Ocular Hypertension Research Articles

Cost-effectiveness of monitoring ocular hypertension based on a risk prediction tool

Background/AimsTo assess the cost-effectiveness of making treatment decisions for patients with ocular hypertension (OHT) based on a risk prediction (RP) tool in the United Kingdom.MethodsA discrete event simulation model was...

Tert-butyl hydroperoxide induces trabecular meshwork cells injury through ferroptotic cell death.

Trabecular meshwork (TM) tissue has a crucial role in regulating aqueous humor circulation in the eye, thus maintaining normal intraocular pressure (IOP). TM dysfunction causes IOP elevation, which leads to glaucoma. To investigate biological changes in TM tissue in patients with glaucoma, we analyzed the mRNA expression microarray dataset, GSE27276. Gene ontology analysis indicated that redox microenvironment imbalance is among the main changes of TM tissue in patients with glaucoma. Subsequently, we induced oxidative stress in TM cells using the tert-butyl hydroperoxide (tBHP) treatment, to generate in vivo and in vitro models, and conducted mRNA sequencing to identify genes with critical roles in maintaining the redox microenvironment balance. We found that the tBHP caused TM dysfunction in vivo, characterized by aqueous humor circulation resistance, IOP elevation, and TM cell death. Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that ferroptosis signaling was enriched in tBHP-treated TMcells. Consistently, in vitro analyses showed that levels of reactive oxygen species, ferric ion, and malondialdehyde were increased after the tBHP treatment, indicating TM cell ferroptosis. Furthermore, inhibiting ferroptosis alleviated tBHP-induced TM cell injury. This study provides new insights suggesting that inhibition of ferroptosis has potential as a treatment for glaucoma.

The Impact of Femtosecond Laser on Intraocular Pressure with Cataract Surgery in Healthy Eyes.

Femtosecond laser-assisted cataract surgery leads to an increase in intraocular pressure (IOP) during the procedure and subsequent IOP reduction after surgery, with greater magnitude in eyes with higher preoperative IOP. To evaluate the effect of femtosecond laser-assisted cataract surgery (FLACS) using the LDVZ8 laser on intraocular pressure (IOP) during and after surgery, and to compare the IOP-lowering effect of FLACS and conventional phacoemulsification cataract surgery (CPCS). This prospective cohort study enrolled 395 healthy eyes (395 patients) scheduled for FLACS (n=245) and CPCS (n=150). FLACS was performed using the LDVZ8 laser. During FLACS, IOP was assessed before and immediately after docking. IOP reduction during a six-month postoperative period was evaluated following FLACS and CPCS. Multivariate analyses were performed. Mean IOP increase after docking was 2.3±4.1mmHg (P<0.0001); maximum increase 17.6mmHg, peak 38mmHg. Sixty-one (61) eyes (25.1%) demonstrated an increase of ≥5mmHg and 10 (3.7%) showed an increase of ≥10mmHg; pre-docking IOP was associated with an IOP increase of ≥5mmHg (P-0.029). IOP reduction over six months post-surgery was similar for FLACS and CPCS (P>0.05),-1.33±3.12mmHg for FLACS (P<0.001) and -1.4±2.87mmHg for CPCS (P<0.001). Preoperative IOP correlated statistically significantly with IOP reduction in both FLACS (β -0.742, P<0.001) and CPCS (β -0.743, P<0.001). Although the LDVZ8 laser procedure causes an increase in IOP in some healthy eyes, a subsequent decrease in IOP is observed after FLACS. The IOP-lowering effect of FLACS is similar to CPCS, and tends to be more pronounced in eyes with higher preoperative IOP. Eyes with higher preoperative IOP are prone to IOP elevation during FLACS, a critical consideration for glaucoma patients.

Effect of Tiotropium on eye findings in the treatment of chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a persistent, chronic inflammatory disease of the lungs. Tiotropium, used in the treatment of COPD, is a muscarinic receptor antagonist that provides long-acting bronchodilation. Our study aimed to investigate the effects of Tiotropium on anterior chamber parameters.MethodsThe study was conducted as an observational cross-sectional and prospectively between October 2023 and April 2024. Patients were examined in three groups: Group 1 consisted of untreated COPD patients; Group 2 consisted of healthy volunteers similar age and gender, and Group 3 included COPD patients receiving Tiotropium 18 mcg via HandiHaler. Anterior chamber parameters, intraocular pressure values, and photopic-mesopic pupil diameters were measured at the initial visit for Group 1 and Group 2 patients, and at the third month of treatment for Group 3 patients.ResultsThirty-six patients were included in each group in the study. No significant differences were observed in ocular findings between the patient and control groups. In COPD patients receiving Tiotropium, narrowing of angle parameters, an increase in photopic-mesopic pupil diameters, and intraocular pressure were observed at the third month of treatment.ConclusionThis study is the first research that investigate the effects of Tiotropium on anterior chamber parameters, pupil diameters, and intraocular pressure in COPD treatment. In conclusion, patients with COPD receiving Tiotropium therapy for three months showed narrowing in angle parameters, an increase in intraocular pressure, and photopic-mesopic pupil diameter; however, no patients developed drug-induced acute angle closure glaucoma.Trial registrationAn independent ethics committee approved the study (Giresun EAH KEAK 2023/180 and 9.10.2023/02) which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice. The study was conducted as prospectively, observational case–control. The Clinical Trial Number obtained for the study is NCT06525051 and was taken on 2024–07-29.

Engineered sensor actuator modulator as aqueous humor outflow actuator for gene therapy of primary open-angle glaucoma

Glaucoma, a blinding eye disease with optic neuropathy, is usually associated with elevated intraocular pressure (IOP). The currently available pharmacological and surgical treatments for glaucoma have significant limitations and side effects, which include systemic reactions to medications, patient non-compliance, eye infections, surgical device failure, and damage to the eye. Here, we present Sensor-Actuator-Modulator (SAM), an engineered double mutant version of the bacterial stretch-activated mechanosensitive channel of large conductance (MscL) that directly senses tension in the membrane lipid bilayer of cells and in response, transiently opens its large nonspecific pore to release cytoplasmic fluid. The heterologously expressed mechanosensitive SAM channel acts as a tension-activated pressure release valve in trabeculocytes. In the trabecular meshwork (TM), SAM is activated by membrane stretch caused by elevated IOP. We have identified several SAM variants that are activated at physiologically relevant pressures. Using this barogenetic technology, we have demonstrated that SAM is functional in cultured TM cells, and successfully transduced in vivo in TM cells by use of AAV2/8. Further, it is effective in enhancing aqueous humor outflow facility leading to lowering the IOP in a mouse model of ocular hypertension.

RNA-seq transcriptomic profiling of TGF-β2-exposed human trabecular meshwork explants: Advancing insights beyond conventional cell culture models

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic in vivo conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-β2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-β2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-β2’s influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways.

A retrospective review of selective laser trabeculoplasty outcomes at Lancashire Teaching Hospitals, UK.

Selective laser trabeculoplasty has been carried out at Lancashire Teaching Hospitals over the past seven years. This work aimed to review the use of SLT in this Trust. The primary objectives were to establish the efficacy of SLT in reducing intraocular pressure, to analyse how prior treatment with different topical medications can influence SLT outcomes and to analyse the outcomes in revisionary patients. We conducted a retrospective review of 288 eyes, with a known history of glaucoma or ocular hypertension and who underwent initial SLT laser treatment between October 2018 and January 2020. SLT was performed on known glaucoma and treatment naïve patients where IOP control was deemed sub-optimal. All patient data was fully anonymised. We found that SLT was effective in lowering IOP. Around two-thirds of the eyes (181/280, 65%) achieved a reduction in IOP of 10% or more. Just under half (127/280, 45%) achieved a reduction of 20% or more. For a pre-SLT IOP of 14.6 mmHg, we found that no mean change in IOP is expected, and for each 1 mmHg by which the pre-SLT IOP exceeds this threshold, the mean reduction in IOP is expected to be 0.61 mmHg. We also found that combination therapies of PGA plus aqueous suppressants gave better outcomes compared with PGA alone. We found that revisionary SLT compared favourably with the first treatment, although first-time outcomes were not a good predictor of success with revisionary SLT. Primary and revisionary SLT has been shown to be effective across the cohort of patients in this study.

Predictive Value of Conjunctival Cytology in Bleb-dependent Glaucoma Surgery.

Metaplasia, chronic inflammation and subconjunctival fibrosis favor failure of bleb-dependent glaucoma surgery. The aim of the study is to identify the patients at a higher risk of post-surgical failure. Prospective, open study, performed in the Glaucoma Unit of the Hospital Universitario Virgen Macarena, from April to November 2021, with a minimum follow-up of one year. 38 eyes with ocular hypertension or chronic open-angle glaucoma were included. All patients underwent preoperative conjunctival sampling in the operating room, under topical or locoregional anesthesia. Sex, age, and laterality; number, type and mean time of preoperative drugs use; type of surgery performed; cytology results and degree of metaplasia; percentage of patients in whom the bleb was closed. Evaluation of potential correlation between bleb closure and any of the other variables. 20 women and 18 men participated, with a mean age of 67 years. The mean number of preoperative hypotensive drugs was 2.7.The mean time of use was 90,97 +/- 48,97 months. Most patients had normal cytology, 8% had inflammatory infiltrate and 21% had squamous metaplasia. When relating bleb failure and cytology, we saw that in those who failed surgery, more than half had cytological alterations. A multiple logistic regression was performed, in which we observed that there was statistically significant association (p = .02) between surgical closure and altered cytology. According to these results, preoperative conjunctival cytology can help predict those cases with a lower probability of surgical success.

Transorbital Alternating Current Stimulation in Glaucoma: State of the Art from Neurophysiological Bases to Clinical Practice

Recovery after visual loss is a key goal of neuroscience and treatments able to improve visual function are still largely lacking. Glaucoma, one of the leading causes of visual disability in the world, is usually associated with elevated intraocular pressure (IOP), but a subset of “normal tension glaucoma” patients develop damage without ever manifesting high IOP. Sometimes, even in patients with good control of IOP, retinal ganglion cell degeneration can progress to forward blindness. Moreover, usually the damage already caused by the disease remains. These considerations underline the need to find new, effective treatments and solutions to add to the standard ones. In this paper, we expose the most important data supporting the use of alternating current stimulation, including the theoretical bases of this approach, in glaucoma.

Factors Related to Raised Intraocular Pressure: In a Tertiary Hospital in Bangladesh

Glaucoma, a leading cause of irreversible blindness globally, accounts for 8% of such cases. The probability of developing glaucoma appears to be elevated in individuals with systemic hypertension or diabetes mellitus. Elevated intraocular pressure (IOP) is the only modifiable risk factor associated with the development and progression of glaucoma, and both medical and surgical interventions are available for its management. This study, conducted in the Ophthalmology department of BSMMU from July 2021 to June 2022, was a hospital-based cross-sectional investigation with a sample size of 153. The majority of participants fell into the 41-50 age group, with a mean age of 37.15±17.14. 41.8% of the responders were men and 58.2% were women. Refractive errors were identified in 7.2% of cases, with primary open-angle glaucoma (POAG) diagnosed in 60% of cases, normal-tension glaucoma (NTG) in 11.1%, and angle-closure glaucoma (PACG) in 10.5%, among other types. The study also observed associations between age groups and IOP levels, with 42% of individuals aged 30-50 having IOP in the 18-22 mmHg range. Additionally, 50% of established glaucoma cases had diabetes mellitus, 30% had hypertension, and 10% had a history of steroid therapy. Together with other variables including steroid usage, diabetes, and hypertension, high IOP continues to be a substantial risk factor for the start and progression of glaucoma. J. of Sci. and Tech. Res. 5(1): 157-162, 2023

Comparative Effects of GLP-1 Receptor Agonists and Metformin on Glaucoma Risk in Type 2 Diabetes Patients

PurposeTo compare effects of glucagon-like peptide-1 (GLP-1) receptor agonists and metformin on the risk of primary open-angle glaucoma (POAG), ocular hypertension, and the need for first-line glaucoma treatments in patients with type 2 diabetes. DesignA retrospective cohort study was conducted using electronic medical records (EMR) data from the from an international electronic health record network, covering a period from May 2006 to May 2024. ParticipantsPatients diagnosed with type 2 diabetes mellitus (T2DM) who were treated with either GLP-1 receptor agonists or metformin. MethodsData from 120 healthcare organizations across 17 countries were analyzed. Patient outcomes were assessed at 1, 2, and 3 years. Propensity score matching (PSM) was used to balance covariates such as demographics, comorbidities, and medication usage. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Main Outcome MeasuresIncidence of POAG, ocular hypertension, and the need for first-line treatments including beta-blockers, prostaglandin analogues, brimonidine, brinzolamide, dorzolamide, netarsudil, and laser trabeculoplasty. ResultsAfter PSM, both groups included 61,998 patients at the 1-year follow-up, 27,414 at the 2-year follow-up, and 14,100 at the 3-year follow-up. Patients treated with GLP-1 receptor agonists had a significantly decreased risk of developing POAG compared to those on metformin at 1 year (RR 0.59, 95% CI 0.39-0.88), 2 years (RR 0.50, 95% CI 0.32-0.78), and 3 years (RR 0.59, 95% CI 0.37-0.94). Similar protective effects were observed for ocular hypertension with risk reductions of 56% at 1 year (RR 0.44, 95% CI 0.31-0.62), 57% at 2 years (RR 0.43, 95% CI 0.30-0.62), and 49% at 3 years (RR 0.51, 95% CI 0.34-0.75). The risk of first-line therapy initiation was also lower in the GLP-1 receptor agonists group at 1 year (RR 0.63, 95% CI 0.53-0.74), 2 years (RR 0.71, 95% CI 0.59-0.85), and 3 years (RR 0.75, 95% CI 0.62-0.91). ConclusionsGLP-1 receptor agonists are associated with a significantly lower incidence of POAG, ocular hypertension, and the need for first-line glaucoma treatments compared to metformin in patients with type 2 diabetes. These findings highlight the potential ocular benefits of GLP-1 receptor agonists and their expanding role in the clinical management of diabetic patients.

Case Study: Compatibility Testing of Pre-Filled Syringe Stopper Technology with Vaporized Hydrogen Peroxide Terminal Sterilization Process.

STERIS and W.L. GORE collaborated on a case study testing the compatibility of a new prefilled syringe plunger design with VHP terminal sterilization. VHP chamber conditions require deep vacuum pulsing, which may represent challenges to prefilled syringe container integrity. The growing industry trend toward VHP sterilization is driven by the FDA search for alternative sterilization methods to EO and the recent publication of a VHP specific process standard. The purpose of the study is to test and report compatibility of the new 0.5 mL GORE IMPROJECT plunger, a silicone free syringe solution for ophthalmic application, with VHP sterilization. Various challenges have been reported when using conventional, siliconized, prefilled syringe systems for intravitreal injections such as subvisible particles, inflammation, silicone floaters, and intraocular pressure increases. The GORE plunger eliminates the need for silicone oil as a lubricant on the plunger and barrel, while meeting strict container closure and terminal sterilization requirements of ophthalmic applications. This case study presents successful results of deep vacuum VHP terminal sterilization process compatibility with the GORE plunger design and material composition. Test results include primary container integrity, stopper off-gassing/ingress, and visual inspection. Principles of VHP vacuum sterilization process, test cycle configuration, and its main parameters are presented.

Acute ocular hypertension in the living human eye: Model description and initial cellular responses to elevated intraocular pressure

This initial methods study presents the initial immunohistochemical and transcriptomic changes in the optic nerve head and retina from three research-consented brain-dead organ donors following prolonged and transient intraocular pressure (IOP) elevation. In this initial study, research-consented brain-dead organ donors were exposed to unilateral elevation of IOP for 7.5 h (Donor 1), 30 h (Donor 2), and 1 h (Donor 3) prior to organ procurement. Optic nerve tissue and retinal tissue was obtained following organ procurement for immunohistological and transcriptomic analysis.Optic nerve sections in Donor 1 exposed to 7.5-hours of unilateral sub-ischemic IOP elevation demonstrated higher levels of protein expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), within the lamina cribrosa with greatest expression inferior temporally in the treated eye compared to control. Spatial transcriptomic analysis performed on optic nerve head tissues from Donor 2 exposed to 30 h of unilateral IOP elevation demonstrated differential transcription of mRNA across laminar and scleral regions. Immunohistochemistry of retinal sections from Donor 2 exhibited higher GFAP and IBA1 expression in the treated eye compared with control, but this was not observed in Donor 3, which was exposed to only 1-hour of IOP elevation. While there were no differences in GFAP protein expression in the retina following the 1-hour IOP elevation in Donor 3, there were higher levels of transcription of GFAP in the inner nuclear layer, and CD44 in the retinal ganglion cell layer, indicative of astrocytic and Müller glial reactivity as well as an early inflammatory response, respectively.We found that transcriptomic differences can be observed across treated and control eyes following unilateral elevation of IOP in brain dead organ donors. The continued development of this model affords the unique opportunity to define the acute mechanotranscriptomic response of the optic nerve head, evaluate the injury and repair mechanisms in the retina in response to IOP elevation, and enable correlation of in vivo imaging and functional testing with ex vivo cellular responses for the first time in the living human eye.

Responsiveness to Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension

Selective laser trabeculoplasty (SLT) is becoming the recommended first choice in the treatment of open-angle glaucoma (OAG). However, whether repeat SLT can be recommended regardless of initial response remains controversial. To assess the potential of OAG and ocular hypertension (OHT) undergoing repeat laser to respond favorably to SLT, termed responsiveness to SLT. This post hoc analysis of the Laser in Glaucoma and Ocular Hypertension Trial in China (LiGHT China) was conducted from March 2015 to April 2023 in Zhongshan Ophthalmic Center. Of 1376 newly diagnosed OAG and OHT eyes of 771 adults in the original trial, 180 eyes of 105 participants were included in the present study, which underwent initial and repeat SLT as primary treatments. Standard SLT was the primary treatment. Repeat SLT was the first choice of treatment escalation regardless of initial response. IOP reduction after SLT and the duration of effect were analyzed. The maximum reduction in IOP within 2 years after initial SLT and repeat SLT was used to identify potential nonresponsiveness. IOP reduction 2 months after SLT. A total of 180 eyes from 105 Chinese participants (mean [SD] age, 45.6 [14.5] years; 58 [55.2%] male and 47 [44.8%] female) underwent repeat SLT. Initial SLT and repeat SLT were both associated with a reduction in IOP (mean, 4.5 mm Hg; 95% CI, 3.9 to 5.1; P < .001 and mean, 3.3 mm Hg; 95% CI, 2.7 to 3.8; P < .001, respectively). The mean (SD) IOP after repeat SLT was 15.8 (3.4) mm Hg, similar to 16.0 (4.0) mm Hg after initial SLT (difference, -0.4mm Hg; 95% CI, -1.0 to 0.3; P = .24). Duration of effect after repeat SLT was longer than after initial SLT (1043 days vs 419 days; hazard ratio, 0.38; 95% CI, 0.29 to 0.50; P < .001). IOP reduction after initial SLT was uncorrelated with that after repeat SLT, and 153 eyes (85.0%) responded favorably to SLT at least once. A subset of 27 eyes (15.0%) was identified as potentially nonresponsive and found distinctive with older age (mean [SD], 54.1 [12.5] years vs 44.2 [14.2] years; difference, 10.5 years; 95% CI, 2.9 to 18.1; P = .009), higher proportion of female participants (difference, 27.5%; 95% CI, 3.6 to 51.5; P = .03), and lower baseline IOP (difference, -3.2 mm Hg; 95% CI, -5.2 to -1.3; P = .001). These post hoc analyses showed that most cases of OAG and OHT were highly responsive to SLT and support the consideration of repeat SLT regardless of initial response, while individuals who are nonresponsive to this treatment may have specific features.

Caveolin-1 protects retinal ganglion cells in glaucoma by reducing TLR4 and activating the Akt/PTEN signaling pathway

Glaucoma is a degenerative disease characterized by retinal ganglion cell (RGC) death and visual impairment caused by elevated intraocular pressure (IOP). Elevated IOP can activate microglia, which participate in ganglion cell injury. Based on the study of caveolin-1 (Cav-1) in glaucoma, we aimed to explore the effect and mechanism of Cav-1 on RGC apoptosis in mice with acute ocular hypertension (AOH). AOH mice were established, and Cav-1 was intravitreally injected. Retinal microglia and RGCs were isolated from neonatal mice. TUNEL staining, hematoxylin-eosin staining, immunohistochemistry, flow cytometry, PCR and western blotting were used to observe the effect of Cav-1 on RGCs and mouse retinas. The thickness of the whole retina and the inner retinal sublayer decreased significantly, retinal cell apoptosis increased after AOH injury, and Cav-1 treatment reversed the effect of AOH injury. In addition, Cav-1 treatment promoted the conversion of proinflammatory M1 microglia to anti-inflammatory M2 microglia. Microglia and RGCs were isolated from neonatal mice. Cav-1 protects RGCs from OGD/R-induced injury by changing the polarization status of retinal microglia in vitro. Further studies revealed that Cav-1 activated the Akt/PTEN signaling pathway and inhibited TLR4. Our study provides evidence that Cav-1 may be a promising therapeutic target for glaucoma.

Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Diagnosing Glaucoma Based on the Ocular Hypertension Treatment Study Dataset Using Chat Generative Pre-Trained Transformer as a Large Language Model

To evaluate the capabilities of Chat Generative Pre-Trained Transformer (ChatGPT), as a large language model (LLM), for diagnosing glaucoma using the Ocular Hypertension Treatment Study (OHTS) dataset, and comparing the diagnostic capability of ChatGPT 3.5 and ChatGPT 4.0. Prospective data collection study. A total of 3170 eyes of 1585 subjects from the OHTS were included in this study. We selected demographic, clinical, ocular, visual field, optic nerve head photo, and history of disease parameters of each participant and developed case reports by converting tabular data into textual format based on information from both eyes of all subjects. We then developed a procedure using the application programming interface of ChatGPT, a LLM-based chatbot, to automatically input prompts into a chat box. This was followed by querying 2 different generations of ChatGPT (versions 3.5 and 4.0) regarding the underlying diagnosis of each subject. We then evaluated the output responses based on several objective metrics. Area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1 score. Chat Generative Pre-Trained Transformer 3.5 achieved AUC of 0.74, accuracy of 66%, specificity of 64%, sensitivity of 85%, and F1 score of 0.72. Chat Generative Pre-Trained Transformer 4.0 obtained AUC of 0.76, accuracy of 87%, specificity of 90%, sensitivity of 61%, and F1 score of 0.92. The accuracy of ChatGPT 4.0 in diagnosing glaucoma based on input data from OHTS was promising. The overall accuracy of ChatGPT 4.0 was higher than ChatGPT 3.5. However, ChatGPT 3.5 was found to be more sensitive than ChatGPT 4.0. In its current forms, ChatGPT may serve as a useful tool in exploring disease status of ocular hypertensive eyes when specific data are available for analysis. In the future, leveraging LLMs with multimodal capabilities, allowing for integration of imaging and diagnostic testing as part of the analyses, could further enhance diagnostic capabilities and enhance diagnostic accuracy. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for primary open-angle glaucoma: A randomized controlled trial.

To report the 2-year efficacy and safety of penetrating canaloplasty versus ab externo canaloplasty for the treatment of primary open-angle glaucoma (POAG). A single surgical site in China. This was a prospective, randomized controlled trial. POAG patients were randomly assigned to the penetrating canaloplasty or ab externo canaloplasty group. This study enrolled POAG patients who underwent penetrating canaloplasty or ab externo canaloplasty randomly. Surgical success, intraocular pressure (IOP), number of glaucoma medications, and surgical complications were evaluated until 24 months post-operatively. Surgical success was defined as 6 mmHg ≤ IOP ≤21 mmHg with an IOP reduction ≥20%, which included qualified success (with or without medications) and complete success (without medications). A total of 52 eyes (45 patients) were randomly assigned to one of two groups: the penetrating canaloplasty group (PCP, n = 26) or the ab externo canaloplasty group (CP, n = 26). The probabilities of qualified success and complete success were 92.3% and 76.9%, respectively, in the PCP group and 64.1% and 52.1%, respectively, in the CP group at 24 months (p = 0.013, p = 0.042, log-rank test). The mean IOP decreased from 30.8 ± 10.7 and 28.6 ± 11.8 mmHg to 14.1 ± 3.3 mmHg in the PCP group and 22.1 ± 13.6 mmHg in the CP group at year two (p = 0.007). The PCP group also received fewer medications (0.2 ± 0.5) than did the CP group (0.7 ± 1.2) at year two (p = 0.038). Post-operative complications were similar, and the most common complications were transient IOP elevation and hyphema in the PCP group (42.3%, 46.2%) and the CP group (38.5%, 23.1%) (p > 0.05). Compared to ab externo canaloplasty, penetrating canaloplasty had a greater surgical success rate and better IOP reduction with a comparable rate of complications.

Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.

Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells. GTM3L cells were fluorescently sorted for viral copy number analysis. CLAN incidence was increased by (i) differential sorting of cells by adhesion, (ii) cell deswelling, and (iii) cell selection based on cell stiffness. GTM3L cells were also cultured on glass or soft hydrogel to determine substrate stiffness effects on CLAN incidence. Computational models were constructed to mimic and study the biomechanical properties of CLANs. All GTM3L cells had an average of 1 viral copy per cell. LifeAct-GFP expression level did not affect CLAN incidence rate, but CLAN rate was increased from ∼0.28% to ∼50% by a combination of adhesion selection, cell deswelling, and cell stiffness-based sorting. Further, GTM3L cells formed more CLANs on a stiff vs. a soft substrate. Computational modeling predicted that CLANs contribute to higher cell stiffness, including increased resistance of the nucleus to tensile stress when CLANs are physically linked to the nucleus. It is possible to greatly enhance CLAN incidence in GTM3L cells. CLANs are mechanosensitive structures that affect cell biomechanical properties. Further research is needed to determine the effect of CLANs on TM biomechanics and mechanobiology as well as the etiology of CLAN formation in the TM.

Comparison of Bimatoprost 0.03% and Brimonidine 0.2% in Managing Intraocular Pressure Elevation Following Nd:YAG Laser Capsulotomy for Posterior Capsule Opacification

ABSTRACT Background: Posterior capsule opacification (PCO) is the most common cause of vision reduction following successful cataract surgery. It is a dynamic process caused by the migration and proliferation of residual lens epithelial cells on the posterior capsule, leading to visual impairment. The standard treatment for PCO is neodymium: yttrium–aluminum–garnet (Nd:YAG) laser capsulotomy. This study aims to compare the efficacy and safety of Bimatoprost 0.03% and Brimonidine 0.2% in preventing intraocular pressure (IOP) elevation post-Nd:YAG laser capsulotomy. Materials and Methods: This study was conducted over a year at the Government Medical College, Jammu. 400 patients with PCO post extracapsular cataract extraction were randomly divided into two groups. Group A received 1 drop of Bimatoprost 0.03% and Group B received 1 drop of Brimonidine 0.2%, both administered 1 hour before Nd:YAG laser capsulotomy. Intraocular pressure was measured using Goldmann applanation tonometry before treatment and at intervals of 1 hour, 3 hours, 24 hours, 3 days, and 7 days post-treatment. Results: The mean age of patients was approximately 65 years with no significant difference between groups. The baseline IOP was similar across both groups. At 1 hour post-capsulotomy, Group A showed a mean IOP increase of 2.2 mmHg, while Group B showed an increase of 3.6 mmHg. At 24 hours, the IOP in Group A returned to baseline levels, whereas Group B still exhibited a slight elevation. No significant adverse effects were reported in either group. Conclusion: Bimatoprost 0.03% is more effective in preventing IOP elevation post Nd:YAG laser capsulotomy compared to Brimonidine 0.2%. It also demonstrated a faster return to baseline IOP levels with fewer side effects. This suggests that Bimatoprost may be a preferable prophylactic treatment for managing post-capsulotomy IOP spikes.