Trabecular Meshwork Regeneration for Glaucoma Treatment Using Stem Cell-Derived Trophic Factors.

Glaucoma is one of the leading causes of irreversible blindness. Stem cell therapy has shown promise in the treatment of primary open-angle glaucoma in animal models. Stem cell-free therapy using stem cell-derived trophic factors might be in demand in patients with high-risk conditions or religious restrictions. In this chapter, we describe methods for trabecular meshwork stem cell (TMSC) cultivation, secretome harvesting, and protein isolation, as well as assays to ensure the health of TMSC post-secretome harvesting and for secretome periocular injection into mice for therapeutic purposes.

Comparison of safety and effectiveness of micropulse transscleral cyclophotocoagulation and "slow cook" diode laser transscleral cyclophotocoagulation in patients with refractory open-angle glaucoma

ABSTRACT Purpose: This study aimed to compare the safety and effectiveness of intraocular pressure reduction between micropulse transscleral cyclophotocoagulation and "slow cook" transscleral cyclophotocoagulation in patients with refractory primary open-angle glaucoma. Methods: We included patients with primary open angle glaucoma with at least 12 months of follow-up. We collected and analyzed data on the preoperative characteristics and postoperative outcomes. The primary outcomes were a reduction of ≥20% of the baseline value (criterion A) and/or intraocular pressure between 6 and 21 mmHg (criterion B). Results: We included 128 eyes with primary open-angle glaucoma. The preoperative mean intraocular pressure was 25.53 ± 6.40 and 35.02 ± 12.57 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean intraocular pressure was reduced significantly to 14.33 ± 3.40 and 15.37 ± 5.85 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups at the last follow-up, respectively (p=0.110). The mean intraocular pressure reduction at 12 months was 11.20 ± 11.46 and 19.65 ± 13.22 mmHg in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The median preoperative logMAR visual acuity was 0.52 ± 0.69 and 1.75 ± 1.04 in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p<0.001). The mean visual acuity variation was −0.10 ± 0.35 and −0.074 ± 0.16 in the micropulse- and "slow cook" transscleral cyclophotocoagulation, respectively (p=0.510). Preoperatively, the mean eye drops were 3.44 ± 1.38 and 2.89 ± 0.68 drugs in the micropulse- and "slow cook" transscleral cyclophotocoagulation groups, respectively (p=0.017), but those were 2.06 ± 1.42 and 1.02 ± 1.46 at the end of the study in the "slow cook" and micropulse transscleral cyclophotocoagulation groups, respectively (p<0.001). The success of criterion A was not significant between both groups. Compared with 11 eyes (17.74%) in the "slow cook" transscleral cyclophotocoagulation group, 19 eyes (28.78%) in the micropulse transscleral cyclophotocoagulation group showed complete success (p=0.171). For criterion B, 28 (42.42%) and 2 eyes (3.22%) showed complete success after micropulse- and "slow cook" transscleral cyclophotocoagulation, respectively (p<0.001). Conclusion: Both techniques reduced intraocular pressure effectively.

Intraocular pressure modulation with thermal stimuli

ABSTRACT Purpose: This study aimed to determine whether early-stage intraocular pressure can be modulated using a thermal face mask. Methods: In this prospective clinical study, healthy participants were randomized on a 1:1:1 allocation ratio to three mask groups: hypothermic (G1), normothermic (G2), and hyperthermic (G3). After randomization, 108 eyes from 108 participants were submitted to clinical evaluations, including measurement of initial intraocular pressure (T1). The thermal mask was then applied for 10 minutes, followed by a second evaluation of intraocular pressure (T2) and assessment of any side effects. Results: The hypothermic group (G1) showed a significant reduction in mean intraocular pressure between T1 (16.97 ± 2.59 mmHg) and T2 (14.97 ± 2.44 mmHg) (p<0.001). G2 showed no significant pressure difference between T1 (16.50 ± 2.55 mmHg) and T2 (17.00 ± 2.29 mmHg) (p=0.054). G3 showed a significant increase in pressure from T1 (16.53 ± 2.69 mmHg) to T2 (18.58 ± 2.95 mmHg) (p<0.001). At T1, there was no difference between the three study groups (p=0.823), but at T2, the mean values of G3 were significantly higher than those of G1 and G2 (p<0.00). Conclusion: Temperature was shown to significantly modify intraocular pressure. Thermal masks allow the application of temperature in a controlled, reproducible manner. Further studies are needed to assess the duration of these effects and whether they are reproducible in patients with pathologies that affect intraocular pressure.

Night-time blood pressure dipping, but not 24-h blood pressure level, is linked to increased 24-h ocular volume slope

ABSTRACT Purpose: This study investigated the relationship between blood pressure and intraocular pressure in treatmentnaive, non-glaucoma patients with different blood pressure statuses, focusing on the 24-h ocular volume and nocturnal blood pressure decline. Methods: Treatment-naive, non-glaucoma patients undergoing hypertension evaluation were enrolled as study participants. Simultaneous 24-h ambulatory blood pressure measurement and 24-h ocular volume recording with a contact lens sensor. We also compared ocular volume curve parameters between normotensive and hypertensive patients, as well as between those with and without nocturnal blood pressure decline. Results: A total of 21 patients, including 7 normotensive and 14 treatment-naive hypertensive individuals, were included in the study. of them, 11 were dippers and 10 were non-dippers. No significant difference in the 24-h ocular volume slope was observed between the hypertensive and normotensive patients (p=0.284). However, dippers had a significantly higher 24-h ocular volume slope (p=0.004) and nocturnal contact lens sensor output (p=0.041) than non-dippers. Conclusion: Nocturnal blood pressure decline, rather than the blood pressure level, is associated with the increased 24-h ocular volume slope and nocturnal ocular volume. Further studies are required to determine whether the acceleration of glaucoma progression in dippers is primarily due to low blood pressure, high intraocular pressure, or a combination of both.

Ocular melanosis in the adult Cairn Terrier population within the United Kingdom.

PURPOSE: Prospective investigation to determine the prevalence of ocular melanosis in adult Cairn Terriers within the United Kingdom using a previously established staging scheme. METHODS: Ophthalmic assessment was performed on adult Cairn Terriers, recruited from various geographic locations within the United Kingdom. Examination included gonioscopy, rebound tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy, performed by one examiner (AM). RESULTS: A total of 93 dogs were examined, including 52 females and 41 males, aged between 15 months and 16 years 4 months. Sixty of 93 dogs (64.5%) were >7 years of age. Nine of 93 dogs (9.6%) demonstrated changes consistent with ocular melanosis. Four of 9 (44.4%) had Stage 1 disease and 5 of 9 (55.6%), Stage 2. Stages 3 or 4 were not identified in any dogs. Mean intraocular pressures in affected and unaffected dogs were 14.7 mmHg (range 12-17 mmHg) and 12.8 mmHg (range 5-21 mmHg), respectively. Incomplete pupil dilation was noted in affected dogs following pharmacologic mydriasis. CONCLUSION: Ocular melanosis was identified in approximately 10% of examined dogs, over half were dogs of breeding age (<7 years of age). It is possible that Grade 1 disease could go undetected, prior to obvious scleral pigment accumulation (Grade 2 disease). It is therefore recommended that dogs undergoing pre-breeding screens have pre-dilation assessment of the anterior segment using slit lamp biomicroscopy with subsequent gonioscopy to clearly assess for circumferential thickening of the iris base that might otherwise go undetected. Additionally, regular reassessment of breeding dogs is advised as disease progression could be rapid.

Self-Assembly Hypoxic and ROS Dual Response Nano Prodrug as a New Therapeutic Approach for Glaucoma Treatments.

Glaucoma is an irreversible blinding eye disease characterized by retinal ganglion cell (RGC) death.Previous studies have demonstrated that protecting mitochondria and activating the CaMKII/CREB signaling pathway can effectively protect RGC and axon. However, currently treatments are often unsatisfactory, and the pathogenesis of glaucoma requires further elucidation. In this study, a ROS-responsive dual drug conjugate (OLN monomer) is first designed that simultaneously bonds nicotinamide and oleic acid. The conjugate self-assembled into nanoparticles (uhOLN-NPs) through the aggregation of multiple micelles and possesses ROS scavenging capability. Then, a polymer with a hypoxic response function is designed, which encapsulates uhOLN-NPs to form nanoparticles with hypoxic and ROS responses (HOLN-NPs). Under hypoxia in RGCs, the azo bond of HOLN-NPs breaks and releases uhOLN-NPs. Meanwhile, under high ROS conditions, the thioketone bond broke, leading to the dissociation of nano-prodrug. The released nicotinamide and oleic acid co-scavenge ROS and activate the CaMKII/CREB pathway, protecting mitochondria in RGCs. HOLN-NPs exhibit a significantly superior protective effect on R28 cells in glutamate models of glaucoma. The accumulation of HOLN-NPs in retinal RGCs lead to significant inhibition of RGC apoptosis and axonal damage in vivo. Notably, HOLN-NPs provide a new therapeutic approach for patients with neurodegenerative disease.

Real-world outcomes of micropulse transscleral laser therapy in glaucoma patients: Efficacy of initial and repeated treatment, transient intraocular pressure spikes.

Purpose: To investigate the clinical outcomes of micropulse transscleral laser therapy (MP-TLT) in a cohort of glaucoma patients, including safety profile, post-operative transient intraocular pressure (IOP) spikes, long-term efficacy and prognostic factors in terms of IOP-lowering. Methods: This was a retrospective observational cohort study. Medical records of all patients who consecutively underwent MP-TLT between May 2019 and February 2023 at a tertiary referral centre were scrutinised and relevant data were retrospectively analysed. Results: A total of 131 patients (138 eyes) with a mean age of 73.2 ± 14.2 years were included. Mean pre-interventional IOP was 24.1 ± 9.1 mmHg. Within 6-12 h following the intervention on the same day, an IOP spike was regularly observed, reaching on average 31.7 ± 10.3 mmHg (p < 0.001 to baseline). Two years after the intervention, mean IOP was 16.1 ± 5.6 mmHg (p < 0.005 to baseline). In 18 eyes, the treatment was repeated, and the IOP lowering effect was more durable after the second intervention compared to the first one (Cox-Mantel test, p=<0.005). Apart from the transient post-interventional IOP spikes, no severe complications were observed. Conclusions: MP-TLT is associated with significant IOP spikes in the first post-operative hours. Thus, close post-interventional IOP monitoring or even preventive (additional) IOP-lowering treatment may be considered. In the long term, the procedure yields favourable outcomes in terms of safety and IOP reduction. Repeated MP-TLT treatment, if necessary, seems to achieve more sustained IOP reduction than the initial treatment.

Novel therapeutic targets for primary open-angle glaucoma identified through multicenter proteome-wide mendelian randomization.

Background: This study aimed to identify novel therapeutic targets for primary open-angle glaucoma (POAG). Methods: The summary-data-based Mendelian randomization (SMR) method was used to evaluate the genetic association between plasma proteins and POAG. Two sets of plasma protein quantitative trait loci (pQTLs) data considered exposures were obtained from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. The summary-level genome-wide association studies data for POAG were extracted from the latest Round 10 release of the FinnGen consortium (8,530 cases and 391,275 controls) and the UK Biobank (4,737 cases and 458,196 controls). Colocalization analysis was used to screen out pQTLs that share the same variant with POAG as drug targets identified. The two-sample Mendelian randomization, reverse causality testing and phenotype scanning were performed to further validate the main findings. Protein-protein interaction, pathway enrichment analysis and druggability assessment were conducted to determine whether the identified plasma proteins have potential as drug targets. Results: After systematic analysis, this study identified eight circulating proteins as potential therapeutic targets for POAG. Three causal proteins with strong evidence of colocalization, ROBO1 (OR = 1.38, p = 1.48 × 10-4, PPH4 = 0.865), FOXO3 (OR = 0.35, p = 4.34 × 10-3, PPH4 = 0.796), ITIH3 (OR = 0.89, p = 2.76 × 10-4, PPH4 = 0.767), were considered tier one targets. Five proteins with medium support evidence of colocalization, NCR1 (OR = 1.25, p = 4.18 × 10-4, PPH4 = 0.682), NID1 (OR = 1.38, p = 1.54 × 10-3, PPH4 = 0.664), TIMP3 (OR = 0.91, p = 4.01 × 10-5, PPH4 = 0.659), SERPINF1 (OR = 0.81, p = 2.77 × 10-4, PPH4 = 0.59), OXT (OR = 1.17, p = 9.51 × 10-4, PPH4 = 0.526), were classified as tier two targets. Additional sensitivity analyses further validated the robustness and directionality of these findings. According to druggability assessment, Pimagedine, Resveratrol, Syringaresinol and Clozapine may potentially be important in the development of new anti-glaucoma agents. Conclusion: Our integrated study identified eight potential associated proteins for POAG. These proteins play important roles in neuroprotection, extracellular matrix regulation and oxidative stress. Therefore, they have promising potential as therapeutic targets to combat POAG.

Association between Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists Exposure and Intraocular Pressure Change: GLP-1 Receptor Agonists and Intraocular Pressure Change.

OBJECTIVE: This study aims to provide data on the effects of glucagon-like peptide 1 receptor (GLP-1R) agonists on intraocular pressure (IOP). DESIGN: Retrospective clinical cohort study. SETTING: Multicenter. STUDY POPULATION: 1247 glaucoma surgery and treatment naïve eyes of 626 patients who were initiated on GLP-1R agonists compared to 1083 glaucoma surgery and treatment naïve eyes of 547 patients who were initiated on other oral antidiabetics. OBSERVATION PROCEDURES: The University of California Health Data Warehouse was queried for patients exposed to GLP-1R agonists or other oral antidiabetics. Index date was defined as the date of first exposure to the medication. Eyes with at least one pre-exposure and one post-exposure tonometry record within 365 days of the index date were included in the analysis. Clinical and laboratory data elements were extracted from the database. Eyes were censored from the analysis upon exposure to glaucoma hypotensive medication or glaucoma surgery. ∆IOP was analyzed using a paired t-test. Regression analysis was conducted using generalized estimating equations (GEE) accounting for inter-eye correlation. Sensitivity analyses were performed to assess the robustness of the findings. MAIN OUTCOME MEASURES: Primary outcome measure was ∆IOP after exposure to the medication. RESULTS: The median age of all included subjects was 66.2 years [IQR=18.3]; 607 (51.7%) were female, and 667 (56.9%) were Caucasian. Median pre-exposure IOP, HbA1c, and BMI were 15.2 mmHg [IQR=3.8], 7.5 [IQR=2.4], and 29.8 [IQR=9.4], respectively. 776 individuals (66.1%) had diabetes, with the median number of active oral antidiabetics being 1.0 [IQR=1.0], and 441 (37.5%) being insulin users. Several pre-exposure characteristics significantly differed between the GLP-1R agonist and the control group. The mean ∆IOP was -0.4±2.8 mmHg (paired t-test p<0.001) and -0.2±3.3 mmHg (paired t-test p = 0.297) in the GLP-1R agonist and other antidiabetics groups, respectively. Pre-exposure IOP was the only independent predictor of ΔIOP in multivariable GEE. Sensitivity analyses yielded similar results. CONCLUSIONS: Although GLP-1R agonists were significantly associated with a decrease in IOP in the paired analysis, they were not associated with ΔIOP in multivariable GEE. Moreover, the difference between the ΔIOP in the two groups was small. Future prospective studies following a standardized dose and delivery method may provide further insights.

Genetic association of lipid traits and lipid-related drug targets with normal tension glaucoma: a Mendelian randomization study for predictive preventive and personalized medicine.

Background: Glaucoma is the leading cause of irreversible blindness worldwide. Normal tension glaucoma (NTG) is a distinct subtype characterized by intraocular pressures (IOP) within the normal range (< 21 mm Hg). Due to its insidious onset and optic nerve damage, patients often present with advanced conditions upon diagnosis. NTG poses an additional challenge as it is difficult to identify with normal IOP, complicating its prediction, prevention, and treatment. Observational studies suggest a potential association between NTG and abnormal lipid metabolism, yet conclusive evidence establishing a direct causal relationship is lacking. This study aims to explore the causal link between serum lipids and NTG, while identifying lipid-related therapeutic targets. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of dyslipidemia in the development of NTG could provide a new strategy for primary prediction, targeted prevention, and personalized treatment of the disease. Working hypothesis and methods: In our study, we hypothesized that individuals with dyslipidemia may be more susceptible to NTG due to a dysregulation of microvasculature in optic nerve head. To verify the working hypothesis, univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were utilized to estimate the causal effects of lipid traits on NTG. Drug target MR was used to explore possible target genes for NTG treatment. Genetic variants associated with lipid traits and variants of genes encoding seven lipid-related drug targets were extracted from the Global Lipids Genetics Consortium genome-wide association study (GWAS). GWAS data for NTG, primary open angle glaucoma (POAG), and suspected glaucoma (GLAUSUSP) were obtained from FinnGen Consortium. For apolipoproteins, we used summary statistics from a GWAS study by Kettunen et al. in 2016. For metabolic syndrome, summary statistics were extracted from UK Biobank participants. In the end, these findings could help identify individuals at risk of NTG by screening for lipid dyslipidemia, potentially leading to new targeted prevention and personalized treatment approaches. Results: Genetically assessed high-density cholesterol (HDL) was negatively associated with NTG risk (inverse-variance weighted [IVW] model: OR per SD change of HDL level = 0.64; 95% CI, 0.49-0.85; P = 1.84 × 10-3), and the causal effect was independent of apolipoproteins and metabolic syndrome (IVW model: OR = 0.29; 95% CI, 0.14-0.60; P = 0.001 adjusted by ApoB and ApoA1; OR = 0.70; 95% CI, 0.52-0.95; P = 0.023 adjusted by BMI, HTN, and T2DM). Triglyceride (TG) was positively associated with NTG risk (IVW model: OR = 1.62; 95% CI, 1.15-2.29; P = 6.31 × 10-3), and the causal effect was independent of metabolic syndrome (IVW model: OR = 1.66; 95% CI, 1.18-2.34; P = 0.003 adjusted by BMI, HTN, and T2DM), but not apolipoproteins (IVW model: OR = 1.71; 95% CI, 0.99-2.95; P = 0.050 adjusted by ApoB and ApoA1). Genetic mimicry of apolipoprotein B (APOB) enhancement was associated with lower NTG risks (IVW model: OR = 0.09; 95% CI, 0.03-0.26; P = 9.32 × 10-6). Conclusions: Our findings supported dyslipidemia as a predictive causal factor for NTG, independent of other factors such as metabolic comorbidities. Among seven lipid-related drug targets, APOB is a potential candidate drug target for preventing NTG. Personalized health profiles can be developed by integrating lipid metabolism with life styles, visual quality of life such as reading, driving, and walking. This comprehensive approach will aid in shifting from reactive medical services to PPPM in the management of NTG. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00373-5.

Patients with hidradenitis suppurativa are associated with risk of new-onset glaucoma: a propensity-score-matched cohort study.

Background: Ocular comorbidities of hidradenitis suppurativa (HS) has been widely evaluated; however real-world evidence was scarce. Moreover, risk of glaucoma in HS patients remained unclear. This study aimed to evaluate the 5-year glaucoma risk in HS patients. Methods: This retrospective cohort study used the TriNetX database covering 2005-2017. In total, 53,281 HS patients were propensity score matched 1:1 to controls based on demographics, including comorbidities, medications, healthcare utilization, etc. Patients were followed for 5 years post-index date. Glaucoma risks were calculated based on hazard ratios and 95% confidence intervals (95% CI). Stratified analyses by sex and age were performed. Results: After matching, baseline characteristics were similar between groups. HS was associated with a 1.25 times higher 5-year glaucoma risk (95% CI, 1.10-1.42). The risk was significant within 1 year (HR=1.37; 95% CI, 1.03-1.82), 3 years (HR=1.31; 95% CI, 1.12-1.54), and 5 years post-index. In subgroup analysis, women had a 1.28 times higher risk (95% CI, 1.10-1.49). Patients aged 18-64 years (HR=1.33; 95% CI, 1.14-1.55) and ≥65 years (HR=1.33; 95% CI, 1.05-1.67) also presented elevated glaucoma risks. Conclusion: This real-world data analysis demonstrated a significantly increased 5-year glaucoma risk in HS patients versus matched controls. Ocular complications should be concerned while managing HS patients.

Comparison of lacrimal gland dimensions and volume in unilateral Ahmed glaucoma valve versus trabeculectomy.

PURPOSE: To evaluate radiographic lacrimal gland (LG) volume and dimensions in Ahmed glaucoma valve (AGV)- versus trabeculectomy-treated eyes and contralateral non-treated eyes. METHODS: In this retrospective cohort study, 1616 medical records acquired between 2010 and 2020 were examined. In AGV-treated (group 1) eyes, there were 19 patients with records sufficient for radiological LG evaluation, and in trabeculectomy-treated (group 2) eyes, there were 18. The hospital workstation software was used to assess high-resolution computed tomography (HRCT) scans conducted under standard protocol using a 128 SL Optima CT 660 scanner. The software (Vitrea™) was used to perform semi-quantitative volumetric measurements. LG dimensions were obtained in the axial and reformatted coronal planes on each side, and four measures were generated using the widest LG tip-to-tip diameters in two planes: coronal length, coronal width (CW), axial length (AL), and axial width. RESULTS: The time interval between surgery and HRCT imaging was 50.97 ± 26.25 months. Group 1 had significantly lower LG volume than group 2 (594.11 ± 259.45 vs. 933.67 ± 294.09 mm3, P = 0.001). When compared to non-treated eyes, AGV-treated eyes had lower LG volume (P = 0.065) while trabeculectomy-treated eyes had higher LG volume (P = 0.031). Further, group 1 had decreased length and width in both the axial and coronal planes as compared to group 2, with AL and CW being significantly different (P < 0.05). CONCLUSIONS: AGV and trabeculectomy had varied impacts on LG volume and dimensions despite being conducted in the same quadrant. HRCT appears to be effective in analysing AGV position, which may be related to LG volumetric and dimensional issues.

Association of contrast sensitivity with vessel density and functional parameters in different stages of glaucoma.

PURPOSE: To evaluate the association between contrast sensitivity (CS), vessel density (VD), and functional parameters in patients with glaucoma of varying severity. METHODS: Ninety-four eyes of 94 patients (57 men and 37 women, aged 56.52 ± 11.28 years) were divided into mild and moderate to advanced glaucoma groups. The mild glaucoma group was further subdivided based on the presence of central visual field defect (CVFD). Pearson's correlations were used to evaluate the associations between area under the log CS function (AULCSF), best-corrected visual acuity (BCVA), 10 - 2 visual field (VF), and structural parameters, including VD. The area under the receiver operating characteristic (AUROC) curve was calculated to detect abnormal CS (AULCSF < 1.2). RESULTS: In mild glaucoma without CVFD, AULCSF was associated with radial peripapillary capillary VD (γ = 0.597, P = 0.001), with an AUROC of 0.840 (P = 0.006) for detecting abnormal CS. In mild glaucoma with CVFD, AULCSF worsened and was associated with superficial parafoveal VD (γ = 0.569, P = 0.017) and macular whole image VD (γ = 0.632, P = 0.007), with AUROCs of 0.833 (P = 0.021) and 0.792 (P = 0.043), respectively. In moderate to advanced glaucoma, the relationship between AULCSF and the mean deviation of 10 - 2 VF and BCVA was more robust than that observed in structural measures. CONCLUSIONS: Decreased VD is linked to early CS impairment. Radial peripapillary capillary and macular VD can serve as indicators of CS function in the early stages of glaucoma. KEY  MESSAGES: What is known Contrast sensitivity loss has been reported in glaucoma patients but its relationship with glaucoma-related structural and functional changes in different glaucoma severity and central visual field defect (CVFD) remains elusive. What is new Decline in RPC peripapillary vessel density was associated with early impairment of contrast sensitivity in mild glaucoma without CVFD. Decline in macular vessel density and central 16 points of 10-2 visual field damage were associated with contrast sensitivity reduction in mild glaucoma with CVFD. Microvasculature change can serve as an indicator for abnormal contrast sensitivity.

The Impact of Intraocular Pressure Changes on Corneal Biomechanics in Primary Open-angle Glaucoma: IOP Changes Impact on Corneal Biomechanics in POAG.

PURPOSE: To investigate the relationship between intraocular pressure (IOP) changes and corneal biomechanical properties, determine the quantitative relationship between IOP changes and corneal biomechanical properties in patients with glaucoma and observe the differences among different types of glaucoma when the effects of high-level IOP were excluded. DESIGN: Prospective clinical cohort study. METHODS: Setting: Institutional. PATIENTS: Treatment-naive patients with primary open-angle glaucoma or ocular hypertension (OHT) were included. OBSERVATION PROCEDURES: IOP was measured using a Goldmann applanation tonometer. Corneal biomechanics were evaluated using a corneal indentation device and corneal visualization Scheimpflug technology. Medication therapy was used for IOP reduction. Repeated measurements were taken at the baseline visit and each week thereafter within a month. Paired t tests were used to compare IOP and corneal biomechanical metrics before and after IOP-lowering therapy. One-way analysis of variance was employed to investigate potential differences across groups, with a Bonferroni post hoc correction administered for multiple intergroup comparisons. MAIN OUTCOME MEASURES: Corneal biomechanical parameters following IOP changes. RESULTS: Eighty-one participants (mean age, 41.63 ± 17.33 years) were included in this study. The cohort comprised 20 patients with normal-tension glaucoma (NTG), 47 with high-tension glaucoma (HTG), and 14 with OHT. The baseline corneal stiffness (88.58±18.30 N/m) and corneal modulus (0.71±0.16 MPa) were greater than the post-IOP reduction values (67.15±9.24 N/m and 0.54±0.08 MPa, respectively; P<0.001). The relationships between changes in IOP and changes in corneal biomechanical parameters were Δ corneal stiffness=2.06*ΔIOP+6.47 (P<0.001) and Δ corneal modulus=0.017*ΔIOP+0.051 (P<0.001). After IOP reduction, the mean corneal stiffness at the 4th week in the NTG group was significantly lower (60.97±6.36 N/m) than that in the HTG (67.25±9.01 N/m) and OHT (75.62±6.52 N/m, P < 0.001) groups. Additionally, the stiffness of HTG patients was lower than that of OHT patients (P = 0.003). CONCLUSIONS: Changes in IOP have an impact on corneal biomechanical parameters. Decreases in corneal stiffness and modulus were observed after IOP reduction. When the effect of high-level IOP was excluded, corneal biomechanics varied according to the type of glaucoma. The HTG corneas were softer than the OHT corneas, and the NTG corneas were even softer.

Neovascular Glaucoma: A Rare Presenting Feature of Vogt-Koyanagi-Harada Syndrome.

Vogt-Koyanagi-Harada syndrome (VKH) is an uncommon multi-system autoimmune inflammatory disorder characterized by bilateral granulomatous panuveitis with serous retinal detachment accompanied by neurological, auditory, and cutaneous manifestations like headache, hearing loss, vitiligo, and poliosis. It has a female preponderance, usually in middle age. We report the case of a 20-year-old male who presented to us with rapidly progressive visual loss accompanying granular panuveitis, complicated cataract, and a mixed mechanism neovascular glaucoma with acute angle closure. He was treated for IOP control and underwent aggressive immunosuppression and, later, bilateral laser iridotomies. It wasn't until one month after the initial presentation that he presented with vitiligo and poliosis of the eyebrows and eyelashes, clinching the diagnosis of VKH syndrome. This case highlights the diagnostic challenge faced due to acute neovascular glaucoma being the initial presenting feature of VKH; hitherto not documented before, although acute angle closure glaucoma or crisis has occasionally been reported at presentation; the classical VKH presentation being an acute posterior segment uveitis or less commonly, a chronic, recurrent panuveitis presenting with/ without complications. This case underlines the importance of considering VKH syndrome in a patient with bilateral granulomatous panuveitis, as dermatological involvement can emerge later in the disease course, by which time vision might have already been compromised significantly.

The Macular Pigment Optical Density (MPOD) Decrease in Chinese Primary Angle Closure Glaucoma Using the One-Wavelength Reflectometry Method.

PURPOSE: The objective of this study was to observe the macular pigment optical density (MPOD) and the relationship between MPOD and retinal thickness in Chinese primary angle-closure glaucoma (PACG) patients by the one-wavelength reflectometry method. METHODS: This study was a prospective comparative observational study, including 39 eyes from 39 PACG patients (15 men and 24 women, mean age 61.89 ± 12.30) and 41 eyes from 41 controls (20 men and 21 women, mean age 63.24 ± 14.02). We measured the MPOD 7-degree area by the one-wavelength reflectometry method and analyzed both the max and mean optical density (OD). The central retinal thickness (CRT) and the total thickness of the macular ganglion cell layer (GCL), and inner plexiform layer (IPL)were measured by spectral-domain-optical coherence tomography (SD-OCT). Statistical methods such as Shapiro-Wilk test, Fisher's exact test, chi-square test, two independent samples test and Spearman's correlation coefficient were used to observe the differences in the MPOD between normal subjects and PACG patients and the correlation between the MPOD and retinal thickness. RESULTS: The max optical density (Max OD) (PACG group: 0.302 ± 0.067d.u, control group: 0.372 ± 0.059d.u., p < .001) and mean optical density (Mean OD) (PACG group: 0.124 ± 0.035d.u., control group: 0.141 ± 0.028d.u., p < 0.05) were significantly reduced in PACG patients compared with control subjects. Significant decreases in GCL + IPL thickness (PACG group: 74.71 ± 39.56 µm, control group:113.61 ± 8.14 µm, p < 0.001) and CRT (PACG group: 254.49 ± 41.47 µm, control group:329.10 ± 18.57 µm, p < 0.001) were also observed in PACG eyes. There was no statistically significant correlation between the MPOD and GCL + IPL thickness (p = .639, p = .828). CONCLUSIONS: MPOD was significantly lower in Chinese PACG patients than in the control group, potentially due to thinning of the GCL + IPL thickness. This study provides insights for the pathophysiology, assessment of PACG and potential guidance for lifestyle modifications.

In this study, we measured the MPOD values of Chinese PACG patients for the first time using the one-wavelength reflectance method and clarified that the MPOD of PACG patients was significantly lower than that of the normal group. This study provides insights for the pathophysiology, assessment of PACG and potential guidance for lifestyle modifications.

Microinterventional system for robot-assisted gonioscopic surgery- technical feasibility and preclinical evaluation in synthetic eye models.

BACKGROUND: Preclinical technical feasibility study of robot-assisted microinvasive glaucoma surgery using a novel ophthalmic robot-assisted surgery system. METHODS: Feasibility was assessed in synthetic eye models in two stages: Stage I, nonimplantable robot-assisted goniotomy; and Stage II, robot-assisted stent implantation using a trabecular bypass stent. Robot-assisted interventions were subsequently compared to the manual approach. RESULTS: Stage I: Two surgeons completed 10 trials each of ab-interno sectoral goniotomy with and without robotic assistance for at least 3 clock hours using a standard goniotomy knife and more than 10 clock hours of extended goniotomy using a flexible, guided goniotomy instrument. Stage II: Trabecular bypass stent deployment was successfully achieved in 100% of the attempts with and without robotic assistance. Surgical time was recorded and compared between the robotic-assisted and the manual approach. CONCLUSIONS: A system for robot-assisted microinvasive glaucoma surgery can successfully achieve implantable and nonimplantable interventions in the anterior segment. This is the first known demonstration of the feasibility of robot-assisted glaucoma surgery.

Loneliness and social isolation are associated with an increased risk of glaucoma: a UK Biobank cohort study.

BACKGROUND: Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. METHODS: A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During a median follow-up of 13.1 (interquartile range: 12.3-13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04-1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01-1.16; P = 0.033) were associated with an increased risk of glaucoma. CONCLUSIONS: In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.

Lycium barbarum glycopeptide promotes neuroprotection in ET-1 mediated retinal ganglion cell degeneration.

BACKGROUND: Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques. METHODS: Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts. RESULTS: ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups. CONCLUSION: LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.

Ocular hypertension after EyeCee One preload lens implantation: a retrospective cohort study.

Objective: In 2022, several cases of ocular hypertension (OHT) related to EyeCee One preloaded IOLs were reported. The aim of this study was to determine the presurgical and surgical variables associated with this response. Methods and analysis: An analysis was conducted on patients who underwent isolated cataract surgery between September 2022 and December 2022 at the Hospital Universitario del Henares. The influence of potential factors was studied using the Kruskal-Wallis test and multiple regression analysis. Results: A total of 353 cataract surgeries were included in the study. No significant differences between the different IOLs were found related to a change in the IOP on the first postoperative day (p = 0.395), but the change in the IOP after 1 month was higher in the EyeCee One group (p = 0.016). Approximately 6.1% of the patients who received EyeCee One had an IOP increase greater than 10 mmHg, compared to only 0.8% of the patients who received other IOLs. The odds ratio (OR) of experiencing an IOP increase greater than 10 mmHg in the EyeCee One group at the 1-month visit was 7.99 (1.52-41.99). The multiple regression analysis showed that receiving the EyeCee One lens was associated with a 2-mmHg increase in IOP. A previous history of glaucoma or OHT was not associated with greater IOP. Two patients in the EyeCee One group developed severe visual loss. Conclusion: Patients who received the EyeCee One IOL experienced significant increases in IOP at the 1-month visit. A small number of patients might suffer visual loss secondary to the rise in IOP.