Plasma levels of sirtuin and adiponectin in patients with primary open-angle glaucoma, exfoliative glaucoma, and healthy controls.

PURPOSE: To compare plasma levels of sirtuin 1 (SIRT1) and adiponectin (APN) in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), and healthy control subjects. METHODS: This prospective case-control study collected plasma samples from 118 participants. All subjects underwent a comprehensive ophthalmologic examination before the acquisition of a plasma sample. Plasma samples were obtained from 40 POAG, 38 XFG, and 40 healthy control subjects without any evidence of systemic or ocular disease. Serum SIRT1 and APN levels were estimated by an enzyme-linked immunosorbent assay, ELISA (Elabscience, Houston, USA) method. Statistical analysis of results relied on Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square, analysis of variance (ANOVA) tests, and linear regression analysis, where appropriate. RESULTS: A significant decrease in SIRT1 levels was observed in POAG patients compared to healthy controls (p = 0.004, Dunn's test). In contrast, no difference was detected between XFG and POAG patients or healthy controls (p = 0.32 and p = 0.34, respectively, Dunn's test). There was no significant difference in plasma APN levels between the three groups under investigation (p = 0.59, ANOVA). CONCLUSION: Alterations in serum level of SIRT1 may suggest a possible role in POAG via potential effects in neuroprotection and oxidative stress.

A Case-Cohort Study of Exfoliation Risk Factors and Literature Review.

The purpose of the study is to evaluate the risk factors associated with exfoliation in a case-cohort setting and literature review. This single-center, prospective, case-cohort study was carried out from January 2010 to April 2020 on patients operated for cataract surgery by a single surgeon in Lebanon. Forty-nine consecutive patients with exfoliation syndrome (XFS) and 62 consecutive control patients were identified and further investigated for selected systemic (diabetes mellitus, systemic hypertension, asthma, or atopy) and ocular variables (baseline vision, severity of nuclear sclerosis, glaucoma, eye rubbing, history of dry eye, or allergic eye disease). The mean baseline Snellen visual acuity was 20/283 in XFS versus 20/145 in control cases (P = 0.012). XFS also demonstrated significantly denser nuclear sclerosis than controls (P = 0.00958). By univariate analysis, allergic conjunctivitis (15 [30.6%] vs. 2 [3.2%]; P < 0.001), dry eye (20 [40.8%] vs. 13 [21.0%]; P = 0.0133), and habitual rubbing of the eyes (33 [67.3%] vs. 19 [30.6%]; P < 0.001) were associated with the presence of XFS. Habitual ocular rubbing was closely associated with allergic conjunctivitis (odds ratio [OR] = 13.0; 95% confidence interval [CI]: 2.8-58.8; P = 0.032). After multivariable analysis, the following variables showed significant results: glaucoma (OR = 34.5; 95% CI: 4.4-250; P = 0.010), duration of surgery (OR = 5.6; 95% CI 2.43-12.9; P < 0.001), and habitual ocular rubbing (OR = 4.42; 95% CI: 1.97-9.90; P = 0.029). This study shows a novel potential correlation between eye rubbing and XFS in a Lebanese cohort. Chronic eye rubbing induces or may exacerbate preexistent zonular damage in subjects with XFS, hence the need to better manage concurrent ocular surface disorder in these patients.

Glaucoma and neuroinflammation: An overview.

Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching, papillary vessel modifications) consequent to retinal ganglion cell loss, axonal degeneration, and lamina cribrosa remodeling. These modifications tend to be progressive and are the main cause of functional damage in glaucoma. Despite the latest findings about the pathophysiology of the disease, the exact trigger mechanisms and the mechanism of degeneration of retinal ganglion cells and their axons have not been completely elucidated. Neuroinflammation may play a role in both the development and the progression of the disease as a result of its effects on retinal environment and retinal ganglion cells. We summarize the latest findings about neuroinflammation in glaucoma and examine the connection between risk factors, neuroinflammation, and retinal ganglion cell degeneration.

Serum Apelin and Asymmetric Dimethylarginine Levels in Patients With Exfoliation Syndrome or Exfoliative Glaucoma.

PRéCIS:: Apelin and asymmetric dimethylarginine (ADMA) concentrations, affecting the nitric oxide pathway, were different in the patient group compared with the control subjects. These 2 molecules may have potential effects in vascular pathologies and their possible role in predisposition to vascular comorbidities in exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). PURPOSE: To evaluate apelin and ADMA levels in serum samples from patients with XFS or XFG compared with healthy control subjects. METHODS: Serum ADMA and apelin concentrations were evaluated from 36 and 32 XFS patients; 27 and 24 XFG patients; and 34 and 30 healthy controls, respectively. Subjects without systemic disease (including diabetes mellitus, hypertension, coronary artery disease, obesity) were included in the study and body mass index was calculated in all participants. An enzyme-linked immunosorbent assay and high-performance liquid chromatography were used to determine serum apelin and ADMA concentrations. Independent sample t test, χ test, analysis of variance test, and Pearson test were used for statistical analysis. RESULTS: Mean serum apelin levels of XFG, XFS, and control group were 1063.3±373.4, 1196.7±433.7, and 1343.3±405.1 ng/mL, respectively. Patients with XFG demonstrated significantly lower level of apelin versus controls (P=0.034). Mean serum ADMA concentration was significantly greater in XFS subjects (2.05±0.98 µmol/L) compared with normal controls (1.57±0.58 µmol/L) (P=0.042). No association was detected between ADMA and apelin concentrations and age, sex, and body mass index for both XFS and XFG groups. CONCLUSIONS: Significant alterations in serum levels of apelin and ADMA may suggest potential effects in vascular pathologies and a possible role in predisposition to vascular comorbidities in XFS/XFG.

A Critical Overview of the Biological Effects of Mitomycin C Application on the Cornea Following Refractive Surgery.

During the last 2 decades, modifying the shape of the cornea by means of laser photoablation has emerged as a successful and popular treatment option for refractive errors. Corneal surface ablation techniques such as photorefractive keratectomy (PRK) and laser-assisted subepithelial keratomileusis (LASEK) offer good refractive results while having a minimal impact on corneal biomechanical stability. Past limitations of these techniques included the long-term regression of refractive outcome and a vigorous healing response that reduced corneal clarity in some patients (giving rise to what is clinically described as "haze"). Mitomycin C (MMC) was introduced as a healing modulator and applied on the corneal surface after refractive surgery to address these drawbacks. This article critically reviews the available evidence on the biological effects, safety, and clinical benefits of the off-label use of MMC in corneal refractive surgery.

Evaluating the novel application of cyclosporine 0.1% in ocular surface disease.

INTRODUCTION: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient's visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD. Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation. Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.

Assessing the role of ranibizumab in improving the outcome of glaucoma filtering surgery and neovascular glaucoma.

INTRODUCTION: Ranibizumab was the first anti-vascular endothelial growth factor (VEGF) agent approved for the treatment of neovascular age-related macular degeneration. The use of ranibizumab and other anti-VEGF medications in recent years has revolutionized the treatment of several sight-threatening retinal disorders. Emerging evidence has demonstrated that anti-VEGF treatment can offer advantages in the management of other ocular conditions where VEGFs play a key role: ocular scarring following glaucoma filtering surgery and neovascular glaucoma (NVG). Areas covered: We critically review available evidence on the use of ranibizumab as a wound healing modulator in glaucoma filtering surgery and as an adjunct in the management of NVG. Expert opinion: Based on the available evidence and the authors' clinical experience, ranibizumab is a valuable adjunct in the management of NVG. In glaucoma filtering surgery, however, the role of ranibizumab is less clear and does not provide a significant advantage over mitomycin C. Drawbacks for its use in glaucoma include cost, its off-label use, uncertainty and limited evidence on the various routes of administration, the optimal dosing schemes and its toxicity profile. Future advances in ranibizumab delivery systems allowing less frequent dosing may change this treatment paradigm.

Epidemiology of Exfoliation Syndrome.

BACKGROUND: From a historical standpoint the epidemiology of exfoliation syndrome (XFS) is one of the most controversial subjects in ophthalmic literature. Current literature abounds with studies on the prevalence of XFS in various ethnic populations and clearly XFS is a common condition, but its true prevalence is difficult to ascertain. Overall, XFS is considered to be the most common identifiable cause of glaucoma worldwide. PURPOSE: This review critically examines the published literature documenting the epidemiological features of XFS and attempts to provide a unified concept concerning existing controversy. METHODS: A critical review of selected literature pertaining to the epidemiology of XFS. RESULTS: It is well established that XFS and the ensuing exfoliative glaucoma have a worldwide prevalence and a progressively increasing age-related incidence. The prevalence of the condition is significantly underestimated. Many past studies have proposed clear geographic variations within and between ethnic groups. In contrast, there has also been some epidemiological evidence suggesting that the prevalence of XFS is similar within various ethnic groups. Published literature fails to address the potential role and impact of suspected exfoliation cases in the reported prevalence figures of the condition. Incidence figures for the condition are limited and vary extensively. Cumulative data have indicated that several, as yet partly understood genetic, ethnic, and environmental factors contribute to the varied prevalence of this condition. CONCLUSIONS: Further understanding on XFS epidemiology is needed. Only a future large prospective study conducted by the same investigators, using similar methodologies for different ethnic populations will prove beyond doubt the hypothesis that significant geographic variations exist. Since patients with exfoliative glaucoma are at significant risk of losing vision it is vital to elucidate the causes and the risk of developing XFS. To reach this goal, it is important to better delineate the early changes of XFS and to focus research efforts on modifiable factors for XFS development.

Preservative-Free Prostaglandin Analogs and Prostaglandin/Timolol Fixed Combinations in the Treatment of Glaucoma: Efficacy, Safety and Potential Advantages.

Glaucoma therapy-related ocular surface disease (OSD) is a serious pathology with a broad spectrum of insidious clinical presentations and complex pathogenesis that undermines long-term glaucoma care. Preservatives, especially benzalkonium chloride (BAK), contained in topical intraocular pressure-lowering medications frequently cause or aggravate OSD in glaucoma. Management of these patients is challenging, and to date often empirical due to the scarcity of controlled long-term clinical trials. Most of the available data are extracted from case series and retrospective analysis. Preservative-free prostaglandins and prostaglandin/timolol fixed combinations are novel options developed to remove the harmful impact of preservatives, especially BAK, upon ocular tissues. Based on what is currently known on the value of preservative-free antiglaucoma therapies it is tempting to speculate how these new therapies may affect the future medical management of all glaucoma patients. This article provides a comprehensive and critical review of the current literature on preservative-free prostaglandins and preservative-free prostaglandin/timolol fixed combinations.

Quality of Life in Glaucoma: A Review of the Literature.

The ultimate goal of glaucoma management is the preservation of patients' visual function and quality of life (QoL). The disease itself as well as the medical or surgical treatment can have an enormous impact on a patient's QoL. Even the mere diagnosis of a chronic, irreversible, potentially blinding disorder can adversely affect the patient's sense of well-being and QoL by eliciting significant anxiety. Patients with primary open-angle glaucoma rarely present with visual symptoms, at least early in the course of the disease. A better understanding of patient-reported QoL can improve patient-physician interaction and enhance treatment adherence by customizing treatment options based on individual patient profile, thus optimizing long-term prognosis. These aspects are summarized and critically appraised in this article.

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

INTRODUCTION: Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. AREAS COVERED: The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). EXPERT OPINION: The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.

Current Perspectives of Prophylaxis and Management of Acute Infective Endophthalmitis.

Endophthalmitis is an intraocular inflammatory condition which may or may not be caused by infective agents. Noninfectious (sterile) endophthalmitis may be attributable to various causes including postoperative retained soft lens matter or toxicity following introduction of other agents into the eye. Infectious endophthalmitis is further subdivided into endogenous and exogenous. In endogenous endophthalmitis there is hematogenous spread of organisms from a distant source of infection whereas in exogenous endophthalmitis direct microbial inoculation may occur usually following ocular surgery or penetrating eye injury with or without intraocular foreign bodies. Acute infective endophthalmitis is usually exogenous induced by inoculation of pathogens following ocular surgery, open-globe injury and intravitreal injections. More infrequently the infective source is internal and septicemia spreads to the eye resulting in endogenous endophthalmitis. Several risk factors have been implicated including immunosuppression, ocular surface abnormalities, poor surgical wound construction, complicated cataract surgery with vitreous loss and certain types of intraocular lens. Comprehensive guidelines and recommendations on prophylaxis and monitoring of surgical cases have been proposed to minimize the risk of acute endophthalmitis. Early diagnosis and prompt management of infective endophthalmitis employing appropriately selected intravitreal antibiotics are essential to optimize visual outcome.

24-h Efficacy of Glaucoma Treatment Options.

Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.

Needle Revision With 5-fluorouracil for the Treatment of Ahmed Glaucoma Valve Filtering Blebs: 5-Fluoruracil Needling Revision can be a Useful and Safe Tool in the Management of Failing Ahmed Glaucoma Valve Filtering Blebs.

PURPOSE: To determine the outcome of needling with adjunctive 5-fluorouracil (5-FU) in patients with a failing Ahmed glaucoma valve (AGV) implant, and to identify predictors of long-term intraocular pressure (IOP) control. METHODS: A prospective observational study was performed on consecutive patients with medically uncontrolled primary open-angle glaucoma (POAG) with AGV encapsulation or fibrosis and inadequate IOP control. Bleb needling with 5-FU injection (0.1 mL of 50 mg/mL) was performed at the slit-lamp. Patients were examined 1 week following the needling, and then at months 1, 3, and 6. Subsequent follow-up visits were scheduled at 6-month intervals for at least 2 years. Needling with 5-FU was repeated no more than twice during the first 3 months of the follow-up. Procedure outcome was determined on the basis of the recorded IOP levels. RESULTS: Thirty-six patients with an encapsulated or fibrotic AGV underwent 67procedures (mean 1.86 ± 0.83). Complete success, defined as IOP ≤ 18 mm Hg without medications, was obtained in 25% at 24 months of observation. The cumulative proportion of cases achieving either qualified (ie, IOP ≤ 18 mm Hg with medications) or complete success at 24 months of observation was 72.2%. In a univariate Cox proportional hazards model, age was the only variable that independently influenced the risk of failing 5-FU needling revision. Fourteen eyes (38.8%) had a documented complication. CONCLUSIONS: Needling over the plate of an AGV supplemented with 5-FU is an effective and safe choice in a significant proportion of POAG patients with elevated IOP due to encapsulation or fibrosis.

Twenty-four-hour intraocular pressure monitoring in normotensive patients undergoing chronic hemodialysis.

PURPOSE: To investigate 24-hour intraocular pressure (IOP) changes caused by hemodialysis (HD). METHODS: A prospective, observational, comparative 24-hour trial was performed on consecutive subjects with normal IOP undergoing maintenance HD 3 days a week between 13:00 and 17:00 hours in an academic setting. Following a comprehensive ocular assessment, those with conditions that may influence IOP were excluded and one eye was randomly selected. Twenty-four-hour IOP monitoring was performed on HD day 1 and then on a day without HD. The IOP was measured at 10:00, 13:00, 15:00, 17:00, 22:00, 02:00, and 06:00 employing Goldmann and Perkins tonometry on habitual position. During the course of 1 year, 18 patients completed the study. RESULTS: Monitoring of IOP on HD day showed a significantly higher mean 24-hour IOP (15.4 ± 2.7 vs 14.1 ± 2.2 mm Hg; p = 0.025), higher mean peak 24-hour IOP (18.5 ± 3.5 vs 15.8 ± 2.5 mm Hg; p = 0.003), and wider 24-hour IOP fluctuation (6.2 ± 2.3 vs 4.0 ± 1.9 mm Hg; p = 0.001). When individual time points were compared, IOP was significantly higher at 17:00 on HD day, reflecting a gradual IOP elevation during HD (p = 0.021). Further, during the HD procedure (13:00-17:00), the mean IOP was significantly higher on a HD day (16.4 ± 3.0 vs 14.7 ± 2.4 mm Hg; p = 0.004). CONCLUSIONS: This prospective, before/after trial suggests that HD significantly impacts 24-hour IOP characteristics in normotensive eyes. The long-term significance of these findings requires further elucidation in normotensive patients and, predominantly, in patients with glaucoma undergoing HD.

Intraocular Pressure Characteristics of Exfoliative Glaucoma and Exfoliation Syndrome as Determined With the Water Drinking Test.

PURPOSE: To investigate the intraocular pressure (IOP) characteristics of patients with exfoliation glaucoma (XFG) and exfoliation syndrome (XFS) during the water drinking test (WDT). METHODS: This was a prospective observational study undertaken at an academic setting. Consecutive patients with XFG whose office IOP levels were <21 mm Hg, normotensive XFS patients, and control subjects underwent WDT, which involved ingestion of 1 L of water within 5 minutes. The IOP was measured before and 4 times after water ingestion at 15-minute intervals. Maximum IOP (IOPmax), mean IOP (IOPmean), IOP increase (IOPΔ) from baseline IOP to IOPmax, and percentage of IOP fluctuation (IOPfluct) during the WDT were compared across groups. One-way analysis of variance (ANOVA) test or the Kruskal-Wallis test was used for comparisons. RESULTS: The age, gender ratios, visual acuity level, central corneal thickness, and office IOP levels were similar between the 3 groups. As compared with patients with XFS and controls, XFG patients revealed significantly higher values for all IOP measurements at 15 minutes intervals as well as IOPmax (25.1±4.0 mm Hg, 18.7±2.8 mm Hg, 18.6±2.5mm Hg; P<0.001), IOPmean (22.6±3.3mm Hg, 17.2±2.6 mm Hg, 17.2±2.4 mm Hg; P<0.001), IOPΔ (9.2±3.4 mm Hg, 4.4±2.1 mm Hg, 3.7±1.5 mm Hg; P<0.001), and IOPfluct (60.1±24.0%, 33.4±20.0%, 25.7±11.3%; P<0.001). CONCLUSIONS: Medically treated XFG patients, but not XFS subjects, reveal significant IOP elevations during WDT indicative of impaired trabecular outflow facility.

Twenty-four hour efficacy of glaucoma medications.

Current medical therapy of glaucoma aims to attain a meaningful and consistent reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which will commensurate with either stability, or delayed progression of visual loss. Glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous. Therefore, it is reasonable that we should endeavor to identify the true efficacy of currently available and future antiglaucoma medications throughout the 24-h period. This review chapter deals first with the concept and value of diurnal and 24-h pressure monitoring. It then evaluates existing evidence on the 24-h efficacy of medical therapy options. Unfortunately, significant gaps exist in our present understanding of the short-term and particularly the long-term 24-h efficacy of most antiglaucoma medications. More long-term controlled evidence is needed in the future to improve our understanding of the 24-h efficacy of current medical glaucoma therapy, the ideal 24-h target pressure and the precise impact of IOP characteristics upon the different stages of the various forms of glaucoma.