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The main objective of this placebo-controlled, triple-blind, balanced crossover study was to assess the acute effects of phenylcapsaicin (PC) intake (2.5 mg) on intraocular pressure (IOP), ocular perfusion pressure (OPP), and heart rate (HR) during a 30-min cycling task performed at 15% of the individual maximal power. Twenty-two healthy young adults performed the cycling task 45 min after ingesting PC or placebo. IOP was measured with a rebound tonometer before exercise, during cycling (every 6 min), and after 5 and 10 min of recovery. OPP was assessed before and after exercise. HR was monitored throughout the cycling task. We found an acute increase of IOP levels related to PC consumption while cycling (mean difference = 1.91 ± 2.24 mmHg; p =.007, η p 2 =.30), whereas no differences were observed for OPP levels between the PC and placebo conditions (mean difference = 1.33 ± 8.70 mmHg; p =.608). Mean HR values were higher after PC in comparison with placebo intake (mean difference = 3.11 ± 15.87 bpm, p =.019, η p 2 =.24), whereas maximum HR did not differ between both experimental conditions (p =.199). These findings suggest that PC intake before exercise should be avoided when reducing IOP levels is desired (e.g., glaucoma patients or those at risk). Future studies should determine the effects of different ergogenic aids on IOP and OPP levels with other exercise configurations and in the long term. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intraocular pressure (IOP) monitoring in glaucoma management is evolving with novel devices. We investigated the reproducibility of 24 hour profiles on two consecutive days and after 30 days of self-measurements via telemetric IOP monitoring. METHODS: Seven primary patients with open-angle glaucoma previously implanted with a telemetric IOP sensor in one eye underwent automatic measurements throughout 24 hours on two consecutive days (day 1 and day 2). Patients wore an antenna adjacent to the study eye connected to a reader device to record IOP every 5 min. Also, self-measurements in six of seven patients were collected for a period of 30 days. Analysis included calculation of hourly averages to correlate time-pairs of day 1 versus day 2 and the self-measurements vers day 2. RESULTS: The number of IOP measurements per patient ranged between 151 and 268 on day 1, 175 and 268 on day 2 and 19 and 1236 during 30 days of self-measurements. IOP time-pairs of automatic measurements on day 1 and day 2 were significantly correlated at the group level (R=0.83, p

PURPOSE: This study uses deep neural network-generated rim-to-disc area ratio (RADAR) measurements and the disc damage likelihood scale (DDLS) to measure the rate of optic disc rim loss in a large cohort of glaucoma patients. METHODS: A deep neural network was used to calculate RADAR and DDLS for each optic disc photograph (ODP). Patient demographics, diagnosis, intraocular pressure (IOP), and mean deviation (MD) from perimetry were analyzed as risk factors for faster progression of RADAR. Receiver operating characteristic (ROC) curves were used to compare RADAR and DDLS in their utility to distinguish glaucoma from glaucoma suspect (GS) and for detecting glaucoma progression. RESULTS: A total of 13,679 ODPs with evidence of glaucomatous optic nerve damage from 4106 eyes of 2407 patients with glaucoma or GS were included. Of these eyes, 3264 (79.5%) had a diagnosis of glaucoma, and 842 (20.5%) eyes were GS. Mean ± SD baseline RADAR of GS and glaucoma were 0.67 ± 0.13 and 0.57 ± 0.18, respectively (P < 0.001). Older age, greater IOP fluctuation, baseline MD, right eye, and diagnosis of secondary open-angle glaucoma were associated with slope of RADAR. The mean baseline DDLS of GS and glaucoma were 3.78 and 4.39, respectively. Both RADAR and DDLS showed a less steep slope in advanced glaucoma. In glaucoma, the change of RADAR and DDLS correlated with the corresponding change in MD. RADAR and DDLS had a similar ability to discriminate glaucoma from GS and detect disease progression. Area under the ROC curve of RADAR and DDLS was 0.658 and 0.648. CONCLUSIONS: Automated calculation of RADAR and DDLS with a neural network can be used to evaluate the extent and long-term rate of optic disc rim loss and is further evidence of long-term nerve fiber loss in treated patients with glaucoma. TRANSLATIONAL RELEVANCE: Our study provides a large clinic-based experience for RADAR and DDLS measurements in GS and glaucoma with a neural network.

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.

BackgroundTo examine long-term retinal nerve fibre layer thickness (RNFLT) variability and associated clinical factors in African (AD) and European descent (ED) individuals with glaucoma.MethodsThis retrospective cohort study included glaucoma eyes of AD and ED from Diagnostic Innovations in Glaucoma Study/The African Descent and Glaucoma Evaluation Study with ≥4 visits/2 years of follow-up. We calculated optic nerve head RNFLT variability per-examination/visit as the absolute error of its residuals across follow-up. Full, baseline and parsimonious linear-mixed models were fit to evaluate the effects of clinical factors (demographics and ocular characteristics, prior/intervening glaucoma surgeries and cataract extraction (CE), RNFLT thinning rate, scan quality, visit/testing frequency, etc) on RNFLT variability in both races.ResultsThere were 376 and 625 eyes (226 and 349 participants) of AD and ED, and the mean (95% CI) RNFLT variability was 1.62 (1.52, 1.71) µm and 1.42 (1.34, 1.50) µm, respectively (p=0.002). AD and ED had some shared predictors of RNFLT variability, including intraocular pressure fluctuation and scan quality, although the effects varied (p

Background/aimsTo investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma.MethodsA longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics.ResultsFaster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively).ConclusionsSignificant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma.

AIM: We tested the hypothesis that visual field (VF) progression can be predicted with a deep learning model based on longitudinal pairs of optic disc photographs (ODP) acquired at earlier time points during follow-up. METHODS: 3919 eyes (2259 patients) with ≥2 ODPs at least 2 years apart, and ≥5 24-2 VF exams spanning ≥3 years of follow-up were included. Serial VF mean deviation (MD) rates of change were estimated starting at the fifth visit and subsequently by adding visits until final visit. VF progression was defined as a statistically significant negative slope at two consecutive visits and final visit. We built a twin-neural network with ResNet50-backbone. A pair of ODPs acquired up to a year before the VF progression date or the last VF in non-progressing eyes were included as input. Primary outcome measures were area under the receiver operating characteristic curve (AUC) and model accuracy. RESULTS: The average (SD) follow-up time and baseline VF MD were 8.1 (4.8) years and -3.3 (4.9) dB, respectively. VF progression was identified in 761 eyes (19%). The median (IQR) time to progression in progressing eyes was 7.3 (4.5-11.1) years. The AUC and accuracy for predicting VF progression were 0.862 (0.812-0.913) and 80.0% (73.9%-84.6%). When only fast-progressing eyes were considered (MD rate < -1.0 dB/year), AUC increased to 0.926 (0.857-0.994). CONCLUSIONS: A deep learning model can predict subsequent glaucoma progression from longitudinal ODPs with clinically relevant accuracy. This model may be implemented, after validation, for predicting glaucoma progression in the clinical setting.

PurposeTo compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images.MethodsForty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included.ResultsThirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27).ConclusionsIn this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.

PurposeMutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFβ) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFβ signaling ameliorated ASD, supporting a role for the TGFβ pathway in disease pathogenesis. Here, we tested whether altered TGFβ signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice.MethodsTo test the role of TGFβ signaling in glaucoma-relevant phenotypes, we genetically reduced TGFβ signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFβ ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry.ResultsCol4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFβ receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice.ConclusionsOur results suggest that elevated TGFβ signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice.

PURPOSE: To evaluate VEGF-C-induced lymphoproliferation in conjunction with 5-fluorouracil (5-FU) antimetabolite treatment in a rabbit glaucoma filtration surgery (GFS) model. METHODS: Thirty-two rabbits underwent GFS and were assigned to four groups (n = 8 each) defined by subconjunctival drug treatment: (a) VEGF-C combined with 5-FU, (b) 5-FU, (c) VEGF-C, (d) and control. Bleb survival, bleb measurements, and IOP were evaluated over 30 days. At the end, histology and anterior segment OCT were performed on some eyes. mRNA was isolated from the remaining eyes for RT-PCR evaluation of vessel-specific markers (lymphatics, podoplanin and LYVE-1; and blood vessels, CD31). RESULTS: Qualitatively and quantitatively, VEGF-C combined with 5-FU resulted in blebs which were posteriorly longer and wider than the other conditions: vs. 5-FU (P = 0.043 for longer, P = 0.046 for wider), vs. VEGF-C (P

Mutations in myocilin (MYOC) are the leading known genetic cause of primary open-angle glaucoma, responsible for about 4% of all cases. Mutations in MYOC cause a gain-of-function phenotype in which mutant myocilin accumulates in the endoplasmic reticulum (ER) leading to ER stress and trabecular meshwork (TM) cell death. Therefore, knocking out myocilin at the genome level is an ideal strategy to permanently cure the disease. We have previously utilized CRISPR/Cas9 genome editing successfully to target MYOC using adenovirus 5 (Ad5). However, Ad5 is not a suitable vector for clinical use. Here, we sought to determine the efficacy of adeno-associated viruses (AAVs) and lentiviruses (LVs) to target the TM. First, we examined the TM tropism of single-stranded (ss) and self-complimentary (sc) AAV serotypes as well as LV expressing GFP via intravitreal (IVT) and intracameral (IC) injections. We observed that LV_GFP expression was more specific to the TM injected via the IVT route. IC injections of Trp-mutant scAAV2 showed a prominent expression of GFP in the TM. However, robust GFP expression was also observed in the ciliary body and retina. We next constructed lentiviral particles expressing Cas9 and guide RNA (gRNA) targeting MYOC (crMYOC) and transduction of TM cells stably expressing mutant myocilin with LV_crMYOC significantly reduced myocilin accumulation and its associated chronic ER stress. A single IVT injection of LV_crMYOC in Tg-MYOCY437H mice decreased myocilin accumulation in TM and reduced elevated IOP significantly. Together, our data indicates, LV_crMYOC targets MYOC gene editing in TM and rescues a mouse model of myocilin-associated glaucoma.

Purpose of reviewAssessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation.Recent findingsWhile the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression.SummarySmoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies.

To assess safety and ocular hypotensive efficacy of VVN539 ophthalmic solution in a first-in-human study. Multicenter, double-masked, randomized, vehicle-controlled, dose-response, parallel-comparison study. Sixty-eight subjects with ocular hypertension (OHT) or open-angle glaucoma enrolled at 5 private practices. After washout of ocular hypotensive medications as required, the subjects were randomized to receive either VVN539 ophthalmic solution 0.02%, 0.04%, or vehicle once-daily (QD) in the morning (5 days), once-daily in the evening (6 days) and then twice-daily (6 days). Comparison of VVNM539 to its vehicle in mean intraocular pressure (IOP) at each diurnal time point (8:00am, 10:00am, and 4:00pm) at visit 4 (day 7), visit 5 (day 14), and visit 6 (day 21). Mean IOP decreased throughout dosing in the active groups to between 18 and 20 mmHg in both active groups, to between 22 to 23 mmHg in the vehicle group. VVN539 0.04% was statistically superior to vehicle at all 9 diurnal time points (QD AM, QD PM, and twice daily, P ≤ 0.0109). VVN539 0.02% was statistically superior to vehicle at only 6 of 9 diurnal time points (selected QD times and twice daily). The most common ocular treatment-emergent adverse event was conjunctival hyperemia (11 [47.8%], 10 [4.5%], and 1 [4.3%]), followed by ocular hyperemia (3 [13.0%], 5 [22.7%] and 0), respectively. There were no clinically significant changes of note in visual acuity, biomicroscopy, dilated ophthalmoscopy, blood chemistry, hematology, or cardiovascular measures. In conclusion, the results of this initial phase II study indicate that VVN539 ophthalmic solution showed clinically and statistically significant ocular hypertensive activity and was relatively well tolerated for the treatment of subjects with primary open-angle glaucoma or OHT. Additional studies will be required for a more complete evaluation of the utility of VVN539 ophthalmic solution. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background/aimsTo assess the long-term variability of macular optical coherence tomography (OCT)/OCT angiography (OCTA) and visual field (VF) parameters.MethodsHealthy and glaucoma eyes with ≥1-year follow-up were included. 24-2 VF and macular OCT/OCTA parameters, including VF mean deviation (MD), whole-image vessel density (wiVD) and ganglion cell complex thickness (wiGCC) were analysed. Intraclass correlation coefficient (ICC), root mean squared error (RMSE), within-subject test-retest SD (Sw) and test-retest variability were calculated for stable eye cohort (max follow-up=1.5 years). Rates of change and RMSE were evaluated in the extended cohort including all eyes (unlimited follow-up).ResultsFrom a total of 230 eyes (150 participants; age=67.7 years), 86 eyes (37%, 62 participants) were stable. In stable eyes, OCT parameters showed the highest mean (95%) ICC (wiGCC=0.99 (0.99, 0.99)), followed by VF (VF MD=0.91 (0.88, 0.93)) and OCTA (wiVD=0.82 (0.75, 0.87)). RMSE and Sw for VF MD were 0.92 dB and 0.81 dB, respectively, for wiVD were 1.64% and 1.48%, respectively, and for wiGCC, 0.91 µm and 0.78 µm, respectively. The long-term test-rest variability of VF MD, wiVD and wiGCC was 2.2 dB, 4.1% and 2.2 µm, respectively. In the extended cohort (mean follow-up=3.0 years), all parameters had significant rates of change (p

Background/aimsTo evaluate the relationship over time between intraocular pressure (IOP) and the rate of macula whole image vessel density (wiVD) loss and whole image ganglion cell complex (wiGCC) thinning in glaucoma METHODS: From 62 patients in the Diagnostic Innovations in Glaucoma Study, 59 Primary open-angle glaucoma and 27 glaucoma suspect eyes with mean follow-up of 3.2 years were followed. Optical coherence tomography angiography (OCT-A)-based vessel density and OCT-based structural thickness of the same 6×6 mm GCC scan slab were evaluated. Univariable and multivariable linear mixed models were performed for all eyes and also a subset of them in which peak IOP

Glaucoma is one of the major causes of irreversible blindness worldwide. Increased intraocular pressure (IOP) is a key factor in the onset and progression of this disease. The drugs used to treat glaucoma influence a variety of biological targets. Azolopyrimidine derivatives have attracted significant attention as potential agents for the treatment of glaucoma because they presumed to be analogs of adenosine receptor (AR) agonists and antagonists. In this study, a series of novel 3(4)‐alkyl‐[1,2,4]triazolo[1,5‐a]pyrimidin‐7‐amines were synthesized to develop promising ophthalmic hypotensive drugs. The synthesized compounds demonstrated significant hypotensive activity against IOP, which opens new possibilities for glaucoma therapy. [ABSTRACT FROM AUTHOR]

Background: Glaucoma, characterized by a high incidence and significant ocular harm, has been elucidated through various mechanisms. Excessive autophagy leading to the loss of retinal ganglion cells (RGCs) is suggested as one potential cause for visual impairment in glaucoma. Methods: A glaucoma model was established through anterior chamber injection of silicone oil in mice. RTA408 and the positive control tafluprost were administered for intervention. The efficacy was preliminarily assessed by intraocular pressure measurement. HE staining and fluorescent staining were used to assess RGC loss, while fluorescent staining and western blot were employed to evaluate the expression of Nrf2. The role of autophagy in the pathogenesis of glaucoma was investigated by artificially modulating autophagy levels. Results: In glaucomatous mice, RTA408 significantly reduces the apoptosis levels of RGCs and decreases RGC loss. Further investigations reveal a notable upregulation of autophagy levels in glaucomatous mice, with RGC loss being associated with autophagy. RTA408 promotes the expression of Nrf2 and downstream antioxidant molecules, enhancing the antioxidant system while downregulating mitochondrial autophagy levels. This reduces RGC apoptosis and loss, demonstrating a protective effect against glaucoma. Conclusion: Autophagy mediates the occurrence of glaucoma in mice, promoting RGC apoptosis. RTA408 alleviates RGCs damage by inhibiting excessive autophagy in the context of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To evaluate the feasibility and acceptability of self‐tonometry by glaucoma patients using iCare® Home2 (ICH2) and a smartphone application, without healthcare personnel supervision.After downloading a smartphone application, participants learned to handle the ICH2 via an instruction film, measured their intraocular pressure (IOP) and transferred the data to the caregiver via the application. Participants' measurements were compared to healthcare personnel measurements using Goldmann applanation tonometry (GAT). Participants answered questionnaires about their experience of self‐tonometry.Twenty‐eight participants were included in the study and three of them dropped off. There was no statistically significant difference between the last measurements obtained with ICH2 by the participants and the GAT measurements for the right and the left eye, p = 0.781 and p = 0.888 respectively. The inter‐user agreement was good to excellent between the last measurements obtained with ICH2 by the participants and the GAT measurements for the right and the left eye (ICC 0.907 and 0.830 respectively). The overall impression of the participants was very positive, with 92% happy (a lot or completely) with the instruction film and 88% happy (a lot or completely) with the smartphone application. Thirty‐six percent would have preferred to have an instructor by their side.Our study showed the feasibility and acceptability of self‐tonometry with iCare® Home2 and a smartphone application without the supervision of a healthcare provider in a group of motivated glaucoma patients. [ABSTRACT FROM AUTHOR]

In this study, we conducted stress and strain analyses on the eyeball under pressure using the finite element simulation software Ansys. The eyeball model was constructed using SolidWorks, and additionally, it simulates a contact-type tonometer, applying pressure to the eyeball through probe force variations and calculating the pressure changes inside the eyeball. Initially, the cornea, sclera, ciliary body, suspensory ligaments, aqueous humor, and vitreous humor were combined using SolidWorks. Subsequently, the model was imported into Ansys for meshing, boundary setting, and simulation calculation. Finally, the analysis results were extracted using the Ansys postprocessor and the simulated data were validated against actual measurement data to ensure accuracy. Material properties necessary for the eyeball under pressure analyses were configured, with the Mooney-Rivlin hyperelastic material being selected. During compression, the cornea and sclera primarily absorbed the concentrated load after compression. Pressure was applied using a probe to observe variations in stress and strain concerning the applied force and intraocular pressure. Three probe materials (rubber, titanium alloy, and glass) were chosen for comparative simulation analyses. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo investigate the long-term outcomes of XEN-45 implantation for glaucoma secondary to Fuchs uveitis syndrome (FUS), juvenile idiopathic arthritis (JIA)-related anterior uveitis and intermediate uveitis (IU).This retrospective study evaluated 19 eyes with FUS, 10 eyes with JIA, and nine eyes with IU that underwent XEN-45 Gel Stent implantation. The primary outcome measure was 3-year surgical success, defined as a ≥20% reduction in intraocular pressure (IOP), with a target IOP of 6–21 mmHg. Success was considered complete when IOP control was achieved without glaucoma medication or surgery other than needling and qualified when medication and/or incisional bleb revision were allowed for IOP control. The secondary outcome measures included IOP changes and revision and complication rates.The 3-year complete success rate was 49% and 67% in the FUS and IU groups, respectively, both significantly higher than the 20% rate in the JIA group (p = 0.01 and 0.02, respectively, log-rank test). The qualified success rate was also significantly higher in the FUS and IU groups than in the JIA group. Significantly more medications were reintroduced in the JIA group within the first year, and the JIA group did not achieve a significantly lower median IOP at the 2- and 3-year visits, contrary to the FUS and IU groups. The bleb revision and secondary glaucoma surgery rates were similar among all groups.XEN-45 demonstrates a favourable safety and efficacy profile for glaucoma secondary to FUS and IU. However, its efficacy is significantly poor for JIA-related uveitic glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma, a leading cause of blindness due to elevated intraocular pressure (IOP), is managed with medications like latanoprost (LAT), a prostaglandin analogue, to enhance aqueous outflow. Despite the challenge posed by eye anatomy and tear dynamics, effective ocular bioavailability via topical administration remains elusive. This study aims to optimize self-assembled nanomicelles incorporating LAT, an anti-glaucoma drug, belonging to BCS Class II (low solubility and high permeability) via a two-level, two-factor full factorial design, the nanomicelles were formulated via direct dissolution method and validated using design of expert. The optimized nanomicelles exhibited a spherical morphology, with a size of 69 nm and encapsulation efficiency of 77.5%, demonstrating a sustained LAT release over 12 h. In normotensive rabbits, the nanomicelles elicited a substantial reduction in intraocular pressure (IOP) by up to 40% for a duration of three days, that was significantly longer than the IOP-lowering efficacy of XALATAN eye drops (24 h). These findings indicated that self-assembled nanomicelles hold promise for enhancing the ocular bioavailability and extending the therapeutic duration of LAT, while providing the physical stability. [ABSTRACT FROM AUTHOR]

iStent (Glaukos, San Clemente, CA, USA), a minimally invasive glaucoma device, reduces intraocular pressure (IOP) by enhancing aqueous humor outflow when implanted into Schlemm's canal. Although it has demonstrated effectiveness in lowering IOP and slowing glaucoma progression, its applicability to the Taiwanese population, known for a higher incidence of normal‐tension glaucoma (NTG) cases, requires validation. This retrospective case‐control study, conducted from January 2018 to December 2020, aimed to assess the effectiveness of combining first‐generation iStent with phacoemulsification (phaco‐iStent) compared to phacoemulsification alone in Taiwanese patients diagnosed with primary open‐angle glaucoma (POAG) and NTG, involving 71 eyes (iStent group: POAG 16 and NTG 8; control group: POAG 28 and NTG 19). The primary outcomes included changes in IOP and the number of antiglaucoma medications, with subgroup analyses for POAG and NTG. Over the 18‐month follow‐up, the iStent group achieved a significantly greater reduction in antiglaucoma medications compared with the control group (p value = 0.003∼<0.001) without significant IOP rebound. After adjusting for confounding factors, the reduction in the number of antiglaucoma medications with iStent remained significant (β = −0.8, p < 0.001) according to the generalized estimating equation. At 18 months, the iStent group demonstrated higher qualified and complete success rates than the control group (73.3% vs. 16.7%, p value = 0.001% and 53.3% vs. 0%, p value = 0.002, respectively). Notably, the NTG‐iStent subgroup achieved the highest complete success rate (85.7% at 18 months). In conclusion, phaco‐iStent emerges as an effective standalone treatment for Taiwanese patients with POAG and NTG, providing substantial IOP reduction and higher success rates, especially in NTG cases. These findings propose that phaco‐iStent could be a promising intervention for managing POAG and NTG within the Taiwanese population. Trial Registration: ClinicalTrials.gov identifier: NCT06630546. [ABSTRACT FROM AUTHOR]

Purpose Animals Studied Procedures Results Conclusions To determine the load at failure of canine intact cadaveric eyes and to describe the anatomic location and length of the rupture following external compression.Sixty‐six canine cadaveric globes.Globes were subjected to an axial force impacting the cornea or equator using a commercially available mechanical testing unit. Following rupture, eyes were inspected to document the anatomical site and length of rupture.The mean ± SD force necessary to induce scleral rupture was 310 ± 120 N OD and 294 ± 113 N OS. Increasing body weight (OD p = .000015, OS p = .0074) as well as cranial‐to‐caudal (OD p = .000045, OS p = .0075) and medial‐to‐lateral (OD p = .00027, OS p = .0083) globe diameter were associated with a higher force necessary to induce rupture. The median (25%, 75%) length of the scleral rupture was 8.5 (7.0, 11.0) mm OS and 10 (7.0, 12.5) mm OD. The median location was 8.0 (5.0, 10.0) mm posterior to the limbus at the most cranial extent OS and 6.5 (3.3, 10.0) mm OD. Rupture orientation in relation to the limbus was perpendicular (n = 35), parallel (n = 13), or other (n = 16). Globe laterality (i.e., OD or OS), sex, and age did not have a significant influence on the force necessary to induce rupture (p > .05).Following external compression, the canine globe frequently ruptures in a region approximating the equator extending 1 cm posteriorly, which may not be readily apparent on clinical examination. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To investigate clinical characteristics of postoperative supraciliary effusion (SCE) development following gonioscopy‐assisted transluminal trabeculotomy (GATT) in patients with pseudoexfoliation glaucoma (PEXG).In this prospective and observational study, 64 eyes (64 patients) with PEXG were examined with spectral‐domain optical coherence tomography (SD‐OCT) after GATT over a 12‐month follow‐up. Outcomes were surgical success, intraocular pressure (IOP), best‐corrected visual acuity (BCVA), number of antiglaucoma medications (AGM) and complications of the SCE (+) group with those of SCE (−) group.SCE was observed in 39 eyes (60.9%) within the first postoperative week. Probability of complete success was significantly higher in the SCE (+) group than in the SCE (−) group (25.6% vs. 16.0%, p = 0.009). IOP was significantly lower at postoperative first day in the SCE (+) group than in the SCE (−) group (p = 0.04), but it was similar thereafter during follow‐up (p > 0.05). Postoperative BCVA did not show significant difference at the end of the follow‐up (p > 0.05). Postoperative number of AGM was found to be significantly lower in the SCE (+) group compared to the SCE (−) group (p < 0.05). A significant IOP rise was observed after SCE resolution (p = 0.002).Presence of SCE accompanied with significantly lower IOP during the early postoperative period after GATT surgery for PEXG. SCE might have a favourable impact on postoperative AGM use. SCE can easily be examined by SD‐OCT, and be used as a prognostic indicator. [ABSTRACT FROM AUTHOR]

Difluprednate (DFP) (difluoroprednisolone butyrate acetate, or DFBA) ophthalmic emulsion 0.05% (Durezol®) was the first potent corticosteroid to be approved for both postoperative pain and inflammation in 2008. In June 2012, it was approved for the treatment of endogenous anterior uveitis. It is a synthetic difluorinated prednisolone derivative that was originally developed in Japan as a dermatologic ointment. The glucocorticoid binding affinity of its active metabolite was demonstrated to be 56 times stronger than prednisolone. Experimental models showed that it reached the anterior and posterior segments of the eye quickly, via both transcorneal and noncorneal (conjunctiva and sclera) absorption routes. Its clinical applications have been expanded to treat patients with uveitic macular edema and anterior scleritis. Case reports and case series also describe its use in some forms of posterior uveitis and in non-uveitic entities. Elevated intraocular pressure and acceleration of cataract formation are the main concerns with DFP as with all corticosteroids. Because IOP elevation is particularly pronounced in the pediatric age group, IOP is to be closely monitored at every visit in children. High incidence of cataract formation and progression was also documented in children, thus necessitating vigilant follow-up of children on chronic treatment. This review aims to give a comprehensive and up-to-date overview of difluprednate’s pharmacological properties, clinical applications, safety profiles, and alternative delivery methods. [ABSTRACT FROM AUTHOR]

Background: To evaluate the changes of retinal and choroidal microvascular including the superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP), choriocapillaris (CC), and central retinal thickness (CRT) in high myopic eyes after the implantable collamer lens with a central hole (ICL V4c) implantation using optical coherence tomography angiography (OCTA). Methods: This retrospective study included 30 eyes of 30 patients (14 males and 16 females) who underwent ICL V4c implantation in Tianjin Aier Eye Hospital from October 2022 to May 2023. Uncorrected distant visual acuity (UDVA), best corrected distance visual acuity (BDVA), intraocular pressure (IOP), spherical equivalent (SE), axial length (AL), and optical coherence tomography angiography (OCTA) were measured and assessed before surgery, and 1 week, 1 month, and 3 months after surgery. OCTA was used to image and measure several key indicators: the foveal avascular zone (FAZ), vascular density (VD) of the SCP and DCP, blood flow density (BD) of the CC, and CRT. All measurement data were obtained utilizing the instrument's proprietary software, ensuring accuracy and consistency. Results: UDVA were significant improvements at the 1 week, 1 month, and 3 months after ICL V4c implantation surgery. BDVA, FAZ, and CRT maintained stable, however, IOP was higher at 1 week and 3 months post-operation compared to 1-month post-operation. The statistically significant difference was identified within the S3, S7, and S9 of SCP at each time point before and after the surgery (P1 = 0.004; P2 = 0.014; P3 = 0.037). However, paired analyses showed that there was a significant decrease in VD of S3 at 1 week after ICL V4c implantation surgery (P < 0.05), which then returned to preoperative levels by 1 month (P > 0.05), and the increase in VD of the S7 region at 1 month after ICL V4c implantation, which is significant compared to 1 week post-surgery, but not compared to preoperative levels. An overall comparison of the BD of the CC (2 mm) at each time point showed a statistically significant difference (P = 0.029). Conclusion: ICL V4c implantation offers a safe and efficient therapy to the high myopic patients. However, the retinal and choroidal microvascular changes need to be paid attention to in post-ICL implantation patients. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively analyze clinical outcomes of patients with "treatment‐resistant" neovascular age‐related macular degeneration or diabetic macular edema who were switched to intravitreal faricimab injections (IFIs) using a "real‐world" treat‐and‐extend (TAE) protocol. Methods: Seventy‐one eyes from 62 patients receiving antivascular endothelial growth factor injections were evaluated before and after switching to IFI. Demographic and clinical data were collected. Primary endpoints were treatment interval extension and presence of intraretinal or subretinal fluid on spectral‐domain optical coherence tomography (OCT) after switching to IFI. Secondary endpoints included best‐corrected visual acuity, average OCT central subfield thickness, and presence of a pigment epithelium detachment and pigment epithelium detachment height. Results: The average treatment interval after switching to IFI significantly increased from 37.6 ± 10.8 days to 45.2 ± 16.6 days (p = 0.0016). At the last follow‐up, 35% of eyes were able to achieve a fluid‐free status post‐IFI. A chi‐square test of independence validated this finding by showing a significant difference in the OCT findings trending towards less or no fluid on follow‐up (X2 [3, N = 71] = 13.0705; p = 0.0003). The average central subfield thickness decreased from 327.2 ± 89.1 μm to 294.8 ± 86.5 μm (p = 0.0294). Best‐corrected visual acuity, intraocular pressure, pigment epithelium detachment presence, and height had no significant difference after switching to IFI. Conclusions: In "treatment‐resistant" patients receiving anti‐VEGF therapy for neovascular age‐related macular degeneration or diabetic macular edema, switching to IFI in a "real‐world" TAE protocol led to statistically significant improvements in treatment interval and retinal fluid on spectral domain OCT. [ABSTRACT FROM AUTHOR]

The cornea is one of the tissues responsible for covering and protecting the inner structures of the eye. Central corneal thickness (CCT) is defined as the distance between the anterior epithelial surface and the posterior surface of the endothelial layer. This parameter plays a very important role regarding intraocular pressure (IOP) measurement, evaluation of corneal uniformity, selection of a suitable technique for corneal refractive surgery and the planning of surgical procedures to overcome corneal disease. This comprehensive review elucidates the multifaceted factors influencing the central corneal thickness. Recognising the impact of these factors not only enhances our understanding of corneal dynamics but also contributes significantly to the refinement of diagnostic and therapeutic strategies in ophthalmology. [ABSTRACT FROM AUTHOR]

Purpose: Glaucoma is a leading cause of irreversible blindness. Glaucomatous intraocular pressure (IOP) triggers deleterious effects, including gliosis, optic nerve (ON) axonal retraction, neurotrophic factor deprivation, inflammation, and other pathological events, leading to retinal ganglion cell (RGC) loss. Trophic factor impairment enhances RGC apoptosis susceptibility. Neuritin 1 (NRN1), a neurotrophic protein downstream of various neurotrophins, exhibited RGC protection and regeneration in axotomy models. We evaluated human recombinant NRN1's impact on human RGCs cultured in pressurized conditions within the ex vivo translaminar autonomous system to simulate glaucoma pathogenesis. Methods: Human glaucomatous and non-glaucomatous donor eyes were obtained from eye banks according to the Declaration of Helsinki. Initially, we evaluated NRN1and RGC marker expression in glaucoma and non-glaucomatous retina to determine the NRN1 level and its association with RGC loss. Further, we evaluated NRN1's therapeutic potential by treating pressurized human eyes at normal and high IOP for seven days. Retina, ON, and conditioned medium were analyzed for RGC survival (THY1, RBPMS), gliosis (GFAP), apoptosis (CASP3, CASP7), and extracellular matrix deposition (COLIV, FN) by qRT-PCR and western blotting. Paraphenylenediamine staining assessed ON axonal degeneration, whereas ex vivo electroretinogram assessed retinal activity. Results: Glaucomatous retinas exhibited significant reductions in both NRN1 (*p = 0.007, n = 5) and RGC marker expression (*p = 0.04, n = 5). NRN1 treatment reduced gliosis, extracellular matrix deposition, ON degeneration, and increased retinal activity in pressure-perfused eyes. Conclusions: Our study confirms that NRN1 enhances human RGC survival and improves retinal function in degenerative conditions, substantiating it as a promising candidate for rescuing human RGCs from degeneration. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were to compare the body temperatures between pregnant and nonpregnant cats from two sites, lacrimal caruncle temperature (LCT) and rectal temperature (RT), and to compare intraocular pressure (IOP) between pregnant and nonpregnant cats. Animal studied: This study was performed on 13 pregnant and 16 anoestrous cats. Procedures: The gestation period of the pregnant cats ranged from 20 to 45 days. A vaginal smear was also performed to determine the sexual cycles of nonpregnant cats. The IOP was measured using a rebound tonometer. Results: The pregnant cats (38 ± 0.7°C) exhibited a lower RT than the nonpregnant cats (38.5 ± 0.5°C) (p < 0.05). No significant differences existed between the pregnant and nonpregnant groups in the right (R)‐LCT or left (L)‐LCT (p > 0.05). The average LCT temperature measured 32.30 ± 2.23°C in cats. The right (R)‐IOP in pregnant cats (17.69 ± 5.6 mm Hg) was significantly lower than in nonpregnant cats (22.37 ± 5.27 mm Hg) (p < 0.029). Pregnant cats exhibited a significantly lower left (L)‐IOP value (17.69 ± 5.76 mm Hg) compared to nonpregnant cats (23.18 ± 5.55 mm Hg) (p < 0.015). Conclusion: This study presents a preliminary report that documents a noteworthy reduction in RT in pregnant cats (38 ± 0.7°C) as compared to cats in anoestrus. Pregnancy also has an effect on the IOP. It was hypothesised that the hormonal changes induced by pregnancy in cats would have a substantial impact on IOP and RT. Although body temperature can be measured using LCT, RT should still be utilised as the reference measurement site. [ABSTRACT FROM AUTHOR]

Introduction: Glaucoma is the second leading cause of blindness in the world. The only known modifiable risk factor for the onset and progression of glaucoma is Intraocular Pressure (IOP). There are a limited number of studies documenting the IOP-lowering effect of Selective Laser Trabeculoplasty (SLT) in Primary Open Angle Glaucoma (POAG) patients, especially within the North Indian population. Understanding the effect of SLT on IOP reduction in this population is crucial for the proper management of glaucoma patients. Aim: To study the IOP-lowering effect of SLT in North Indian POAG patients (who had not achieved target IOP on two or more antiglaucoma drugs) after a period of six months. Materials and Methods: A hospital-based, single-arm, prepost type of prospective analytical study was conducted at Lady Hardinge Medical College and associated hospitals in New Delhi, India, from January 2021 to June 2022. POAG patients aged 18 years or older, who had not achieved the target IOP while on two or more Antiglaucoma Medications (AGM), were given the option of treatment with SLT. A total of 33 eyes were considered for the study as per sample size calculations. Pre-SLT, IOP was recorded along with other baseline parameters. The SLT procedure was carried out according to the standard protocol. IOP was recorded during follow-ups at one week, one month, three months, and six months. The Friedman test was used to compare IOP values, with a significance level set at 0.05. Spearman correlation was employed to explore the correlation between baseline IOP and the change in IOP at six months. Results: A total of 33 eyes were included in the study. Of these, 28 (84.8%) eyes had advanced glaucoma, while 5 (15.2%) eyes had moderate glaucoma according to International Classification of Diseases, Tenth Revision (ICD-10) staging. Patients were on two or more commonly used AGMs, including prostaglandin analogues, beta blockers, alpha agonists, topical carbonic anhydrase inhibitors, and rho kinase inhibitors. The mean number of topical AGMs that patients were using was 3.03. The number and type of AGMs for each patient remained consistent pre and post-SLT throughout the study period. The mean IOP (baseline) was 16.39±2.73 mmHg, and after six months, the mean IOP was 13.86±1.99 mmHg. The mean IOP reduced by 2.53 mm Hg (15.44%). There was a strong negative correlation between baseline IOP and the change in IOP at six months, which was statistically significant (rho=-0.78, p-value<0.001). Conclusion: The present study indicates that SLT can be considered an adjunctive treatment for lowering IOP in North Indian POAG patients. A strong negative correlation was found between baseline IOP and IOP at six months post-SLT, suggesting that a higher reduction can be expected in patients with elevated baseline IOP. [ABSTRACT FROM AUTHOR]

Background: A high‐frequency point‐of‐care (POC) ultrasound instrument was used to evaluate the microstructural and biomechanical properties of the anterior sclera in vivo using parameters computed from quantitative ultrasound (QUS) methods. Methods: In this cross‐sectional study, both eyes of 85 enrolled patients were scanned with the POC instrument and ultrasound data were processed to obtain QUS parameters. Pearson correlation and multi‐linear regression were used to identify relationships between QUS parameters and refractive error (RE) or axial length. After categorising eyes based on RE, binary support vector machine (SVM) classifiers were trained using the QUS or ophthalmic parameters (anterior chamber depth, central corneal thickness, corneal power, and intraocular pressure) to classify each eye. Classifier performance was evaluated by computing the area under the receiver‐operating characteristic curve (AUC). Results: Individual QUS parameters correlated with RE and axial length (p < 0.05). Multi‐linear regression revealed significant correlation between the set of QUS parameters and both RE (R = 0.49, p < 0.001) and axial length (R = 0.46, p = 0.001). Classifiers trained with QUS parameters achieved higher AUC (푝 = 0.06) for identifying myopic eyes (AUC = 0.71) compared to classifiers trained with ophthalmic parameters (AUC = 0.63). QUS‐based classifiers attained the highest AUC when identifying highly myopic eyes (AUC = 0.77). Conclusions: QUS parameters correlate with progressing myopia and may be indicative of myopia‐induced microstructural and biomechanical changes in the anterior sclera. These methods may provide critical clinical information complementary to standard ophthalmic measurements for predicting myopia progression and risk assessment for posterior staphyloma formation. [ABSTRACT FROM AUTHOR]

Background/Objectives: As one of the most efficacious glaucoma surgical techniques, trabeculectomy is considered by many surgeons to be the "gold standard" intra-ocular pressure (IOP)-reducing intervention. The purpose of this study is to present our intra-operative flow-adjusted surgical method, which aims to provide safety and efficacy more simply than previous methods. Methods: Retrospectively, we evaluated outcomes for trabeculectomy or phacotrabeculectomy in surgery-naïve eyes over three years for patients with glaucoma not associated with other ocular co-morbidities. We defined complete success as an IOP between 5 and 18 mmHg plus at least a 20% reduction from baseline, without concomitant medications. Relative success was the same result, with glaucoma medication(s). Failure was regarded as an IOP less than 5 or higher than 18 mmHg, or by the need for a subsequent glaucoma operation. Results: We assessed the results from 186 eyes of 186 patients. After exclusion, a group of 45 trabeculectomies and 35 phacotrabeculectomies were analyzed. In eyes undergoing a trabeculectomy, over a mean follow-up of 16.0 months, IOP fell from 28.1 ± 8.0 mmHg with 3.6 ± 1.1 medications to 9.7 ± 3.6 mmHg (66% reduction) with 0.4 ± 1.0 medications (each p < 0.00001). The success rate was 88.9% (75.6% complete success). In eyes undergoing a phacotrabeculectomy, over a mean of 19.1 months, IOP fell from 26.1 ± 10.2 mmHg with 3.5 ± 1.3 medications to 10.0 ± 3.6 mmHg (62% reduction) on 0.9 ± 1.4 medications (each p < 0.00001). The success rate was 91.4% (57.1% complete success). Complication rates were low, with no major complications in either group. Conclusion: To lower IOP, our intra-operative flow-adjusted trabeculectomy and phacotrabeculectomy techniques appear to be safe and effective. [ABSTRACT FROM AUTHOR]

Background/Objectives: This study investigated intraocular pressure (IOP) changes after a blood draw in older adults considering sex, age, and baseline IOP. Methods: Fifty-three subjects (54.7% females; age: 68.50 ± 4.46 years; Visual Function Index [VF14]: 94.50 ± 7.50 points; mean contrast sensitivity function (CSF) for both eyes in each spatial frequency [cdp]: 1.5 cdp [1.41 ± 0.20 log], 3 cdp [1.57 ± 0.29 log], 6 cdp [1.45 ± 0.39 log], 12 cdp [1.04 ± 0.40 log], 18 cdp [0.63 ± 0.31 log]) voluntarily participated. Subjects fasted for at least 8 h before attending the laboratory. First, IOP was measured in a seated position using a portable rebound tonometer. Ten minutes after the initial measurement, two 10 mL tubes of blood were drawn. Five minutes after the blood draw IOP was measured again following the same procedure as the initial measurement. We evaluated the differences using an analysis of variance. Results: Significant, but not clinically relevant, decreases were found in the right eye, with small effect sizes (p = 0.013–0.079, d = 0.35). Only males and subjects older than 68 years showed trends toward IOP reduction in the right eye. Subjects with baseline IOP ≥ 14 mmHg experienced significant IOP reductions in both eyes, with moderate effect sizes (p = 0.001–0.002, d = 0.56–0.69). Conclusions: Our findings suggest that a blood draw of 20 mL is safe for the IOP levels of older adults with baseline IOP between 11 and 21 mmHg. Variations in IOP were observed based on baseline IOP, sex, and age, suggesting the importance of personalized clinical assessments. The primary factor influencing IOP changes appears to be the baseline IOP level. [ABSTRACT FROM AUTHOR]

Multiple iterations required to design ocular implants, which will last for the desired operational period of months or even years, necessitate the use of in-silico models for ocular drug delivery. In this study, we developed an in-silico model to simulate the flow of Aqueous Humor (AH) and drug delivery from an implant to the Trabecular Meshwork (TM). The implant, attached to the side of the intraocular lens (IOL), and the TM are treated as porous media, with their effects on AH flow accounted for using the Darcy equation. This model accurately predicts the physiological values of Intraocular Pressure (IOP) for both healthy individuals and glaucoma patients, as reported in the literature. Results reveal that the effective diffusivity of the drug within the implant is the critical parameter that can alter the bioavailability time period (BTP) from a few days to months. Intuitively, BTP should increase as effective diffusivity decreases. However, we discovered that with lower levels of initial drug loading, BTP declines when effective diffusivity falls below a specific threshold. Our findings further reveal that, while AH flow has a minimal effect on the drug release profile at the implant site, it significantly impacts drug availability at the TM. [Display omitted] • Developed an in-silico model that can simulate drug delivery from ocular implants. • Validated the predicted intra-ocular pressure values with the values reported in the literature. • For lower levels of loaded drug in the implant, bioavailability time period starts reducing as effective diffusivity is reduced below a certain threshold level. • Neglecting Aqueous Humor (AH) flow effects can result in substantially wrong predictions of drug availability at the Trabecular Meshwork. [ABSTRACT FROM AUTHOR]

Background: Glaucoma stands as a prominent contributor to irreversible vision impairment on a global scale. For decades, the Baerveldt Glaucoma Implant (BGI) has been used to treat refractory glaucoma. Yet, the cost‐effective Aurolab Aqueous Drainage Implant (AADI) has gained clinical attention as a viable alternative for managing glaucoma. Objective: The purpose of this study was to evaluate and compare the efficacy and safety of AADI and BGI in the treatment of refractory glaucoma. Methods: Following PRISMA guidelines, we conducted a systematic search of multiple databases, identifying relevant comparative studies assessing AADI versus BGI in patients with refractory glaucoma. Key outcomes included postoperative IOP, surgical success rates, antiglaucoma medication reduction (AGMR), and complication rates. Quality assessment was performed using the Newcastle–Ottawa Scale (NOS). Results: Three studies comprised a total of 176 individuals with refractory glaucoma, with 107 patients receiving the AADI and 69 patients receiving the BGI. The meta‐analysis revealed a statistically borderline significant reduction in postoperative IOP favoring the AADI at 3 months (mean difference [MD] = −2.74, p = 0.05). There was no significant difference in the MD of AGMR between the AADI and BGI groups. The rates of total complications and surgical success did not differ significantly between the AADI and BGI groups. Conclusion: AADI demonstrates promising results in reducing IOP at 3 months compared to BGI, with comparable surgical outcomes and complication rates over the long term. Further studies with larger samples are warranted to validate these findings and assess cost‐effectiveness, particularly in developing countries. [ABSTRACT FROM AUTHOR]

Corneal hysteresis (CH) is associated with glaucomatous structural changes. We retrospectively investigated the association between CH and the regional circumpapillary retinal nerve fibre layer thickness (cpRNFLT) in 419 eyes of 419 patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). CH was used as the explanatory variable, and cpRNFLT (total and quadrant) was used as the dependent variable. Standardized β coefficients were compared both overall and between the NTG and POAG groups. Multiple regression analysis with CH as the explanatory variable and cpRNFLT parameters as the dependent variables suggested that even after adjusting for age, sex, intraocular pressure (IOP), axial length, and central corneal thickness, all areas of the cpRNFLT were significantly associated with CH, except for the nasal quadrant. In the stratified analysis by glaucoma type, a positive relationship between CH and regional cpRNFLT tended to be maintained in the NTG group but not in the POAG group (P = 0.060 for interaction). Additionally, in the NTG group, the CH-inferior cpRNFLT relationship was particularly strong in the less-IOP fluctuation group. These results suggest that CH may be a potential predictor of anatomical vulnerability around the optic nerve, particularly enhancing the inferior regions of NTG. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionCataract surgery is a common operation, typically carried out on older adults who have many comorbid medical conditions. Many of these patients may be undergoing aspirin therapy for diverse cardiovascular causes. Nevertheless, there is ongoing controversy regarding the administration of aspirin therapy during the perioperative period, as there are concerns regarding the risk of bleeding problems compared to thromboembolic events. Although aspirin is commonly used, there is no agreement on whether to continue or stop taking it before cataract surgery. This systematic review and meta-analysis attempt to assess the safety of continuing or discontinuing aspirin in the setting of cataract surgery.We conducted a systematic review and meta-analysis following PRISMA guidelines. Four databases were searched until January 25, 2024, for studies assessing the safety and efficacy of aspirin continuation or discontinuation before cataract surgery. The risk ratios (RR) of the extracted data and their 95% confidence interval (95% CI) were pooled using RevMan 5.4 software. We registered our protocol in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42024529986).We included nine studies with a total of 65,196 patients comprising various study designs and global populations. The analysis revealed a significant increase in subconjunctival hemorrhage risk with aspirin continuation (RR: 1.74, 95% CI: 1.22, 2.50, p = .002). However, the risk of hyphema, retrobulbar hemorrhage, vitreous hemorrhage, intraocular pressure spike, corneal edema, posterior capsule rupture, and visual acuity changes did not significantly differ between aspirin continuation and discontinuation or aspirin and placebo groups.Although the use of aspirin before cataract surgery raises the likelihood of subconjunctival bleeding, it does not increase the risk of potentially sight-threatening bleeding events. We recommend continuation of aspirin in patients undergoing cataract surgery. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe the clinical presentation, histopathologic characteristics, and management of phacolytic glaucoma. Patients and Methods: The database at the Florida Lions Ocular Pathology Laboratory was searched for surgical specimens at the Bascom Palmer Eye Institute. Patients with a diagnosis of "phacolytic glaucoma" on cytopathology between the years of 1997 and 2023 were included (n = 15). Patient demographics, anatomic site, laterality, clinical features, and ocular examination findings were obtained from available medical records. Results: The diagnosis of phacolytic glaucoma was established by light microscopic examination of cytology specimens in 15 eyes (Right = 8, Left = 6, not specified = 1). Between 1997 and 2023, there were 32 cytopathology cases with a preoperative diagnosis of phacolytic glaucoma. From this group of 15 cases, there were nine males and six females. Mean age was 64.2 years (Range: 39–87). Thirteen samples were from the anterior chamber and two were obtained from the vitreous. All 15 cases (100%) demonstrated histiocytes with engulfed foamy and/or granular presumed lenticular material. CD68 immunohistochemistry was positive within histiocytes in four cases that were stained (100%). Of the available medical records, clinical features, and ocular examination findings included: eye redness, decreased vision, eye pain, anterior chamber inflammation, dislocated or subluxed crystalline lens, cataract, and elevated intraocular pressure (average = 41.3 ± 8.67 mm Hg). Conclusions: Phacolytic glaucoma is a rare complication of mature/hypermature cataracts that presents with ocular pain, decreased vision, and anterior chamber inflammation. AC paracentesis with cytopathologic evaluation is a minimally invasive, rapid technique that can aid in the diagnosis and management of this disease. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis are the most common ocular diseases caused by CMV infections in immunocompetent patients. The incidence of CMV corneal endotheliitis is relatively high in middle-aged men. CMV corneal endotheliitis presents with mild anterior chamber inflammation, corneal edema, keratic precipitates, and elevated intraocular pressure. It resembles Posner–Schlossman syndrome and Fuchs uveitis because of the elevated intraocular pressure. Without proper diagnosis and treatment, it may progress to bullous keratopathy or glaucoma, necessitating keratoplasty or glaucoma surgery. Therefore, early diagnosis and treatment are important for a good prognosis. Aqueous humor analysis can facilitate the diagnosis of CMV corneal endotheliitis, and early antiviral treatment can decrease the risk of corneal compensation or glaucomatous optic atrophy. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CMV corneal endotheliitis along with the evidence for early clinical diagnosis and active antiviral treatment. [ABSTRACT FROM AUTHOR]

Purpose: To assess the risk of gonioscopy-assisted transluminal trabeculotomy (GATT) inducing an uveitic flare-up in patients with uveitic glaucoma (UG). Methods: This retrospective study included consecutive UG patients who underwent GATT at a single medical center between June 2020 and September 2022. The main outcome measure was the occurrence of a surgery-related uveitic complication defined as either an uveitic flare-up defined by the Standardization of Uveitis Nomenclature (SUN) criteria, or the appearance of cystoid macular edema (CME) from 2 weeks to 3 months after surgery. Results: A total of 25 eyes of 22 patients were included in the study. Age ranged from 10–78 and 64% were women. The most common uveitic etiologies were juvenile idiopathic arthritis (JIA, 24%) and herpetic infection (24%). A total of 48%of the patients were on systemic immunosuppressants prior and unrelated to surgery. Eight eyes (32%) had severe glaucomatous damage prior to surgery, and 20% of the patients had undergone previous glaucoma surgery. Two cases (8%) demonstrated uveitic flare-up in the early postoperative period: a case of mild anterior chamber reaction and a case of CME with persistent edema prior to surgery. Average intraocular pressure (IOP) was reduced from 26.7 mm Hg on four medications to 12.2 on 1.1 after 1 year. One patient required reoperation for IOP control. Conclusions: With careful pre and postoperative care, GATT seems to be a low-risk procedure for uveitic flare-ups in patients with UG. [ABSTRACT FROM AUTHOR]

Purpose: Uveitis can lead to secondary glaucoma, a condition with challenging management that can carry irreversible visual loss. Filtering surgery has demonstrated a higher failure rate, increased incidence of postoperative complications and reinterventions in uveitic patients. There is no consensus on the optimal surgical approach for uveitic glaucoma (UG) due to limited data comparing various intraocular pressure (IOP)-lowering surgeries. This retrospective cohort aims to assess the clinical outcomes of trabeculectomy (TBT), non-penetrating deep sclerectomy (NPDS), Ex-PRESS shunt and Ahmed glaucoma valve, providing additional insights into the long-term IOP control and safety of filtering surgeries in UG. Methods: The filtering surgery was performed on 32 eyes of 27 UG patients. Complete success was defined as IOP ≤ 18 mmHg or a 30% reduction. Qualified success allowed topical hypotensive treatment. Results: Complete success was 40.63% (13/32) at 12 months and 36.67% (11/30) at 36 months. Qualified success was 84.38% (27/32) at 12 months and 63.33% (19/30) at 36 months. In the survival analysis, both NPDS and Ex-PRESS demonstrated decreased failure rates compared to TBT (NPDS vs TBT: HR = 0.20, p = 0.049; Ex-PRESS vs TBT: HR = 0.28, p = 0.13). One or more reinterventions were required in 34.38% (11/32) of the eyes. NPDS had the lowest incidence of hypotony. Secondary cataract was a common complication in all groups. Conclusion: Various filtering surgeries are safe and effective procedures for lowering IOP and reducing the requirement of topical antihypertensives in UG at 36 months. However, one-third of the patients will require another IOP-lowering procedure. [ABSTRACT FROM AUTHOR]

Purpose: To explore the expression of matrix metalloproteinase-3 (MMP-3) in the aqueous humor of patients with Posner-Schlossman syndrome (PSS), and the association between MMP-3 and PSS. Methods: Peripheral blood and aqueous humor were routinely collected from 29 patients with PSS (PSS group) and 30 patients with age-related-cataract (ARC) (control group). The content of MMP-3 in serum and aqueous humor was measured by immunoturbidimetry. The correlation between MMP-3 and ophthalmic examination results were verified by Spearman's correlation analysis. Results: The MMP-3 level in the aqueous humor of the PSS group was (25.86 ± 13.4)ng/ml, significantly higher than that in the control group (3.9 ± 2.7)ng/ml(p < 0.001), while there was no significant difference in serum MMP-3 level between the two groups (p = 0.125). The endothelial cell density (ECD) in the aqueous humor of the PSS group was (2078 ± 440) cell/mm2, intraocular pressure (IOP) in the aqueous humor of the PSS group was (33 ± 12) mmHg. The correlation analysis of aqueous humor MMP-3 and various ophthalmic examination results showed that aqueous humor MMP-3 had a moderate correlation with IOP and the difference in ECD between the affected eye and the fellow eye. Conclusions: MMP-3 level is elevated in the aqueous humor of PSS patients, and it may play an important role in the pathogenesis of PSS. [ABSTRACT FROM AUTHOR]

Central serous chorioretinopathy (CSC) is a frequently occurring chorioretinal disease, that is commonly associated with subretinal fluid accumulation in a generally young population. Even though choroidal abnormalities have been found to be of importance, the exact pathogenesis of CSC is still being learned. The origin of pigment epithelial detachments, seen in many CSC patients, is also unclear. Based on the follow‐up of a CSC patient for more than 5 years, we hypothesize that intraocular pressure and, by extension, the pressure gradient across the Bruch's membrane, may be one factor in the pathogenesis of pigment epithelial detachments in CSC, which might very well have implications for the occurrence of and possible ways to prevent subretinal fluid in CSC. [ABSTRACT FROM AUTHOR]

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP‐lowering is the most important treatment strategy, mostly through topical eyedrops. Well‐functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative‐free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP‐lowering eye drops on the meibomian glands. [ABSTRACT FROM AUTHOR]

Purpose: To determine vision‐related quality of life (VR‐QoL) and functional and structural parameters associated with VR‐QoL in patients with glaucoma before and 12 months after trabeculectomy. Methods: Fifty‐eight patients undergoing trabeculectomy were included. Participants completed the 25‐item National Eye Institute Visual Function Questionnaire (VFQ‐25) prior to and 12 months after trabeculectomy. Functional (visual acuity and visual fields) and structural (ganglion cell layer volume) parameters were evaluated for their association with VR‐QoL using multiple linear regression of VFQ‐25 subscale scores. Intraocular pressure and the number of glaucoma medications were also included in the analyses. Results: The VFQ‐25 composite score did not change after trabeculectomy (before: 74.9; 12 months: 74.0; p = 0.512). The subscale mental health had a significantly higher score 12 months after trabeculectomy (before: 65.6; 12 months: 71.4; p = 0.017). The VFQ‐25 scores for general health (before: 68.5; 12 months: 62.5; p = 0.009) and role difficulties (before: 78.9; 12 months: 53.7; p < 0.001) were significantly lower 12 months after trabeculectomy. No functional or structural parameters were associated with VFQ‐25 composite score. Conclusion: Overall, VR‐QoL in glaucoma patients was similar before and after trabeculectomy, reflecting the procedure's stabilizing effect on both objective and subjective visual function. The absence of correlations between VR‐QoL and clinical parameters emphasizes the multifaceted nature of VR‐QoL and highlights the limitations of depending solely on objective clinical metrics to evaluate patients' subjective experiences. Using both objective measures and VR‐QoL, clinicians can better understand the challenges patients face due to glaucoma and trabeculectomy, potentially leading to better solutions. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association of glycated haemoglobin (HbA1c) and serum glucose with intraocular pressure (IOP) in a large UK general population. Materials and Methods: Participants were selected from the UK Biobank, excluding those with eye conditions that may affect IOP. IOP was measured using an ocular response analyser. Goldmann‐correlated IOP (IOPg) and corneal‐compensated IOP (IOPcc) were outcomes of interest, and ocular hypertension was defined as left‐eye IOPg or IOPcc > 21 mmHg. HbA1c and random (non‐fasting) serum glucose were the exposures of interest. Multivariate restricted cubic spline models, as well as linear regression, were applied to explore the associations of interest. Results: Among 68 806 participants (46.5% male), the mean age was 56.7 years. The mean (standard deviation) for IOPg was 15.7 (3.6) mmHg and 15.9 (3.6) mmHg for IOPcc. Occular hypertension was prevalent in 8055 participants (11.7%) and 4178 participants (6.1%) had diabetes. Those with diabetes had higher IOP and a higher prevalence of ocular hypertension. After adjustment for demographic and clinical variables, HbA1c was positively associated with IOP in participants with diabetes, but not in those without diabetes. For every 10‐mmol/mol increase in HbA1c, IOPg increased by 0.20 mmHg (95% confidence interval [CI] 0.12, 0.28) and IOPcc by 0.15 mmHg (95% CI 0.07, 0.23); the odds of ocular hypertension was increased by 6% (95% CI 1.00, 1.13) in participants with diabetes. A borderline positive association between serum glucose and IOP was found only in participants without diabetes. Conclusions: Impaired glycaemic control was associated with elevated IOP and a possible risk of ocular hypertension among participants with diabetes but of normal ocular health. [ABSTRACT FROM AUTHOR]

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Silicone oil (SO) is commonly used as a retinal tamponade during pars plana vitrectomy for complicated retinal detachments. Although fairly inert, complications such as cataract formation, intraocular pressure elevation, corneal changes, inner retinal thinning, and optic neuropathy have been noted. We report two cases of postoperative subfoveal outer retinal lucency and hyperreflective deposits following SO insertion and resolution following removal. [Ophthalmic Surg Lasers Imaging Retina 2024;55:675–678.] [ABSTRACT FROM AUTHOR]

Objective: Acute compartment syndrome (ACS) is a serious medical condition that can be encountered in tibial plateau fractures. However, no studies of compartment pressure changes in patients with tibial plateau fractures compared to patient without fractures have been reported. To obtain a comprehensive understanding of the pressure changes in patients with fractures, we monitored and recorded the compartment pressure and attempted to reveal the potential pressure release function of the human fascia. Materials and methods: Cohorts of 43 normal individuals and 23 patients (initial 33, 10 were excluded due to inclusion criteria) and include the number of patients who completed the study with closed tibial fractures (the fracture group, FG, which comprised 6 men and 17 women) were included in this retrospective research. Compartment pressures were measured with Icare, a device that is traditionally used to measure intraocular pressure. Results of measurements at 6 different locations in the lower limb were recorded and compared for three days (days 2, 3, and 4 post fracture) between normal cohort (CG) and fracture cohort (FG) patients. Results: The compartment pressures were comparable at each pressure measurement site (upper, middle and lower) in patients of the CG and the FG. Compared with the CG patients, there was a significant increase in compartment pressure at the upper lateral location in 18-45-year-old patients in the FG (P = 0.013) and at the upper lateral (P = 0.004) and medial locations (P = 0.005) in 46-69-year-old patients, and the values tended to normalize over time. Compared with the contralateral normal limb of patients in the FG, there was a significant increase in compartment pressure at the upper lateral location in 18-45-year-old patients (P = 0.009) and at the upper lateral (P = 0.015) and medial locations (P = 0.016) in 46-69-year-old patients on the fractured side. Based on different fracture classifications, there were no significant differences in compartment pressure at the medial (upper, middle and lower) locations when compared with pressures at the corresponding lateral sites of measurement. Conclusion: The results of this study revealed that the fascial compartment as a whole can release the increased intracompartment pressure after fracture to prevent complications such as acute compartment syndrome caused by a continued increase in pressure. The Icare as a portable device, is potentially useful in compartmental pressure measurement especially in emergency room. [ABSTRACT FROM AUTHOR]