Refractive outcomes using Barrett formulas and patient characteristics of cataract surgery patients with and without prior LASIK/PRK.

PURPOSE: The goal of this study is to describe characteristics of cataract surgery patients who previously underwent laser in situ keratomileusis/photorefractive keratectomy (LASIK/PRK) in comparison to non-LASIK/PRK cataract surgery patients including psychiatric comorbidities, as well as describe refractive prediction error after cataract surgery while accounting for axial length (AL) using the Barrett True-K and Barrett Universal II formulas. METHODS: This was a retrospective study of patients from the University of Colorado Cataract Outcomes Registry. The primary outcomes were refraction prediction error (RPE), mean absolute RPE, and median absolute RPE. Outcomes were stratified by five axial length groups. Univariate and multivariate models for RPE were stratified by the AL group. RESULTS: Two hundred eighty-one eyes with prior LASIK/PRK and 3101 eyes without are included in the study. Patients with prior LASIK/PRK were significantly younger: 67.0 vs 69.9 years, p < 0.0001. The LASIK/PRK group had significantly better mean pre-operative BCVA in comparison to the non-LASIK group, logMAR 0.204 vs logMAR 0.288, p = 0.003. The LASIK/PRK group had significantly lower rates of cardiovascular disease (18.5% vs 29.3%, p < 0.001), hypertension (49.1% vs 59.3%, p < 0.012), and type 2 diabetes (10.7% vs 26.0%, p < 0.001), and no significant difference in psychiatric disease. The absolute RPE was higher for the LASIK group for all ALs, but only significantly higher for eyes with AL less than 25 mm. CONCLUSION: Patient eyes with prior LASIK/PRK surgery undergoing cataract surgery were significantly younger, had significantly less comorbidities, and a significantly better pre-operative BCVA. Using the Barrett formulas, absolute prediction error for eyes with longer ALs was not significantly worse for LASIK/PRK eyes than those without and the difference was smaller for eyes with longer AL.

Dexamethasone targets actin cytoskeleton signaling and inflammatory mediators to reverse sulfur mustard-induced toxicity in rabbit corneas.

PURPOSE: Sulfur mustard (SM), a bi-functional alkylating agent, was used during World War I and the Iran-Iraq war. SM toxicity is ten times higher in eyes than in other tissues. Cornea is exceptionally susceptible to SM-injuries due to its anterior positioning and mucous-aqueous interphase. Ocular SM exposure induces blepharitis, photosensitivity, dry eye, epithelial defects, limbal ischemia and stem cell deficiency, and mustard gas keratopathy leading to temporary or permanent vision impairments. We demonstrated that dexamethasone (Dex) is a potent therapeutic intervention against SM-induced corneal injuries; however, its mechanism of action is not well known. Investigations employing proteomic profiling (LC-MS/MS) to understand molecular mechanisms behind SM-induced corneal injury and Dex efficacy were performed in the rabbit cornea exposed to SM and then received Dex treatment. PEAKS studio was used to extract, search, and summarize peptide identity. Ingenuity Pathway Analysis was used for pathway identification. Validation was performed using immunofluorescence. One-Way ANOVA (FDR < 0.05; p < 0.005) and Student's t-test (p < 0.05) were utilized for analyzing proteomics and IF data, respectively. Proteomic analysis revealed that SM-exposure upregulated tissue repair pathways, particularly actin cytoskeleton signaling and inflammation. Prominently dysregulated proteins included lipocalin2, coronin1A, actin-related protein2, actin-related protein2/3 complex subunit2, actin-related protein2/3 complex subunit4, cell division cycle42, ezrin, bradykinin/kininogen1, moesin, and profilin. Upregulated actin cytoskeleton signaling increases F-actin formation, dysregulating cell shape and motility. Dex reversed SM-induced increases in the aforementioned proteins levels to near control expression profiles. Dex aids corneal wound healing and improves corneal integrity via actin cytoskeletal signaling and anti-inflammatory effects following SM-induced injuries.

Establishing a Dexamethasone Treatment Regimen To Alleviate Sulfur Mustard-Induced Corneal Injuries in a Rabbit Model.

Sulfur mustard (SM) is an ominous chemical warfare agent. Eyes are extremely susceptible to SM toxicity; injuries include inflammation, fibrosis, neovascularization (NV), and vision impairment/blindness, depending on the exposure dosage. Effective countermeasures against ocular SM toxicity remain elusive and are warranted during conflicts/terrorist activities and accidental exposures. We previously determined that dexamethasone (DEX) effectively counters corneal nitrogen mustard toxicity and that the 2-hour postexposure therapeutic window is most beneficial. Here, the efficacy of two DEX dosing frequencies [i.e., every 8 or 12 hours (initiated, as previously established, 2 hours after exposure)] until 28 days after SM exposure was assessed. Furthermore, sustained effects of DEX treatments were observed up to day 56 after SM exposure. Corneal clinical assessments (thickness, opacity, ulceration, and NV) were performed at the day 14, 28, 42, and 56 post-SM exposure time points. Histopathological assessments of corneal injuries (corneal thickness, epithelial degradation, epithelial-stromal separation, inflammatory cell, and blood vessel counts) using H&E staining and molecular assessments (COX-2, MMP-9, VEGF, and SPARC expressions) were performed at days 28, 42, and 56 after SM exposure. Statistical significance was assessed using two-way ANOVA, with Holm-Sidak post hoc pairwise multiple comparisons; significance was established if P < 0.05 (data represented as the mean ± S.E.M.). DEX administration every 8 hours was more potent than every 12 hours in reversing ocular SM injury, with the most pronounced effects observed at days 28 and 42 after SM exposure. These comprehensive results are novel and provide a comprehensive DEX treatment regimen (therapeutic-window and dosing-frequency) for counteracting SM-induced corneal injuries. SIGNIFICANCE STATEMENT: The study aims to establish a dexamethasone (DEX) treatment regimen by comparing the efficacy of DEX administration at 12 versus 8 hours initiated 2 hours after exposure. DEX administration every 8 hours was more effective in reversing sulfur mustard (SM)-induced corneal injuries. SM injury reversal during DEX administration (initial 28 days after exposure) and sustained [further 28 days after cessation of DEX administration (i.e., up to 56 days after exposure)] effects were assessed using clinical, pathophysiological, and molecular biomarkers.

Nitrogen Mustard-Induced Ex Vivo Human Cornea Injury Model and Therapeutic Intervention by Dexamethasone.

Sulfur mustard (SM), a vesicating agent first used during World War I, remains a potent threat as a chemical weapon to cause intentional/accidental chemical emergencies. Eyes are extremely susceptible to SM toxicity. Nitrogen mustard (NM), a bifunctional alkylating agent and potent analog of SM, is used in laboratories to study mustard vesicant-induced ocular toxicity. Previously, we showed that SM-/NM-induced injuries (in vivo and ex vivo rabbit corneas) are reversed upon treatment with dexamethasone (DEX), a US Food and Drug Administration-approved, steroidal anti-inflammatory drug. Here, we optimized NM injuries in ex vivo human corneas and assessed DEX efficacy. For injury optimization, one cornea (randomly selected from paired eyes) was exposed to NM: 100 nmoles for 2 hours or 4 hours, and 200 nmoles for 2 hours, and the other cornea served as a control. Injuries were assessed 24 hours post NM-exposure. NM 100 nmoles exposure for 2 hours was found to cause optimal corneal injury (epithelial thinning [∼69%]; epithelial-stromal separation [6-fold increase]). In protein arrays studies, 24 proteins displayed ≥40% change in their expression in NM exposed corneas compared with controls. DEX administration initiated 2 hours post NM exposure and every 8 hours thereafter until 24 hours post-exposure reversed NM-induced corneal epithelial-stromal separation [2-fold decrease]). Of the 24 proteins dysregulated upon NM exposure, six proteins (delta-like canonical Notch ligand 1, FGFbasic, CD54, CCL7, endostatin, receptor tyrosine-protein kinase erbB-4) associated with angiogenesis, immune/inflammatory responses, and cell differentiation/proliferation, showed significant reversal upon DEX treatment (Student's t test; P ≤ 0.05). Complementing our animal model studies, DEX was shown to mitigate vesicant-induced toxicities in ex vivo human corneas. SIGNIFICANCE STATEMENT: Nitrogen mustard (NM) exposure-induced injuries were optimized in an ex vivo human cornea culture model and studies were carried out at 24 h post 100 nmoles NM exposure. Dexamethasone (DEX) administration (started 2 h post NM exposure and every 8 h thereafter) reversed NM-induced corneal injuries. Molecular mediators of DEX action were associated with angiogenesis, immune/inflammatory responses, and cell differentiation/proliferation, indicating DEX aids wound healing via reversing vesicant-induced neovascularization (delta-like canonical Notch ligand 1 and FGF basic) and leukocyte infiltration (CD54 and CCL7).

Subjective and Objective Measurement of Sleep Quality and Activity in Glaucoma.

PRCIS: Glaucoma patients exhibit worse indices of sleep function by both objective and subjective metrics compared with controls. PURPOSE: The purpose of this study is to characterize the sleep parameters and physical activity levels of glaucoma patients compared with controls. PATIENTS AND METHODS: A total of 102 patients with a diagnosis of glaucoma in at least 1 eye and 31 control subjects were enrolled in the study. Participants completed the Pittsburgh Sleep Quality Index (PSQI) during enrollment and then wore wrist actigraphs for 7 consecutive days to characterize circadian rhythm, sleep quality, and physical activity. The primary outcomes of the study were subjective and objective metrics of sleep quality using the PSQI and actigraphy devices, respectively. The secondary outcome was physical activity, measured by the actigraphy device. RESULTS: From the PSQI survey, glaucoma patients had higher (worse) scores compared with controls for sleep latency, sleep duration, and subjective sleep quality, whereas scores for sleep efficiency were lower (better), suggesting more time spent in bed asleep. By actigraphy, time in bed was significantly higher in glaucoma patients as was time awake after sleep onset. Interdaily stability, quantifying the synchronization to the 24-hour light-dark cycle, was lower in glaucoma patients. There were no other significant differences between glaucoma and control patients with regard to rest-activity rhythms or physical activity metrics. In contrast to the survey data, findings from the actigraphy demonstrated that there were no significant associations between the study group and controls regarding sleep efficiency, onset latency, or total sleep time. CONCLUSIONS: In this study, patients with glaucoma demonstrated several subjective and objective differences in sleep function when compared with controls, whereas physical activity metrics were similar.

Comparison of Outcomes of Phacoemulsification Combined with Endoscopic Cyclophotocoagulation, iStent, or Both in the Management of Open-Angle Glaucoma.

INTRODUCTION: To compare outcomes of phacoemulsification combined with endoscopic cyclophotocoagulation (phaco/ECP), first generation iStent implantation (phaco/iStent), or both (phaco/iStent/ECP) in patients with open-angle glaucoma. METHODS: A retrospective chart review was performed on patients at the University of Colorado Department of Ophthalmology. Outcomes included intraocular pressure (IOP), medication use, best corrected visual acuity (BCVA), and surgical complications were analyzed. Success was defined as IOP reduction of ≥ 20% and/or reduction by at least one glaucoma medication. RESULTS: A total of 394 eyes were included in the study. There were 170 eyes (43.1%) in the phaco/ECP group, 175 eyes (44.4%) in the phaco/iStent group, and 49 eyes (12.4%) in the phaco/iStent/ECP group. The mean pre-operative IOP was 15.9 mmHg for phaco/ECP, 15.8 mmHg for phaco/iStent, and 15.2 mmHg for phaco/iStent/ECP. At 24 months, the mean IOP was 13.7 mmHg (p < 0.0001), 14.2 mmHg (p = 0.0001), and 13.0 mmHg (p = 0.0007), respectively. The mean pre-operative number of glaucoma medications was 2.0 for phaco/ECP, 1.4 for phaco/iStent, and 2.2 for phaco/iStent/ECP and at 24 months post-surgery decreased to, 1.8 (p = 0.011), 0.9 (p < 0.0001), and 1.7 (p = 0.01), respectively. The success rate at 24 months was 54.4% for phaco/ECP, 75.3% for phaco/iStent, and 55.6% for phaco/iStent/ECP. CONCLUSION: Phacoemulsification when combined with ECP, iStent, or both, lowered IOP and glaucoma medication reliance at 24 months. The success rate for phaco/iStent was significantly higher than phaco/ECP. When iStent was added to phaco/ECP, the success rate was higher at earlier postoperative visits compared to the phaco/ECP alone.

Outcomes and Risk Factors for Complications in Cataract Patients with Hepatitis C Virus Infection.

PURPOSE: To describe outcomes of patients with hepatitis C virus (HCV) seropositivity undergoing cataract surgery, as well as investigate risk factors for surgical complications. METHODS: This is a retrospective cohort study of all consecutive patients who underwent cataract surgery at a tertiary care hospital in the United States between 2014 and 2019. The exposure of interest was HCV seropositivity and outcomes included surgical complications and associated risk factors, visual acuity, and post-operative complications. RESULTS: A total of 11,276 eyes of 6,858 patients were included in the study, of which 122 patients (1.78%) and 210 eyes (1.86%) were HCV positive. Average age at surgery was 63.4 (8.4) years for HCV positive patients and 69.1 (10.6) years for HCV negative patients. Patients with HCV were more likely to suffer a complication during cataract surgery, 2.9% versus 1.2% (OR 2.27, 95% CI 1.03 to 5.01, p = .0415). Postoperative best corrected visual acuity was excellent: median and range 0.00 (-0.13, 3.00) logMAR for HCV positive eyes versus 0.00 (-0.30, 3.00) logMAR for HCV negative eyes. Among HCV positive patients, elevated alanine transaminase (>52 U/L) was associated with a higher intraoperative complication rate (10.0% vs 1.8%, OR 5.53, 95% CI 1.05 to 29.2, p = .044). CONCLUSION: While patients with HCV are more likely to have complications during cataract surgery, final best corrected visual acuity was excellent regardless of HCV status. Patients with HCV are more likely to undergo cataract surgery at a younger age, and those with elevated alanine transaminase are at highest risk for complications.

AAV2-Mediated Expression of HspB1 in RGCs Prevents Somal Damage and Axonal Transport Deficits in a Mouse Model of Ocular Hypertension.

Purpose: Ocular hypertension is a significant risk factor for vision loss in glaucoma caused by the death of retinal ganglion cells (RGCs). We investigated whether small heat shock proteins (sHsps) expressed in RGCs protect those cells against ocular hypertension in mice. Methods: AAV2 vectors encoding genes for one of the following four human sHsps: HSPB1, HSPB4, HSPB5, or HSPB6 were constructed for RGC-specific expression. Ischemia/reperfusion was induced by elevating the intraocular pressure (IOP) to 120 mm Hg for one hour, followed by a rapid return to normal IOP. Microbeads (MB) were injected into the anterior chamber of mice to induce ocular hypertension. RGC death and glial activation were assessed by immunostaining for Brn3a, RBPMS, Iba1, and glial fibrillary acid protein in retinal flat mounts. RGC axonal defects were evaluated by anterograde transport of intravitreally injected cholera toxin-B. RGC function was assessed by pattern electroretinography. Results: Among the sHsps, HspB1 offered the best protection against RGC death from ischemia/reperfusion injury in the mouse retina. Intravitreal administration of AAV2-HSPB1 either two weeks before or one week after instituting ocular hypertension resulted in significant prevention of RGC loss. The MB-injected mice showed RGC axonal transportation defects, but AAV2-HSPB1 administration significantly inhibited this defect. AAV2-HSPB1 prevented glial activation caused by ocular hypertension. More importantly, a single injection of AAV2-HSPB1 protected RGCs long-term in MB-injected eyes. Conclusions: The administration of AAV2-HSPB1 inhibited RGC death and axonal transport defects and reduced glial activation in a mouse model of ocular hypertension. Translational Relevance: Our results suggested that the intravitreal delivery of AAV2-HSPB1 could be developed as a gene therapy to prevent vision loss on a long-term basis in glaucoma patients.

Peptains block retinal ganglion cell death in animal models of ocular hypertension: implications for neuroprotection in glaucoma.

Ocular hypertension is a significant risk factor for vision loss in glaucoma due to the death of retinal ganglion cells (RGCs). This study investigated the effects of the antiapoptotic peptides peptain-1 and peptain-3a on RGC death in vitro in rat primary RGCs and in mouse models of ocular hypertension. Apoptosis was induced in primary rat RGCs by trophic factor deprivation for 48 h in the presence or absence of peptains. The effects of intravitreally injected peptains on RGC death were investigated in mice subjected to retinal ischemic/reperfusion (I/R) injury and elevated intraocular pressure (IOP). I/R injury was induced in mice by elevating the IOP to 120 mm Hg for 1 h, followed by rapid reperfusion. Ocular hypertension was induced in mice by injecting microbeads (MB) or silicone oil (SO) into the anterior chamber of the eye. Retinal flatmounts were immunostained with RGC and activated glial markers. Effects on anterograde axonal transport were determined by intravitreal injection of cholera toxin-B. Peptain-1 and peptain-3a inhibited neurotrophic factor deprivation-mediated RGC apoptosis by 29% and 35%, respectively. I/R injury caused 52% RGC loss, but peptain-1 and peptain-3a restricted RGC loss to 13% and 16%, respectively. MB and SO injections resulted in 31% and 36% loss in RGCs following 6 weeks and 4 weeks of IOP elevation, respectively. Peptain-1 and peptain-3a inhibited RGC death; the loss was only 4% and 12% in MB-injected eyes and 16% and 15% in SO-injected eyes, respectively. Anterograde transport was defective in eyes with ocular hypertension, but this defect was substantially ameliorated in peptain-injected eyes. Peptains suppressed ocular hypertension-mediated retinal glial activation. In summary, our results showed that peptains block RGC somal and axonal damage and neuroinflammation in animal models of glaucoma. We propose that peptains have the potential to be developed as therapeutics against neurodegeneration in glaucoma.

Glycosaminoglycans Influence Extracellular Matrix of Human Trabecular Meshwork Cells Cultured on 3D Scaffolds.

Glaucoma is a multifactorial progressive optic neuropathy characterized by the loss of retinal ganglion cells leading to irreversible blindness. It is the leading cause of global irreversible blindness and is currently affecting over 70 million people. Elevated intraocular pressure (IOP) is considered the only modifiable risk factor and is a target of numerous treatment modalities. Researchers have assigned this elevation of IOP to accumulation of extracellular matrix (ECM) components in the aqueous humor (AH) outflow pathway. The major drainage structure for AH outflow is the trabecular meshwork (TM). The ECM of the TM is important in regulating IOP in both normal and glaucomatous eyes. In this work, we have studied the role of exogeneous glycosaminoglycans (GAGs), glucocorticoids, and culture conditions on the expression of the ECM gene and proteins by human TM (hTM) cells cultured on biomaterial scaffolds. Gene and protein expression levels of elastin, laminin, and matrix metalloproteinase-2 (MMP-2) were evaluated using quantitative PCR and immunohistochemistry. Pressure gradient changes in cell-laden scaffolds in perfusion cultures were also monitored. Our findings show that GAGs and dexamethasone play an influencing role in hTM ECM turnover at both transcriptional and translational levels by altering expression levels of elastin, laminin, and MMP-2. Understanding the role of exogeneous factors on hTM cell behavior is helpful in gaining insights on glaucoma pathogenesis and ultimately pivotal in development of novel therapeutics against the disease.

Outcomes of Kahook Dual Blade Goniotomy for Uveitis Associated Open Angle Glaucoma or Ocular Hypertension.

PRCIS: Kahook Dual Blade (KDB) goniotomy can successfully lower intraocular pressure in some patients with uveitis-associated ocular hypertension or glaucoma. PURPOSE: The purpose of this study was to report a case series of patients that underwent KDB goniotomy at a single institution for uveitis-associated ocular hypertension or glaucoma with an open angle. METHODS: We performed a retrospective chart review of all patients with uveitis-associated ocular hypertension or glaucoma who underwent KDB goniotomy with trabecular meshwork excision alone or in combination with phacoemulsification cataract surgery at a single center between August 2017 and February 2020. The case series included 45 eyes of 37 patients. All eyes developed ocular hypertension refractory to maximum-tolerated medical therapy and required surgical intervention. Two eyes were excluded as they were lost to follow-up before 5 months postoperatively. Surgical success was defined as reaching the goal intraocular pressure or lower for each patient, including ongoing medical therapy. RESULTS: At most recent follow-up, 25 (55.6%) of 45 eyes had an intraocular pressure that was at goal. Mean follow-up time was 15.2±12.1 months ranging from 0.5 to 36 months postoperatively, considering that patients were eliminated from the data analysis once they required a second surgery. The mean number of preoperative medications, including oral carbonic anhydrase inhibitors was 3.7±1.2 medications. The mean number of postoperative medications through the last clinic visit was 2.5±1.9 medications for a mean reduction of 1.2±1.6 medications ( P -value <0.0001*). CONCLUSIONS: This larger case series shows that some patients with uveitis-associated ocular hypertension or glaucoma with an open angle may have success with KDB goniotomy.

Selective Laser Trabeculoplasty and Outcomes of Subsequent Phacoemulsification Combined with Kahook Dual Blade Goniotomy.

INTRODUCTION: To investigate the relationship between intraocular pressure (IOP)-lowering success of selective laser trabeculoplasty (SLT) and combined phacoemulsification/Kahook Dual Blade (phaco/KDB) goniotomy in eyes with mild to severe open angle glaucoma (OAG). METHODS: Eyes undergoing combined phaco/KDB goniotomy and that had previously undergone SLT were analyzed. Data collected included demographics, glaucoma type and severity, IOP, and topical IOP-lowering medications before and after both procedures. Eyes were divided into two groups based on success of SLT, defined as IOP reduction of at least 20% maintained on at least two consecutive follow-up visits without any subsequent medication additions or interventions. Phaco/KDB goniotomy success was defined as IOP reduction of at least 20% and/or reduction in the number of IOP-lowering medications of at least one up to 12 months of follow-up. RESULTS: Overall, SLT was successful in 20 of 43 eyes (46.5%), of which 63.6% (7/11) had successful phaco/KDB goniotomy at 12 months follow-up. Among eyes with unsuccessful SLT, 60.0% (9/15) had successful phaco/KDB at 12 months follow-up. Phaco/KDB success rate was similar in patients regardless of their previous response to SLT at all postoperative time points up to 12 months follow-up (p = 0.87). CONCLUSIONS: The presence or lack of IOP-lowering response to SLT did not influence the success rate of subsequent phaco/KDB goniotomy in eyes with mild to severe OAG. Patients who did not respond to SLT still benefited from phaco/KDB goniotomy at a later date.

Iris Retraction Without Hypotony.

PURPOSE: All published cases of iris retraction syndrome have been associated with low intraocular pressure. We report here a case clinically indistinguishable from iris retraction syndrome except for the absence of hypotony, which has not been previously described in the literature. OBSERVATIONS: A 35-year-old woman with a history of atopic dermatitis developed a rapidly progressive anterior subcapsular cataract and acute uveitis. During follow-up, the presence of bilateral iris retraction was noted, while ocular pressure was either normal or elevated, and the position did not normalize with pupillary dilation. The clinical course was complicated by retinal detachment and posterior cyclitic membrane, which was managed with pars plana vitrectomy, lensectomy, and dissection of cyclitic membrane. The case was further complicated by ocular hypertension attributed to steroid response and formation of an epiretinal membrane. Following micropulse cyclophotocoagulation, placement of an Ahmed tube shunt, epiretinal membrane peel, and placement of secondary intraocular lens, our patient eventually had a good visual outcome. CONCLUSIONS AND IMPORTANCE: Hypotony is generally recognized as a key physiological step in the development of iris retraction syndrome. Our case demonstrates that posterior bowing of the iris can occur in the absence of hypotony, and suggests that an alternative mechanism involving posterior cyclitic membrane may be responsible.

Hydrus Microstent malposition with uveitis-glaucoma-hyphema syndrome.

Intraocular implants, specifically those used in the treatment of glaucoma, are each associated with various implant related risks and complications of which surgeons placing these devices must be aware. Here we present a case of uveitis-glaucoma-hyphema (UGH) syndrome associated with the Hydrus Microstent.

The Utility of iCare HOME Tonometry for Detection of Therapy-Related Intraocular Pressure Changes in Glaucoma and Ocular Hypertension.

PURPOSE: To assess whether iCare HOME rebound tonometry can detect therapy-related changes during self-monitoring of intraocular pressure (IOP). DESIGN: Prospective clinical trial. PARTICIPANTS: A total of 43 eyes (n = 27 subjects) with open-angle glaucoma or ocular hypertension were enrolled during standard-of-care clinic visits. Participants were grouped into control eyes managed on stable therapy (n = 18 eyes) or therapy change eyes undergoing selective laser trabeculoplasty (SLT, n = 8 eyes), initiating topical therapy (n = 8 eyes), or adding a second medication to existing monotherapy (n = 9 eyes). METHODS: Subjects recorded IOP 4 times daily for 1 week using iCare HOME tonometry. Upon tonometer return, subjects underwent SLT or new medication start; an additional week of iCare HOME measurements was collected after 4 to 6 weeks. Control subjects recorded an additional week of measurements after 6 weeks. Measurements were grouped into 4 time periods (5-10 am, 10 am to 3 pm, 3-8 pm, 8 pm to 1 am). Goldmann applanation tonometry (GAT) was performed at each study visit for comparison. MAIN OUTCOME MEASURES: Detection of therapy response defined as an IOP reduction of ≥20%. RESULTS: For eyes that demonstrated a therapy response by GAT (n = 11), iCare HOME detected a therapy response in 90.9% of eyes in ≥1 time period and 45.5% of eyes in all 4 time periods. In eyes without a GAT-measured therapy response (n = 14), iCare HOME detected a response for 71.4% (n = 10) of eyes in ≥1 time period and for 7.1% of eyes (n = 1) at all 4 time periods. In treatment eyes, intraday and interday average minimum and maximum IOP, as well as interday IOP range, were significantly reduced after therapy without a significant change in intraday IOP range. Control group eyes did not demonstrate a significant change in average IOP minimum, maximum, or range between study weeks. CONCLUSIONS: Home tonometry with iCare HOME reliably detects therapy-related IOP changes in patients with glaucoma and ocular hypertension. Treatment responses correlated well with in-office GAT and may detect treatment responses missed by GAT. Intraocular pressure measurements via home tonometry provide additional clinical information regarding intraday and interday IOP fluctuation beyond standard of care in office GAT measurements. The iCare HOME is a valuable tool to monitor therapeutic efficacy in patients with glaucoma.

A Comparison of Clinical Outcomes After XEN Gel Stent and EX-PRESS Glaucoma Drainage Device Implantation.

PRECIS: Although the XEN stent offers a lower risk of hypotony and choroidal effusions with fewer clinic visits postoperatively, its surgical success rate was inferior to the EX-PRESS shunt. PURPOSE: To compare the clinical efficacy and safety outcomes of the XEN stent and EX-PRESS glaucoma drainage device in glaucomatous eyes. MATERIALS AND METHODS: One hundred eyes from 88 patients underwent ab interno XEN stent or EX-PRESS shunt implantation (52 XEN and 48 EX-PRESS) for uncontrolled glaucoma at the University of Colorado Eye Center. The primary outcome was surgical success defined as intraocular pressure (IOP) ≥6 and ≤18 mm Hg, without reoperation for uncontrolled glaucoma, loss of light perception, or use of glaucoma medications (complete success). Secondary outcomes were the same requirements allowing for medications (qualified success), mean IOP, medication use, adverse events, and number of postoperative clinic visits in the first 3 months. RESULTS: Baseline characteristics including glaucoma type and severity were similar between groups, with the exception of XEN patients having fewer men (17% vs. 46%), older patients (median age, 78 vs. 68), and a higher percentage of white patients (89% vs. 69%). Adjusted hazard ratio of failure of XEN relative to EX-PRESS was 3.94 (95% confidence interval, 1.73-9.00, P=0.001) for complete success and 1.61 (95% confidence interval, 0.40-6.38, P=0.501) for qualified success. There were significantly fewer postoperative clinic visits during the first 3 months in the XEN group (5.3 vs. 9.1 visits, P<0.001). The incidence of serous choroidal effusions and hypotony was significantly less after XEN compared with EX-PRESS (1 vs. 9, P=0.02 and 15 vs. 25, P=0.023, respectively). Three XEN stents (5.8%) required removal. CONCLUSIONS: In this population, although the XEN stent offers a better safety profile and fewer postoperative clinic visits, complete surgical success was inferior to the EX-PRESS shunt.

Transforming growth factor-ß2-mediated mesenchymal transition in lens epithelial cells is repressed in the absence of RAGE.

Transforming growth factor-ß2 (TGFß2)-mediated epithelial to mesenchymal transition (EMT) in lens epithelial cells (LECs) has been implicated in fibrosis associated with secondary cataracts. In this study, we investigated whether the receptor for advanced glycation end products (RAGE) plays a role in TGFß2-mediated EMT in LECs. Unlike in the LECs from wild-type mice, TGFß2 failed to elicit an EMT response in LECs from RAGE knockout mice. The lack of RAGE also diminished TGFß2-mediated Smad signaling. In addition, treatment with TGFß2 increased IL-6 levels in LECs from wild-type mice but not in those from RAGE knockout mice. Treatment of human LECs with the RAGE inhibitor FPS-ZM1 reduced TGFß2-mediated Smad signaling and the EMT response. Unlike that in wild-type lenses, the removal of fiber cell tissue in RAGE knockout lenses did not result in elevated levels of α-smooth muscle actin (α-SMA), fibronectin (FN), and integrin ß1 in capsule-adherent LECs. Taken together, these results suggest that TGFß2 signaling is intricately linked to RAGE. Targeting RAGE could be explored as a therapeutic strategy against secondary cataracts.

Endoscopic Cyclophotocoagulation Combined with Phacoemulsification Increases Risk of Persistent Anterior Uveitis Compared to Phacoemulsification Surgery Alone.

PURPOSE: To evaluate if the addition of endoscopic cyclophotocoagulation (ECP) to uncomplicated phacoemulsification cataract extraction increases the risk of persistent anterior uveitis (PAU) compared to phacoemulsification alone. PATIENTS AND METHODS: Retrospective analysis of patients who had either phacoemulsification alone or combined with endoscopic cyclophotocoagulation from January 1, 2014 to December 31, 2017. Visual acuity, intraocular pressure, presence of anterior chamber cells, and steroid usage were analyzed pre- and post-operatively. Patient eyes with a history of uveitis, autoimmune disease, complicated cataract surgery, combined surgery other than ECP, and less than 3 months of follow-up were excluded. RESULTS: This study consisted of 4423 eyes from 2903 patients, meeting the inclusion criteria (phacoemulsification only group n=4242 and phacoemulsification/ECP group n=181 eyes). PAU developed in 14.9% in the phacoemulsification with ECP group compared to 1.7% who had phacoemulsification alone. White patients had a 17.9 (95% CI: 7.8-41.1, p<0.0001) increased odds of developing persistent anterior uveitis with a combined procedure compared to phacoemulsification only, while Non-white patients had a 5.8 (95% CI: 2.8-12.1, p<0.0001) increased odds. Despite the higher odds ratio in White patients, this group had a significantly lower rate of PAU compared to Non-white patients after phacoemulsification/ECP. CONCLUSION: The addition of endoscopic cyclophotocoagulation to phacoemulsification significantly increases the risk of developing PAU in the post-operative period compared to phacoemulsification alone.