidative DNA damage and subsequent cell death. In vivo, α-MSH treatment, mitigated the loss of CEnC density, deterioration of cell morphology and suppression of the resultant corneal swelling. These results underline the potential application of α-MSH as a therapeutic agent for mitigating corneal endothelial damage.

Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes

BackgroundAge-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes.MethodsInstrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates.ResultsThe results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E−04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (β = −0.190 year, 95% CI −0.374 to −0.008, P = 0.041). The EEA of HannumAge (β = −0.85 μm, 95% CI −1.57 to −0.14, P = 0.019) and HorvathAge (β = −0.63 μm, 95% CI −1.18 to −0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (β = 0.06 μm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05).ConclusionThe present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.

Low-cost do-it-yourself (DIY) kit for glaucoma procedures.

Surgical skill training in ophthalmology is pivotal for ensuring optimal and safe patient outcomes. Access to traditional training resources such as cadaveric or animal eyes, as well as modern alternatives such as silicone eyeballs and simulators, remains limited, especially in resource-constrained settings. We present a series of innovative and low-cost do-it-yourself (DIY) models for glaucoma training using readily available hospital waste materials. These models allow ophthalmic assistants, fellows, and junior consultants to practice various procedures before transitioning to live patients, thereby enhancing surgical proficiency and minimizing the financial burden on both trainees and training institutions. We were able to practice procedures such as tonometry, central corneal thickness measurement, laser suture lysis, laser iridotomy, anterior chamber decompression, bleb needling, trabeculectomy flap construction, and suturing. By providing a practical and easy training solution, these models have the potential to boost confidence among glaucoma trainees and thus address the growing demand for skilled glaucoma surgeons.

Differentiating optic neuropathies using laser speckle flowgraphy: Evaluating blood flow patterns in the optic nerve head and peripapillary choroid.

To compare blood flow (BF) impairment patterns in different optic neuropathies using laser speckle flowgraphy (LSFG). This retrospective study enrolled 24 eyes of 24 patients with non-arteritic anterior ischemic optic neuropathy (NAAION), 59 eyes of 59 patients with optic neuritis (ON), 677 eyes of 677 patients with open-angle glaucoma (OAG), and 110 eyes of 110 controls. The patient backgrounds of all groups were compared. Ophthalmologic findings were evaluated, adjusting for age, sex, blood pressure, pulse rate, and underlying systemic diseases with 1:1 optimal propensity score matching. We used LSFG to obtain optic nerve head (ONH) vessel-area mean blur rate (MBR; ONH-MV), ONH tissue-area MBR (ONH-MT), and choroidal MBR. The NAAION and ON groups were compared with the control and OAG groups. Best-corrected visual acuity was worse in the NAAION, ON, and OAG groups than in controls (p < 0.001). Circumpapillary retinal nerve fibre layer thickness was higher in the NAAION and ON groups and lower in the OAG group than in controls (p < 0.001). Compared to controls, the NAAION and OAG groups had significantly lower ONH-MV, ONH-MT, and choroidal MBR (p < 0.05). Additionally, the NAAION group had lower ONH-MV and choroidal MBR than the OAG group (p = 0.003 and p < 0.001, respectively) but no difference in ONH-MT (p = 0.857). The ON group had significantly lower ONH-MV and choroidal MBR compared to the controls (p < 0.001 and p = 0.022, respectively) but no difference in ONH-MT (p = 0.773). Optic neuropathies showed different patterns of ocular BF impairment. Therefore, LSFG can be a useful tool for differentiating optic neuropathies.

Identification of Optic Nerve-Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization.

Glaucoma is the primary cause of permanent vision loss worldwide. However, the pathogenesis of primary open-angle glaucoma (POAG), the main type of glaucoma, has not yet been completely understood. In our study, the POAG cohorts were obtained from the Gene Expression Omnibus (GEO) database (GSE45570). Biomarkers with diagnostic utility for POAG were identified through combining differentially expressed analysis, enrichment analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. The regulatory networks (including a competing endogenous RNA (ceRNA) regulatory network and a small molecule compounds-mRNA network) were created. In addition, the Mendelian randomization (MR) analysis was used to identify exposures causally associated with POAG. Finally, the expression of the biomarkers was validated via real-time quantitative polymerase chain reaction (RT-qPCR). The Gene Ontology (GO) items that the differentially expressed genes (DEGs) between POAG and control groups enriched were relevant to light stimulation and DNA methylation. A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients. Besides, the ceRNA regulatory network contained 88 nodes and 93 edges, and a small molecule compounds-mRNA network included 66 nodes and 76 edges. The MR results indicated a causal association between DNA methylation GrimAge acceleration and POAG. Additionally, the results of RT-qPCR revealed that the expression trend of RAB8A was consistent with that of GSE45570. Taken together, this study provides three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) for the diagnosis of POAG, providing scientifically valuable insights for further studies of POAG. Discovering biomarkers that possess diagnostic significance for POAG has the potential to offer new insights into the pathogenesis of POAG and present novel objectives for clinical intervention.