Lower Intraocular Pressure Research Articles

Exploring the relationship between accommodation and intraocular pressure: a systematic literature review and meta-analysis.

To investigate the relationship between accommodation and intraocular pressure (IOP). Systematic literature search and meta-analysis following PRISMA guidelines was conducted on studies analyzing the relationship between accommodation and intraocular pressure. After removal of duplicates, title and abstract screening, full-text analysis was performed to select relevant articles and meta-analysis was then conducted as well. Of the 1357 records identified, 17 met the selection criteria and were included. Overall, all studies showed that accommodation can influence IOP levels and meta-analysis indicated a significant IOP reduction of 1.10 mmHg (95%CI, -1.77; -0.42) following accommodative stimulus in healthy individuals, albeit with high heterogeneity among studies. Differences in IOP changes between emmetropic and progressing myopic individuals were not significant. Controversial results were obtained in patients with glaucoma with significantly lower IOP fluctuations being noted in eyes with previous trabeculectomy; however, the clinical heterogeneity of enrolled patients among studies made it not possible to combine results. Type of accommodative task, extraocular muscle contraction, head and body position all could potentially play a role in the measured IOP changes with, interestingly, near reading on a smartphone suggesting IOP increase. Accommodation has an impact on IOP measurements and, overall, determines IOP decrease in healthy individuals. While such variations might not hold clinical significance for individuals in good health, their impact in patients with glaucoma should be considered. Further studies focused on specific components of such relationship are required to elucidate their individual impact and to define their potential role as non-pharmacological strategies to reduce IOP levels in selected patient categories.

A Detailed Study of Glaucoma in Adults, Its Pathogenesis, Diagnosis and Management

As the second most prevalent cause of blindness in the world, after cataracts, glaucoma diagnosis and treatment are crucial topics for general physicians to know. Glaucomas can often be categorised based on three key factors: the extent to which the anterior chamber angle is open or closed, the intensity of the onset (acute or chronic), and the underlying cause (primary or secondary). Most cases of glaucoma are primary, indicating the absence of any comorbidities. Nevertheless, secondary glaucomas may arise from a range of visual illnesses as their root cause. Individuals who are susceptible to developing chronic glaucoma should undergo regular eye examinations in order to detect the condition at an early stage and prevent the progressive deterioration of vision that may occur prior to diagnosis. Glaucoma leads to impairments in both central and peripheral vision fields due to damage to the optic nerve and the retinal nerve fibre layer. All current treatments, including drugs, lasers, and procedures, aim to reduce intraocular pressure (IOP) because it is the only factor that can be changed and is crucial in the progression of the condition. Pharmacotherapy is the usual first-line treatment, although its effectiveness is constrained by noncompliance, adverse effects, and cost. While laser and surgical methods offer the ability to effectively lower intraocular pressure (IOP) for extended periods and at a lower cost compared to medicine, they come with increased risks during the process and a higher likelihood of treatment not being successful. Various modern minimally invasive glaucoma operations have replaced conventional incisional therapies because they offer improved safety and reduced efficacy decreases. While the long-term success of minimally invasive glaucoma surgeries still needs to be determined by large-scale randomised trials, these methods have greatly transformed the surgical treatment of glaucoma.

A 4-Year Retrospective Study: Clinical Outcomes of XEN45 in Patients with Glaucoma.

The main purpose of the current study was to evaluate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with cataract surgery, in patients with glaucoma. Retrospective and single center study conducted on consecutive patients who underwent a XEN45 implant, either alone or in combination with cataract surgery, between November 2016 and October 2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values. Among the 230 screened patients, 206 eyes (176 patients) were included. Fifty-three (25.7%) eyes had undergone XEN alone and 153 (74.3%) eyes had undergone a combined procedure (XEN+phacoemulsification). The mean preoperative IOP was significantly higher in the XEN-alone (22.2 ± 5.9 mm Hg) than in the XEN+Phaco (19.8 ± 4.5 mm Hg) group (p = 0.0035). In the overall study population, the mean preoperative IOP was significantly lowered from 20.5 ± 5.0 mm Hg to 15.8 ± 4.4 at year-4, p < 0.0001. The mean preoperative (95% confidence interval) IOP was significantly lowered from 22.2 (20.6-23.8) mm Hg and 19.8 (19.1-20.6) mm Hg to 15.6 (12.2-16.9) mm Hg and 15.9 (15.2-16.5) mm Hg at year-4 in the XEN-alone and XEN+Phaco groups, respectively (p < 0.0001 each, respectively). The number of ocular hypotensive medications was significant reduced from 2.6 ± 1.0 drugs to 1.3 ± 1.3 drugs, with no significant differences between XEN-alone and XEN+Phaco groups (p = 0.1671). On the first postoperative day, 62 (30.1%) eyes presented some type of complication. Fifteen (7.3%) eyes underwent a needling procedure. XEN45, either alone or in combination with phacoemulsification, significantly lowered the IOP and reduced the need of ocular hypotensive medication in the long-term.

TRPV4 subserves physiological and pathological elevations in intraocular pressure.

Ocular hypertension (OHT) caused by mechanical stress and chronic glucocorticoid exposure reduces the hydraulic permeability of the conventional outflow pathway. It increases the risk for irreversible vision loss, yet healthy individuals experience nightly intraocular pressure (IOP) elevations without adverse lifetime effects. It is not known which pressure sensors regulate physiological vs. pathological OHT nor how they impact the permeability of the principal drainage pathway through the trabecular meshwork (TM). We report that OHT induced by the circadian rhythm, occlusion of the iridocorneal angle and glucocorticoids requires activation of TRPV4, a stretch-activated cation channel. Wild-type mice responded to nocturnal topical administration of the agonist GSK1016790A with IOP lowering, while intracameral injection of the agonist elevated diurnal IOP. Microinjection of TRPV4 antagonists HC067047 and GSK2193874 lowered IOP during the nocturnal OHT phase and in hypertensive eyes treated with steroids or injection of polystyrene microbeads. Conventional outflow-specific Trpv4 knockdown induced partial IOP lowering in mice with occluded iridocorneal angle and protected retinal neurons from pressure injury. Indicating a central role for TRPV4-dependent mechanosensing in trabecular outflow, HC067047 doubled the outflow facility in TM-populated steroid-treated 3D nanoscaffolds. Tonic TRPV4 signaling thus represents a fundamental property of TM biology as a driver of increased in vitro and in vivo outflow resistance. The TRPV4-dependence of OHT under conditions that mimic primary and secondary glaucomas could be explored as a novel target for glaucoma treatments.

Two-Year Results of XEN Gel Stent Implantation for Pseudoexfoliative Glaucoma in Phakic versus Pseudophakic Eyes.

Objectives: To investigate whether phakia affects the outcome of XEN-45 gel stent implantation in the treatment of pseudoexfoliative glaucoma (PXG). Methods: A retrospective, comparative cohort study of 30 phakic and 55 pseudophakic PXG patients who received the XEN-45 gel stent at a tertiary centre. The primary outcome measure was two-year success defined as a ≥20% lowering of intraocular pressure (IOP) and a target IOP of 6-21 mmHg. Success was complete without and qualified irrespective of antiglaucoma medication use. Further glaucoma surgery other than needling was regarded as a failure. The secondary outcome measures included changes in IOP, revision and complication rates. Results: The complete two-year success rates were 70% and 59% in the phakic and pseudophakic groups, respectively (p = 0.75, log-rank test), and the qualified rates were 80% and 72%, respectively (p = 0.89). The median IOP reduction from baseline was 54% in phakic, and 46% in pseudophakic eyes. While needling rates were similar, the incidence of early incisional bleb revisions was significantly higher in the phakic eyes (13% vs. 0% within 3 months; p = 0.0098, chi-square). Increasing after a year, significantly more pseudophakic eyes failed due to secondary glaucoma surgery (16% vs. 0%; p = 0.0191). Conclusions: The XEN-45 gel stent offers equally effective IOP control for both phakic and pseudophakic patients. However, the onset of bleb revisions and the necessity for secondary glaucoma surgery differed significantly between the groups.

Travoprost Intracameral Implant Demonstrates Superior IOP Lowering Versus Topical Prostaglandin Analog Monotherapy in Patients with Open-Angle Glaucoma or Ocular Hypertension.

This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of -5.76mmHg and -7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: -2.01, -0.60; P = 0.0003). The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124.

Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma

PurposeTo identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DesignRetrospective cohort study. MethodsA total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of cirrus OCT. ResultsThirty-two eyes displayed choroidal MvD (62.7 (95% CI 58.4-67.0) years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV≥1400cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P=0.023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P=0.025). ConclusionsIn NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Long-term effectiveness and safety of XEN45 in open-angle glaucoma patients.

To investigate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with phacoemulsification, in eyes with open-angle glaucoma (OAG). Retrospective and single center study conducted on consecutive OAG patients who underwent a XEN45 implant between February-2017 and December-2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values. Surgical success was defined as an IOP-lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 13mmHg, without (Complete-success) or with (Qualified-success) antiglaucoma medications. A total of 158 eyes (34 (21.5%) eyes XEN-solo and 124 (78.5%) XEN + Phaco) were included. The median follow-up time was 28.5months. In the overall study population, the mean preoperative IOP was significantly lowered from 19.4 ± 6.5mmHg to 12.4 ± 5.0mmHg. The mean preoperative (95% confidence interval) IOP was significantly lowered from 21.3 (19.3-23.2)mmHg and 18.8 (17.7-20.0)mmHg to 12.0 (10.4-13.6)mmHg and 12.5 (11.6-13.5)mmHg in the XEN-Solo and XEN + Phaco groups, respectively (p < 0.0001 each, respectively). The mean number of ocular-hypotensive medications was significantly reduced in the overall study sample (from 3.4 ± 0.9 to 0.9 ± 1.3, p < 0.0001), XEN-Solo (from 3.5 ± 1.1 to 0.6 ± 1.0, p < 0.0001, and XEN + Phaco (from 3.4 ± 1.1 to 0.9 ± 1.3, p < 0.0001) groups. Eighty-four (53.2%) eyes were categorized as success, with 49 (58.3%) classified as complete success. Eighty-one (51.3%) eyes underwent needling and 15 (9.5%) eyes required an additional surgical procedure. One (0.6%) eye had endophthalmitis. XEN implant, either alone or in combination with phacoemulsification significantly lowered IOP and reduced the need of ocular-hypotensive medication, while maintaining a good safety profile.

The Impact of Baseline Intraocular Pressure on Initial Treatment Response in the LiGHT Trial: Selective Laser Trabeculoplasty versus Medication

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.

Subconjunctival Administration of an Adeno-Associated Virus Expressing Stanniocalcin-1 Provides Sustained Intraocular Pressure Reduction in Mice

PurposeTo investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express Stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained intraocular pressure (IOP) lowering agent with a reduced ocular surface side effect profile. DesignIn vivo pre-clinical investigation in mice SubjectsC57BL/6J, DBA/2J, FP receptor knockout mice MethodsNormotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 x 109 viral genomes [VGs]) in one eye and the same volume and concentration of ssAAV2-GFP or the same volume of PBS in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. FP receptor knockout mice were injected subconjunctivally with 6 x 109 VGs of ssAAV2-STC-1-FLAG or PBS. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. IOP was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1 and other treatments including daily topical latanoprost. Main outcome measuresIOP assessment ResultsSubconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 2 post injection (17.4%; 17.1 ± 0.8 vs 14.1 ± 0.8 mmHg, P<0.001). After the IOP-lowering effect had waned, a second injection restored the ocular hypotensive effect. Subconjunctivally delivered ssAAV2-STC-1-FLAG lowered IOP in DBA/2J mice (16.9%; 17.8 ± 2.0 vs 14.8 ± 0.9 mmHg, P<0.001) and steroid-mediated ocular hypertensive mice (19.4%; 18.7 ±0.9 vs 15.1 ± 0.5 mmHg, P<0.001) over the experimental period. This construct also reduced IOP to a similar extent in wild type (15.9%) and FP receptor knockout (15.7%) mice compared to the fellow eye. A related construct also lowered IOP without the FLAG tag in a similar manner. Reduction in conjunctival TNFα was seen when comparing subconjunctivally delivered ssAAV2-STC-1-FLAG to daily topical latanoprost. ConclusionsSubconjunctival delivery of the STC-1 transgene with a vector system may represent a novel treatment strategy for sustained IOP reduction and improved ocular tolerability that also avoids the daily dosing requirements of currently available medications.

Secondary Glaucoma after Cataract Surgery Performed in Infancy in Congenital Rubella Syndrome: A Case Control Study

ObjectiveTo compare the incidence of secondary glaucoma after cataract surgery performed in infancy in children with congenital rubella syndrome (CRS) and children with non-rubella cataracts and to identify associated risk factors. DesignRetrospective case control study. ParticipantsChildren with CRS who had undergone cataract surgery in infancy and age matched infants who had undergone cataract surgery for infantile cataracts were included. MethodsIncidence of glaucoma and probability of survival was compared among the two groups. Risk factors for the development of glaucoma were assessed. The minimum follow up was 1 year after cataract surgery. ResultsThe study included 211 eyes of 115 children. The CRS group (cases) had 101 eyes (58 children) and the non-rubella cataract group (controls) included 110 eyes (57 children). There was no significant difference in the mean age at surgery among the two groups (p=0.96). Cumulative incidence of secondary childhood glaucoma for the entire study period of 14 years was 32.7% in the CRS group and 24.5% in the control group (p=0.19). Mean follow-up was 5.8 ± 3.7years for CRS group and 6.4± 3.4years for the non-rubella group. A significant difference in the cumulative probability of glaucoma free survival at 10 years after cataract surgery (cases 0.53 versus controls 0.8; log rank p-0.034) was present. Both groups had no significant difference in the time of onset of secondary glaucoma, average number of intraocular pressure lowering medications and number of eyes with surgical intervention for glaucoma (p>0.05). Microcornea was associated with the development of glaucoma (hazard ratio 2.83, 95% confidence interval 1.44-5.57; p=0.002) in CRS eyes. ConclusionThere was no significant difference in the incidence of secondary glaucoma after cataract surgery performed in infants with CRS compared to infants who had undergone surgery for infantile cataracts. Since the ten year probability of glaucoma free survival was significantly less in children with CRS, a closer and longer follow up is recommended especially in eyes with at-risk features.

Racial and Ethnic Differences in the Prevalence and Treatment Patterns for Neovascular Glaucoma in the American Academy of Ophthalmology IRIS® Registry

PurposeTo examine racial and ethnic differences in the prevalence and treatment patterns for neovascular glaucoma (NVG) in at-risk individuals in the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight). ParticipantsEyes in the IRIS Registry with a retinal ischemia based on a history of proliferative diabetic retinopathy (PDR), retinal vein occlusion (RVO), and/or ocular ischemic syndrome (OIS). MethodsRace and ethnicity was defined as Asian, Black, Hispanic/Latino, Non-Hispanic White, and Other/Unknown. In eyes with retinal ischemia, the outcome was neovascular glaucoma (NVG). In eyes with NVG, outcomes included treatment of retinal ischemia with pan-retinal photocoagulation (PRP), and surgery to lower intraocular pressure (IOP) with trabeculectomy, tube shunt, and cyclophotocoagulation (CPC). Covariates included age, sex, region of residence, insurance type, smoking status, and systemic and ocular comorbidities. Cox proportional hazards regression was used to examine adjusted associations between race and ethnicity and NVG and each type of NVG treatment. Main Outcome MeasuresIncidence of NVG, PRP, trabeculectomy, tube shunt, CPC, and any IOP-lowering surgery ResultsOf 312,106 eyes with retinal ischemia, there were 5,885 (1.9%) with NVG. Compared to eyes of individuals who identified as Non-Hispanic White, eyes of individuals who were Black and Hispanic/Latino had higher hazards of NVG in adjusted analyses (hazards ratio [HR]=1.28, 95% confidence interval [CI]=1.15, 1.43 for Black; HR=1.32, 95% CI=1.17, 1.47 for Hispanic/Latino). Compared to eyes of individuals who were Non-Hispanic White, there was higher hazards of trabeculectomy in eyes of individuals who were Hispanic/Latino (adjusted HR=1.91, 95% CI=1.08, 3.39) and higher hazards of tube shunt (adjusted HR=1.35, 95% CI=1.07, 1.69) and of any IOP-lowering surgery (adjusted HR=1.29, 95% CI=1.09, 1.53) in eyes of individuals who were Black. There were no statistically significant differences in the hazards of PRP or CPC. ConclusionsEyes of Black and Hispanic/Latino individuals with retinal ischemia in the IRIS Registry had higher likelihood of NVG and of IOP-lowering surgery for NVG. Further study is needed to examine the medical and social factors that preclude optimal management of diabetic eye disease, in order to prevent its blinding complications.

Advances in Glaucoma Drug Therapy

Abstract Glaucoma remains the leading cause of irreversible blindness, but timely treatment to lower intraocular pressure is effective at slowing the rate of vision loss from glaucoma. Medical management remains the first line of treatment in adult glaucoma, and the evolution of medical therapy for glaucoma has followed an exponential curve. This narrative review briefs the rapid development of new medications and drug delivery systems in recent years. Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need for glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.

The Effects of the STREAMLINE™ Surgical System versus Endoscopic Cyclophotocoagulation in Primary and Secondary Glaucoma

Introduction: Glaucoma is an optic neuropathy that is the second most common cause of blindness worldwide and affects over three million Americans. Currently, the only known modifiable risk factor to prevent glaucomatous damage is to decrease the intraocular pressure (IOP). The STREAMLINE™ Surgical System (SSS) is a microinvasive glaucoma (MIGs) device that can create a goniotomy and dilates the drainage system of the eye to reduce IOP. Question &amp; Significance: This study aims to compare the effects on intraocular pressure of patients that had cataract surgery combined the SSS, endoscopic cyclophotocoagulation (ECP), or ECP with SSS in patients with primary and secondary glaucoma’s for 6 months post operatively. Methods: This is a retrospective chart review of patients that had cataract surgery with either ECP, SSS, or SSS + ECP from April 1st, 2022 through April 1st, 2023. Primary endpoints were mean IOP reductions and medication reliance at 6 months compared to baseline. Secondary outcomes were best corrected visual acuity (BCVA), number of patients with  20% decrease in IOP, number of patients with a decrease in IOP lower medications, and significant complications after treatment. Results: Comparing 6-month post-operative mean IOPs in these treatment groups, a significant reduction was noted only in the ECP group at the 6-month visit (p&lt;0.003). No statistically significant reduction was found in either the SSS (p=0.333) or SSS+ECP (p=0.134) groups. The percent of patients having a  20% decrease in IOP from baseline were 52%, 10%, and 38% for ECP, SSS, and SSS+ECP groups, respectively. Conclusions: In the SSS only group, we found a significantly smaller proportion of patients able to achieve the  20% IOP reduction at only 10% of patients compared to other previous studies. This difference is likely due no medication washout in our study. This study did find similar decrease in IOP lowering medications.

Assessing the Impact of PRESERFLO MicroShunt on Intraocular Pressure in Porcine Eyes Ex Vivo Using Infusion Pump System.

To evaluate the effectiveness of the PRESERFLO MicroShunt (PFM) in reducing intraocular pressure (IOP) ex vivo in porcine eyes using an infusion pump system and to simulate various IOP conditions, In this study, porcine eyes received increasing flows between 2 and 20 μL/min. IOP measurements were taken under conditions with and without the PFM [PFM (+) and PFM (-), respectively]. In the PFM (-) group, IOP increased from 7.4 mmHg to 46.3 mmHg as the flow rate increased from 2 μL/min to 20 μL/min. The rate of IOP reduction (%ΔIOP) rose with increasing flow rates, although the absolute IOP values achieved with the PFM insertion also increased. The correlation between IOPs in the PFM (-) conditions and the %ΔIOP was modeled as %ΔIOP = 22.4 Ln [PFM(-) IOP] - 41.7. According to this equation, IOP reduction by PFM insertion is 0% at IOPs of 6.4 mmHg or lower. IOP reductions of 10%, 20%, 30%, and 40% were observed when the pre-insertion IOPs were 10.1, 15.7, 24.6, and 38.4 mmHg, respectively. Achievable post-insertion IOP levels of ≤21 mmHg, ≤18 mmHg, ≤15 mmHg, and ≤12 mmHg corresponded to the initial IOPs of 33 mmHg, 26 mmHg, 20 mmHg, and 14.8 mmHg, respectively. In conclusion, the PFM effectively reduced IOP within a specific range of IOP values in an ex vivo experimental system. In clinical situations, the PFM is unlikely to be effective at low IOP levels. At higher levels, the PFM reduces IOP, but it may be insufficient to achieve the target IOP.

Long-term efficacy and safety of XEN-45 gel stent implantation in patients with normal-tension glaucoma

BackgroundMinimally invasive bleb surgery using the XEN-45 gel stent has not been established for the treatment of normal-tension glaucoma (NTG). The main objective of this study was to evaluate the long-term treatment efficacy and safety of XEN-45 in eyes with uncontrolled NTG.MethodsA retrospective analysis of patients with NTG who underwent XEN-45 gel stent implantation at university hospital Tuebingen between 2016 and 2021. The primary outcome measure was surgical success after three years defined as lowering of intraocular pressure (IOP) of ≥ 20%, with target IOP between 6 and 15 mmHg. Success was complete without and qualified irrespective of topical antiglaucoma medication use. The need for further glaucoma surgery, except for needling, was regarded as a failure. The secondary outcome measures included changes in mean IOP, number of antiglaucoma medications, and needling and complication rates.ResultsTwenty-eight eyes from 23 patients were included in the final analysis. Complete and qualified success rates were 56.5% and 75% after three years, respectively. Mean postoperative IOP ± standard deviation decreased significantly after three years from 19.3 ± 2.0 mmHg at baseline to 13.7 ± 4.2 mmHg (n = 22; p < 0.0001). The median number of antiglaucoma medications decreased from 2 (range 0–4) to 0 after three years (range 0–3; p < 0.0001). Sixteen eyes (57%) required a median of 1 (range 1–3) needling procedures. One eye required further glaucoma surgery. No sight-threatening complications were observed.ConclusionThe XEN-45 stent is effective and safe for the long-term treatment of NTG. However, needling was frequently required to improve outcomes.

Evaluation of Intrascleral Lakes after Phaco-Viscocanalostomy using Anterior Segment Optical Coherence Tomography.

This study aimed to investigate the results of combined phacoemulsification and viscocanalostomy (phaco-VC) in a six-month follow-up and its relationship with intrascleral lake (IL) using anterior segment optical coherence tomography (AS-OCT) in patients with primary open-angle glaucoma (POAG). In total, 36 eyes with POAG eligible for phaco-VC were enrolled in this prospective observational study. All patients underwent AS-OCT evaluation and ophthalmologic examination including Goldman tonometry, cup-disc ratio assessment, best corrected visual acuity (BCVA) measurement, and antiglaucoma medication(s) prior to surgery and one, three, and six months after the surgery. The width, length, area, and circumference of the ILs were evaluated using AS-OCT at each follow-up. A total of 36 eyes of 34 patients with POAG were investigated in this study. According to the results, the mean age of the patients was 70.09 8.73 years, and the majority of the cases were male (n = 23; 63.9%). The mean preoperative intraocular pressure (IOP) was 20.11 7.22 mmHg on 2.47 1.1 medications, and the mean postoperative IOP reduced to 11.11 2.58 mmHg on 0.11 medications, which was statistically significant (P 0.001). ILs were detectable in all cases which resulted in a 100% qualified success rate. The reduction in the width, area, and circumference of the IL was significant during the six-month follow-up. The relationship between IOP changes and IL parameters on AS-OCT was not significant. This study evaluated the associations between IL changes and IOP reduction after phaco-VC. A six-month follow-up showed a notable reduction in the IL, but unexpectedly, IOP control did not decline. A reduction in IL diameter, when there is sufficient IOP control, indicates that there may be various IOP lowering mechanisms through VC other than the IL diameters. Further evaluation of VC focusing on long-term changes in IL and Schlemm's canal diameter is necessary to explain the precise mechanisms of lowering the IOP.

The TGFβ Induced MicroRNAome of the Trabecular Meshwork.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma.