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Introduction: To investigate the effects of long- and short-term use of different types of contact lenses on corneal metabolism and corneal thickness. Materials and Method: The participants were divided into two groups in the study. In the first group, 20 of the 42 patients were administered a rigid gas-permeable lens (RGPL) with a Dk value of 92x10-11, while the remaining wore a soft contact lens with a water content of 38%. We then explored their Lactate Dehydrogenase (LHD) levels to evaluate the hypoxic effect on tear films in short- (8 hours) and long-term (2nd, 3rd, 5th months) and albumin levels to assess mechanical trauma. In the second group, the corneal thickness was measured using a Haag-Streit optical pachymeter before and at the 8th hour and 2nd month following the first set of lenses, and LDH and albumin values were simultaneously evaluated in tear film. Results: The results yielded no significant increase in tear film LDH and albumin levels in the short- and long-term in both the RGPL and the soft contact lens groups with similar age and sex distribution. In the second part, the corneal thickness measurements resulted in an increase of 5.5% in the RGPL group and 3.63% in the soft lens group at the 8th hour of lens use. However, the groups did not significantly differ by baseline corneal thickness at the 2nd-month follow-up. Similarly, there was no significant increase in LDH and albumin levels in the tear film samples of the same group. Conclusion: The absence of a long-term increase in corneal thickness and no elevated levels of albumin and LDH in tear films indicate that contact lenses fit corneal physiology.

We sought to investigate alterations in the corneal subbasal nerve plexus and endothelium in patients with Behçet's disease (BD).This cross-sectional study included 64 patients with BD and 30 age- and gender-matched healthy control subjects. Those with BD were classified as having ocular or non-ocular disease. All subjects underwent a corneal endothelial and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). The differences among groups were analyzed using the Kruskal-Wallis test followed by Dunn's multiple comparison procedure.The mean age of study participants was 35.7 ± 10.2 years (16-58) in the ocular BD group, 39.6 ± 14.9 years (11-66) in the non-ocular BD group, and 34.1 ± 11.2 years (21-55) in the control group. No statistical significance was found in terms of age (p = 0.259) or sex (p = 0.560) between groups. The mean endothelial cell density determined with IVCM was 2124.9 [Formula: see text] 417.4 cells/mmOcular BD could be responsible for changes in the corneal layers, especially endothelial and corneal nerve structures. Nerve density and tortuosity differences could be inflammatory indicators for BD.

To assess the effects of systemic isotretinoin therapy (SIT) on the ocular surface, meibomian glands (MG) and cornea microstructure in acne vulgaris (AV) patients.Patients with AV (Schirmer II test with anaesthesia, BUT, corneal sensitivity, fluorescein and LG staining grades and OSDI score results showed no difference between the control group and the baseline of the patient group. Whereas the meibomian gland dysfunction (MGD) grades, UE and LE meiboscores were higher in the patient group at the baseline (This prospective study showed that systemic Isotretinoin treatment effects not only ocular surface parameters but also corneal and Meibomian glands structure. Considering early alterations in the course of treatment, ophthalmological assessment and follow-up during SIT are mandatory.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Purpose: To evaluate silicone hydrogel contact lens (SH-CL) effects on the meibomian glands, corneal structure, and ocular surface parameters. Methods: Fifty SH-CL wearers for at least 6 months, and 50 sex and age-matched control subjects were recruited for this cross-sectional study. Visual display terminal (VDT) work and CL wear duration were questioned, ocular surface and tear functions were evaluated using OSDI questionnaire, tear break-up time (TBUT), corneal fluorescein staining, and Schirmer test. Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry. Meibography and in vivo confocal microscopy (IVCM) were performed to evaluate meibomian glands and corneal structure. Intergroup comparisons were made using the Chi-square test, Wilcoxon test, or Kruskal–Wallis test. Results: In the CL group, TBUT was shorter (P=0.01), corneal fluorescein staining (P=0.04), OSDI scores (P0.05). IVCM showed that endothelial cell density was lower (P=0.01) and polymegethism was higher (P0.05). The longer VDT work duration was associated with increased CFS in the CL group (P=0.05). Conclusion: The results showed that SH-CL wear increased DED symptoms, especially in longer VDT work duration. Meibography revealed significantly worse results in SH-CL wearers. SH-CL-related DED seems to be more associated with MGD rather than neurosensorial alterations.

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.

Introduction In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma. Areas covered We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options. Expert opinion Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

BACKGROUND Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. AIM To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. METHODS This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. RESULTS The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p

Spheroidal corneal degeneration is predominantly seen in advanced age and hereditary predisposition to this disorder is very rare. This report describes the occurrence of bilateral band-shaped spheroidal corneal degeneration in two siblings.

To evaluate the effects of video display terminal (VDT) work and meibomian gland dysfunction (MGD) on ocular surface parameters, tear cytokine and substance P (SP) levels, and their association with dry eye disease (DED).This cross-sectional study included 60 patients with evaporative DED and 20 healthy individuals. The DED patients were divided into three groups according to daily VDT work time and presence of MGD. The ocular surface and tear film were assessed using the Ocular Surface Disease Index questionnaire (OSDI), tear film break-up time (TBUT), ocular surface staining, Schirmer II test, and corneal sensitivity. MGD was evaluated with meibography. Corneal nerve alterations were evaluated using in vivo confocal microscopy (IVCM). The tear levels of 30 cytokines and SP were examined.Compared to controls, DED patients had higher OSDI score (p 0.001), increased corneal staining with fluorescein and lissamine green (p = 0.046, p = 0,038), and lower TBUT (p 0.001). Tear interleukin-6 levels were higher in DED patients, while tear SP levels did not differ between the groups (p = 0.265). VDT work time showed a weak positive correlation with OSDI (r = 0.274, p = 0.014) and SP level (r = 0.284, p = 0.011).The results of this study show that VDT use and MGD have an adverse effect on the ocular surface. It was also observed that the combination of VDT use and MGD did not significantly increase the ocular surface disease, but longer VDT exposure may be associated with more complaints of ocular discomfort.

OBJECTIVES: To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer. METHODS: This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet–Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman’s and Post-hoc Dunn tests were used for the statistical analysis. RESULTS: TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p

Purpose This study aimed to assess the possible effect of environmental factors and eating habits on patients with the exfoliation syndrome (XFS) and exfoliative glaucoma (XFG) in a Turkish population. Methods A questionnaire was applied to 1,000 individuals, including 290 patients with XFS, 210 patients with XFG, and 500 age- and sex-matched healthy control participants. Sociodemographic characteristics, home type and warming methods, living and working conditions (indoor–outdoor), dietary habits based on the the guidance of Turkey Dietary Guidelines, (Determination of Nutritional Status Report and Turkey National Nutrition and Health Survey) and using sunglasses were evaluated. The chi-square test, Student t test, and analysis of variance were used for the statistical analysis with SPSS v. 23.0 software. Results The case–control groups were matched during data collection, and age and sex distribution in groups was analyzed; however, no difference was found. The average years and hours spent outdoor were statistically different between case and control groups ( P Conclusion This case–control study showed that time spent outdoors, wearing sunglasses, home type, heating method, and eating habits might be associated with XFS and XFG.

Objectives Topical application of fluoroquinolone antibiotics is thought to be as effective as fortified antibiotics. The aim of this study was to evaluate the efficacy of fluoroquinolones as an alternative to fortified antibiotic therapies. Materials and methods The medical records of 31 patients who were hospitalized in our department due to bacterial keratitis were retrospectively reviewed. Fluoroquinolone was started as the first treatment for 20 (64.5%) patients and upon no response fortified antibiotic was initiated, and 11 (35.5%) patients were started with fortified treatment. Cultures and smears were recorded before treatment. Lesions were evaluated as superficial or deep according to their depth. Treatment response was evaluated based on reduction of infiltrate depth and size, change in visual acuity, and regression of hypopyon. Results Central, paracentral, and peripheral location were detected in 9 (29.0%), 10 (32.2%) and 12 (38.7%) eyes, respectively. According to lesion depth, 15 (48.3%) were deep and 16 (51.6%) were superficial. Response of superficial lesions was found to be statistically earlier (p=0.037). Culture was positive in 9 (29.0%) eyes. The initial best corrected visual acuity (BCVA) was 0.5±0.7 logMAR (-0.1-2.3) and 0.3±0.3 logMAR (-0.1-0.9) after treatment. Treatment response showed moderate but statistically nonsignificant correlation with time to treatment initiation and initial BCVA (r=0.527, p=0.184; r=0.517, p=0.120). Conclusion Although fluoroquinolones are the first choice for the treatment of bacterial keratitis, fortified antibiotics have been shown to be effective in patients who do not respond to treatment. Fortified therapy should be kept in mind in the treatment of bacterial keratitis.

PReCIS:: 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.

This cross-sectional study of 20 patients with primary open-angle glaucoma (POAG), 20 with exfoliative glaucoma (XFG), 20 with exfoliation syndrome (XS) showed that exfoliative group had a significantly lower smell identification level as compared with the control groups.To investigate smell sensitivity in POAG, XFG, and XFS in comparison with healthy controls.This prospective, cross-sectional study included 20 patients with POAG, 20 with XFG, and 20 with XFS. The control group consisted of 20 age-matched and sex-matched healthy subjects with no evidence of ocular disease. The Sniffin' Sticks smell test was used to determine the, threshold values, and to assess the ability of smell identification, and differentiation in all patients One eye per patient was included for statistical purposes. One-way analysis of variance was used to compare the differences between the groups. Tukey honestly significant difference was used as a post hoc test when significant differences were detected among the 3 groups.The XFG, POAG, and control groups showed a significant difference in the odor discrimination, odor identification, and threshold discrimination identification scores. The median (minimum-maximum) smell threshold levels for the POAG, XFG, and XFS groups and healthy controls were 4.5 (0 to 7.5), 4 (0 to 7.5), 5 (4.5 to 6), and 5.5 (4 to 7.5), respectively. The smell differentiation values for the POAG, XFG, and XFS groups and healthy controls were 12 (2 to 14), 8 (0 to 13), 11 (10 to 13), and 12 (9 to 14), respectively. Smell sensitivity for the POAG, XFG, and XFS groups and healthy controls were 26 (4 to 30.5), 19 (0 to 29.5), 28.3 (22.8 to 30.5), and 29 (26.5 to 32), respectively. The smell sensitivity and differentiation were significantly different among the groups (P0.001). The XFG group had a significantly lower smell identification level than the POAG, XFS, and control groups.Patients with XFS and XFG revealed reduced smell sensitivity and identification compared with patients with POAG and those without glaucoma. These findings provide new insights into neural degeneration and pseudoexfoliation.

Mucins are key actors in tear film quality and tear film stability. Alteration of membrane-bound mucin expression on corneal and conjunctival epithelial cells and/or gel-forming mucin secretion by goblet cells (GCs) promotes in ocular surface diseases and dry eye disease (DED). Changes in the mucin layer may lead to enhanced tear evaporation eventually contributing to tear hyperosmolarity which has been associated with ocular surface inflammation. Inflammatory mediators in turn may have a negative impact on GCs differentiation, proliferation, and mucin secretion. This sheds new light on the position of GCs in the vicious circle of DED. As contributor to ocular surface immune homeostasis, GC loss may contribute to impaired ocular surface immune tolerance observed in DED. In spite of this, there are no tools in routine clinical practice for exploring ocular surface mucin deficiency/dysregulation. Therefore, when selecting the most appropriate treatment options, there is a clear unmet need for a better understanding of the importance of mucins and options for their replacement. Here, we comprehensively revisited the current knowledge on ocular surface mucin biology, including functions, synthesis, and secretion as well as the available diagnostic tools and treatment options to improve mucin-associated homeostasis. In particular, we detailed the potential link between mucin dysfunction and inflammation as part of the uncontrolled chronic inflammation which perpetuates the vicious circle in DED.

Purpose To evaluate corneal subbasal nerve alterations in contact lens (CL)-naive silicone hydrogel CL wearers and to investigate the relationship between structural subbasal nerve changes with corneal sensitivity. Methods Twenty eyes of 20 neophyte daily silicone hydrogel CL wearers and 20 eyes of age-matched control subjects were recruited for this prospective longitudinal study. Corneal subbasal nerve densities were evaluated using in vivo confocal microscopy. Central corneal tactile sensitivity was measured using Cochet-Bonnet esthesiometers. In vivo confocal microscopy and Cochet-Bonnet esthesiometry were performed before and at the 6-month time point after the initiation of CL wear. Two-way repeated measures analysis of variance, χ, and Wilcoxon signed-rank tests were used for statistical analyses. Results The mean ages of CL users and control subjects were 21.8 ± 1.8 years (range = 19-24 years) and 21.5 ± 2.3 years (range = 20-24 years), respectively (P = 0.579). Compared with their baseline values, there were no significant changes at the 6-month follow-up period in the mean total subbasal nerve fiber length (2266.6 ± 414.6 vs. 2277.9 ± 405.0 μm/frame; P = 0.432), mean total subbasal nerve branch density (10.4 ± 1.5 vs. 10.5 ± 1.3 nerves/frame; P = 0.655), or the mean long nerve fiber density (4.7 ± 0.7 vs. 4.8 ± 0.7 nerves/frame; P = 0.564) of CL users. Mechanical corneal sensitivity remained unaltered during the 6-month period in CL users (11.2 ± 0.5 vs. 11.2 ± 0.5; P = 1.000). No significant changes were observed in the subbasal nerve plexus or corneal tactile sensitivity of the control subjects during the study interval. Conclusions Sensory adaptation to CL wear is not mediated through attenuation of the subbasal nerve or reduction of corneal tactile sensitivity in CL-naive users.

Purpose: The aim of this study was to investigate the association between alterations in corneal subbasal nerve plexus and tactile corneal sensitivity in patients with Fuchs' endothelial corneal dystrophy (FECD). Methods: This retrospective, cross-sectional study included 24 (10 M/14 F) patients with FECD and 25 age- and sex-matched (10 M/15 F) healthy subjects as controls. Subjects with FECD were classified as having early (grades 1 and 2) and late (grades 3 and 4) disease. All subjects underwent central corneal tactile sensitivity measurements with the Cochet–Bonnet esthesiometer (Luneau Ophthalmologie, Chartres, France) and subbasal nerve density evaluation using in vivo confocal microscopy (IVCM). Association between corneal nerve plexus density and corneal sensitivity alterations were evaluated using the Mann–Whitney U test and the Spearman correlation test. Results: Compared to healthy subjects (mean age = 60.4 ± 7.5 years), patients with FECD (mean age = 60.6 ± 8.0 years) had worse central corneal sensitivity scores (5.9 ± 0.1 cm vs. 4.2 ± 0.8 cm; P < 0.001), reduced corneal nerve fibers (3.4 ± 1.3 nerves/frame vs. 5.0 ± 0.9 nerves/frame; P < 0.001) and lower corneal subbasal nerve plexus densities (2229.4 ± 364.3 μm/mm2 vs. 1901.6 ± 486.8 μm/mm2; P = 0.050). Patients with late stage FECD demonstrated lower subbasal nerve densities as compared to those with early disease (2204.3 ± 313.1 μm/mm2 (range = 1523–2552 μm/mm2); 1397.1 ± 227.4 μm/mm2 (range = 1120-1834 μm/mm2); P < 0.001). In the FECD group, subbasal nerve density was found to be directly correlated with corneal sensitivity scores (r = 0.457, P = 0.025). Conclusion: Progressive loss of the corneal subbasal nerve plexus appears to be a consistent feature of FECD. Reduction of the corneal nerve plexus parallels the decrease in corneal sensitivity in this patient population.

Introduction: Preservative-free (PF) medications represent a valuable treatment strategy in the lifelong management of glaucoma. By removing preservative toxicity, PF formulations provide tangible clinical benefits to glaucoma patients worldwide. They improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control.Areas covered: A critical review of the subject is provided, including selected evidence on the safety and tolerability of currently available topical PF formulations. Cumulative evidence confirms that topical PF medications are at least equally efficacious to their preserved equivalents. There is convincing short-term evidence for superior tolerability and safety of PF formulations compared to preserved medications. The long-term benefits and success of PF therapy requires further elucidation.Expert opinion: Successful stepwise administration of medical therapy for glaucoma remains elusive. There is a greater risk for ocular toxicity and therapy failure with preserved topical glaucoma therapy. Currently available and emerging PF therapy options potentially optimize lifelong stepwise glaucoma therapy and may enhance outcome. To avert complications from preservatives leading to poor adherence, ideally, future antiglaucoma therapy should become 100% PF. There are still key aspects of PF therapy that warrant further investigation.

Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to.We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs.It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.

[No Abstract Available]

Objectives: To evaluate the efficacy and safety of transscleral cyclophotocoagulation (TS-CPC) limited to 180° of ciliary body ablation in patients with various forms of refractory glaucoma. Materials and Methods: Thirty eyes with refractory glaucoma treated with 180° TS-CPC were retrospectively analyzed for intraocular pressure (IOP) reduction and success rates. Patients’ age, gender, type of glaucoma, number of diode laser treatment sessions, postoperative complications, number of hypotensive medications required to control IOP, and best corrected visual acuity (BCVA) were evaluated. The criteria for success were defined as postoperative IOP 20% decrease in IOP with or without additional medical treatment. Results: The mean age of all patients was 51.3±26.9 years (range,1-84 years). The mean postoperative IOP level (23.9±8.5 mmHg) was significantly lower than preoperative IOP (39.2±8.9 mmHg) (p

Purpose: To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. Materials and methods: Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. Results: Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p < 0.001) and lissamine green staining score (0.6 ± 0.4 vs 0.2 ± 0.4, p = 0.007). Break-up time score (9.3 ± 3.0 vs 9.9 ± 1.9, p = 0.481) and Schirmer I test score (16.5 ± 9.2 vs 19.3 ± 8.4, p = 0.323) did not differ significantly. Corneal sensation was 0.4 g/mm2 in all eyes. Patients with myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p < 0.001) and total nerve density (1956.1 ± 373.3 vs 2277.9 ± 405.0, p = 0.012) and higher subbasal nerve tortuosity (1.9 ± 0.8 vs 1.6 ± 0.7, p = 0.007) than controls. A significant increase in Ocular Surface Disease Index scores was found with decreasing basal epithelial cell density (rho = −0.518, p = 0.001). There was a significantly moderate negative correlation between the duration of myasthenia gravis and the number of corneal nerves (rho = −0.497, p = 0.022). Conclusion: Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.

International audience; Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations,and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR= 25, P=2.9 x 10-14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 x 10-8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

To evaluate the ocular surface, meibomian gland alterations, and in vivo confocal microscopy (IVCM) parameters through correlation with nicotine dependency level (NDL) and duration of smoking (DS) in chronic smokers. This cross-sectional study included 50 eyes of 50 chronic smokers, and 50 eyes of 50 age- and gender-matched healthy nonsmokers. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet esthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index (OSDI) questionnaire were performed consecutively. Basal epithelial cell, keratocyte, and endothelial cell density, the percentage of endothelial polymegethism/pleomorphism, and subbasal nerve plexus were evaluated using IVCM. Meibomian gland density was evaluated with a meibography unit. The Fagerstrom test was used to measure NDL, and DS was recorded. In the chronic smokers group, the basal epithelial cell density, anterior and posterior keratocytes, endothelial cell density, and long and total subbasal nerve numbers were lower, and LG staining, meiboscore, and OSDI scores were higher, compared with the control group, whereas other parameters were similar. The percentage of polymegethism was higher and the percentage of pleomorphism was lower in the chronic smokers group. In the correlation analysis, no significant relationship was found between the DS, NDL and ocular surface, and IVCM findings. Decreased corneal basal epithelium, anterior and posterior keratocytes, endothelial cell density, meibomian gland density, and subbasal nerve numbers were found in chronic smokers. The results of the study show that smoking has an adverse effect on ocular surface parameters.

IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 x 10(-6). The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 x 10(-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4%[interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings. National Research Foundation of SingaporeNational Research Foundation, Singapore [NRF-NRFI2018-01]; US National Eye Institute of the National Institutes of Health [R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, EY015473]; Glaucoma Research Foundation of Canada [X052, CIRG17may053]; National Medical Research Council of SingaporeNational Medical Research Council, Singapore The study was funded by grant NRF-NRFI2018-01 from the National Research Foundation of Singapore. Additional support was provided by grants R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, and EY015473 from the US National Eye Institute of the National Institutes of Health, funding from the Glaucoma Research Foundation of Canada, and grants X052 and CIRG17may053 from the National Medical Research Council of Singapore.

The present report discusses a new case of dacryoadenitis with extraocular muscle inflammation associated with Acanthamoeba keratitis (AK) in a contact lens wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an extended basis for about 10 years, attended with the complaints of vision disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5 month ago, he had been diagnosed with allergic conjunctivitis and had used steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis, and ring infiltration, radial keratoneuritis and an epithelial defect in the cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with edematous changes consistent with inflammation due to dacryoadenitis. There were also thickening and edema of the right superior oblique and lateral rectus muscle. The treatment protocol for AK was applied with no specific treatment for dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK more frequently than expected and previously known. The evaluation of the lacrimal gland and extraocular muscles in presence of AK might be beneficial for understanding better the exact clinical picture and course of the keratitis.

To evaluate ophthalmic involvement of systemic immunoglobulin-G4-related disease (IgG4-RD) and describe the changes in both ocular surface parameters and corneal subbasal nerve plexus.Twenty eyes of 10 patients with systemic IgG4-RD and 20 eyes of 10 control subjects were enrolled in this study. Demographic information, medical history, serum IgG4 levels, orbital imaging, and follow-up data of subjects were recorded. Ocular surface tests were carried out in the order of tear break-up time (BUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire for all participants. Corneal subbasal nerves and basal epithelial cell layer were evaluated using in vivo confocal microscopy.Among the 10 patients with IgG4-RD, 11 eyes of 7 patients had orbital involvement. Among these 7 patients with IgG4-related ophthalmic disease, 4 presented with painless eyelid or periorbital swelling, 2 with diplopia and restricted ocular motility, and 1 with proptosis. Patients with IgG4-RD had higher OSDI (5.9 ± 6.6 vs. 1.7 ± 2.4, P0.001) and LG staining scores (0.7 ± 1.0 vs. 0.0 ± 0.0, P = 0.011) and lower BUT (5.6 ± 1.4 vs. 10.2 ± 1.0, P0.001) and Schirmer values (11.9 ± 10.3 vs. 18.3 ± 4.4, P = 0.021) as compared with those of control subjects. Total nerve density and nerve fiber length were found to be significantly lower in patients with IgG4-RD.The orbit is frequently involved during the course of IgG4-RD. These patients should be evaluated in terms of ocular surface disease and dry eye, which may be associated with lacrimal gland and/or orbital nerve involvement.

Purpose To evaluate the association of long-term prostaglandin analog (PGA) use with meibomian gland dysfunction (MGD) in medically treated glaucoma patients. Materials and methods This was a prospective cross-sectional study conducted at a single academic setting. In total, 70 eyes of 70 patients with a medical diagnosis of glaucoma who were on long-term (>12 mo) topical hypotensive medication(s) were included. Patients were classified based on whether they were on PGA or non-PGA class of medication(s). MGD was defined based on meibomian gland terminal duct obstruction and graded between 1 and 5 based on severity. For all subjects, ocular surface disease index questionnaire, break-up time, lissamine green staining, and Schirmer test (under topical anesthesia) was administered. Student t test, Mann-Whitney U test, and χ test was used in statistical evaluations. Forty-five age-matched healthy control subjects who were not on any topical medications were also included. Results In total, 25 patients (35.7%) were on PGA monotherapy, 21 (30.0%) were treated with fixed or unfixed PGA combination regimens, and 24 (34.3%) were on non-PGA medications. MGD prevalence was higher in patients treated with PGA monotherapy (92.0%) compared with those receiving non-PGA therapy (58.3%) (P=0.02). Obstructive type of MGD was detected in the majority of patients treated with PGAs (95.7%). Grade 2 and 3 MGD was noted in 80.5% of patients on PGA. Patients on PGA had worse ocular surface disease index and ocular surface test results (P Conclusions Long-term administration of PGA is associated with obstructive type of MGD.

This report aims to describe the facilitating role of in vivo confocal microscopy in differentiating inflammatory cells from a metastatic process in a patient with uveal melanoma and multiple systemic metastases who developed anterior uveitis while under ipilimumab treatment. A 43-year-old woman developed systemic metastases 11 months after treatment of amelanotic choroidal melanoma in her right eye with 30 Gy fractionated stereotactic radiotherapy. She first received temozolomide and then 4 cycles of ipilimumab 3 mg/kg/day. After the third cycle, severe anterior uveitis with coarse pigment clumps on the lens was seen in the left eye. Her left visual acuity declined from 20/20 to 20/80. Confocal microscopy revealed globular keratic precipitates with hyperreflective inclusions and endothelial blebs all suggestive of granulomatous uveitis. The uveitic reaction subsided after a 3-week course of topical corticosteroids, and her visual acuity was 20/20 again. Although uveal melanoma metastatic to the intraocular structures of the fellow eye is exceedingly rare and metastasis masquerading uveitis without any identifiable uveal lesion is even more unusual, it was still mandatory to rule out this distant possibility in our particular patient who already had widespread systemic metastases. Confocal microscopy was a useful complementary tool by identifying the inflammatory features of the keratic precipitates.

Novel drug delivery systems have emerged to treat bacterial keratitis, an acute infection of the cornea. In this study, besifloxacin HCl loaded insert formulations were designed and investigated in vitro, ex vivo and in vivo for the treatment of bacterial keratitis. Besifloxacin HCl (BH) or BH-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) complex containing poly(caprolactone)/polyethylene glycol (PLC/PEG) fibrous inserts were prepared with an electrospinning method. These fibrous inserts were coated with mucoadhesive polymers such as sodium alginate (SA) or thiolated sodium alginate (TSA). Developed inserts compared to commercially available drug and it was found that coating of the insert surfaces with SA and TSA, increases bioadhesion of the formulations. Insert formulations showed a burst release in the first 2 days followed by a slow-release profile. Ex vivo transport studies showed that HP-beta-CD possessed a drug delivery level close to the commercial drug. Both TSA coated inserts as well as inserts containing HP-beta-CD-drug complex were effectively reducing bacterial keratitis in rabbit eyes upon single-dose application compared to multiple dosing with the commercial drug. Consequently, TSA coated inserts as well as the inserts containing HP-beta-CD-drug complex, may be potential alternatives to conventional market product by reducing the application frequency in the clinic leading to increased patient compliance.

Objectives To determine whether silicone hydrogel (SH) contact lens (CL) use, with or without meibomian gland dysfunction (MGD), promotes ocular surface inflammation. Methods Subjects wearing SH-CL for at least 6 months who also had coexisting MGD (group 1, n=20), SH-CL users who did not have MGD (group 2, n=20), patients who had MGD but did not use CL (group 3, n=20), and healthy CL-naive individuals with no known systemic or ocular diseases (group 4, n=20) were included in this cross-sectional, single-center study. All subjects underwent tear function tests consisting of tear break-up time (tBUT), ocular surface staining, Schirmer test, and the Ocular Surface Disease Index (OSDI) questionnaire, as well as determination of tear IL-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-α, IFN-γ, TNF-α, granulocyte-macrophage colony-stimulating factor, IP-10, monokine induced by gamma interferon, RANTES, eotaxin, MIP-1α, MIP-1β, and MCP-1 levels using Luminex multicytokine immunobead assay. Intergroup comparisons were made using one-way analysis of variance or Kruskal-Wallis test. Results The tBUT was lower (P=0.048) and ocular surface staining (P=0.032) as well as OSDI scores (P=0.001) were higher in group 1 but not in groups 2 or 3 when compared with those in the control group. Tear cytokine levels were similar across all groups. None of the tear cytokine levels were elevated in CL wearers (groups 1 and 2) or those with MGD (groups 1 and 3) as compared to those in control subjects. Conclusion Silicone hydrogel contact lens use with concomitant MGD is not associated with cytokine-driven ocular surface inflammation but may impact tear function leading to dry eye symptoms.

To evaluate the prognostic value of metal-metal contact during nasolacrimal duct (NLD) probing in patients with simple membranous versus complex congenital NLD obstructions (CNLDO).Retrospective case series.Infants diagnosed with CNLDO.Seventy-nine eyes of 70 infants with CNLDO who underwent probing were recruited. Metal-metal contact was sought during probing in every patient. CNLDO was classified into simple membranous versus complex type of obstruction. Complete resolution of epiphora, increased tear meniscus, and mucous discharge were defined as successful outcome.The mean age of patients at the time of probing was 21.0 ± 8.3 (range 1-42) months. Postoperative evaluations were performed in all patients between the first and second postoperative months. Overall success rate of probing was 84.9%. A higher success rate was obtained in membranous (89.7%) versus complex (54.5%) obstructions (p = 0.01). A metal-metal contact could be established in 62 (78.5%) eyes. Treatment success was achieved in 93.5% of cases in which metal-metal contact was detected versus 52.9% of cases without metal-metal contact (p0.001). Among cases with metal-metal contact, a trend toward successful outcomes was observed with membranous as compared with complex obstructions (96.4% vs 71.4%, p = 0.059). Logistic regression analysis revealed the presence of metal-metal touch (odds ratio [OR] 13.3, p = 0.001) and membranous type obstruction (OR 7.7, p = 0.019) as significant factors for a successful outcome.Establishment of metal-metal contact is an important prognostic sign for surgical success in both the membranous and the complex type of CNLDO.

Objectives In this study, by presenting four cases, we aimed to discuss the clinical presentation, diagnosis, therapy, and methods for prevention of Acanthamoeba keratitis (AK) and to emphasize that inflammatory dacryoadenitis can be seen together with it. Methods This is a retrospective case series of four eyes of four wearers of hydrophilic soft contact lenses who developed AK. The diagnosis was based on clinical signs, disease course, and confocal microscopy results. In cases with dacryoadenitis, in addition to clinical findings, magnetic resonance imaging was used to establish the diagnosis. Results All of the cases were using their contact lenses without supervision of an ophthalmologist under inappropriate conditions such as swimming in a pool and during steam bath. The diagnosis was established, and the treatment was performed within the standard protocol for AK. Two of the patients had low visual acuity at the level of counting fingers with corneal scar, cataract, and glaucoma, whereas the other two healed with fewer complications and achieved better vision. Two of the 4 cases (50%) presented with dacryoadenitis accompanying the AK. Lacrimal gland swelling improved in conjunction with symptoms of keratitis without specific treatment for dacryoadenitis in these two cases. Conclusions Despite the improvements in diagnostic tests and treatment strategies for AK, the role of prevention becomes apparent because of the bad prognosis of this serious complication; thus, contact lens wearers should be aware of the importance of using lenses under ophthalmologist's supervision. In addition, we would like to emphasize that AK may be frequently associated with lacrimal gland inflammation.

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.

To quantify the morphology of corneal basal epithelium and subbasal nerves and to evaluate the ocular surface alterations in patients with fibromyalgia (FM).Patients with FM (n = 34) and healthy controls (n = 42) were enrolled. All participants underwent ocular surface tests in the following order: corneal sensitivity, tear film breakup time, lissamine green staining, Schirmer test, and the Ocular Surface Disease Index questionnaire. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy (IVCM). Demographic characteristics, Visual Analog Scale for Pain (VAS), American College of Rheumatology 1990, the Widespread Pain Index (WPI), and the Symptom Impact Questionnaire (SIQR) scores of patients with FM were obtained.Corneal sensitivity was 0.4 g/mm (fiber length: 6.0 cm) in all eyes. Patients with FM had a higher Ocular Surface Disease Index (42.2 ± 18.9 vs. 1.2 ± 1.7, P0.001), higher lissamine green staining scores (0.5 ± 0.5 vs. 0.05 ± 0.2, P0.001), and lower tear breakup time scores (9.0 ± 3.6 vs. 10.3 ± 1.5, P = 0.003) than the controls. Basal epithelial cell density (2709 ± 494 vs. 4491 ± 724), total nerve density (1563 ± 620 vs. 2545 ± 973), long nerve fibers (3.4 ± 1.3 vs. 4.5 ± 1.0), and the number of nerves (5.0 ± 1.8 vs. 10.3 ± 2.1) were all lower in patients with FM compared with those of the controls (P0.001 for all). There was a statistically significant negative correlation between the WPI score and Schirmer test results (rho = -0.374, P = 0.03) and between WPI and total nerve density (rho = -0.334, P = 0.054).To the best of our knowledge, this is the first study that evaluated ocular surface alterations in the context of corneal IVCM characteristics. Patients with FM should be evaluated in terms of ocular surface diseases. IVCM may be used in FM to assess small fiber neuropathy.

Botulinum toxin injection is widely used for many purposes, including neuromuscular diseases, movement disorders and strabismus.To evaluate and report the impact of botulinum toxin injection on ocular surface parameters in patients with strabismus.Twenty-six consecutive patients who underwent botulinum toxin A injection for ocular misalignment were recruited for this prospective study.Testing of ocular surface parameters including tear break-up time (BUT), lissamine green (LG) staining and Schirmer test (under topical anesthesia) was performed, and Ocular Surface Disease Index (OSDI) questionnaire scores were recorded before and at certain time points after injection (one week, two weeks, one month, three months and six months after botulinum toxin A injection). Two-way analysis of variance (ANOVA) with repeated measures, Friedman's test and Wilcoxon test were used for statistical analysis.Twenty six patients (15 eso- and 11 exo-deviations) with a mean age of 32.46 ± 14.41 (17-65) years were recruited for the study. All injections were performed in one eye. The mean amount of deviation at near and distance reduced after injection. The change of BUT, LG staining and OSDI scores was found to be significant during follow-up in treated eyes (p = 0.001, p = 0.007 and p = 0.009, respectively) whereas the change was insignificant for the Schirmer test results (p = 0.266).The ocular surface parameters appear to be altered by botulinum toxin injection in strabismic patients. Even though these effects seemed to be temporary, the findings of the present study support the notion of botulinum toxin effects on ocular surface parameters.