[Fully recognizing selective laser trabeculoplasty].

Selective laser trabeculoplasty (SLT), as one of the main methods for the treatment of open-angle glaucoma, has again aroused wide concern in recent years. Although SLT has a clear effect on reducing intraocular pressure, its role needs to be fully recognized. In order to provide guidance for the clinical SLT practice, this article summarizes and discusses the current status of SLT treatment for glaucoma, its therapeutic effects on primary open-angle glaucoma, ocular hypertension, and other types of glaucoma, surgical details, and application prospects.

Comparative proteomic analysis of retinal hypoxia-ischemia in an acute ocular hypertension model using tandem mass tag-based quantitative proteomics.

The main symptom of acute glaucoma is acute ocular hypertension (AOH), which leads to the death of retinal ganglion cells (RGCs) and permanent loss of vision. However, effective treatments for these conditions are lacking. This study aimed to identify major regulators and overall protein changes involved in AOH-induced RGC death. Proteomic patterns of the retinal protein extracts from the AOH and sham groups were analyzed using mass spectrometry (MS), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Proteomic analysis revealed 92 proteins in the AOH group compared to the control group; 58 proteins were upregulated and 34 were downregulated. Alterations in fatty acid-binding protein 7 (FABP7) and caveolin-1 (Cav-1), which are related to fatty acid metabolism and ocular inflammatory signaling, were detected using western blotting and biochemical assays. Variations in the expression of galectin-1 (Gal-1), S100 calcium-binding protein A6 (S100a6), and visinin-like protein-1 (VILIP) have been associated with neuronal ischemia. Our investigation demonstrates that neuroinflammation and fatty acid metabolism are involved in retinal impairment following AOH, suggesting a possible treatment approach for acute glaucoma.

Lack of ceramide synthase 5 protects retinal ganglion cells from ocular hypertensive injury.

Ceramides with varying acyl-chain lengths can have unique biological actions and hence, cellular responses to ceramides may depend not on their overall concentration but on that of individual ceramide species. The purpose of this study was to determine individual ceramide species impacting retinal ganglion cell (RGC) loss under the ocular hypertensive condition. Induced pluripotent stem cell (iPSC)-derived RGCs and primary cultures of human astrocytes were used to determine the effect of individual ceramide species on both RGC viability and astrocyte secretion of inflammatory cytokines in vitro. In in vivo experiments with wild-type (WT) and ceramide synthase 5 (CerS5) knockout mice, intraocular pressure was unilaterally elevated with microbead injection. Retinal function and morphology were evaluated using pattern electroretinography (pERG) and immunofluorescence, respectively. Ceramide levels were determined by LC-MS/MS analysis. Exposure to C16:0-, C18:0-, C18:1-, C20:0- and C24:0-ceramides significantly reduces RGC viability in vitro, with the very long chain C24:0-ceramide being the most neurotoxic; treatment with C18:0-, C18:1- and C24:0-ceramides stimulates an increase of TNF-α secretion by astrocytes. The retinas of CerS5 KO mice have significantly reduced levels of C16:0- and C18:1-ceramides compared to WT; ocular hypertensive eyes of these mice maintain higher pERG amplitudes and RGC numbers compared to WT. Individual ceramides with different chain lengths have different effects on RGCs and astrocytes. Our results demonstrate that suppressing C16:0- and C18:1-ceramide species effectively protects RGCs against ocular hypertensive injury. These results provide a basis for targeting specific ceramide species in the treatment of glaucoma.

Activation of the ROCK/MYLK Pathway Affects Complex Molecular and Morphological Changes of the Trabecular Meshwork Associated With Ocular Hypertension.

Purpose: The Rho-associated protein kinase and myosin light chain kinase (ROCK/MYLK) pathway undeniably plays a pivotal role in the pathophysiology of primary open-angle glaucoma (POAG). In our study, we utilized both ocular hypertension (OHT) rabbit models and clinical investigations to gain invaluable insights that propel the development of novel treatments targeting proteins and genes associated with the trabecular meshwork (TM), thereby offering promising avenues for the management of POAG. Methods: Following microbead injections into the anterior chamber of the ocular cavity of rabbits, we observed elevated histiocyte numbers and immune scores for MYLK-4/ pMLC-2, alongside a reduction in the void space within the TM. Notably, treatment was performed with 0.1% ITRI-E-(S)-4046, a compound with dual kinase inhibitor (highly specific inhibitor of ROCK1/2 and MYLK4), significantly reduced intraocular pressure (IOP; P < 0.05) and expanded the void space within the TM (P < 0.0001) compared with OHT rabbits. In clinical investigations, we utilized whole transcriptome sequencing to analyze gene expression specifically related to the TM, obtained from patients (5 early-onset and 5 late-onset) undergoing trabeculectomy. Results: Our findings revealed 103 differential expression genes (DEGs) out of 265 molecules associated with the Rho family GTPase pathway, exhibiting a P value of 1.25E-10 and a z-score of -2.524. These results underscore significant differences between the early-onset and late-onset POAG and highlight the involvement of the ROCK/MYLK pathway. Conclusions: These findings underscore the critical involvement of the ROCK/MYLK pathway in both OHT-related and different onsets of POAG, providing valuable insights into the TM-related molecular mechanisms underlying the disease.

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-1ß (IL-1ß) 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.

Severe intraocular pressure rise after implantable collamer lens implantation.

A 22-year-old woman with a history of high myopia (-8.00 -3.75 × 011, right eye; -6.75 -3.75 × 174, left eye) presented to our clinic for implantable collamer lens (ICL) evaluation. Medical history was noncontributory. The patient's father had a history of glaucoma. Slitlamp and dilated fundus examination were unremarkable with a cup-to-disc ratio of 0.5 in both eyes and a myopic fundus. Intraocular pressures (IOPs) were 20 mm Hg in the right eye and 19 mm Hg in the left eye. Galilei G4 (Ziemer USA, Inc.) measured a white-to-white (WTW) distance of 12.98 mm in the right eye and 13.05 mm in the left eye and central corneal thickness of 512 µm in the right eye and 504 µm in the left eye. Ultrasound biomicroscopy (UBM) (Sonomed Escalon) displayed a sulcus-to-sulcus distance of 12.76 mm in the right eye and 12.75 mm in the left eye and an anterior chamber depth (ACD) of 3.57 mm in the right eye and 3.79 mm in the left eye (Figure 1JOURNAL/jcrs/04.03/02158034-202409000-00014/figure1/v/2024-08-19T175148Z/r/image-tiff). Prednisolone acetate 0.1% ophthalmic suspension eye drops and ofloxacin 0.3% ophthalmic solution eye drops 4 times daily were prescribed prophylactically 2 days preoperatively. A -12.5 and -12 D EVO+ Visian toric ICL -13.2 mm (STAAR Surgical Co.) was implanted along the 180-degree meridian in the right eye and left eye, respectively. Immediate postoperative IOPs were 23 mm Hg in both eyes. The patient was instructed to continue ofloxacin drops for 1 week and taper prednisolone acetate drops over 1 month. On postoperative day (POD) 1, uncorrected distance visual acuity (UDVA) was 20/20 in the right eye and 20/25 in the left eye. The patient's IOP was 24 mm Hg in the right eye and 26 mm Hg in the left eye. Anterior chambers (ACs) were unremarkable with minimal edema at the clear temporal corneal incision sites. Anterior segment optical coherence tomography (AS-OCT) vault measurements were 766 µm in the right eye and 697 µm in the left eye. Subsequently, the prednisolone dosage was reduced to 3 times a day, and brimonidine eye drops 3 times a day in both eyes were added to the regimen. On POD 5, the patient returned to the clinic reporting sudden-onset blurred vision with severe retro-orbital pain in the left eye upon awakening. Her UDVA was 20/25 in the right eye and 2/40 in the left eye. IOP was 30 mm Hg in both eyes. The ACs were deep, and there was minimal corneal edema in both eyes. Vaults were 674 µm in the right eye and 623 µm in the left eye (Figure 2JOURNAL/jcrs/04.03/02158034-202409000-00014/figure2/v/2024-08-19T175148Z/r/image-tiff). The patient was instructed to reduce prednisolone to 2 times a day, discontinue brimonidine, and start brimonidine/timolol (Combigan) 2 times a day and latanoprost at bedtime in both eyes. At the routine 1-week postoperative appointment, the patient's IOP was 30 mm Hg in the right eye and 29 mm Hg in the left eye. The patient was instructed to reduce prednisolone to once a day, continue brimonidine/timolol 2 times a day and latanoprost at bedtime, and start acetazolamide (Diamox) 250 mg 2 times a day. The patient was told to return to the office in a few days for an IOP check. What are the differential diagnoses concerning this case? What is the most likely mechanism underlying this patient's elevated IOP? What additional diagnostic workup would aid you in making the correct diagnosis?

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.

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

BACKGROUND/AIMS: To 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. METHODS: A discrete event simulation model was constructed to compare the cost-effectiveness of an alternative care pathway in which the treatment decision was guided by a validated RP tool in secondary care against decision-making based on the standard care (SC). Individual patient sampling was used. Patients diagnosed with OHT and with an intraocular pressure of 24 mm Hg or over entered the model with a set of predefined individual characteristics related to their risk of conversion to glaucoma. These characteristics were retrieved from electronic medical records (n=5740). Different stages of glaucoma were modelled following conversion to glaucoma. RESULTS: Almost all (99%) patients were treated using the RP strategy, and less than half (47%) of the patients were treated using the SC strategy. The RP strategy produced higher cost but also higher quality-adjusted life years (QALYs) than the SC strategy. The RP strategy was cost-effective compared with the SC strategy in the base-case analysis, with an incremental cost-effectiveness ratio value of £11 522. The RP strategy had a 96% probability of being cost-effective under a £20 000 per QALY threshold. CONCLUSIONS: The use of an RP tool for the management of patients with OHT is likely to be cost-effective. However, the generalisability of the result might be limited due to the high-risk nature of this cohort and the specific RP threshold used in the study.

GSK3ß Inhibitors Inhibit TGFß Signaling in the Human Trabecular Meshwork.

Purpose: Primary open-angle glaucoma (POAG) is a leading cause of blindness, and its primary risk factor is elevated intraocular pressure (IOP) due to pathologic changes in the trabecular meshwork (TM). We previously showed that there is a cross-inhibition between TGFß and Wnt signaling pathways in the TM. In this study, we determined if activation of the Wnt signaling pathway using small-molecule Wnt activators can inhibit TGFß2-induced TM changes and ocular hypertension (OHT). Methods: Primary human TM (pHTM) cells and transduced SBE-GTM3 cells were treated with or without Wnt and/or TGFß signaling activators and used for luciferase assays; for the extraction of whole-cell lysate, conditioned medium, cytosolic proteins, and nuclear proteins for Western immunoblotting (WB); or for immunofluorescent staining. Human donor eyes were perfusion cultured to study the effect of Wnt activators on IOP. Results: We found that the small-molecule Wnt activators (GSK3ß inhibitors) (BIO, SB216763, and CHIR99021) activated canonical Wnt signaling in pHTM cells without toxicity at tested concentrations. This activation inhibited TGFß signaling as well as TGFß2-induced extracellular matrix deposition and formation of cross-linked actin networks in pHTM cells or SBE-GTM3 cells. We also observed nuclear translocation of both Smad4 and ß-catenin in pHTM cells, which suggested that the cross-inhibition between the TGFß and Wnt signaling pathways may occur in the nucleus. Using our ex vivo model, we found that CHIR99021 inhibited TGFß2-induced OHT in perfusion-cultured human eyes. Conclusions: Our results showed that small-molecule Wnt activators have the potential for treating TGFß signaling-induced OHT in patients with POAG.

Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVß5/AMPK and promoting autophagy.

Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.

Progression to bilaterality in unilateral primary congenital glaucoma.

PURPOSE: To evaluate the incidence of rise in intraocular pressure (IOP) in fellow eyes of patients with unilateral primary congenital glaucoma (PCG) and to identify risk factors for IOP increase over long-term follow-up. METHODS: The medical records of unilateral PCG patients who had completed at least 5 years of follow-up were reviewed retrospectively. The incidence of developing ocular hypertension / glaucoma in fellow eyes was analyzed. Fellow eye progressors were those which showed an increase in optic nerve cupping by at least 0.2 since the first presentation or had IOP of >21 mm Hg on two occasions. The risk factors for progression that were analyzed included IOP, visual acuity, axial length, central corneal thickness (CCT), corneal diameters (CD), presence or absence of angle dysgenesis on high-resolution anterior segment optical coherence tomography (AS-OCT), and morphology of aqueous outflow pathways. RESULTS: After a median follow-up of 8.2 years (range, 5-25.5) progression to bilateral disease was found in 17 of 54 patients (32%), of whom 8 (15%) developed ocular hypertension and 9 (17%) developed glaucoma in the fellow eye. Among the unaffected fellow eyes, those with a larger CD (>12 mm), measured after at least 5 years' follow-up, were ten times more likely to progress (P = 0.01; OR = 9.5 [95% CI, 1.7-54.3]). The presence of a patent supraciliary channel was significantly more frequently associated in fellow eyes compared with affected eyes on AS-OCT (OR = 1.4 [95% CI, 0.46-4.68]). CONCLUSIONS: One-third of unaffected fellow eyes of unilateral PCG eventually progress over time, most often after 5 years. Larger CD at follow-up in the fellow eye is strongly predictive for progression.

Neuroprotection of the P2X7 receptor antagonist A740003 on retinal ganglion cells in experimental glaucoma.

The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1ß and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.

A phase III, multicentre, randomised, investigator-masked, cross-over, comparative, non-inferiority trial evaluating the efficacy and tolerability of generic preservative-free Latanoprost (Polpharma S.A.) compared to Xalatan® (Pfizer) in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).

[Spontaneous rupture of the anterior lens capsule in Alport syndrome (case study)]. / Samoproizvol'noe vskrytie perednei kapsuly khrustalika pri sindrome Al'porta (klinicheskoe nablyudenie).

Alport syndrome is a hereditary disease characterized by glomerulopathy, manifested by hematuria and/or proteinuria, progressive decline in renal function, often combined with hearing and vision pathology. This article presents a clinical case of spontaneous opening of the anterior lens capsule in a patient with Alport syndrome, accompanied by uveitis and ophthalmic hypertension, and describes the features of the surgical aid and the postoperative period.

Differences in Systemic Pulse Waveform Between Individuals With Glaucoma, Glaucoma Suspects, and Healthy Controls.

Purpose: It has been hypothesized that compromised ocular circulation in glaucoma may be concomitant of systemic changes. The purpose of this study is to test whether systemic blood flow pulse waveform patterns differ between individuals with glaucoma (GL), glaucoma suspects (GLS), and normal healthy controls (HC). Methods: The study included 35 bilateral GL, 67 bilateral GLS, 29 individuals with unilateral GL who were considered GLS in the other eye, and 44 healthy controls. Systemic pulsatile blood pressure waveforms were recorded using a finger cuff. A continuous 200 Hz plethysmography recording is made to obtain a pulse waveform. Waveform parameters were extracted using custom software from an average of eight pulse cycles. These were compared between GL, GLS, and HC groups on a per-eye basis, using generalized estimating equation models to account for intereye correlations; and plotted against disease severity by visual field linearized mean deviation (MDlin) and retinal nerve fiber layer thickness (RNFLT). Results: Averaged blood pressure was significantly lower in the HC group (mean ± standard deviation 91.7 ±11.7 mm Hg) than the GLS (102.4 ± 13.9) or GL (102.8 ± 13.7) groups, with P < 0.0001 (generalized estimating equation regression). Waveform parameters representing vascular resistance were higher in both GLS and GL groups than the HC group; and were correlated with RNFLT and MDlin (P ≤ 0.05). Conclusions: The shape of the systemic pulsatile waveform differs in individuals with GL/GLS suspects, compared to HC eyes. Blood pressure changes more rapidly in individuals with GL, which suggests higher arterial stiffness.

Biomechanic, proteomic and miRNA transcriptional changes in the trabecular meshwork of primates injected with intravitreal triamcinolone.

Although biomechanical changes of the trabecular meshwork (TM) are important to the pathogenesis of glucocorticoids-induced ocular hypertension (GC-OHT), there is a knowledge gap in the underlying molecular mechanisms of the development of it. In this study, we performed intravitreal triamcinolone injection (IVTA) in one eye of 3 rhesus macaques. Following IVTA, we assessed TM stiffness using atomic force microscopy and investigated changes in proteomic and miRNA expression profiles. One of 3 macaques developed GC-OHT with a difference in intraocular pressure of 4.2 mmHg and a stiffer TM with a mean increase in elastic moduli of 0.60 kPa versus the non-injected control eye. In the IVTA-treated eyes, proteins associated with extracellular matrix remodeling, cytoskeletal rearrangement, and mitochondrial oxidoreductation were significantly upregulated. The significantly upregulated miR-29b and downregulated miR-335-5p post-IVTA supported the role of oxidative stress and mitophagy in the GC-mediated biomechanical changes in TM, respectively. The significant upregulation of miR-15/16 cluster post-IVTA may indicate a resultant TM cell apoptosis contributing to the increase in outflow resistance. Despite the small sample size, these results expand our knowledge of GC-mediated responses in the TM and furthermore, may help explain steroid responsiveness in clinical settings.

Longitudinal evaluation of morphological, functional and vascular alterations in a rat model of experimental glaucoma.

Glaucoma, the leading cause of irreversible blindness worldwide, is a neurodegenerative disease characterized by chronic axonal damages and progressive loss of retinal ganglion cells, with increased intraocular pressure (IOP) as the primary risk factor. While current treatments focus solely on reducing IOP, understanding glaucoma through experimental models is essential for developing new therapeutic strategies and biomarkers for early diagnosis. Our research group developed an ocular hypertension rat model based on limbal plexus cautery, which provides significant glaucomatous neurodegeneration up to four weeks after injury. We evaluated long-term morphological, functional, and vascular alterations in this model. Our results showed that transient ocular hypertension, lasting approximately one week, can lead to progressive increase in optic nerve cupping and retinal ganglion cells loss. Remarkably, the pressure insult caused several vascular changes, such as arteriolar and venular thinning, and permanent choroidal vascular swelling. This study provides evidence of the longitudinal effects of a pressure insult on retinal structure and function using clinical modalities and techniques. The multifactorial changes reported in this model resemble the complex retinal ganglion cell degeneration found in glaucoma patients, and therefore may also provide a unique tool for the development of novel interventions to either halt or slow down disease progression.

Predicting Glaucoma Before Onset Using a Large Language Model Chatbot.

PURPOSE: To investigate the capability of ChatGPT for forecasting the conversion from ocular hypertension (OHT) to glaucoma based on the Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective case-control study. PARTICIPANTS: A total of 3008 eyes of 1504 subjects from the OHTS were included in the study. METHODS: We selected demographic, clinical, ocular, optic nerve head, and visual field (VF) parameters 1 year before glaucoma development from the OHTS participants. Subsequently, we developed queries by converting tabular parameters into textual format based on both eyes of all participants. We used the ChatGPT application program interface (API) to automatically perform ChatGPT prompting for all subjects. We then investigated whether ChatGPT can accurately forecast conversion from OHT to glaucoma based on various objective metrics. MAIN OUTCOME MEASURE: Accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and weighted F1 score. RESULTS: ChatGPT4.0 demonstrated an accuracy of 75%, AUC of 0.67, sensitivity of 56%, specificity of 78%, and weighted F1 score of 0.77 in predicting conversion to glaucoma 1 year before onset. ChatGPT3.5 provided an accuracy of 61%, AUC of 0.62, sensitivity of 64%, specificity of 59%, and weighted F1 score of 0.63 in predicting conversion to glaucoma 1 year before onset. CONCLUSIONS: The performance of ChatGPT4.0 in forecasting development of glaucoma 1 year before onset was reasonable. The overall performance of ChatGPT4.0 was consistently higher than ChatGPT3.5. Large language models (LLMs) hold great promise for augmenting glaucoma research capabilities and enhancing clinical care. Future efforts in creating ophthalmology-specific LLMs that leverage multimodal data in combination with active learning may lead to more useful integration with clinical practice and deserve further investigations.

Managing a rare case of familial Radius Maumenee syndrome.

Idiopathic elevated episcleral venous pressure (IEEVP), also known as Radius-Maumenee syndrome, is a rare condition which can pose a diagnostic and management challenge for clinicians. Filtration surgery is often required due to medical treatment proving ineffective. We describe to our knowledge the first case of familial Radius-Maumenee syndrome in a father and son duo. Primary management using a glaucoma drainage device is an effective option in addition to being a safer alternative when compared to trabeculectomy. Patients will require rigorous monitoring in the post-operative period to reduce the risk of complications.

Effects of intraocular pressure change on intraocular lens power calculation in primary open-angle glaucoma and ocular hypertension.

This study aimed to assess the effect of intraocular pressure (IOP) changes on biometry and intraocular lens (IOL) power calculation in patients diagnosed with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). This prospective non-randomized cohort study enrolled patients with diagnosed POAG and OHT, presenting with IOP levels exceeding 25 mmHg. Thai Clinical Trials Registry number was TCTR20180912007. Optical biometry, encompassing measurements such as corneal thickness (CCT), keratometry, anterior chamber depth (ACD), and axial length, was conducted before and after IOP reduction. The IOL power was also determined using the SRK/T formula. The main outcomes measured were alterations in biometry and IOL power. Correlations between IOP, biometric parameters, and IOL power were analyzed. In total, 28 eyes were included in the study, with a mean patient age of 65.71±10.2 years. After IOP reduction, all biometric parameters, except CCT and ACD, exhibited a decrease without reaching statistical significance (all p>0.05). Meanwhile, IOL power showed a slight increase of 0.214±0.42 diopters (P = 0.035). The correlation between IOP and biometric parameters was found to be weak. However, there was a moderate correlation between IOP and IOL power (r2 = 0.267). Notably, IOL power tended to increase by more than 0.5 diopters when IOP decreased by more than 10 mmHg (p < 0.001). In conclusion, changes in IOP among patients with POAG and OHT do not significantly impact biometry and IOL power calculations. Nonetheless, it may be prudent to consider a slight adjustment in IOL power when IOP is lowered by more than 10 mmHg.