[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.

Antioxidant effect of gallic acid on retinal ganglion cells in glaucoma model.

To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p < 0.05). DHE staining showed that ROS content in the simple high IOP group was significantly increased compared with the normal control group, and ROS content was significantly decreased after the application of gallic acid (p < 0.05). Immunofluorescence staining with Brn-3a antibody confirmed that the number of RGCs was significantly reduced in the simple high IOP group compared with the normal control group, whereas after application of gallic acid, the number of RGCs was significantly more in the gallic acid group than in the simple high IOP group (p < 0.05). Western Blot and q-PCR confirmed that hypoxia-inducing factor 1α (HIF-1α) protein content and transcription level were significantly increased in the retinal tissue of the simple high IOP group, and gallic acid could inhibit HIF-1α protein content (p < 0.05) and reduce transcription factor level (p < 0.05). Gallic acid exerts a protective effect on RGC by inhibiting oxidative stress in rats with acute IOP elevation.

[Standardizing the diagnosis and treatment of ocular hypertension based on evidence-based medicine].

Ocular hypertension (OHT) refers to a condition in which the intraocular pressure increases without causing glaucomatous optic nerve changes or visual field damage. The incidence rate of OHT in people over 40 years old is as high as 4% to 10%. According to the OHT Treatment Study (OHTS), the incidence of primary open angle glaucoma (POAG) among OHT patients is increasing year by year, so it is necessary to conduct long-term follow-up. This article elaborates on five major risk factors for the progression of OHT to POAG: age, intraocular pressure, vertical cup-disc ratio, pattern standard deviation of visual field, and central corneal thickness. It also summarizes other potential risk factors, such as long-term fluctuations in intraocular pressure, asymmetry of intraocular pressure and visual field between the two eyes, structural phenotypes of the optic disk, and optic disk hemorrhage. Predicting the risk of OHT progression to POAG based on risk factors, patients with different risk levels require different timing for treatment initiation and follow-up intervals. Those with higher risks should start preventive treatment earlier and have shorter follow-up intervals. Both drug therapy and selective laser trabeculoplasty can serve as initial treatment options for OHT. Combining evidence-based medicine research and individualized evaluation of treatment can enhance the clinical diagnosis and treatment level of OHT.

Repeatability of a Virtual Reality Headset Perimeter in Glaucoma and Ocular Hypertensive Patients.

Purpose: The VisuALL S is an automated, static threshold, virtual reality-based perimeter for mobile evaluation of the visual field. We examined same-day and 3-month repeatability. Methods: Adult participants with a diagnosis of glaucoma or ocular hypertension underwent two VisuALL 24-2 Normal T- Full threshold strategy tests at baseline and one additional exam at 3 months for each eligible eye. Spearman, intraclass correlation coefficients (ICCs), and Bland-Altman plots were used to assess the correlation of individual point sensitivities and mean deviation (MD) among three tests. Results: Eighty-eight eyes (44 participants) were included. Average age was 68.1 ± 14.3 years, and 60.7% were male. VisuALL MD was highly correlated between tests (intravisit: r = 0.89, intervisit: r = 0.82; P < 0.001 for both). Bland-Altman analysis showed an average difference in intravisit MD of -0.67 dB (95% confidence interval [CI], -6.04 to 4.71 dB) and -0.15 dB (95% CI, -8.04 to 7.73 dB) for intervisit exams. Eight-five percent of pointwise intravisit ICCs were above 0.75 (range, 0.63 to 0.93), and 65% of pointwise intervisit ICCs were above 0.75 (range, 0.55 to 0.91). Conclusions: VisuALL demonstrated high correlation of MD between tests and good repeatability for individual point sensitivities among three tests in 3 months, except at the points around the blind spot and superiorly. Translational Relevance: The preliminary reproducibility results for VisuALL are encouraging. Its portable design makes it a potentially useful tool for patients with glaucoma, enabling more frequent assessments both at home and in clinical settings.

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.

Development and characterization of a chronic high intraocular pressure model in New Zealand white rabbits for glaucoma research.

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).

[Minoxidil-induced ophthalmic hypertension (case report)]. / Indutsirovannaya minoksidilom oftal'mogipertenziya (klinicheskoe nablyudenie).

This article presents a case of a 31-year-old male patient who presented to the outpatient department of the Krasnov Research Institute of Eye Diseases with complaints of diplopia and increased intraocular pressure (IOP) up to 30 mm Hg. The patient had been using minoxidil topically for androgenic alopecia for 8 years. On examination, mild swelling of the bulbar conjunctiva in the upper fornix was revealed; optical coherence tomography showed thinning of the ganglion cell layer, most likely due to moderate myopia. The patient responded well to discontinuation of minoxidil and topical therapy with prostaglandin analogues. After 4 months, an attempt was made to replace topical hypotensive therapy with carbonic anhydrase inhibitors, but the previous hypotensive regimen had to be resumed due to an increase in IOP. During 10 months of observation, no signs of progression were detected according to optical coherence tomography and static perimetry.

Rate of Initial Optic Nerve Head Capillary Density Loss and Risk of Visual Field Progression.

Importance: Rapid initial optic nerve head capillary density loss may be used to assess the risk of glaucoma visual field progression. Objective: To investigate the association between the rate of initial optic nerve head capillary density loss from optical coherence tomography angiography (OCTA) and visual field progression. Design, Setting, Participants: This was a retrospective study of a longitudinal cohort at a glaucoma referral center. A total of 167 eyes (96 with primary open-angle glaucoma and 71 with glaucoma suspect) of 109 patients were monitored for a mean (SD) of 5.7 (1.4) years from January 2015 to December 2022. Data analysis was undertaken in April 2023. Main Outcomes and Measures: The rates of initial capillary density and average retinal nerve fiber layer loss were calculated from the first 3 optic nerve head OCTA and OCT scans, respectively, during the initial follow-up (mean [SD], 2.0 [1.0] years). Based on the median rate, eyes were categorized into fast and slow progressor groups. The association between initial capillary density change or retinal nerve fiber layer thinning and visual field progression was evaluated using linear-mixed and time-varying Cox models. Results: A total of 167 eyes of 109 patients (mean [SD] age, 69.0 [11.1] years; 56 [51.4%] female and 53 [48.6%] male) were assessed. Eighty-three eyes were slow OCTA progressors, while 84 eyes were fast with mean capillary density loss of -0.45% per year and -1.17% per year, respectively (mean difference, -0.72%/year; 95% CI,-0.84 to -0.60; P < .001). Similarly, 83 eyes were slow OCT progressors, while 84 eyes were fast with mean retinal nerve fiber layer thinning of -0.09 µm per year and -0.60 µm per year, respectively (mean difference, -0.51 µm/year; 95% CI,-0.59 to -0.43; P < .001). The fast OCTA and OCT progressors were associated with more rapid visual field loss (mean difference, -0.18 dB/year; 95% CI,-0.30 to -0.06; P = .004 and -0.17 dB/year; 95% CI,-0.29 to -0.06; P = .002, respectively). Fast OCTA progressing eyes were more likely to have visual field progression (hazard ratio, 1.96; 95% CI, 1.04-3.69; P = .04). Seventeen of 52 eyes (32.7%; 95% CI, 32.5-32.8) with fast OCTA and OCT progression developed subsequent visual field likely progression. Conclusion and Relevance: Rapid initial optic nerve head capillary density loss from OCTA was associated with a faster rate of visual field progression and a doubling of the risk of developing event progression in this study. These findings may support clinical use of OCTA and OCT optic nerve head measurements for risk assessment of glaucoma progression.

Pilot study comparing a new virtual reality-based visual field test to standard perimetry in children.

PURPOSE: To assess the feasibility and performance of Vivid Vision Perimetry (VVP), a new virtual reality (VR)-based visual field platform. METHODS: Children 7-18 years of age with visual acuity of 20/80 or better undergoing Humphrey visual field (HVF) testing were recruited to perform VVP, a VR-based test that uses suprathreshold stimuli to test 54 field locations and calculates a fraction seen score. Pearson correlation coefficients were calculated to evaluate correlation between HVF mean sensitivity and VVP mean fraction seen scores. Participants were surveyed regarding their experience. RESULTS: A total of 37 eyes of 23 participants (average age, 12.9 ± 3.1 years; 48% female) were included. All participants successfully completed VVP testing. Diagnoses included glaucoma (12), glaucoma suspect (7), steroid-induced ocular hypertension (3), and craniopharyngioma (1). Sixteen participants had prior HVF experience, and none had prior VVP experience, although 7 had previously used VR. Of the 23 HVF tests performed, 9 (39%) were unreliable due to fixation losses, false positives, or false negatives. Similarly, 35% of VVP tests were unreliable (as defined by accuracy of blind spot detection). Excluding unreliable HVF tests, the correlation between HVF average mean sensitivity and VVP mean fraction seen score was 0.48 (P = 0.02; 95% CI, 0.09-0.74). When asked about preference for the VVP or HVF examination, all participants favored the VVP, and 70% were "very satisfied" with VVP. CONCLUSIONS: In our cohort of 23 pediatric subjects, VVP proved to be a clinically feasible VR-based visual field testing, which was uniformly preferred over HVF.

Priorities for health outcomes in glaucoma in an ethnically diverse UK cohort: an observational study.

OBJECTIVES: To assess whether patients from minority ethnic groups have different perceptions about the quality-of-life outcomes that matter most to them. DESIGN: Cross-sectional observational study. SETTING: High volume eye centres serving the most ethnically diverse region in the UK, recruiting from July 2021 to February 2022. PARTICIPANTS: 511 patients with primary open-angle glaucoma and the predisease state of ocular hypertension. MAIN OUTCOME MEASURES: The main outcome was participants' self-reported priorities for health outcomes. RESULTS: Participants fell into one of four clusters with differing priorities for health outcomes, namely: (1) vision, (2) drop freedom, (3) intraocular pressure and (4) one-time treatment. Ethnicity was the strongest determinant of cluster membership after adjusting for potential confounders. Compared with white patients prioritising vision alone, the OR for black/black British patients was 7.31 (95% CI 3.43 to 15.57, p<0.001) for prioritising drop freedom; 5.95 (2.91 to 12.16, p<0.001) for intraocular pressure; and 2.99 (1.44 to 6.18, p=0.003) for one-time treatment. For Asian/Asian British patients, the OR was 3.17 (1.12 to 8.96, p=0.030) for prioritising intraocular pressure as highly as vision. Other ethnic minority groups also had higher ORs for prioritising health outcomes other than vision alone: 4.50 (1.03 to 19.63, p=0.045) for drop freedom and 5.37 (1.47 to 19.60, p=0.011) for intraocular pressure. CONCLUSIONS: Ethnicity is strongly associated with differing perceptions about the health outcomes that matter. An individualised and ethnically inclusive approach is needed when selecting and evaluating treatments in clinical and research settings.

Profiling IOP-Responsive Genes in the Trabecular Meshwork and Optic Nerve Head in a Rat Model of Controlled Elevation of Intraocular Pressure.

Purpose: The rat controlled elevation of intraocular pressure (CEI) model allows study of in vivo responses to short-term exposure to defined intraocular pressures (IOP). In this study, we used NanoString technology to investigate in vivo IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals. Methods: Male and female rats (N = 35) were subjected to CEI for 8 hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5× IOP (CEI-50). Naïve animals that received no anesthesia or surgical interventions served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA was isolated, and samples were analyzed with a NanoString panel containing 770 genes. Postprocessing, raw count data were uploaded to ROSALIND for differential gene expression analyses. Results: For the TM, 45 IOP-related genes were significant in the CEI-50 versus CEI-20 and CEI-50 versus naïve comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and transforming growth factor beta (TGFß) pathways to be the most up- and downregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. For ONH, 22 significantly differentially regulated genes were identified in the CEI-50 versus naïve comparison. Pathway analysis identified defense response and immune response as two significantly upregulated biological process pathways. Conclusions: This study demonstrated the ability to assay short-term IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGFß pathway genes suggests that TM responses may reduce TGFß-induced extracellular matrix synthesis. For ONH, the initial response to short-term elevated IOP may be protective.

[Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs]. / Mestnoe primenenie gipotenzivnykh preparatov s tsel'yu profilaktiki povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii anti-VEGF-preparatov.

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.

Reverse pupillary block with pigment dispersion and elevated intraocular pressure following bilateral phakic intraocular lens implantation.

The authors describe a case of reverse pupillary block with pigment dispersion following sequential phakic intraocular lens (pIOL) implantation for high myopia, in a young female patient. The intraocular pressure (IOP) elevation began 3 weeks postoperatively, for which Nd-YAG laser peripheral iridotomies (PIs) were attempted elsewhere. Despite maximum medical therapy, the IOP was uncontrolled. She was referred to our institute for further management. Examination showed anteriorly displaced iris-pIOL diaphragm, iris pigment dispersion and raised IOP. The PIs were incomplete. Based on clinical evaluation and investigations, we concluded that the excess area of contact of the posterior iris over the pIOL caused a reverse pupillary block and pigment dispersion. The IOPs were controlled by repeating laser iridotomies and with medical therapy. Subsequently, the patient developed a low lens vault leading to bilateral cataract. Sequential explantation of the pIOL along with cataract extraction was performed and her vision was restored.

The Robust Lamina Cribrosa Vasculature: Perfusion and Oxygenation Under Elevated Intraocular Pressure.

Purpose: Elevated intraocular pressure (IOP) is thought to cause lamina cribrosa (LC) blood vessel distortions and potentially collapse, adversely affecting LC hemodynamics, reducing oxygenation, and triggering, or contributing to, glaucomatous neuropathy. We assessed the robustness of LC perfusion and oxygenation to vessel collapses. Methods: From histology, we reconstructed three-dimensional eye-specific LC vessel networks of two healthy monkey eyes. We used numerical simulations to estimate LC perfusion and from this the oxygenation. We then evaluated the effects of collapsing a fraction of LC vessels (0%-36%). The collapsed vessels were selected through three scenarios: stochastic (collapse randomly), systematic (collapse strictly by the magnitude of local experimentally determined IOP-induced compression), and mixed (a combination of stochastic and systematic). Results: LC blood flow decreased linearly as vessels collapsed-faster for stochastic and mixed scenarios and slower for the systematic one. LC regions suffering severe hypoxia (oxygen <8 mm Hg) increased proportionally to the collapsed vessels in the systematic scenario. For the stochastic and mixed scenarios, severe hypoxia did not occur until 15% of vessels collapsed. Some LC regions had higher perfusion and oxygenation as vessels collapsed elsewhere. Some severely hypoxic regions maintained normal blood flow. Results were equivalent for both networks and patterns of experimental IOP-induced compression. Conclusions: LC blood flow was sensitive to distributed vessel collapses (stochastic and mixed) and moderately vulnerable to clustered collapses (systematic). Conversely, LC oxygenation was robust to distributed vessel collapses and sensitive to clustered collapses. Locally normal flow does not imply adequate oxygenation. The actual nature of IOP-induced vessel collapse remains unknown.

NADPH and NAC synergistically inhibits chronic ocular hypertension-induced neurodegeneration and neuroinflammation through regulating p38/MAPK pathway and peroxidation.

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients. We constructed a modified chronic ocular hypertensive rat model and an oxygen-glucose deprivation (OGD) cell model. After applying NADPH and N-acetylcysteine (NAC), a precursor to cysteine, the rate-limiting substrate in GSH biosynthesis, to cells, apoptosis, axonal damage and peroxidation were reduced in the RGCs of the NAC group and p-p38 levels were decreased in the RGCs of the NADPH group, while in stimulated Müller cells cultured individually or cocultured with RGCs, gliosis and p38/MAPK, rather than JNK/MAPK, activation were inhibited. The results were more synergistic in the rat model, where either NADPH or NAC showed crossover effects on inhibiting peroxidation and p38/MAPK pathway activation. Moreover, the combination of NADPH and NAC ameliorated RGC electrophysiological function and prevented Müller cell gliosis to the greatest extent. These data illustrated conjoined mechanisms in glaucomatous RGC injury and Müller cell gliosis and suggested that NADPH and NAC collaborate as a neuroprotective and anti-inflammatory combination treatment for glaucoma and other underlying human neurodegenerative diseases.

A Comparative Study on Efficacy of Intraocular Pressure Lowering of Two Fixed-Dose Antiglaucoma Drug Combination Brinzolamide-Brimonidine Versus Latanoprost-Timolol in Primary Open-Angle Glaucoma and Ocular Hypertension.

Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.

Factors Associated With Visual Field Testing Reliability in Children With Glaucoma or Suspected Glaucoma.

PURPOSE: To evaluate Humphrey Visual Field (HVF) test reliability and its associated risk factors in children with glaucoma or glaucoma suspect. DESIGN: Retrospective cohort study. METHODS: None. SETTING: Single-center childhood glaucoma clinic. PATIENT POPULATION: One hundred thirty-six patients aged ≤18 years with glaucoma/glaucoma suspect, and least 1 completed 24 to 2 HVF test between 2018 and 2023. OBSERVATION PROCEDURE: Demographic and clinical characteristics including age, primary language, visual acuity (VA), and glaucoma diagnosis were extracted from electronic health records. MAIN OUTCOME MEASURES: HVF 24 to 2 testing metrics, including FP, FN, and FL. Tests were defined as reliable using manufacturer guidelines of ≤33% FP, ≤33% FN, and ≤20% FL. For each patient, a reliability score was calculated as the percentage of reliable tests among all tests completed. A multivariable logistic regression model was used to determine factors associated with test-level reliability (yes/no). A multivariable linear regression model was used to determine factors associated with patient-level reliability score. RESULTS: Among 634 HVFs from 136 patients (Mean ± SD age at first test 12.0 ± 3.2 years, 47.8% female), 51.3% were reliable. Older age, better baseline VA, and English as primary language were associated with greater odds of test-level reliability (P < .04). Mean ± SD patient-level reliability score was 51.7 ± 38.1%. Older age at first clinic visit, better baseline VA, and English as primary language were associated with higher reliability scores (all P < .02), and number of prior VF tests was not (P = .56). CONCLUSIONS: Younger age, worse visual acuity, and non-English as primary language were associated with decreased reliability and should be considered when interpreting VF testing in children. A significant learning effect was not observed with repeated testing.

Understanding the treatment paradigm and the sequencing of antiglaucoma fixed-dose combinations in a tertiary center in South India.

PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. RESULTS: Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta-blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with ß-blockers being the most consistent one. CONCLUSION: This study is a fairly large study with a minimum of a 5-year follow-up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time.

Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway.

BACKGROUND: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat. METHODS: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study. RESULTS: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst. CONCLUSIONS: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.