Ocular Hypertension Research Articles

Serous Choroidal Detachment Associated with Suspected Contralateral Cavernous Sinus Thrombosis.

To describe a case of choroidal detachment (CD) secondary to cavernous sinus thrombosis (CST). Case report. A 73-year-old male with a history of primary open angle glaucoma and pseudophakia presented with retrobulbar pain, blurred vision, and diplopia of the right eye. Exam revealed severe non-hemorrhagic bullous chemosis, tortuous retinal vessels, and elevated intraocular pressure (IOP) in the right eye. Although computed tomography venography findings initially raised suspicion of a carotid-cavernous fistula (CCF), the diagnostic angiogram showed no such evidence, instead raising concern for cavernous sinus thrombosis (CST). Dilated fundus exam and MRI were notable for multiple serous choroidal detachments in the right eye, which resolved with systemic management of CST and topical steroids. The possibility of choroidal detachment during the clinical course of a CST should be recognized. CST may be related to impaired venous drainage that forces transudate into perivascular spaces and results in choroidal effusion.

Insulin restores retinal ganglion cell functional connectivity and promotes visual recovery in glaucoma.

Dendrite pathology and synaptic loss result in neural circuit dysfunction, a common feature of neurodegenerative diseases. There is a lack of strategies that target dendritic and synaptic regeneration to promote neurorecovery. We show that daily human recombinant insulin eye drops stimulate retinal ganglion cell (RGC) dendrite and synapse regeneration during ocular hypertension, a risk factor to develop glaucoma. We demonstrate that the ribosomal protein p70S6 kinase (S6K) is essential for insulin-dependent dendritic regrowth. Furthermore, S6K phosphorylation of the stress-activated protein kinase-interacting protein 1 (SIN1), a link between the mammalian target of rapamycin complexes 1 and 2 (mTORC1/2), is required for insulin-induced dendritic regeneration. Using two-photon microscopy live retinal imaging, we show that insulin rescues single-RGC light-evoked calcium (Ca2+) dynamics. We further demonstrate that insulin enhances neuronal survival and retina-brain connectivity leading to improved optomotor reflex-elicited behaviors. Our data support that insulin is a compelling pro-regenerative strategy with potential clinical implications for the treatment and management of glaucoma.

Glaucoma and the ocular renin-angiotensin-aldosterone system: Update on molecular signalling and treatment perspectives

Glaucoma, a leading cause of blindness worldwide, encompasses a group of pathological conditions affecting the optic nerve and is characterized by progressive retinal ganglion cell loss, cupping of the optic nerve head, and distinct visual field defects. While elevated intraocular pressure (IOP) is the main risk factor for glaucoma, many patients do not have elevated IOP. Consequently, other risk factors, such as ocular blood flow abnormalities and immunological factors, have been implicated in its pathophysiology. Traditional therapeutic strategies primarily aim to reduce IOP, but there is growing interest in developing novel treatment approaches to improve disease management and reduce the high rates of severe visual impairment. In this context, targeting the ocular renin-angiotensin-aldosterone system (RAAS) has been found as a potential curative strategy. The RAAS contributes to glaucoma development through key effectors such as prorenin, angiotensin II, and aldosterone. Recent evidence has highlighted the potential of using RAAS modulators to combat glaucoma, yielding encouraging results. Our study aims to explore the molecular pathways linking the ocular RAAS and glaucoma, summarizing recent advances that elucidate the role of the RAAS in triggering oxidative stress, inflammation, and remodelling in the pathogenesis of glaucoma. Additionally, we will present emerging therapeutic approaches that utilize RAAS modulators and antioxidants to slow the progression of glaucoma.

Fabry Disease Rat Model Develops Age- and Sex-Dependent Anterior Segment Ocular Abnormalities.

Fabry disease is an X-linked lysosomal storage disorder that results in multi-systemic renal, cardiovascular, and neuropathological damage, including in the eyes. We evaluated anterior segment ocular abnormalities based on age, sex (male and female), and genotype (wild-type, knockout [KO] male, heterozygous [HET] female, and KO female) in a rat model of Fabry disease. The α-Gal A KO and WT rats were divided into young (6-24 weeks), adult (25-60 weeks), and aged (61+ weeks) groups. Intraocular pressure (IOP) was measured. Eyes were clinically scored for corneal and lens opacity as well as evaluated for corneal epithelial integrity and tear break-up time (TBUT). Anterior chamber depth (ACD) and central corneal thickness (CCT) using anterior segment-optical coherence tomography (AS-OCT). The Fabry rats showed an age-dependent increase in IOP, predominantly in the male genotype. TBUT was decreased in both male and female groups with aging. Epithelial integrity was defective in KO males and HET females with age. However, it was highly compromised in KO females irrespective of age. Corneal and lens opacities were severely affected irrespective of sex or genotype in the aging Fabry rats. AS-OCT quantification of CCT and ACD also demonstrated age-dependent increases but were more pronounced in Fabry versus WT genotypes. Epithelial integrity, corneal, and lens opacities worsened in Fabry rats, whereas IOP and TBUT changes were age-dependent. Similarly, CCT and ACD were age-related but more pronounced in Fabry rats, providing newer insights into the anterior segment ocular abnormalities with age, sex, and genotype in a rat model of Fabry disease.

Mitochondria in Retinal Ganglion Cells: Unraveling the Metabolic Nexus and Oxidative Stress.

This review explored the role of mitochondria in retinal ganglion cells (RGCs), which are essential for visual processing. Mitochondrial dysfunction is a key factor in the pathogenesis of various vision-related disorders, including glaucoma, hereditary optic neuropathy, and age-related macular degeneration. This review highlighted the critical role of mitochondria in RGCs, which provide metabolic support, regulate cellular health, and respond to cellular stress while also producing reactive oxygen species (ROS) that can damage cellular components. Maintaining mitochondrial function is essential for meeting RGCs' high metabolic demands and ensuring redox homeostasis, which is crucial for their proper function and visual health. Oxidative stress, exacerbated by factors like elevated intraocular pressure and environmental factors, contributes to diseases such as glaucoma and age-related vision loss by triggering cellular damage pathways. Strategies targeting mitochondrial function or bolstering antioxidant defenses include mitochondrial-based therapies, gene therapies, and mitochondrial transplantation. These advances can offer potential strategies for addressing mitochondrial dysfunction in the retina, with implications that extend beyond ocular diseases.

Relationship between persistence with topical antiglaucomatous prescription and patient socioeconomic status at a tertiary university hospital in Jerez de la Frontera (Spain).

To study the relationship between socioeconomic status and persistence with topical antiglaucomatous medication. A retrospective epidemiological observational cohort study was conducted with a sample of 1563 patients. The main dependent variable was persistence (medication possession ratio), the independent variable was socioeconomic status (deprivation index). Additional independent variables were used for multivariate analysis: individual health card index, sex, age, pharmacological group, number of eye drops, preservatives, diagnosis and concurrent medications. Bivariate statistical analysis was obtained using non-parametric tests. Logistic regression was used for multivariate analysis. The level of statistical significance was set at p < 0.05. We obtained data showing greater persistence in the groups with a higher socioeconomic level (deprivation index 1 and 2), with medication possession ratio values of 79.97 and 75.30, respectively) as opposed to the groups at lower socioeconomic levels (deprivation index 4 and 5, with medication possession ratio values of 73.75 and 69.85, respectively. Logistic regression corroborated this difference, reaching a significant value (no persistence in deprivation index group 5 versus 1) with OR = 1.62; 95%CI: 1.13-2.31. Additionally, lower persistence was detected in males, under 60 years of age, undergoing treatment with alpha-agonists, and in patients with ocular hypertension. Low socioeconomic status of the patient was significantly associated with decreased persistence with topical antiglaucomatous therapy.

Xen gel stent implant for persistent glaucoma after silicone oil removal.

To evaluate the effectiveness and safety of the XEN-Stent for managing unresponsive to medical therapy secondary glaucoma after silicone oil (SO) removal. This retrospective chart reviewed 12 patients who underwent vitrectomy and SO endotamponade. They experienced intraocular pressure (IOP) elevation after SO removal despite taking the maximum tolerated glaucoma medication. Eleven eyes underwent an XEN-implant, while 1 underwent an XEN-implant with phacoemulsification/IOL implantation. The primary outcome was to achieve success criteria: IOP <18 mmHg and >20% IOP reduction without medication (complete success) or with medication (qualified success) and without a secondary IOP-lowering procedure. IOP, best-corrected visual acuity (BCVA), and the number of glaucoma medications (Glaucoma Medication Score-GMS) were recorded at baseline, 1 day, 1 week, 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months postoperatively. Baseline characteristics included males percentage 66.6%, mean age of 61.8 ± 5.7 years, BCVA 0.69 ± 0.3 logMAR, IOP 30 ± 4.2 mmHg, and GMS 3.1 ± 0.5. There was a significant reduction in IOP by 14 ± 1.9 mmHg and GMS by 0.27 ± 0.6 at M12 compared to baseline (p < 0.01), but no significant change in BCVA (p = 0.21). Complete success dropped to 50% (M3), rising to 75% (M6, M12) after needling. Two patients achieved qualified success at M12. Needling was performed in 6 eyes, with 3 requiring a second procedure. Ex-PRESS was required in 1 eye. One eye experienced hypotony and hyphema, which resolved within a week. XEN implant may be an initial treatment for persistent post SO removal glaucoma with minimal complications. Needling procedures can help maintain or restore surgical success.

Identifying Factors Associated With Fast Visual Field Progression in Patients With Ocular Hypertension Based on Unsupervised Machine Learning.

We developed unsupervised machine learning models to identify different subtypes of patients with ocular hypertension in terms of visual field (VF) progression and discovered 4 subtypes with different trends of VF worsening. We then identified factors associated with fast VF progression. To identify ocular hypertension (OHT) subtypes with different trends of visual field (VF) progression based on unsupervised machine learning and to discover factors associated with fast VF progression. Cross-sectional and longitudinal study. A total of 3133 eyes of 1568 ocular hypertension treatment study (OHTS) participants with at least 5 follow-up VF tests were included in the study. We used a latent class mixed model (LCMM) to identify OHT subtypes using standard automated perimetry (SAP) mean deviation (MD) trajectories. We characterized the subtypes based on demographic, clinical, ocular, and VF factors at the baseline. We then identified factors driving fast VF progression using generalized estimating equation (GEE) and justified findings qualitatively and quantitatively. Rates of SAP mean deviation (MD) change. The LCMM model discovered four clusters (subtypes) of eyes with different trajectories of MD worsening. The number of eyes in clusters were 794 (25%), 1675 (54%), 531 (17%), and 133 (4%). We labeled the clusters as improvers (cluster 1), stables (cluster 2), slow progressors (cluster 3), and fast progressors (cluster 4) based on their mean of MD decline rate, which were 0.08, -0.06, -0.21, and -0.45dB/year, respectively. Eyes with fast VF progression had higher baseline age, intraocular pressure (IOP), pattern standard deviation (PSD) and refractive error (RE), but lower central corneal thickness (CCT). Fast progression was associated with being male, heart disease history, diabetes history, African American race, and stroke history. Unsupervised clustering can objectively identify OHT subtypes including those with fast VF worsening without human expert intervention. Fast VF progression was associated with higher history of stroke, heart disease and diabetes. Fast progressors were more from African American race, males, and had higher incidence of glaucoma conversion. Subtyping can provide guidance for adjusting treatment plans to slow vision loss and improve quality of life of patients with a faster progression course.

Use of a dexamethasone implant to treat macular edema following pars plana vitrectomy and removal of the primary epiretinal membrane.

The purpose of this study was to evaluate the effectiveness and safety of an intravitreal dexamethasone (DEX) implant for the treatment of macular edema (ME) following pars plana vitrectomy (PPV) and removal of the primary epiretinal membrane (ERM) and to assess the impact of the integrity of the ellipsoid zone (EZ) and disorganization of the retinal inner layer (DRIL) grade on visual and anatomical outcomes. Forty-two pseudophakic patients who developed ME following PPV and removal of the primary stage 2-3 ERM were included. Patients were divided into two groups when ME was diagnosed via spectral domain optic coherence tomography (SD-OCT). In the DEX group (n = 22), DEX was implanted for the treatment of ME. In the control group (n = 20), only observation was conducted, without any treatment. The best-corrected visual acuity (BCVA) and macular thickness (MT) of the two groups were compared at baseline and 1, 6, and 12months after DEX implantation. The effects of OCT parameters such as EZ integrity and DRIL grade were also evaluated in terms of decreases in MT and increases in VA in the treatment of ME with DEX implantation. Intraocular pressure (IOP), number of DEX implantations and adverse effects were also recorded. While a statistically significant increase in the mean BCVA was observed in the DEX group (p < 0.001 at months 1, 6, and 12, respectively), no such increase was detected in the control group (p = 0.169, p = 0.065, and p = 0.058 at months 1, 6 and 12, respectively) compared with the baseline. A statistically significant decrease in the mean MT was observed in the DEX group (p < 0.001 at months 1, 6, and 12); however, no significant difference was observed in the control group (p = 0.081, p = 0.065, and p = 0.054 at months 1, 6 and 12, respectively) compared with the baseline. Significant differences were found between the two groups in terms of the increase in BCVA (p < 0.01) and decrease in MT (p < 0.01) at all visits, with the outcomes being more favorable in the DEX group. A statistically significant relationship was found between the increase in VA and EZ integrity and DRIL grade in both groups. Ten patients (45.4%) received two injections of DEX during the follow-up. An increase in IOP was observed in five patients (22.7%) who were treated with topical antiglaucomatous drops. No significant side effects were observed. DEX implantation was found to be effective and safe for the treatment of ME following PPV and primary ERM removal, although some eyes may require repeated injections to achieve visual and anatomical success. Additionally, a relationship was found between EZ integrity, DRIL grade and visual-anatomical outcomes.

Intraocular Pressure Measurements in Standing, Sitting, Prone, and Supine Positions.

In this study, intraocular pressure (IOP) was measured in sitting, supine, prone, and standing (ST) positions and again five minutes after standing (ST-5) utilizing a Tono-Pen AVIA in 124 eyes of 62 healthy subjects with ages ranging from 21 to 59 years (mean 30 ± 10 years). In each subject, the average IOP of both eyes was used for the statistical evaluation. The mean IOP difference between the ST and sitting positions was -0.13 ± 1.63 mmHg (p = 0.548); between ST-5 and sitting, it was 0.53 ± 1.24 mmHg (p = 0.001); between supine and sitting, it was 1.30 ± 1.48 mmHg (p < 0.001); between ST and supine, it was -1.43 ± 1.74 mmHg (p < 0.001); between ST-5 and supine, it was -0.77 ± 1.59 mmHg (p < 0.001); between prone and supine, it was 2.24 ± 1.92 mmHg (p < 0.001); between ST and ST-5, it was -0.67 ± 1.84 mmHg (range: -7.5 to 5 mmHg) (p = 0.007); between prone and ST, it was 3.46 ± 2.01 mmHg (p < 0.001); between ST-5 and prone, it was -2.46 ± 1.67 mmHg (p < 0.001); and between sitting and prone, it was -3.22 ± 1.56 mmHg (p < 0.001). The results show a significant IOP increase in the ST-5 position, suggesting that such measurements need to be performed in an attempt to explain the progression of glaucoma in apparently normal-tension patients.

CASE REPORTS: Secondary glaucoma as a late complication of a primary iris stromal cyst

An 18-year-old woman with a congenital iris stromal cyst was referred for sudden-onset increased intraocular pressure (IOP) that did not respond to medical therapy. Ultrasound biomicroscopy demonstrated synechial angle closure from 9:00 to 12:00 in addition to a large cyst occupying much of the inferior angle. After implantation of an Ahmed glaucoma valve, her visual acuity returned to baseline, and IOP normalized. Although primary iris cysts are generally stationary and have rarely been reported to cause ocular complications, secondary glaucoma can present as a rare complication of primary iris cysts. This case highlights the importance of serial examinations to monitor iris cysts and consideration of glaucoma as a late complication.

Anatomic Features of the Lamina Cribrosa and Optic Disc in Ocular Hypertension, Glaucoma and Healthy Eyes.

Central lamina cribrosa thickness (LCT) was found to be higher in eyes with ocular hypertension (OHT) compared with primary open angle glaucoma (POAG) and healthy controls (HCs). To evaluate the anatomic features of lamina cribrosa (LC) and the optic disc (OD) using swept-source optical coherence tomography (OCT) in eyes with OHT. Treatment naive eyes with OHT and POAG and healthy eyes were included. All eyes underwent a complete ophthalmological examination in addition to swept-source OCT of the OD. Anatomic features of LC, including central LCT, LC depth, prelaminar depth (PLD), and prelaminar tissue thickness, were measured manually using the internal caliper function of the OCT device and compared within groups. OD ovality, disc-foveal angle, and OD torsion were measured on colored photographs, using imageJ software. Seventy-one eyes of 37 patients in the OHT group, 41 eyes of 26 patients in the POAG group, and 30 eyes of 30 patients in the HC group were enrolled in the study. Groups were similar in age and sex distribution. Central LCT was significantly higher in the OHT group, compared with HCs (333.8 ± 50.5 vs 304.5 ± 46.3 µm, P = 0.02) and POAG group (286.7 ± 140.4, P = 0.001). PLD and LC depth were both highest in POAG (282.3 ± 145.5 µm and 471.3 ± 195.2 µm), followed by OHT (244.8 ± 30.2 µm and 440.7 ± 18.7 µm) and HCs (170.1 ± 152.6 µm and 412.8 ± 80 µm), only the difference between POAG and HCs in PLD was statistically significant ( P = 0.03). Prelaminar tissue thickness, OD torsion, disc-foveal angle, and disc ovality showed no significant difference. LC was significantly thicker in eyes with OHT, compared with POAG and HCs. This finding may be relevant to optic nerve protection from high intraocular pressure in patients with OHT.

Exploring Methylphenidate-Induced Intraocular Pressure: A Cautionary Tale in Pediatric ADHD Management.

This case report explores the intricate relationship between methylphenidate (MTX) use and increased intraocular pressure (IOP) in a pediatric patient with a preexisting history of eye disease. Despite existing literature presenting cases of IOP elevation linked to MTX, a significant gap remains in understanding nuanced risk factors. This case study used patients' medical records and a comprehensive literature review. A 6-year-old girl with attention deficit hyperactivity disorder and a family history of eye conditions exhibited elevated IOP after 12 days of MTX use, prompting discontinuation. The patient successfully transitioned to atomoxetine with normalized IOP and improved attention duration. Existing cases emphasize the potential link between sympathetic nerve activity and IOP elevation induced by central nervous system stimulants like MTX. Notably, the patient's high hyperopia contributed to the impact of MTX on IOP, suggesting the need for cautious use in susceptible individuals. This case underscores the importance of individualized treatment strategies, particularly in attention deficit hyperactivity disorder patients with family history and additional eye findings, emphasizing safety and comprehensive patient care.

Intraocular Pressure Response to Perceived Stress in Juvenile-Onset Open Angle Glaucoma.

High perceived stress from academic pressure is associated with intraocular pressure (IOP) elevation and reduced fluctuation in juvenile-onset open angle glaucoma patients. Personalized stress assessment and relief strategies may serve as an adjunct therapy in glaucoma. To evaluate the effect of higher perceived stress, resulting from academic pressure, on IOP in juvenile-onset open angle glaucoma (JOAG) patients compared with healthy individuals. The study included 48 university students aged 18-27 years, comprising 24 JOAG patients on antiglaucoma eyedrops and 24 healthy controls. In an examiner-blind pretest-posttest design, participants' IOP was measured weekly using Goldmann tonometry during three follow-up visits at the beginning and end of the academic semester. Perceived Stress Scale (PSS) scores were also evaluated at these 2-time points to capture the contrast in perceived stress between periods of low and high academic pressure. The baseline PSS score at the semester's start was lower in both groups (14.1±1.9 in glaucoma vs. 13.5±2.4 in control) and significantly increased by the end of the semester (29.2±2.1 vs. 28.5±1.3; P <0.001), indicating increased perceived stress. Concurrently, IOP rose from 22.01±5.87 to 25.08±5.84mmHg in the glaucoma group and from 11.36±2.03 to 13.65±2.11mmHg in the control group. Factorial analysis revealed a significant interaction between stress and JOAG ( F(1,94) =15.94, P =0.001), partial η 2 =0.08, with stress having a greater increase on IOP in the glaucoma group (+3.10mmHg) compared with the control group (+2.23mmHg) ( t(94) =4.457, P <0.001). Higher perceived stress significantly increases IOP, especially in JOAG patients, suggesting personalized stress management as a potential adjunct therapy for patients.

Ten-Year Effectiveness and Safety of Trabecular Micro-BypassStentImplantation with Cataract Surgery in Patients with Glaucoma or Ocular Hypertension.

This study evaluated 10-year results of implanting one iStent trabecular micro-bypass stent during cataract surgery in eyes with open-angle glaucoma (OAG) or ocular hypertension. This retrospective, non-randomized study examined 10-year outcomes of iStent trabecular micro-bypass stent implantation with cataract surgery by one surgeon in eyes with OAG [including primary OAG (POAG) and pseudoexfoliative glaucoma (PXG)] or ocular hypertension at a multi-specialty German ophthalmology center. Study visits were conducted preoperatively and at 2.5, 3, 5, and 10years postoperatively; examinations included intraocular pressure (IOP), medications, corrected-distance visual acuity (CDVA), and adverse events. A total of 63 eyes of 45 patients with OAG (n = 60 eyes) or ocular hypertension (n = 3 eyes) and data through 10years were analyzed. Mean preoperative IOP was 18.6 ± 4.4mmHg on 1.83 ± 1.03 mean medications. At study visits through 10years postoperative, mean IOP reduced by 12.9-19.0% (p < 0.005 at all points), and mean medication burden reduced by 37.8-51.4% (p ≤ 0.006 at all points). At 10years postoperatively, 77.8% of eyes had IOP ≤ 18mmHg and 47.6% had IOP ≤ 15mmHg (vs. 50.8% and 25.4% preoperatively, respectively; p = 0.016). One-third (33.3%) of eyes were medication-free vs. 3.2% preoperatively (p < 0.001); 17.5% were on 2-5 medications (vs. 55.6% preoperatively, p = 0.005); and 93.7% of eyes were on the same or fewer medications vs. preoperative. Post-phacoemulsification CDVA improvement was maintained; no filtering surgeries were completed over 10-year follow-up. Significant and safe IOP and medication reductions were observed through 10years after iStent implantation with cataract surgery in patients with OAG or ocular hypertension.

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

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. 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. 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. 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.

GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.

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 TGFβ 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 TGFβ2-induced TM changes and ocular hypertension (OHT). Primary human TM (pHTM) cells and transduced SBE-GTM3 cells were treated with or without Wnt and/or TGFβ 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. We found that the small-molecule Wnt activators (GSK3β inhibitors) (BIO, SB216763, and CHIR99021) activated canonical Wnt signaling in pHTM cells without toxicity at tested concentrations. This activation inhibited TGFβ signaling as well as TGFβ2-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 β-catenin in pHTM cells, which suggested that the cross-inhibition between the TGFβ and Wnt signaling pathways may occur in the nucleus. Using our ex vivo model, we found that CHIR99021 inhibited TGFβ2-induced OHT in perfusion-cultured human eyes. Our results showed that small-molecule Wnt activators have the potential for treating TGFβ signaling-induced OHT in patients with POAG.

Special Commentary: Reporting Clinical Endpoints in Studies of Minimally Invasive Glaucoma Surgery

Minimally invasive glaucoma surgery (MIGS) refers to a group of procedures generally characterized by an ab interno approach, minimal trauma to ocular tissue, moderate efficacy, an excellent safety profile, and rapid recovery. The number of MIGS procedures continues to increase, and their use has become widespread among glaucoma and cataract specialists. Standardization of the methodology and reporting of clinical endpoints in MIGS investigations enhances interpretation and comparison across different studies. The assessment of surgical interventions not only should consider statistical significance, but also whether the outcome is meaningful to patients. Minimal clinically important difference (MCID) is defined as the smallest change in a treatment outcome that is considered beneficial for an individual patient and prompts a change in their clinical management. Expert consensus is an accepted approach to determine the MCID. The American Academy of Ophthalmology's Glaucoma Preferred Practice Pattern® Committee is an expert panel that develops guidelines identifying characteristics and components of quality eye care. The Committee recommends that the cumulative probability of surgical success at 2 years with Kaplan-Meier survival analysis be used as the primary efficacy endpoint in MIGS studies. The Committee suggests that surgical success for standalone MIGS be defined as intraocular pressure (IOP) of 21 mmHg or less and reduced by 20% or more from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The proposed MCID for the cumulative probability of success of standalone MIGS at 2 years is 50%. The panel recommends that surgical success for MIGS combined with cataract extraction with intraocular lens implantation (CE-IOL) be defined as a decrease in glaucoma medical therapy of 1 medication or more from baseline without an increase in IOP or IOP of 21 mmHg or less and reduced by 20% or more from baseline without an increase in glaucoma medications, additional laser or incisional glaucoma surgery, loss of light perception vision, or hypotony. The suggested MCID for the cumulative probability of success for MIGS combined with CE-IOL at 2 years is 65%. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A cross-sectional study on the impact of hemodialysis duration on retinal nerve fiber layer thinning in hemodialysis patients

This study aimed to investigate the relationship between hemodialysis duration (HDD) and retinal nerve fiber layer (RNFL) thickness. A total of 60 patients receiving maintenance hemodialysis and 67 healthy controls were analyzed. Spectral domain optical coherence tomography (SD-OCT) was employed to measure annular RNFL thicknesses. The hemodialysis group exhibited reduced temporal and inferior RNFL thicknesses relative to the control group. In hemodialysis patients, the inferior RNFL thickness was negatively correlated with HDD and positively correlated with intraocular pressure (IOP). Moreover, IOP was positively correlated with HDD. Mediation analysis showed that the negative correlation between HDD and inferior RNFL thickness was mediated by IOP. In conclusion, hemodialysis leads to temporal and inferior RNFL thinning, and the thickness reduction is proportional to hemodialysis duration. However, such changes are not induced by an increase in IOP.

Blocking Air in the Filtering Bleb: Effects on Graft Adhesion After Descemet's Stripping Automated Endothelial Keratoplasty.

To evaluate the outcome of Descemet's stripping automated endothelial keratoplasty (DSAEK) with "blocking air" in the filtering bleb in patients with previous trabeculectomy. In total, 299 eyes in 283 patients who underwent DSAEK were retrospectively reviewed. Endothelial graft adhesion, intraocular pressure (IOP), and air volume in the anterior chamber with (group A) or without (group B) a filtering bleb were compared between the groups. Group A was divided into two subgroups according to the presence (group A1) or absence (group A2) of air in the filtering bleb; the same three factors were compared between the subgroups. The graft detachment rate was significantly higher in group A (14.3%) than in group B (6.5%) (p = 0.04). IOP was significantly lower in group A than in group B before surgery (p = 0.01), at the end of surgery (p = 0.04), at three hours (p < 0.001), and one week postoperatively (p = 0.02). The graft detachment rate did not significantly differ between groups A1 and A2. There were no differences in IOP at each follow-up time, whereas there was a statistically significant increase in IOP from the preoperative measurement to the end of surgery in group A1 (21.0±7.0 mmHg) compared with group A2 (14.2±8.6 mmHg) (p = 0.02). The presence of blocking air in the filtering bleb helps ensure increased IOP during the early postoperative period but had no significant effect on graft detachment rates.