To summarize recent evidence about the association between different lifestyle modifications and environmental risk factors and glaucoma.

Incorporating moderate exercise into the routine of glaucoma patients may help slow the progression of the condition. However, caution should be taken when using swim goggles, and it may be advisable to avoid certain yoga positions and heavy weight-lifting exercises, as they have been linked to intraocular pressure (IOP) spikes and potential risks for glaucoma patients. Various relaxation techniques may lower IOP. The evidence remains inconclusive about the association between vitamins intake and glaucoma. Dietary nitric oxide has been associated with a lower risk of glaucoma. Higher smoking intensity has been linked to faster visual field decline and retinal nerve fiber layer thinning. Additionally, there is currently insufficient evidence to support the use of marijuana in managing glaucoma, with side effects outweighing the proposed benefits. A significant association has been found between air pollutants and ganglion cell layer thinning, as well as a greater burden of glaucoma.

Lifestyle and environmental factors are increasingly recognized as significant contributors to glaucoma development and progression. These modifications should be integrated into a comprehensive treatment approach alongside medications or surgical interventions.

To describe the results of iStent inject implantation as a standalone procedure in early-stage uncontrolled glaucoma, with results up to 24 months.

A retrospective, single-center case series that recruited patients with open-angle glaucoma (OAG), uncontrolled IOP (defined as ≥18 mmHg), and who are receiving 1-4 glaucoma medications were implanted the iStent inject as a standalone procedure. Exclusion criteria were the contraindications of iStent inject implantation. Primary outcome measures were IOP at 6, 12, 18, and 24 months compared to baseline, and the number of medications at baseline and 24 months.

Eighty-eight eyes from 88 patients, aged 57.6 ± 9.8 years, were included. Ten eyes underwent a subsequent glaucoma procedure during follow-up and were excluded from the analysis. The mean IOP (mmHg) was reduced from 20.54 ± 1.42 at baseline to 15.99 ± 1.98 and 16.15 ± 2.21 (n = 78, p < 0.001) at the 12- and 24-month follow-up, respectively, and the mean number of medications was reduced from 2.35 ± 0.70 to 1.31 ± 0.80 (p < 0.001) at 24 months. Of those eyes, 59% had ≥20% reduction in IOP at 24 months, 91% had an IOP ≤18 mmHg at 24 months, and 71.8% were receiving fewer medications. At 24 months, 14.1% of eyes were medication-free, compared to none at baseline. No serious intraoperative or postoperative adverse events occurred.

iStent inject can effectively control intraocular pressure in mild glaucoma, reducing medication reliance and improving patient quality of life.

To evaluate the real-world efficacy and safety of iStent implanted standalone or combined with phacoemulsification in open-angle glaucoma (OAG) patients.

This is a retrospective observational study of OAG patients who underwent standalone or combined iStent procedures were reviewed. Inclusion criteria included age over 18 years and open angle on gonioscopy. Exclusion criteria were prior incisional glaucoma surgeries, missing data, or follow-up shorter than 6 months. The primary outcome was surgical success between the two groups after one year. Secondary outcomes included differences in IOP reduction and medication use.

We included 48 eyes with primary (n = 44) and secondary OAG (n = 4). Nineteen eyes had standalone while 29 eyes had combined procedures. Kaplan-Meier analysis revealed overall surgical success in 31.3% of eyes after one year. Qualified success was higher in the combined group than the standalone group [62.5% (10 eyes) vs 27.3% (3 eyes), p = 0.239]. At 24 months, mean IOP reduced by 2.2 ± 2.5 mmHg vs 3.3 ± 2.9 mmHg, p = 0.333), and the number of medications reduced by 1.1 ± 1.2 vs 1.3 ± 0.1, p < 0.001) in the standalone and combined group, respectively. Stent occlusion occurred in two eyes.

While both standalone and combined iStent procedures provide safe IOP reduction throughout 12 months, there was no statistically significant difference in surgical success between them.

This literature review evaluates any possible links between primary open-angle glaucoma (POAG) and caloric restriction (CR), body mass index (BMI), and exercise, aiming to map the extent of the literature. Its primary objective is to recognise the nature and breadth of research evidence, identify possible gaps in these topics and develop future studies. The databases searched were MEDLINE (PudMed), Scopus and ScienceDirect, in April 2023 for articles published in English, with no date restriction. A total of 447 search results were retrieved. Of these, 73 were related to CR, 249 to BMI, and 125 to exercise. Records identified included systematic reviews, meta-analyses, randomised controlled trials, cohort studies and animal studies. CR has been shown to halt the degeneration of retinal ganglion cells and protect against various glaucomatous processes in animal models. Low BMI has been shown to be associated with an increased risk of POAG and a faster rate of visual field deterioration in POAG. However, the association between high BMI and POAG is not consistent. Exercise has been shown to cause mechanical, vascular, and neurobiological changes affecting the pathophysiology of POAG. The present review helps identify key characteristics and factors relating to the impacts of CR, BMI, or exercise on POAG.

Glaucoma is the leading cause of irreversible visual loss worldwide, and as yet, there is no cure. The only evidence-based treatment to slow progression is by lowering intraocular pressure (IOP). Despite the development of new topical medications to reduce IOP, the major limitation of eyedrops lies in human and anatomical factors, namely patient compliance and poor bioavailability, making current medical glaucoma treatment ineffective. In this manuscript, we summarise the limitations of traditional topical anti-glaucoma therapy and study current drug delivery systems to lower IOP, with focus on the only two that have made FDA-approval- Durysta and iDose TR. We highlight their limitations and discuss real-world economic challenges that make it prohibitively difficult for these drug delivery systems to be more widely adopted in daily practice. In this perspective, we also introduce gene therapy as a novel therapeutic option to target downstream pathways of IOP regulation, neuroprotection of the optic nerve, and reducing mitochondrial stress to delay the progression of glaucoma. We discuss promising results of gene therapy for glaucoma treatment in in vivo animal models as well. We also explore the concept of novel nanoparticle-based drug delivery systems, which have the advantage of being highly modifiable and customisable, able to incorporate large amounts of cargo while maintaining a high transfection efficacy, and at a fraction of the cost. Lastly, we propose that nanomedicine, in conjunction with gene therapy, offers a promising solution to the aforementioned challenges of current glaucoma therapy, and can herald a new era of sustained glaucoma treatment.

This retrospective study compares the surgical outcomes of ab interno trabeculotomy using the Kahook Dual Blade (KDB) and Tanito microhook (TMH) combined with cataract surgery.

Twenty-four eyes from 19 and 17 patients with glaucoma in the KDB and TMH groups, respectively, were included. Background factors were matched for medication score and disease type using propensity scores.

Preoperative age, sex, intraocular pressure (IOP), medication scores, and disease type were comparable between the groups. The intraoperative incision range was lower in the KDB than TMH group. The postoperative medication scores and IOPs were 2.7±1.6 mmHg and 14.5 ± 2.8 mmHg in the KDB group, and 2.0±1.8 and 13.8 ± 3.4 mmHg in the TMH group, respectively. There were no significant differences between the groups regarding changes in medication scores, IOP reduction rate, or survival 6 months postoperatively. Postoperative IOP changes were significantly associated with preoperative IOP in both groups, and trabeculotomy range in the KDB group. There were no significant between-group differences regarding the incidence of postoperative complications, excluding a higher incidence of hyphema in the TMH group.

Surgical outcomes for ab interno trabeculotomy using the KDB and TMH were not significantly different. There was no significant difference in the occurrence of postoperative complications, except hyphema, which may reflect the difference in the incision range of trabeculotomy between the hooks. Finally, in the KDB group, where narrow incisions range up to just over one quadrant, the trabeculotomy incision range correlated with IOP.

Primary selective laser trabeculoplasty (SLT) is a safe primary treatment for open-angle glaucoma (OAG) and ocular hypertension (OHT). However, there is limited evidence on its use as a secondary treatment, ie, after prior use of ocular hypotensive eye drops.

To evaluate outcomes following SLT after using hypotensive eye drops for at least 3 years.

This is a post hoc exploratory analysis of data from a multicenter randomized clinical trial conducted within the UK National Health Service. Participants were patients with OAG or OHT who participated in the LiGHT trial. Data were analyzed from February 2021 to December 2024.

Participants were initially randomized to either primary SLT or primary hypotensive eye drops and remained on the allocated treatment pathway for 3 years. Participants using eye drops were then allowed to have secondary SLT as a treatment switch (to reduce their medication load) or as a treatment escalation (if more intense treatment was needed). Participants were treated and monitored according to a predefined protocol.

The outcomes of interest were rates of incisional glaucoma surgery, medication use, and intraocular pressure.

In total, 633 participants entered the extension of the LiGHT trial, and 524 participants (82.8%) completed the extension (72 months). Of 320 participants receiving primary hypotensive eye drops, 112 (35.0%) received SLT: 70 participants switched to SLT, 29 participants had SLT as a treatment escalation, and 13 participants had SLT as a treatment escalation in 1 eye and as a treatment switch in the other eye. Switching to SLT was associated with a reduction in the number of medications (mean [SD], 1.38 [0.62] to 0.59 [0.92] active ingredients; mean difference, 0.79 [95% CI 0.66 to 0.93] active ingredients; P < .001). At 72 months, 69 eyes that switched to SLT (60.5%) needed no medical or surgical treatment, and 62 eyes receiving 1 drug before switching (83.8%) needed no medical treatment. Escalating to SLT was associated with a mean intraocular pressure reduction of 4.6 mm Hg (21.8%), and 30 eyes (62.5%) reached target intraocular pressure at 72 months without the need for surgery; 9 eyes (18.7%) needed a trabeculectomy.

This secondary analysis of a randomized clinical trial found that secondary SLT was associated with a reduction in the medication load for stable, medically treated eyes. For medically uncontrolled eyes, there is evidence that SLT could provide additional intraocular pressure control, but the need for trabeculectomy was not eliminated.

isrctn.org Identifier: ISRCTN32038223.

Reviewing validated glaucoma disease-specific tools for measuring adherence could encourage adherence monitoring to avoid progressive visual field losses in people living with glaucoma.

To review the literature on validated disease-specific tools for measuring adherence to glaucoma medications.

Relevant peer-reviewed publications from the year 2000 to 2022 from PubMed, EMBASE, Scopus, and PROquest were retrieved. For each search conducted, the name of the search engine used, date of search, number of publications retrieved, and keywords used were documented. The selected articles were reviewed for inclusion and assessed for biases and quality. Each tool was described by the type of measurement, technique for measurement, strengths and weaknesses, and method of validation, respectively.

Out of the 10 included articles, seven glaucoma disease-specific tools were identified namely; Glaucoma Treatment Compliance Assessment Tool-Short form (GTCAT-S), Glaucoma Treatment Compliance Assessment Tool-Long form (GTCAT-L), Travatan Dosing Aid (TDA), Eye-Drop Satisfaction Questionnaire (EDSQ), Glaucoma Adherence Questionnaire-Revised (GAQ-R), Glaucoma Adherence Questionnaire-Old (GAQ-O), and Schwartz Adherence Questionnaire (SAQ). Three studies had a low risk of bias, and seven recorded a moderate risk of bias. The TDA, GTCAT-S, and GTCAT-L were rated as high-quality tools.

Seven glaucoma disease-specific tools for measuring adherence were found. Integration of regular measurement of medication adherence as part of care for glaucoma patients would be beneficial for both patients and providers of eye care.

We used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts.

Secondary analysis of 4 prospective population-based studies.

We included four European-ancestry cohorts: the United States-based Nurses' Health Study, Nurses' Health Study 2, and the Health Professionals Follow-up Study and the Rotterdam Study (RS) in The Netherlands. The United States cohorts included female nurses and male health professionals ≤ 55 years of age. The RS included residents ≤ 45 years of age living in Rotterdam, The Netherlands.

Polygenic risk score weights were estimated by applying the lassosum method on imputed genotype and phenotype data from the UK Biobank. This resulted in 144 020 variants, single nucleotide polymorphism and insertions or deletions, with nonzero βs that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits.

The relative risk for POAG and Harrell's C statistic.

Among 1046 patients and 38 809‬ control participants, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08-5.18) times higher in the United States cohorts and 4.89 (2.93-8.17) times higher in the RS, compared with participants with median genetic risk (third quintile). Combining age, sex, intraocular pressure of more than 25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (95% CI, 0.73-0.75). Adding the PRS to this model improved the concordance to 0.82 (95% CI, 0.80-0.84). In a meta-analysis of all cohorts, patients in the highest tertile showed a larger cup-to-disc ratio at diagnosis, by 0.10 (95% CI, 0.06-0.14), and a 2.07-fold increased risk of requiring glaucoma surgery (95% CI, 1.19-3.60).

Incorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The long-term patterns in first-line glaucoma medication are not well established. Exploring these in longitudinal and population-based settings would provide information for the healthcare systems to plan glaucoma care accordingly.

To evaluate patterns in first-line glaucoma monotherapy in Finland during 1995-2019 based on nationwide survey and register data.

A population-based cohort study with 25 years of total follow-up. The cohort (n = 9288) is a random sample drawn from the nationwide health examination survey FinHealth 2017 which represents the Finnish population aged 30 years or older in 2017. Glaucoma patients were selected from the survey participants based on linked register data that included prescriptions and special reimbursements for glaucoma medication. The patterns, length of use, age at initiation, and persistence of first-line glaucoma drug monotherapies were observed during 1995-2019.

A total of 141 glaucoma patients with glaucoma drug monotherapy as a first-line glaucoma therapy were identified from the sample. The proportion of patients continuing with their first-line monotherapy was 64% after 1 year, 37% after 3 years, and 21% after 5 years of follow-up. During the 25 years there was a shift from beta-blockers to prostaglandin analogues as the prominent first-line glaucoma drug class. The length of use was longer for prostaglandin analogues compared with beta-blockers among patients continuing with their first-line monotherapy after 5 years of follow-up. The non-persistence rate was 38% of all patients during their first-line monotherapy. Timolol fixed-combinations were the most common second-line glaucoma therapy with a share of 39% after 5 years of follow-up.

During the 25-year follow-up a shift from beta-blockers to prostaglandin analogues had occurred and long initial therapies of over 5 years had become more common. However, the decline in the continuation of the initial therapy still occurred early with 1 out of 3 patients continuing after 3 years. This decline together with the consistent problem of non-persistence remain clinical challenges in topical drug therapy of glaucoma.

High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and external environments. O-methylascorbate has been reported to be associated with IOP. In addition, researchers have identified several genetic variants which are associated with metabolite concentrations, including O-methylascorbate and another vitamin C related metabolite, ascorbic acid 2-sulfate. We aimed to understand how O-methylascorbate and ascorbic acid 2-sulfate, or genetic variants associated with these metabolites, modify the associations between dietary environmental variables and IOP. We used data from 8060 participants of the Canadian Longitudinal Study on Aging. Using linear models adjusted for relevant covariates, we tested for interactions between six genetic variants previously found to be associated with O-methylascorbate and ascorbic acid 2-sulfate and four environmental variables related to diet (alcohol consumption frequency, smoking status, fruit consumption, and vegetable consumption). We also tested for interactions between serum concentrations of O-methylascorbate and ascorbic acid 2-sulfate and these environmental factors. We used a False Discovery Rate approach to correct for the 32 interaction tests performed. One interaction was suggestively significant after multiple testing correction (adjusted P-value < 0.1): rs8050812 and alcohol consumption frequency. Understanding how genetic variants and metabolites interact with the environment could shed light on biological pathways controlling IOP and lead to improved prevention and treatment of glaucoma.

Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of the optic nerve, or glaucoma. Although macrophages reside throughout the conventional outflow tract, their role in regulating intraocular pressure remains unknown. Using macrophage lineage tracing approaches, we uncovered a dual macrophage ontogeny with distinct spatial organizations across the mouse lifespan. Long-lived, resident tissue macrophages concentrated in the trabecular meshwork and Schlemm's canal, whereas short-lived monocyte-derived macrophages, instead, were abundant around distal vessels. Specific depletion of resident tissue macrophages triggered elevated intraocular pressure and outflow resistance, linked to aberrant extracellular matrix turnover in the resistance-generating tissues of the trabecular meshwork. This dysregulated physiology and tissue remodeling were not observed when we depleted monocyte-derived macrophages. Results show ontogeny and tissue-specific macrophage function within the outflow tract, uncovering the integral homeostatic role of resident tissue macrophages in resistance-generating tissues whose dysfunction is responsible for glaucoma.

This study compared the efficacy safety profiles of the Xen 63 and Preserflo MicroShunt devices, both standalone, in patients with primary open-angle glaucoma (POAG). It is a retrospective and single-center study conducted on consecutive on patients with medically uncontrolled POAG who underwent either a standalone Xen 63 or a standalone Preserflo and had a 12-month follow-up visit. The primary outcome was the mean IOP at month-12. Sixty eyes were included, 30 eyes in each Xen 63 and Preserflo groups, respectively. Preoperative IOP was significantly lowered from 20.8 ± 3.6 mmHg and 19.1 ± 3.8 mmHg to 14.2 ± 4.5 mmHg and 12.8 ± 2.3 mmHg in the Xen 63 and Preserflo groups, respectively (p < 0.0001 each, respectively); without significant differences between groups (p = 0.1346). Preoperative number of ocular-hypotensive drugs was significantly reduced from 2.3 ± 0.6 to 0.2 ± 06 drugs and from 2.3 ± 0.7 to 0.3 ± 0.6 drugs, in the Xen 63 and Preserflo groups, respectively (p < 0.0001 each, respectively); without significant differences between groups (p = 0.5212). Regarding safety, one (3.3%) eye in the Preserflo group required a device removal due to maculopathy. Three (10.0%) eyes in the Xen 63 group underwent needling. In conclusion, both the Xen 63 and the Preserflo devices effectively and safely reduced IOP and the requirement for IOP-lowering medications, exhibiting comparable IOP levels after 12 months.

To investigate the impact of blood pressure (BP) on rates of retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes with focal ischemic (FI) vs. generalized cup enlargement (GE) optic disc phenotypes.

Prospective cohort study.

The study included 122 eyes from 101 patients diagnosed with primary open-angle glaucoma. Eyes were classified as FI (n = 31, 25%) or GE (n = 91, 75%) based on masked grading of stereophotographs at baseline.

Subjects underwent comprehensive ophthalmic examinations, including intraocular pressure (IOP) measurement and spectral-domain OCT scans, every 6 months for an overall mean follow-up of 4.2 years ± 1.5 years. Brachial artery BP was measured concurrently, and mean arterial pressure (MAP), systolic arterial pressure (SAP), and diastolic arterial pressure (DAP) were calculated. Rates of global RNFL thickness change over time were assessed using linear mixed models, evaluating the impact of BP parameters in each optic disc phenotype, adjusting for IOP and other confounders. Interaction terms were used to test for differences in the effects of BP and IOP between the FI and GE phenotypes.

Effect of MAP, SAP, and DAP on rates of RNFL loss over time in FI and GE optic disc phenotypes.

In the adjusted FI group models, each 10 mmHg decrease in MAP, SAP, and DAP was associated with -0.397 μm/year (P = 0.006), -0.211 μm/year (P = 0.029), and -0.471 μm/year (P = 0.005) faster RNFL thinning, respectively. In contrast, BP parameters were not significantly associated with RNFL loss in the GE group. In the multivariable model with interaction terms, the interaction between DAP and phenotype was statistically significant (P = 0.019), indicating the FI phenotype exhibited greater sensitivity to lower diastolic pressure compared to GE eyes. In contrast, interaction terms between IOP and optic disc phenotype were not significant in any of the models, suggesting a similar effect of IOP in both phenotypes.

Lower systemic BP levels were associated with faster RNFL thinning in the FI optic disc phenotype but not in the GE phenotype. These findings highlight the importance of considering both IOP and systemic BP when managing patients with the FI optic disc phenotype.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To investigate the effect of average intraocular pressure (IOP) on the true rate of glaucoma progression (RoP) in the United Kingdom Glaucoma Treatment Study (UKGTS).

UKGTS participants were randomized to placebo or Latanoprost drops and monitored for up to two years with visual field tests (VF, 24-2 SITA standard), IOP measurements, and optic nerve imaging. We included eyes with at least three structural or functional assessments (VF with <15% false-positive errors). Structural tests measured rim area (RA) with Heidelberg retina tomography (HRT) and average peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT). One eye of 436 patients (222 on Latanoprost) was analyzed. A Bayesian hierarchical model estimated the true RoP of VF and structural metrics, and their correlations, using sign-reversed multivariable exponential distribution. RA and pRNFL measurements were converted to a dB scale, matching the VF metric (mean deviation [MD]). The effect of average IOP on the true RoPs was estimated.

True RoP at the mean average IOP (17 mm Hg) was faster (P < 0.001) for VF-MD (-0.59 [-0.73, -0.48] dB/year) than HRT-RA (-0.05 [-0.07, -0.03] dB/year) and OCT-pRNFL (-0.08 [-0.11, -0.06] dB/year). The proportional acceleration of RoP per mm Hg increase was, however, not significantly different (smallest P = 0.15). Accounting for the structural floor-effect largely eliminated the differences in RoPs (smallest P = 0.25).

VF appeared to deteriorate at a faster rate than structural measurements. However, this could be explained by the floor-effect from nonfunctional tissue. IOP induced a similar acceleration in RoP per mm Hg increase.

Effective strategies for the neuroprotection and preservation of retinal ganglion cells (RGCs) remain elusive in the management of glaucoma. A spontaneous genetic model of glaucoma has been identified in cats and extensively characterized as a viable translational model, with eye size and anatomy similar to humans. In this study we sought to establish initial proof of concept for gene delivery to feline RGCs via intravitreal injection of AAV2 in normal cats. Pre-retinal, posterior vitreal injection of AAV2/2-CMV-GFP, was performed overlying the area centralis in 5 adult cats. Immunosuppressive oral prednisolone was administered perioperatively and gradually tapered over 6-10wks post-injection. Ophthalmic examination was performed pre- and post-injection. The GFP reporter expression and morphological effects of viral transduction on the retina were monitored in vivo using confocal scanning laser ophthalmoscopy (cSLO) and optical coherence tomography (OCT), respectively (Spectralis OCT-HRA, Heidelberg), at 1-2wk intervals over 6-10wks. Full-field electroretinograms (ERG) and visual evoked potentials (VEP) were recorded at baseline and post-injection. Retinas were examined by histology and immunolabeling for the RGC marker RBPMS and Müller cell and astrocyte marker SOX9, and GFP expression was examined in the retina, optic nerve (ON), optic tract and lateral geniculate nucleus (LGN). GFP+ retinal cells and RGC axons were visualized by cSLO at 1-2 weeks post-injection. No retinal morphological changes were observed by OCT in vivo but 3/5 eyes exhibited mild retinal inflammation on histology. Retinal and ON function were preserved in injected eyes compared to baseline and untreated eyes. GFP expression was predominantly identified in RBPMS+ RGC cells as well as SOX9+ Müller cells. GFP fluorescence was observed throughout RGC nerve fiber tract in the central visual pathway. Peak transduction in RGCs (up to ∼ 20 %) was observed in the regions with high GFP expression, but < 1 % of RGCs expressed GFP across the whole retina. Our data provide proof of concept that pre-retinal injection of AAV2/2 may represent a feasible platform for gene delivery to feline RGCs in vivo but highlight a need for further refinement to improve RGC transduction efficiency and control low-grade retinal inflammation.

Evidence to support the hypothesis that visual field (VF) status can improve after initiation of intraocular pressure (IOP) reducing treatment is controversial. We take advantage of participant eligibility data from the United Kingdom Glaucoma Treatment Study (UKGTS) to test this hypothesis in newly diagnosed glaucomatous patients randomized to IOP-lowering therapy or placebo.

Multicentre, randomized, triple-masked, placebo-controlled trial.

Participants were newly diagnosed open-angle glaucoma patients in the UKGTS with eligibility and baseline data (n = 202 and n = 205 participants from the treatment and placebo groups, respectively). UKGTS eligibility data, including two reliable VFs (Humphrey 24-2 SITA Standard) and IOP measurements were compared to UKGTS trial baseline data acquired after allocation to treatment (topical prostaglandin analog) or placebo eye drops. Mean change in VF mean deviation (MD) and proportion of eyes that improved MD by more than different thresholds were compared across this interval in the treatment and placebo groups. Secondary analyses included stratifying the groups by level of IOP, level of VF loss, and age, along with pointwise analyses including change in subsets of VF locations. The main outcome measure was the mean change in VF MD.

Mean (standard deviation [SD]) time between eligibility/baseline visits and reduction in IOP was 12 (3) weeks and 4.8 (4.2) and 1.0 (3.6) mmHg for the treated and placebo eyes, respectively. Mean (SD) change in MD was almost the same for the treated (-0.03 [1.45] dB) and placebo groups (+0.08 [1.72] dB; P = .47). The proportions of participants with an MD improvement of 1 dB or more were similar for both groups (P = .25). No association was found between MD improvement and magnitude of IOP lowering. Stratifying data by IOP, level of VF loss and age did not reveal any differences between the treated and placebo groups, nor did any of the pointwise VF analyses.

Initial short-term VF changes in the treatment and placebo arms of UKGTS were the same. In these newly diagnosed patients with non-advanced glaucoma, we found no evidence to support the hypothesis that VF status improves after initial lowering of IOP by medical therapy.

Among 1861 adults with ocular hypertension or mild or moderate primary open angle glaucoma, those with Medicaid or no insurance had a statistically significantly lower likelihood of receiving laser trabeculoplasty compared with those with other insurance.

To determine whether social determinants of health are associated with undergoing treatment with laser trabeculoplasty (LTP) among individuals with ocular hypertension (OHT) or mild or moderate primary open angle glaucoma (POAG).

In this cross-sectional study, we included patients with OHT or mild or moderate POAG from the National Institutes of Health All of Us Research Program, a diverse US nationwide data set. Logistic regression was performed to study the association between LTP treatment status and 7 covariates (diagnosis severity, age, gender, race/ethnicity, income, insurance status, and education).

A total of 1861 subjects were included (median age of 72 y). In univariable logistic regression, diagnosis severity, older age, higher income, and insurance (non-Medicaid) were associated with LTP treatment. On multivariable logistic regression models, those with mild POAG (OR, 3.49; 95% CI: 2.12-5.87) and moderate POAG [OR, 7.15 (4.49-11.8)] were still more likely than OHT patients to have received LTP. Moreover, compared with participants with Medicaid or no insurance, participants with other insurance (eg, employer-provided, Medicare) were still more likely to have received LTP [OR, 2.24 (1.08-5.29)]. There was no significant difference in the LTP treatment likelihood based on race/ethnicity.

After controlling for confounders, the likelihood of receiving LTP appears to be driven primarily by insurance rather than income or race/ethnicity. Potential reasons for decreased utilization of LTP among Medicaid patients include higher rates of declining the procedure, or LTP may have been offered less frequently due to Medicaid's lower levels of reimbursement and longer reimbursement delays.

Microinvasive procedures have become established in glaucoma surgery and are preferred for patients with target pressure values that are not too low. Excimer laser trabeculotomy (ELT) represents such a minimally invasive approach and can easily be combined with cataract surgery.

Over 12 months the reduction in intraocular pressure (IOP), the number of antiglaucoma drugs and the incidence of adverse events were evaluated using the new EliosTM method (Elios Vision GmbH, Germering, Germany) for real-life data from a heterogeneous patient population undergoing ELT in combination with cataract surgery (phaco-ELT).

In this study 20 eyes of 13 patients who underwent phaco-ELT were retrospectively analyzed. After standard phacoemulsification with posterior chamber lens implantation, 10 microchannels were created using the excimer laser. The patients were followed for 12 months and the intraocular pressure (IOP), number of antiglaucoma drugs and the occurrence of adverse events were analyzed.

The average age was 65 years. The preoperative IOP was 17.5 (± 5.3) mm Hg. The mean IOP reduction was 4.8 mm Hg (27.4%, p < 0.001) on the first postoperative day, 3.2 mm Hg (18.3%, p = 0.22) after 6 months and 2.5 mm Hg (14.3%, p = 0.14) at 12 months. The number of antiglaucoma drugs decreased from an average of 3.2 (± 1.3) preoperatively to 0.5 (± 0.9) on day 1 (p < 0.001), 1.9 (± 1.2) after 6 months (p = 0.008) and 2.2 (± 1.3) after 12 months (p = 0.013).

In our cohort ELT in combination with cataract surgery is a safe minimally invasive procedure leading to an IOP reduction of 14.3% and a reduction of pressure-lowering medication by 1 active ingredient in patients with low initial pressure at 1‑year follow-up. As no implant is used in ELT and the conjunctiva remains untouched, subsequent procedures, including bleb-related surgery, are not negatively affected.

The glaucoma treatment paradigm is in evolution. The topical medications-first approach is limited by significant barriers such as high rates of nonadherence and side effects including ocular surface disease. The era of interventional glaucoma has seen the development of selective laser trabeculoplasty (SLT), procedural pharmaceuticals, and minimally invasive glaucoma surgeries (MIGS). New and emerging data support the use of these interventional treatment modalities early in the course of glaucoma rather than reserving them for advanced or treatment-recalcitrant cases. The various treatments available represent multiple mechanisms (e.g., trabecular outflow, uveoscleral outflow, aqueous suppression) and modalities (medications, laser, incisional surgery) by which intraocular pressure (IOP) is reduced. Many patients require more than one treatment to achieve adequate IOP reduction and glaucoma control. Comprehensive IOP control-reduction of both mean IOP and IOP fluctuation-can best be achieved by targeting multiple mechanisms of IOP reduction and taking advantage of the attributes of multiple treatment modalities.

To investigate patients with primary aldosteronism (PA) and the prevalence of normal-tension glaucoma (NTG).

Cross-sectional study.

Newly diagnosed PA patients were evaluated in this cross-sectional study, with ophthalmic examinations such as intraocular pressure measurements by a Goldmann applanation tonometer, central corneal thickness, slit-lamp biomicroscopic examination, gonioscopy, ophthalmoscopy, fundus photography, visual field test with a Humphrey Field Analyzer 24-2 SITA Standard program, and optical coherence tomography of the peripapillary retinal nerve fiber layer, performed in each of the subjects. Optic disc appearance, perimetric results, optical coherence tomography results, and other ocular findings were all used for determining the glaucoma diagnosis. The primary outcome was shown the prevalence of NTG in patients with PA.

NTG prevalence in the 212 PA patients was 11.8% (95% confidence interval [CI], 4.7%-20.7%). As compared to the hypertensive patients without PA, the hypertensive patients with PA exhibited a significantly increased NTG prevalence (odds ratio; 4.019, 95% CI, 1.223-13.205; P = .022). Increased NTG prevalence was associated with age, ranging from 8.8% (95% CI, 2.1%-15.6%) for those aged 40 to 49 years, to 37.5% (95% CI, 13.8%-61.2%) for those aged 70 years and older. In 72 hypertensive patients without PA, who were used as the controls, NTG prevalence was 5.2%, with a 95% CI ranging from 0.5% to 14.4%.

There was an 11.8% prevalence of NTG in PA patients, with these patients at an elevated risk of NTG, which was not mediated by blood pressure.

Extended glucocorticoid (GC) treatment can lead to ocular hypertension and induce iatrogenic open-angle glaucoma. GC-induced glaucoma mimics many clinical and pathological features of primary open-angle glaucoma (POAG), and therefore mouse models of GC-induced glaucoma are utilized to study pathophysiology of glaucoma. We have recently demonstrated that weekly periocular injections of dexamethasone-21-acetate (Dex-Ac) lead to robust and significant intraocular pressure (IOP) elevation, retinal ganglion cell (RGC) loss, and optic nerve degeneration in mice. Our mouse model exhibits signature features of POAG including significant IOP elevation due to reduced outflow facility, progressive optic nerve degeneration, and structural and functional loss of RGCs. Dex-induced IOP elevation is associated with increased aqueous outflow resistance due to trabecular meshwork (TM) dysfunction including excessive extracellular matrix deposition and induction of endoplasmic reticulum stress. Mouse model of Dex-induced glaucoma represents an ideal animal model to investigate both glaucomatous damage to the TM and RGC axons and to develop novel therapies. Here, we present a detailed protocol for developing this model in laboratory settings.

There have been a number of clinical trials in glaucoma research published in the past two decades. Most of these trials were designed to evaluate very specific issues in selected populations placing them in the explanatory end of the pragmatic-explanatory continuum. The purpose of this study was to assess the level of pragmatism of published randomized controlled trials in glaucoma.

A PubMed search using 'glaucoma' from 1995 to 2022 and randomized controlled trial (RCT) article type was done. Each study was assessed by three independent examiners using the Pragmatic-Explanatory Continuum Indicator Summary version 2 (PRECIS-2) toolkit. Scores were calculated for each study to determine the level of pragmatism. A summed score ≥36 was indicative of a very pragmatic study.

Thirty-two different articles were included in the analysis. These papers represented 13 different landmark trials. The median PRECIS-2 score was 32 (range, 25 for the Early Manifest Glaucoma Trial (EMGT) to 34 to the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Ocular Hypertension Treatment Study). The Treatment of Advanced Glaucoma Study (TAGS), was considered very pragmatic and scored 33 points.

Despite the number of RCTs in glaucoma, there is still a need for more pragmatic studies.

Glaucoma is the leading cause of irreversible blindness with early detection and intervention critical to slowing disease progression. However, half of those affected are undiagnosed. This is largely due to the early stages of disease being asymptomatic; current population-based screening measures being unsupported; and a lack of current efficient prediction models. Research investigating polygenic risk scores (PRS) for glaucoma have shown predictive ability to identify individuals at higher risk. Potential clinical applications include identification of high-risk individuals, resulting in earlier diagnosis and treatment to prevent glaucoma blindness, and adjusted monitoring for low-risk individuals. However, the psychological impact of receiving glaucoma PRS is unknown. There is a critical need to evaluate risk information communication and assess the impact of receiving results, to support clinical implementation of glaucoma PRS testing. In this prospective study, 300 individuals from the GRADE (Genetic Risk Assessment of Degenerative Eye disease) study will be recruited to investigate the psychosocial impact of disclosing polygenic risk results for glaucoma. GRADE aimed to apply PRS testing on 1,000 unexamined individuals aged 50 years or older from the general population and examine a subset of these individuals to assess the clinical validity of PRS to detect glaucoma. In this study, individuals each from the bottom decile (10%), top decile (10%), and middle (45-55%) of the PRS distributions will be invited to receive research glaucoma PRS results. Participants who choose to receive their results will complete up to four questionnaires (prior to receiving their results, and subsequently two-weeks, six- and 12-months after receiving their result). The questionnaires will include health belief model measures and assess glaucoma anxiety, general anxiety and depression, test-related distress, decisional regret, and recall and understanding of results. This research will provide guidance for the implementation of polygenic risk testing into clinical practice and inform delivery strategies.

This study investigates the incidence and causes of diagnostic changes from primary open-angle glaucoma suspect (POAGS) to primary open-angle glaucoma (POAG), and vice versa, in clinical practice.

This is a retrospective, single-site, case-control study.

It includes patients > 40 years of age diagnosed with either POAG or POAGS between 2013 and 2020. Controls had a minimum of 24 months of follow-up without a diagnostic change, whereas cases underwent a diagnostic change from glaucoma to suspect (POAG to POAGS) or from suspect to glaucoma (POAGS to POAG) within 2 years.

At initial and follow-up visits, diagnosis, treatment, type of ophthalmic provider, and performance of pachymetry, visual fields (VFs), OCT, disc examination, and gonioscopy were recorded.

Data were then analyzed to determine if baseline characteristics, type of provider seen, or ophthalmic testing performed were protective or risk factors in regards to diagnostic change.

Nine hundred twenty-two subjects were included, and the incidence of diagnostic changes was 13.8% (127/922), of which 99 (78%) were upstaged from POAGS to POAG and 28 (22%) changed from POAG to POAGS. Pre-existing nonglaucomatous VF defect (P < 0.001) was significantly higher in cases than controls. Cases were significantly less likely to be seen by a glaucoma specialist at the initial visit compared with controls (P < 0.001), and less cases underwent VF testing (P < 0.001), OCT testing (P = 0.017), or gonioscopy (P = 0.013) at the initial visit. On multivariate analysis, performing VFs or OCT at both visits reduced the odds of short-term diagnostic change, whereas changing providers from a nonglaucoma specialist to a glaucoma specialist between visits increased the odds of diagnostic change. In the POAG-to -POAGS cases, 39% (11/28) were treated with either medications or laser trabeculoplasty, whereas 72% (71/99) of the POAGS-to-POAG cases were left untreated between visits.

It is important to understand risk factors for diagnostic changes in glaucoma, in order to prevent undertreatment of disease and overtreatment of suspects. Here we find specialist type and adherence to American Academy of Ophthalmology (AAO) recommended testing to be important factors in preventing short term diagnostic changes.

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background/Objectives: Primary open-angle glaucoma (POAG), if caused by elevated intraocular pressure (IOP), may require a trabeculotomy (LOT), in which the trabecular meshwork (TM) and Schlemm's canal (ISC) are incised. However, the association between the incision angle and outcomes remains unclear. Therefore, in this study, we investigated the surgical outcomes of a trabeculotomy combined with cataract surgery in patients with POAG over a 12-month follow-up period. Methods: We included 66 patients (corresponding to 83 eyes) with POAG who underwent trabeculotomy ab externo with a metal probe (M-LOT: 120° incision of the TM and ISC), ab interno with a Kahook Dual Blade® (K-LOT: 180° incision of the TM and ISC), or ab interno with a 5-0 nylon suture (S-LOT: 360° incision of the TM and ISC) between January 2015 and December 2022. We assessed IOP, the percentage reduction from preoperative IOP, the number of IOP-lowering medications taken, the incidence of postoperative complications, and the success rate using Kaplan-Meier survival analysis. Results: The median IOP was significantly lower than the baseline across all three groups. The number of IOP-lowering medications taken was significantly reduced only in the M-LOT group. The mean percentage reduction from the preoperative IOP in the K-LOT group was significantly lower than that in the M and S-LOT groups. Beween those subjected to an ab ineterno LOT, the S-LOT group demonstrated a significantly higher rate of IOP reduction 12 months after the operation compared to the K-LOT group. Kaplan-Meier cumulative survival analyses revealed a lower success rate for the K-LOT group than for the M and S-LOT groups. The M-LOT group had the lowest incidence of hyphema and IOP spikes, whereas the S-LOT group had the highest incidence of these complications. Conclusions: The M-, K-, and S-LOTs had different surgical outcomes during the 12 months of follow-up, with the M-LOT group showing the fewest complications. These results will help in selecting the most suitable trabeculotomy strategy for patients with POAG. Based on the postoperative outcomes of the ab interno K- and S-LOTs, a wider incision of the TM and ISC leads to effective IOP reduction.

To report the safety and effectiveness of selective laser trabeculoplasty (SLT) using the SLT mode of the VISULAS® green laser in patients with primary open-angle glaucoma (POAG). Twelve months results are presented. Retrospective extension in 4 German centers of an initially prospective interventional multicenter 3-month clinical investigation using the VISULAS® green SLT (Carl Zeiss Meditec AG, Jena, Germany) in patients with POAG who either needed treatment escalation or commenced treatment and had an IOP ≥ 17mmHg at baseline, with no previous glaucoma or other ocular surgery. Non-overlapping laser spots (100) were applied in a single session to 360° of the trabecular meshwork (TM). Glaucoma medications were not changed up to the 3-month visit. From 3 to 12 months, patients were managed according to routine standard of care. Outcome measures included IOP reduction, further glaucoma interventions, and adverse events from baseline to month 12. 25 eyes of 25 POAG patients (mean age 65.8 ± 8.5; modified intention to treat - mITT -group) were included in the extension study. Six eyes (24%) underwent additional glaucoma treatment or changed glaucoma therapy; the remaining 19 eyes (76%) had stable glaucoma therapy (SGT group) with no further glaucoma intervention or change in glaucoma medications (mean number of preoperative glaucoma medications: 2.3 ± 1.34). In the SGT group, mean baseline IOP (mmHg) was reduced from 20.0 ± 2.11 at baseline to 17.4 ± 3.25 and 16.2 ± 1.83 at 6 to 12 months, respectively (p < 0.0001): 52.6% had ≥ 20% IOP reduction at 12 months. Potential device- or procedure-related adverse events were mild to moderate and resolved without sequelae. SLT performed with the VISULAS® green laser reduced IOP in eyes with POAG up to 12 months with no relevant safety issues. The results are comparable to other reported SLT studies.

In primary open angle glaucoma, the rate of retinal nerve fiber layer thickness decrease was negatively correlated with lamina cribrosa strain, which was associated with intraocular pressure and optic nerve head geometric factors.

We hypothesized that the biomechanical deformation of the optic nerve head (ONH) contributes to the progression of primary open angle glaucoma (POAG). This study investigated the biomechanical stress and strain on the ONH in patients with POAG using computer simulations based on finite element analysis and analyzed its association with disease progression.

We conducted a retrospective analysis that included patients diagnosed with early-to-moderate stage POAG. The strains and stresses on the retinal nerve fiber layer (RNFL) surface, prelaminar region, and lamina cribrosa (LC) were calculated using computer simulations based on finite element analysis. The correlations between the rate of RNFL thickness decrease and biomechanical stress and strain were investigated in both the progression and nonprogression groups.

The study included 71 and 47 patients in the progression and nonprogression groups, respectively. In the progression group, the factors exhibiting negative correlations with the RNFL thickness decrease rate included the maximum and mean strain on the LC. In multivariate analysis, the mean strain on the LC was associated with optic disc radius, optic cup deepening, axial length, and mean intraocular pressure (IOP), whereas the maximum strain was only associated with mean IOP.

In early-to-moderate stage POAG, the rate of RNFL thickness decrease was influenced by both the mean and maximum strain on the LC. Strains on the LC were associated with mean IOP, optic disc radius, axial length, and optic cup deepening. These results suggest that not only IOP but also ONH geometric factors are important in the progression of glaucoma.

The Laser in Glaucoma and Ocular Hypertension Trial demonstrated the efficacy and safety of selective laser trabeculoplasty (SLT) compared with topical hypotensive medication as first-line therapy for ocular hypertension and open-angle glaucoma. This substudy explored the impact of pretreatment (baseline) intraocular pressure (IOP) on treatment response.

Post hoc analysis of randomized control trial data.

A total of 1146 eyes from 662 patients were included in this analysis: 559 eyes in the SLT group and 587 in the medication group.

Intraocular pressure reduction at 8 weeks after treatment with either SLT or prostaglandin analog (PGA) eye drops was assessed at different levels of baseline IOP, and the groups were compared. Differences in absolute and percentage IOP lowering between SLT and PGA groups were tested with a linear mixed-effects model. Differences in the probability of achieving ≥ 20% IOP lowering between SLT and PGA groups, at different levels of baseline IOP, were estimated using a logistic mixed-effects model.

Intraocular pressure-lowering response to SLT versus PGA eye drops.

Mean IOP was not significantly different between the groups at baseline or 8 weeks after treatment initiation. Both treatments showed greater IOP lowering at higher baseline IOP and less IOP lowering at lower baseline IOP. Selective laser trabeculoplasty tended to achieve more IOP lowering than PGA drops at higher baseline IOP. Prostaglandin analog drops performed better at lower baseline IOP, and the difference compared with SLT, in terms of percentage IOP reduction, was significant at baseline IOP of ≤ 17 mmHg. A significant difference was found in the relationship between baseline IOP and probability of ≥ 20% IOP lowering between the two treatments (P = 0.01), with SLT being more successful than PGA at baseline IOP of more than 22.5 mmHg.

We confirm previous reports of greater IOP lowering with higher baseline IOP for both SLT and PGA drops. In treatment-naïve eyes, at higher baseline IOP, SLT was more successful at achieving ≥ 20% IOP lowering than PGA drops. At lower baseline IOP, a statistically greater percentage, but not absolute, IOP lowering was seen with PGA drops compared with SLT, although the clinical significance of this is uncertain.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

High myopia (HM) is a significant risk factor for the occurrence and progression of primary open-angle glaucoma (POAG). Identification with POAG in the HM population is an emergent challenge. Patients with HM have a significantly higher probability of complicating POAG than those without HM. When HM is associated with POAG, the changes to the fundus caused by both of them are confused with each other, making the diagnosis of early glaucoma difficult. This article reviews available researches on HM with POAG, summarizing the characteristics of the fundus structure such as epidemiology, intraocular pressure, optic disc, ganglion cell layer, retinal nerve fiber layer, vascular density, and visual field.

To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up.

A retrospective analysis of prospectively collected data from the Fight Glaucoma Blindness observational registry. Complete success (CS) was defined as intraocular pressure (IOP) reduction ≥20% from preoperative and an IOP ≤18 mm Hg and ≥6 mm Hg with no secondary procedure at 2 years and without IOP-lowering medications. Qualified success (QS) was defined similarly, allowing the use of IOP-lowering medications.

The Xen 45 gel stent implant was implanted in 646 eyes of 515 patients. Preoperative IOP was 21.4±7.6 (mean±SD) mm Hg on 2.7±1.3 IOP-lowering medication and mean deviation was -10.2±8.4 dB. After 24-month follow-up, IOP was 16.8±7.3 mm Hg (mean reduction of 21.7%) on 1.2±1.4 IOP-lowering medications. CS and QS rates at 24 months were 26% and 48%, respectively. CS and QS were higher in the Xen stand-alone group (33% and 52%, respectively) than in the Xen+cataract group (16% and 42%, respectively). Bleb needling was performed in 28.4% of cases, and 18% underwent a secondary procedure.

The Xen 45 gel stent implant offers acceptable long-term efficacy for the treatment of open-angle glaucoma. However, there is a significant rate of reoperation and needling, and outcomes are less effective if combined with cataract surgery.

Topical agents to lower intraocular pressure (IOP) are the most common initial therapeutic measure in glaucoma prevention. This study aims to assess treatment success duration among patients initiating or intensifying topical glaucoma medication.

Medical records (2013‒2018) for adults initiating/intensifying topical glaucoma medication were extracted from five secondary-care and tertiary-care UK ophthalmology centres. Main study outcomes were time from treatment initiation/intensification to treatment failure (<20% IOP reduction or IOP >21 mm Hg at consecutive clinic visits, or intensification of glaucoma treatment) and time from treatment change to subsequent treatment intensification.

Study eyes (n=6587) underwent treatment intensification 0-to-1 glaucoma drop (5358 events), 1-to-2 drops (1469 events) and 2-to-3 drops (857 events) during the observation period. Median time to treatment failure was 1.60 (95% CI 1.57 to 1.65), 1.00 (95% CI 0.94 to 1.07) and 0.92 (95% CI 0.81 to 1.02) years following escalation 0-to-1, 1-to-2 and 2-to-3 drops, respectively. Median time to treatment intensification (non-IOP-based criterion) was 4.68 (95% CI 4.50 to 5.08) years for treatment initiators, 3.83 (95% CI 3.36 to 4.08) years on escalation 1-to-2 drops and 4.35 (95% CI 3.82 to 4.88) years on escalation 2-to-3 drops. On multivariable regression, significant risk factors for both treatment failure and intensification were lower baseline visual field mean deviation, primary open-angle glaucoma and lower eyedrop count in the fellow eye; lower baseline IOP was associated with treatment failure, higher baseline IOP with treatment intensification.

Large-scale survival analyses provide the expected duration of treatment success from topical glaucoma medication.

This review evaluates the impact of transient intraocular pressure (IOP) elevations during common ophthalmic surgical and diagnostic procedures on glaucoma patients. Elevated IOP is a key risk factor in glaucoma, and while transient IOP spikes are frequently encountered during surgeries like cataract extraction, laser in situ keratomileusis (LASIK), and femtosecond laser-assisted cataract surgery (FLACS), the clinical significance of these short-term elevations remains uncertain, particularly for eyes with compromised optic nerves. There is still a lack of data on which IOP level and duration of IOP insult the glaucoma damage occurs. Still, it is known that the combination of the degree of IOP elevation, duration of the insult and optic nerve susceptibility are important determinants of this event. While transient IOP elevations during these procedures are generally well tolerated, patients with advanced glaucoma and severely compromised optic nerves may be at greater risk for further damage. More research is needed to fully understand the long-term implications of acute IOP spikes, particularly in patients with advanced disease.

The risk for developing primary open-angle glaucoma (POAG) correlates with the magnitude of ocular hypertension (OHT) and the concentration of transforming growth factor-β2 (TGFβ2) in the aqueous humor. Effective treatment of POAG requires detailed understanding of interaction between pressure sensing mechanisms in the trabecular meshwork (TM) and biochemical risk factors. Here, we employed molecular, optical, electrophysiological and tonometric strategies to establish the role of TGFβ2 in transcription and functional expression of mechanosensitive channel isoforms alongside studies of TM contractility in biomimetic hydrogels, and intraocular pressure (IOP) regulation in a mouse model of TGFβ2 -induced OHT. TGFβ2 upregulated expression of TRPV4 and PIEZO1 transcripts and time-dependently augmented functional TRPV4 activation. TRPV4 activation induced TM contractility whereas pharmacological inhibition suppressed TGFβ2-induced hypercontractility and abrogated OHT in eyes overexpressing TGFβ2. Trpv4-deficient mice resisted TGFβ2-driven increases in IOP. Nocturnal OHT was not additive to TGFβ-evoked OHT. Our study establishes the fundamental role of TGFβ as a modulator of mechanosensing in nonexcitable cells, identifies TRPV4 channel as the final common mechanism for TM contractility and circadian and pathological OHT and offers insights future treatments that can lower IOP in the sizeable cohort of hypertensive glaucoma patients that resist current treatments.

To evaluate the sustainability of IOP reduction with continuous negative pressure application over an extended duration with use of the Ocular Pressure Adjusting Pump.

Prospective, controlled, open-label, randomized, single site, pilot study. Subjects with primary open-angle glaucoma (OAG) were enrolled. One eye of each subject was randomized to receive negative pressure application; the fellow eye served as a control. The study eye negative pressure setting was programmed for 60% of the baseline IOP. Subjects wore the Ocular Pressure Adjusting Pump for 8 consecutive hours and IOP measurements occurred at 2-hour intervals for a total of 5 IOP measurements (08:00, 10:00, 12:00, 14:00, 16:00).

Nine subjects successfully enrolled and completed the study. The mean programmed negative pressure setting was -12.0 mmHg. At baseline, the mean IOP in the study eye was 21.4 ± 4.3 mmHg. The mean IOP reduction in the study eye at hours 0, 2, 4, 6, and 8 was 8.1 (37%), 6.4 (28%), 6.3 (29%), 7.3 (34%) and 6.7 (31%), respectively. All IOP measurements during negative pressure application were reduced from baseline. There were no serious adverse events.

The Ocular Pressure Adjusting Pump provides a sustained reduction in IOP while the device is worn with negative pressure applied with an IOP reduction exceeding 25% across 8 hours of continuous wear.

Nocturnal intraocular pressure (IOP) profiling has shown that the peak IOP usually occurs at night, particularly in patients with glaucoma. Multiple studies have demonstrated that these nocturnal IOP elevations drive glaucomatous progression, often despite stable daytime IOP. Existing vascular dysregulation and decreased nighttime blood pressure compound the damage via low ocular perfusion pressure while elevated nocturnal IOP disrupts axonal transport. These findings are consistent with studies that indicate lowering nocturnal IOP is important for slowing glaucoma progression. Many of the current treatment options lower nighttime IOP significantly less than daytime IOP. Non-invasive IOP-lowering treatments that effectively lower nocturnal IOP remain an unmet need in the treatment of glaucoma.

IOP-induced mechanical insult on retinal ganglion cell axons within the optic nerve head (ONH) is believed to be a key factor in axonal damage and glaucoma. However, most studies focus on tissue-level mechanical deformations, overlooking that axons are long and thin, and that their susceptibility to damage likely depends on the insult's type (e.g. stretch/compression) and orientation (longitudinal/transverse). We propose an axon-centric approach to quantify IOP-induced mechanical insult from an axon perspective.

We used optical coherence tomography (OCT) scans from a healthy monkey eye along with histological images of cryosections to reconstruct the axon-occupied volume including detailed lamina cribrosa (LC) pores. Tissue-level strains were determined experimentally using digital volume correlation from OCT scans at baseline and elevated IOPs, then transformed into axonal strains using axon paths estimated by a fluid mechanics simulation.

Axons in the LC and post-LC regions predominantly experienced longitudinal compression and transverse stretch, whereas those in the pre-LC and ONH rim mainly suffered longitudinal stretch and transverse compression. No clear patterns were observed for tissue-level strains.

Our approach allowed discerning axonal longitudinal and transverse mechanical insults, which are likely associated with different mechanisms of axonal damage. The technique also enabled quantifying insult along individual axon paths, providing a novel link relating the retinal nerve fiber layer and the optic nerve through the LC via individual axons. This is a promising approach to establish a clearer connection between IOP-induced insult and glaucoma. Further studies should evaluate a larger cohort.

Our purpose was to develop a protocol for prolonged anesthesia in mice and evaluate optic nerve axon injury in response to 4 h of controlled elevation of intraocular pressure (CEI). During CEI, C57BL/6 male mice (3-5 months old) were anesthetized with 1.5% isoflurane with 100% oxygen for 4 h and placed on a warm platform, with expired gas and anesthetic actively evacuated. Lactated ringers (0.5 ml) with 5% dextrose was administered subcutaneously at the start and end of CEI. Physiological parameters (oxygen saturation = O2, heart rate = HR, systolic blood pressure = SBP, and temperature) were monitored throughout the 4-h CEI. One eye was cannulated with polyurethane tubing connected to a balanced salt solution reservoir and IOP elevated to 20 (N = 18), 30 (N = 13), 50 (N = 14), and 60 mmHg (N = 16). An additional group of 22 female mice was exposed to CEI of 60 mmHg. Fourteen days after CEI, optic nerves were assessed for axonal injury by masked observers that assigned a grade on a scale from 1 (normal) to 5 (>50% of axons degenerating). CEI optic nerve injury was compared to injury assessed in contralateral optic nerves (N = 84) and naïve optic nerves (N = 18) using a one-way ANOVA followed by Kruskal-Wallis test for multiple comparisons. The relationship between optic nerve injury, physiological parameters, and IOP were assessed by linear regression analyses. Physiologic parameters remained stable throughout CEI (O2 = 95 ± 9%; HR = 450 ± 39; SBP = 102 ± 15 mmHg, and temperature = 38 ± 0.7 °C) and were not statistically different between groups (all comparisons had P > 0.5). Mean optic nerve injury grades (±SD) for naïve optic nerves (1.01 ± 0.02) were not significantly different from fellow/contralateral optic nerves (1.03 ± 0.07, P > 0.99), or from CEI of 20 mmHg (1.04 ± 0.08, P > 0.99) or 30 mmHg (1.05 ± 0.06, P = 0.6). However, animals exposed to CEI of 50 mmHg (2.09 ± 1.43, P = 0.0005) and 60 mmHg (male: 2.86 ± 1.30, P < 0.0001, female: 1.63 ± 1.00, P = 0.0006) developed significant optic nerve injury relative to their fellow/contralateral optic nerves. Axonal injury grades following a CEI of 60 mmHg were not significantly different between male and female mice (P = 0.19). Optic nerve injury positively correlated (P < 0.0001) with IOP and not with physiological parameters, indicating that the optic nerve injury is IOP-related. In conclusion, prolonged anesthesia in mice requires careful attention to animal physiology. With this, a 4-h exposure to elevated IOP can produce significant optic nerve injury with IOPs equal to or greater than 50 mmHg. We provide detailed descriptions of methods and materials for producing prolonged elevations of IOP in mice while maintaining and monitoring their physiology, as well as a unique, cost-effective transducer system for monitoring pressure delivery.

Glaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context. In this study, we evaluated mitochondrial genome variation and heteroplasmy using massively parallel sequencing of mtDNA in a cohort of patients with POAG, and in a subset assess the role of somatic mitochondrial genome mutations in disease pathogenesis using paired samples of peripheral blood leukocytes and ocular tissue (Tenon's ocular fibroblasts). An enrichment of potentially pathogenic nonsynonymous mtDNA variants was identified in Tenon's ocular fibroblasts from participants with POAG. The absence of oxidative DNA damage and predominance of transition variants support the concept that errors in mtDNA replication represent the predominant mutation mechanism in Tenon's ocular fibroblasts from patients with POAG. Pathogenic somatic mitochondrial genome mutations were observed in people with POAG. This supports the role of somatic mitochondrial genome variants in the etiology of glaucoma.

To evaluate the intraocular pressure (IOP) behavior after applying a standardized protocol to induce psychological stress in patients with primary open-angle glaucoma (POAG).

Randomized controlled trial.

A total of 39 patients with POAG were included: 18 in the stress group and 21 in the control group.

Patients were randomized to undergo the Trier Social Stress Test (TSST) or to be included in the control group. All participants were submitted to a modified diurnal tension curve (DTC) 1-4 weeks before randomization, with 3 IOP measurements performed between 8:00 am and 2:00 pm. We evaluated the response to the TSST by measuring the levels of salivary cortisol, salivary amylase, IOP, mean arterial pressure, and heart rate before, immediately after, and 40 minutes after the TSST. The State Trait Anxiety Inventory (STAI) was applied to evaluate the levels of anxiety at the same time intervals.

Changes in IOP (mmHg), salivary cortisol and amylase, heart rate, mean arterial pressure, and STAI scores.

At baseline, there were no significant differences between the groups regarding age (P = 0.661), sex (P = 0.669), salivary cortisol (P = 0.104), and mean DTC IOP for the right (P = 0.439) and left (P = 0.576) eyes. We observed a significant mean IOP increase of 3.8 mmHg (right eye; P < 0.001) and 4.1 mmHg (left eye; P < 0.001) when we compared IOP measurements obtained during the DTC and immediately after TSST. Salivary cortisol (5.9 nmol/L; P = 0.004), salivary amylase (323 388 UL; P = 0.004), mean arterial pressure (10.1 mmHg; P < 0.001), and heart rate (12.9 bpm; P < 0.001) also increased significantly after the TSST. In addition, 61.1% (11 of 18) of the patients in the TSST group showed an IOP increase > 4 mmHg following the test. The STAI-state score significantly increased after the TSST compared to baseline (P < 0.001) and decreased from poststress to the recovery period (P < 0.001).

Patients with POAG present significant elevations of IOP, salivary cortisol and amylase, mean arterial pressure, heart rate, and STAI scores after psychological stress induced by the TSST.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intraocular pressure (IOP) is the most important modifiable risk factor for glaucoma and fluctuates considerably within patients over short and long time periods. Our field's understanding of IOP has evolved considerably in recent years, driven by tonometric technologies with increasing accuracy, reproducibility, and temporal resolution that have refined our knowledge regarding the relationship between IOP and glaucoma risk and pathogenesis. The goal of this article is to review the published literature pertinent to the following points: 1) the factors that determine IOP in physiologic and pathologic states; 2) technologies for measuring IOP; 3) scientific and clinical rationale for measuring diverse IOP metrics in patients with glaucoma; 4) the impact and shortcomings of current standard-of-care IOP monitoring approaches; 5) recommendations for approaches to IOP monitoring that could improve patient outcomes; and 6) research questions that must be answered to improve our understanding of how IOP contributes to disease progression. Retrospective and prospective data, including that from landmark clinical trials, document greater IOP fluctuations in glaucomatous than healthy eyes, tendencies for maximal daily IOP to occur outside of office hours, and, in addition to mean and maximal IOP, an association between IOP fluctuation and glaucoma progression that is independent of mean in-office IOP. Ambulatory IOP monitoring, measuring IOP outside of office hours and at different times of day and night, provides clinicians with discrete data that could improve patient outcomes. Eye care clinicians treating glaucoma based on isolated in-office IOP measurements may make treatment decisions without fully capturing the entire IOP profile of an individual. Data linking home blood pressure monitors and home glucose sensors to dramatically improved outcomes for patients with systemic hypertension and diabetes and will be reviewed as they pertain to the question of whether ambulatory tonometry is positioned to do the same for glaucoma management. Prospective randomized controlled studies are warranted to determine whether remote tonometry-based glaucoma management might reduce vision loss and improve patient outcomes.