Changing from preserved, to preservative-free cyclosporine 0.1% enhanced triple glaucoma therapy: impact on ocular surface disease-a randomized controlled trial.

OBJECTIVE: Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. METHODS: A single-centre, masked, prospective, placebo-controlled, crossover trial of 41 well-controlled open-angle glaucoma subjects with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination (DTFC) therapy was conducted. Subjects were randomized to preservative-free (PF) tafluprost and DTFC with either placebo or cyclosporine 0.1% drops for 6 months and were then crossed over to the opposite therapy. Oxford score of ocular staining was the primary outcome; osmolarity, matrix-metalloproteinase-9 (MMP-9) testing, tear film break-up time (TFBUT), meibomian gland dysfunction (MGD), punctum evaluation, adverse events and diurnal intraocular pressure (IOP) comprised secondary outcomes. RESULTS: GTR-OSD findings improved with PF therapy. At 6 months the triple PF with placebo group showed improvement compared to baseline in mean Oxford score (mean difference [MD]:-3.76; 95% confidence interval [CI]:-4.74 to -2.77; p < 0.001), osmolarity (MD:-21.93; 95%CI:-27.61 to -16.24 mOsm/l; p < 0.001), punctum stenosis (p = 0.008) and conjunctival hyperaemia (p < 0.001). Similar improvements occurred in the cyclosporine enhanced period, which also provided greater improvement in MMP-9 positivity (24 vs 66%; p < 0.001) and TFBUT (p = 0.022). The cyclosporine group was superior vs placebo in mean Oxford score (MD:-0.78; 95%CI:-1.40 to -0.15); p < 0.001), itchiness and objective adverse events (p = 0.034). Cyclosporine elicited more stinging vs placebo (63 vs 24%; p < 0.001). Both PF regimens reduced mean diurnal IOP more than preserved therapy (14.7 vs 15.9 mmHg; p < 0.001). CONCLUSIONS: Changing from preserved to PF glaucoma medications improves ocular surface health and IOP control. Topical cyclosporine 0.1% further reverses GTR-OSD.

Development and Validation of the Life for Low Vision Questionnaire (LIFE4LVQ) Using Rasch Analysis: A Questionnaire Evaluating Ability and Independence.

Low vision (LV) has a substantial impact on an individual's daily functionality and patient-reported outcome measures (PROMs) are increasingly incorporated into the evaluation of this problem. The objective of this study was to describe the design of the new "Life for Low Vision Questionnaire (LIFE4LVQ)", as a measure of daily functionality in LV and to explore its psychometric properties. A total of 294 participants completed the LIFE4LVQ and the data were subjected to Rasch analysis to determine the psychometric properties of the questionnaire, including response category ordering, item fit statistics, principal component analysis, precision, differential item functioning, and targeting. Test-retest reliability was evaluated with an interval of three weeks and intraclass correlation coefficients (ICC) were used. The correlation between the questionnaire score and Best Corrected Visual Acuity (BCVA) was examined using Spearman's correlation coefficient. Rasch analysis revealed that for most items the infit and outfit mean square fit values were close to 1, both for the whole scale and its subscales (ability and independence). The separation index for person measures was 5.18 with a reliability of 0.96, indicating good discriminant ability and adequate model fit. Five response categories were found for all items. The ICC was 0.96 (p < 0.001; 95% CI, 0.93-0.98), suggesting excellent repeatability of the measure. Poorer BCVA was significantly associated with worse scores (rho = 0.559, p < 0.001), indicating excellent convergent validity. The functional, 40-item LIFE4LVQ proved to be a reliable and valid tool that effectively measures the impact of LV on ability and independence.

Correction to: 24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

In the original article, the incorrect Open Access License type has been incuded.

Rare Persistent Corneal Infection by Phoma sp. - A Case Report.

We report a case of severe Phoma sp. corneal infection in a middle-aged, otherwise healthy, female patient who was using a soft contact lens. This is the first time that such an infection has been reported in Greece. Our case demonstrates the clinical difficulties and management challenges presented by these recalcitrant corneal infections. Management steps included corneal grafting, vitrectomy, and intravitreal antibiotics.

Cyclodestructive Procedures in Glaucoma: A Review of Current and Emerging Options.

The first surgical modalities to reduce aqueous humor production by damaging the ciliary body date back to the early twentieth century. Until recently, however, cyclodestructive procedures (e.g., cyclocryotherapy and transscleral diode laser photocoagulation) have been reserved as last option procedures in refractory glaucoma patients with poor visual potential. Emerging technologic innovation has led to the development of promising, safer and less destructive techniques, such as micropulse diode cyclophotocoagulation, endoscopic cyclophotocoagulation and ultrasound cyclodestruction. Consequently, an emerging paradigm shift is under way with the selection of these surgical options in eyes with less severe glaucoma and good visual potential. Although existing evidence has not, as yet, adequately defined the role and value of these procedures, their emergence is a welcome expansion of available options for patients with moderate-to-severe glaucoma. This article reviews the pertinent evidence on both established and evolving cyclodestructive techniques and describes their growing role in the management of glaucoma.

Preservative-free tafluprost/timolol fixed combination: comparative 24-h efficacy administered morning or evening in open-angle glaucoma patients.

Background: Ideal dosing for the preservative-free (PF) tafluprost/timolol fixed combination (TTFC) remains to be elucidated. Research design and methods: This study was a prospective, observer-masked, placebo-controlled, crossover, comparison in 42 consecutive open-angle glaucoma patients whose intraocular pressure (IOP) was insufficiently controlled with preserved latanoprost monotherapy (mean 24-h IOP >20 mmHg). Patients were randomized to either morning (08:00) or evening (20:00) PF TTFC for 3 months and then crossed over. After each treatment period, patients underwent habitual 24-h IOP monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Results: Mean 24-h IOP on latanoprost was 22.2±3.9 mmHg. Both PF TTFC dosing regimens obtained greater reduction in mean 24-h, daytime, nighttime, and peak 24-h IOP (P < 0.001). Evening dosing provided tighter 24-h IOP fluctuation versus latanoprost (P < 0.001). Evening dosing was superior to morning dosing at four time points (P < 0.01), for the mean daytime IOP (P < 0.001) and mean 24-h IOP fluctuation (P < 0.001). Hyperemia was more common with preserved latanoprost (21.4 vs. 7.1%; P = 0.031). Patients (n = 19; 45%) preferred evening dosing. Conclusions: PF TTFC provided greater 24-h IOP control and less hyperemia compared with preserved latanoprost. Evening administration of this novel medication offered superior 24-h efficacy. Trial registration: Clinicaltrials.gov (NCT03612817).

Targeting Schlemm's Canal in the Medical Therapy of Glaucoma: Current and Future Considerations.

Schlemm's canal (SC) is a unique, complex vascular structure responsible for maintaining fluid homeostasis within the anterior segment of the eye by draining the excess of aqueous humour. In glaucoma, a heterogeneous group of eye disorders afflicting approximately 60 million individuals worldwide, the normal outflow of aqueous humour into SC is progressively hindered, leading to a gradual increase in outflow resistance, which gradually results in elevated intraocular pressure (IOP). By and large available antiglaucoma therapies do not target the site of the pathology (SC), but rather aim to decrease IOP by other mechanisms, either reducing aqueous production or by diverting aqueous flow through the unconventional outflow system. The present review first outlines our current understanding on the functional anatomy of SC. It then summarizes existing research on SC cell properties; first in the context of their role in glaucoma development/progression and then as a target of novel and emerging antiglaucoma therapies. Evidence from ongoing research efforts to develop effective antiglaucoma therapies targeting SC suggests that this could become a promising site of future therapeutic interventions.

A Review of Minimally Invasive Strabismus Surgery (MISS): Is This the Way Forward?

Minimally invasive surgery is rapidly becoming the norm in medicine, as it often leads to better outcomes and earlier rehabilitation. This article reviews the principles and different techniques employed to perform minimally invasive strabismus surgery (MISS). In these techniques, strabismus surgery is performed through keyhole openings, thus reducing the risk of postoperative corneal complications, minimizing postoperative discomfort, and better preserving muscle function. MISS can be used to perform all types of strabismus surgery, namely rectus muscle recessions, resections, plications, reoperations, retroequatorial myopexy, transpositions, oblique muscle recessions, or plications even in the presence of limited motility. Of note, ocular alignment outcomes with MISS versus more traditional techniques have not been compared in randomized trials. Consequently, more controlled evidence is still needed to better delineate the future role and value of MISS in clinical management.

Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma.

The approval of one of the first anti-vascular endothelial growth factor (VEGF) agents for the treatment of neovascular age-related macular degeneration one decade ago marked the beginning of a new era in the management of several sight-threatening retinal diseases. Since then, emerging evidence has demonstrated the utility of these therapies for the treatment of other ocular conditions characterized by elevated VEGF levels. In this article we review current perspectives on the use of anti-VEGF drugs as adjuvant therapy in the management of neovascular glaucoma (NVG). The use of anti-VEGFs for modifying wound healing in glaucoma filtration surgery (GFS) is also reviewed. Selected studies investigating the use of anti-VEGF agents or antimetabolites in GFS or the management of NVG have demonstrated that these agents can improve surgical outcomes. However, anti-VEGF agents have yet to demonstrate specific advantages over the more established agents commonly used today. Further studies are needed to evaluate the duration of action, dosing intervals, and toxicity profile of these treatments.

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

INTRODUCTION: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). METHODS: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. RESULTS: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). CONCLUSIONS: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02802137). FUNDING: Santen.

24-hour efficacy of the bimatoprost-timolol fixed combination versus latanoprost as first choice therapy in subjects with high-pressure exfoliation syndrome and glaucoma.

AIM: To compare the 24-h intraocular pressure (IOP) control obtained with the bimatoprost-timolol fixed combination (BTFC) versus latanoprost in newly diagnosed, previously untreated exfoliation syndrome (XFS) or exfoliative glaucoma (XFG) patients with baseline morning IOP greater than 29 mm Hg. METHODS: One eye of 41 XFS/XFG patients who met inclusion criteria was included in this prospective, observer-masked, crossover, comparison protocol. All subjects underwent a 24-h untreated curve and were then randomised to either evening administered BTFC or latanoprost for 3 months and then switched to the opposite therapy. At the end of each treatment period, patients underwent a treated 24-h IOP assessment. RESULTS: 37 patients completed the trial. At baseline, mean untreated 24-h IOP was 31.1 mm Hg. Mean 24-h IOP with BTFC was significantly lower than with latanoprost (18.9 vs 21.2 mm Hg; p<0.001). Furthermore, BTFC reduced IOP significantly more than latanoprost at every time point, for the mean peak and trough 24-h IOP (p<0.001). There was no difference, however, in mean 24-h IOP fluctuation between the two medications (3.8 with BTFC vs 4.2 with latanoprost; p=0.161). Both treatments were well tolerated and there was no statistically significant difference for any adverse event between them. CONCLUSIONS: As first choice therapy in high-pressure, at-risk exfoliation patients, BTFC controlled mean 24-h IOP significantly better than latanoprost monotherapy.