Associations with Intraocular Pressure in a Large Cohort: Results from the UK Biobank

Purpose: To describe the associations of physical and demographic factors with Goldmann-correlated intraocular pressure (IOPg) and corneal-compensated intraocular pressure (IOPcc) in a British cohort. Design: Cross-sectional study within the UK Biobank, a large-scale multisite cohort study in the United Kingdom. Participants: We included 110 573 participants from the UK Biobank with intraocular pressure (IOP) measurements available. Their mean age was 57 years (range, 40–69 years); 54% were women, and 90% were white. Methods: Participants had 1 IOP measurement made on each eye using the Ocular Response Analyzer noncontact tonometer. Linear regression models were used to assess the associations of IOP with physical and demographic factors. Main Outcome Measures: The IOPg and IOPcc. Results: The mean IOPg was 15.72 mmHg (95% confidence interval [CI], 15.70–15.74 mmHg), and the mean IOPcc was 15.95 mmHg (15.92–15.97 mmHg). After adjusting for covariates, IOPg and IOPcc were both significantly associated with older age, male sex, higher systolic blood pressure (SBP), faster heart rate, greater myopia, self-reported glaucoma, and colder season (all P < 0.001). The strongest determinants of both IOPg and IOPcc were SBP (partial R2: IOPg 2.30%, IOPcc 2.26%), followed by refractive error (IOPg 0.60%, IOPcc 1.04%). The following variables had different directions of association with IOPg and IOPcc: height (−0.77 mmHg/m IOPg; 1.03 mmHg/m IOPcc), smoking (0.19 mmHg IOPg, −0.35 mmHg IOPcc), self-reported diabetes (0.41 mmHg IOPg, −0.05 mmHg IOPcc), and black ethnicity (−0.80 mmHg IOPg, 0.77 mmHg IOPcc). This suggests that height, smoking, diabetes, and ethnicity are related to corneal biomechanical properties. The increase in both IOPg and IOPcc with age was greatest among those of mixed ethnicities, followed by blacks and whites. The same set of covariates explained 7.4% of the variability of IOPcc but only 5.3% of the variability of IOPg. Conclusions: This analysis of associations with IOP in a large cohort demonstrated that some variables clearly have different associations with IOPg and IOPcc, and that these 2 measurements may reflect different biological characteristics

Evaluation of risk of falls and orthostatic hypotension in older, long-term topical beta-blocker users

Background: Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their combinations in eye drops, and falls, dizziness and orthostatic hypotension in older patients. Methods: All participants were long-term users of eye drops containing beta-blockers, prostaglandins or their combinations. They underwent a structured falls interview and blood pressure measurement for testing of orthostatic hypotension. The odds ratio for presence of orthostatic hypotension or a positive falls history according to use of beta-blocker eye drops was calculated with a binary logistic regression analysis. The main outcome measures were a positive falls history and the presence of orthostatic hypotension. Results: In total, 148 of 286 subjects participated. After adjustment for age, gender, and use of fall-risk-increasing drugs other than beta-blocker eye drops, we found no significant difference in fall risk [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.268-1.327] between patients using ophthalmic beta-blockers or a combination of ophthalmic beta-blockers and prostaglandins, and patients using ophthalmic prostaglandins only. Although prevalence of orthostatic hypotension was higher in the beta-blocker group (OR: 1.67; 95% CI: 0.731-3.793) compared to the prostaglandin group, this was a non-significant difference. Conclusions: In our study, we did not find a significant association between long-term use of beta-blockers eye drops and falls, dizziness or orthostatic hypotension in older ophthalmic outpatients, compared to long-term use of prostaglandin eye drops

Selective laser trabeculoplasty: past, present, and future

Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle glaucoma and ocular hypertensive patients. In this review we trace the origins of SLT from previous argon laser trabeculoplasty and review the current role it has in clinical practice. We outline future directions of SLT research and introduce emerging technologies that are further developing this intervention in the treatment paradigm of glaucoma.Eye advance online publication, 5 January 2018; doi:10.1038/eye.2017.273

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Five-year experience with non penetrating deep sclerectomy.

PURPOSE: To assess the long-term safety and effectiveness of non penetrating deep sclerectomy (DS) and to compare the incidence and the severity of postoperative complications and the IOP results according to surgical adjuvants (implant device, antimetabolite or both) were used or not. MATERIAL-METHODS: Retrospective non randomised study including 171 eyes (136 patients), mean age: 63.9 years) with medically uncontrolled open-angle glaucoma and without previous filtering surgery. 81 eyes (48.2%) had severe glaucomatous damage. All procedures were performed according to the Kozlov's and Memoud's technique. Except for 8 eyes, they were associated with the placement of an implant device (SKGEL or T-FUX) and/or intra-operative application of low dose antimetabolite (5-FU in 58 eyes and mitomycine C in 53 eyes). RESULTS: Mean follow-up was 39.6 +/- 18.3 months. According to surgery, DS were categorized in 4 groups: Group 1: DS with Healon GV (n=8)(4.7%); Group 2: DS with antimetabolite application (n=26) (15.2%); Group 3: DS with placement of an implant (n=53) (31%). Group 4: intraoperative antimetabolite +implant device (n=84 eyes) (49.1%). Peroperative microperforations without iris hernia occurred in 35 eyes (21%). 1st month postoperative complications were observed in 90 eyes (52.6%) with mild to moderate hyperfiltration in 27 eyes, excessive scarring of filtration bleb in 38 eyes, and iris incarceration in 10 eyes. 5-FU injections were given in 58 eyes (34%). YAG gonioperforation was needed in 107/171 eyes (63%) and was complicated by iris incarceration in 9 eyes. Early and late spontaneous iris incarceration was observed in 10 eyes. A second filtering procedure was needed in 10 eyes

Non penetrating deep sclerectomy (NPDS) with SKGEL implant and/or 5-fluorouracile (5-FU).

PURPOSE: To assess effectiveness and safety of DS with reticulated hyaluronic acid implant (SKGEL) and/or 5-Fluorouracile (5-FU). MATERIAL-METHODS: 61 eyes (48 patients) (mean age: 64.5 +/- 10.5 years) with medically uncontrolled open angle glaucoma and comparable surgical risk failure were included in this retrospective non randomized study and were categorized into DS + SKGEL (10 eyes), DS + 5-FU (25 eyes) and DS + SKGEL + 5-FU simultaneously (26 eyes). The 3 groups were comparable in respect of age of patients, diagnosis, severity of VF defects, and bleb failure risk factors. All procedures were performed according to the Kozlov's and Mermoud's technique. Complete ocular examination was carried out preoperatively and at day 1, 7, at 1, 2 and 3 months and every three months thereafter. RESULTS: Mean follow up was 11 +/- 4.9 months and was significantly shorter in group C. For all 61 eyes, mean IOP was significantly decreased from 27.8 +/- 8.6 mm Hg to 15.1 +/- 3.5 mm Hg. Complete (target IOP reached without medication or YAG laser goniopuncture) and qualified (target IOP reached with medication and/or YAG laser goniopuncture) final success rates were respectively of 54% and 90%. Complete success probability was 95% at 6 months and 72% at 12 months. Qualified success probability increased to 89.5% at 12 months. The IOP results, the distribution of success rates and complications were similar within the first postoperative year whatever using SKGEL or intra-operative 5-FU application or both. The need for additional glaucoma medication and the percentage of YAG goniopuncture appeared to be lower in the SKGEL group. Success probability appeared to be improved in SKGEL group comparatively with the other 2 groups. CONCLUSIONS: NPDS is a valid, effective and relatively safe alternative to trabeculectomy although adjunctive medications and/or Nd:YAG goniopuncture are frequently needed. Considering the limitations of our study, we can conclude that the IOP results, success rates and complications are similar within the 1st postoperative year whatever using peroperative 5-FU or SKGEL implant. A longer follow up is needed to confirm that SKGEL implant seems to improve the IOP control and the long term patency of the sclerectomy site by comparison with intra-operative application of 5-FU

Side effects of glaucoma medications.

The safety profile of the different glaucoma medications is an important issue when initiating therapy in glaucomatous patients. The decision on which medication to prescribe depends not only on the type of glaucoma, but also on the patient's medical history and needs a detailed knowledge of the potential side-effects of each medication. Medications side effects may be an important cause of non adherence for the individual patient The properties of the drugs, the composition of the glaucoma eyedrops and the dynamics of ocular drug absorption must be considered. The ocular surface changes induced by long-term antiglaucomatous treatment especially by their preservatives are a major cause of intolerance or poor tolerance to glaucoma eyedrops. Moreover topically applied ophthalmic medications can attain sufficient serum levels through absorption into conjunctival and nasal mucosas to have systemic effects and to potentially interact with other drugs. Then this presentation will deal with the ocular and systemic side-effects which can be encountered with the different classes of the currently available glaucoma topical medications. Recommendations than can be applied to reduce both frequency and severity of side-effects of glaucoma medications will be stressed on. Concurrently patients should be fully informed not only about their disease but also the medications they used and what side-effects they have to expect