Prescription trends for preservative free glaucoma medication in a public health system.

PURPOSE: To analyze the prescribing trends over a 7-years period, between 2013 and 2020, in a tertiary hospital (Hospital Clinico San Carlos, Madrid, Spain) and its health area. MATERIAL AND METHODS: A retrospective study on the data collected from the information systems, "farm@web" and "Farmadrid", of glaucoma prescriptions in the framework of a public health system (Spanish National Health System) during the last seven years. RESULTS: Prostaglandin analogues were the most commonly used drugs in monotherapy during the study period (range: 36.82% - 47.07%). Fixed combinations of topical hypotensives had an upward trend since 2013 (range: 39.99% - 54.21%), becoming the most dispensed drugs in 2020 (48.99%). Preservative-free eye drops (lacking benzalkonium chloride, BAK) have displaced preservative containing topical treatments in all pharmacological groups. In 2013, BAK-preserved eye drops accounted for 91.1% of the total prescriptions, however in 2020 they only accounted for 34.2% of total prescriptions. CONCLUSIONS: The results of the present study highlight the current trend to avoid BAK-preserved eye drops for the treatment of glaucoma.

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.

[Effectiveness and safety of a hypotensive preservative-free drug in long-term therapy of glaucoma]. / Effektivnost' i bezopasnost' primeneniya gipotenzivnogo beskonservantnogo preparata pri dlitel'noi terapii glaukomy.

PURPOSE: To investigate the condition of the ocular surface and the effectiveness of Taflotan for long-term therapy in patients with newly diagnosed primary open-angle glaucoma in real clinical practice. MATERIAL AND METHODS: This publication presents data form a retrospective observational study that analyzed newly diagnosed glaucoma patients that have been using 1 drop/day of Taflotan in the evening for 12 months. All patients were examined at baseline, and after 1 month and 12 months of treatment, recording intraocular pressure (IOP), retinal photosensitivity indicators (MD, PSD), thickness of the retinal nerve fiber layer (RNFL), and assessing the condition of the ocular surface by Schirmer test, tear breakup time (TBUT), ocular surface disease index (OSDI) questionnaire, as well as measurement of the lacrimal meniscus height and corneal staining with lissamine green. RESULTS: IOP effectively decreased in all patients using Taflotan, reaching the target pressure by 1 month after therapy initiation. IOP decreased from 25±4 mm Hg at baseline to 17±3mm Hg after 1 month with further decrease down to 16±3 mm Hg after 12 months of therapy. Retinal photosensitivity (MD and PSD) and RNFL thickness did not differ from baseline, and correlated to glaucoma stage. The indicators of the condition of the ocular surface had no significant differences between the baseline, 1-month and 12-month time points. CONCLUSION: Taflotan effectively decreases IOP in newly diagnosed glaucoma patients, maintains stable automated perimetry indices and RNFL thickness, and does not affect the ocular surface throughout 12 months of therapy.

A comparison of country-level data from the VISIONARY study examining treatment outcomes with preservative-free tafluprost/timolol fixed-dose combination therapy.

OBJECTIVE: Analysis and comparison of country-level data from the VISIONARY study, examining treatment outcomes with the topical fixed-dose combination of preservative-free tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) who were insufficiently treated with or unable to tolerate either beta-blocker or prostaglandin analogue (PGA) topical monotherapy. METHODS: A European, prospective, observational study was conducted in 11 countries. Adults with OAG/OHT were switched to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Statistical analysis examined changes in mean standard deviation (SD) intraocular pressure (IOP) from baseline at Week 4, Week 12 and Month 6. Data were documented for each eye separately at baseline and during follow up visits, with the eye reported to have the higher IOP (mmHg), as measured using Goldmann applanation tonometry, being selected for analysis (study eye). Country-level subanalysis examined outcomes by prior monotherapy, diagnosis and timing of dosing for those countries recruiting ≥20 patients (Country-level Subanalysis Population). Two-sided paired t-test was used to assess significance regarding mean IOP reduction from baseline and a compound symmetry covariance model was used in cross-country comparisons regarding variation in IOP change from baseline. Treatment-related adverse events (AEs) were evaluated. RESULTS: Mean (SD) age among patients recruited to the VISIONARY study ranged between 63.9 (11.8) and 72.4 (10.6) years across all countries. The majority of participants (>50%) were female in each country. The Country-level Subanalysis Population included 551 eyes. Mean (SD) IOP was significantly reduced from baseline in each country at Week 4, Week 12 and Month 6 (p < .0001). Mean IOP reduction at Month 6 ranged from 5.0 mmHg (22.6%, Hungary) to 7.8 mmHg (31.8%, Latvia) and varied significantly between countries (p < .001). The greatest reductions were in Latvia and Russia, where baseline IOP was highest. Country-level IOP reductions were significant irrespective of prior monotherapy, diagnosis or dosing time (p < .0001). Most treatment-related AEs occurred in the UK (26 events, 73% mild). One serious AE was reported (Russia, status asthmaticus). Tolerability with PF tafluprost/timolol FC therapy was rated as good/very good by most patients (85.7-100%) in all countries. CONCLUSION: Subanalysis of VISIONARY study data revealed significant IOP reductions following a switch to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Cross-country variation was likely due to baseline IOP differences. Within country, outcomes were consistent regardless of diagnosis, dosing or prior monotherapy. Treatment was generally well tolerated.

Comparison of a preservative-free nonsteroidal anti-inflammatory drug and preservative-free corticosteroid after uneventful cataract surgery: multicenter, randomized, evaluator-blinded clinical trial.

PURPOSE: To compare the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal eyedrops for inflammation management after cataract surgery using slitlamp indicators. SETTING: 11 eye centers in South Korea. DESIGN: Randomized prospective multicenter study with a blinded evaluator. METHOD: In 125 (250 eyes) patients who underwent cataract surgery, bromfenac sodium hydrate 0.1% (NSAID group) was applied twice a day in 1 eye, whereas the other eye was treated with fluorometholone 0.1% (steroid group), 4 times a day for 4 weeks postoperatively. The primary efficacy outcome was the presence of anterior chamber cells and flare at 1 week postoperatively. Anterior chamber cells and flare at 4 to 8 weeks, corrected distance visual acuity, central corneal thickness, conjunctival hyperemia, dry eye parameters, foveal thickness, and ocular and visual discomfort were evaluated as secondary outcomes. RESULTS: At week 1, residual anterior chamber inflammation was not statistically significantly different between the groups (-1.03 ± 1.27 vs -0.95 ± 1.24, P = .4850). However, the NSAID group recovered from conjunctival hyperemia more rapidly than the steroid group (0.30 ± 0.52 vs 0.44 ± 0.81, P = .0144 at week 1). The increase in central corneal thickness in the NSAID group was less than that in the steroid group 1 week postoperatively (7.87 ± 22.46 vs 29.47 ± 46.60 µm, P < .0001). The change in foveal thickness in the NSAID group was significantly less than that in the steroid group (18.11 ± 68.19 vs 22.25 ± 42.37 µm, P = .0002). Lower levels of postoperative ocular and visual discomfort were reported in the NSAID group than in the steroid group under treatment. CONCLUSIONS: Preservative-free bromfenac was as effective as preservative-free fluorometholone eyedrops in anterior chamber inflammation control and showed better signs and symptoms after cataract surgery.

Ocular Surface Disease in Glaucoma Patients Randomized to Benzalkonium Chloride-Containing Latanoprost and Preservative-Free Bimatoprost.

Purpose: To investigate the influence of benzalkonium chloride (BAK) on ocular surface disease (OSD) in glaucoma patients receiving ocular-hypotensive agent. Methods: Patients were randomized to receive BAK-containing latanoprost (Xalatan) or preservative-free bimatoprost (Lumigan PF). Intraocular pressure (IOP), basal Schirmer's test, noninvasive keratograph tear-breakup time (TBUT), conjunctival redness score (R score), OSD index (OSDI), and corneal Oxford staining were recorded and compared between the 2 groups at 1-month and 4-month visits. The influence of BAK was analyzed by a generalized estimating equation model. Results: We enrolled 74 and 76 eyes treated with latanoprost and bimatoprost, respectively. The IOP decreased in both groups, although greater reduction was observed for latanoprost (13.95 vs. 15.42 mmHg, P = 0.0264). There was a significantly negative association between tear flow and latanoprost use (ß = -0.763, P = 0.0243). The first and average TBUT did not show intergroup differences, but the area with unstable tear film increased with latanoprost use and showed marginal significance at 4-month visit (9.33% vs. 5.94% P = 0.055). In both groups, OSDI decreased, whereas Oxford stain increased over time, and R scores showed improvement after transient increase in the first month. The bimatoprost group had significantly worse conjunctival hyperemia, whereas a negative association with conjunctival hyperemia was revealed for latanoprost use (R score-bulbar nasal: ß = -0.045, P = 0.0423). Conclusions: BAK-containing latanoprost was associated with decreased tear secretion and may be associated with tear-film instability, whereas bimatoprost was associated with worse conjunctival hyperemia. Ocular surface side effects should be considered when prescribing BAK-containing medication to glaucoma patients.

Corneal epithelium and limbal region alterations due to glaucoma medications evaluated by anterior segment optic coherence tomography: a case-control study.

AIM: To investigate the corneal epithelial and limbal epithelial alterations in patients under topical glaucoma treatment using anterior segment-OCT (AS-OCT) and to determine the changes of the limbal region due to the preservatives and glaucoma drugs, that can progress to limbal stem cell deficiency (LSCD). Limbal thickness was measured by AS-OCT to evaluate limbal cell deficiency. METHODS: Forty-seven patients using topical medication for glaucoma, and 48 control subjects were enrolled in this matched case-control study. The patients were divided into four groups according to the treatment regimens. Group 1: One-drug regimen, Group 2: Two-drug regimen, Group 3: Three-drug regimen, Group 4: Four-drug regimen For the ocular surface evaluation; tear break-up time with standard fluorescein sodium sterile strip application, Schirmer test-I, Ocular Surface Disease Index Questionnaire, and AS-OCT were performed. RESULTS: A total of 95 subjects were included: 47 eyes of 47 patients with glaucoma medication and 48 eyes of 48 healthy subjects. There was a statistically significant difference between patients and controls according to BUT, SCH, and OSDI (p < 0.001). The mean central corneal epithelium thickness was 48.5 ± 5.3 in patients and 54.5 ± 5.9 in controls (p < 0.001). The mean central total corneal thickness was 529.2 ± 41.2 in patients and 536 ± 35.3 in controls (p = 0.335). The mean limbal epithelium thickness was 64.1 ± 9.1 in patients and 76 ± 11.5 in controls (p < 0.001). CONCLUSION: Using at least one glaucoma drug caused limbal area injury, changed ocular surface measurements, and significantly reduced the limbal epithelial thickness where the stem cells reside. The limbal epithelial thickness measurement by AS-OCT seems to be an innovative, non-invasive, and promising technique for detecting and staging corneal damage in topical glaucoma therapy.

New strategies for the management of ocular surface disease in glaucoma patients.

PURPOSE OF REVIEW: Glaucoma patients commonly suffer from ocular surface disease (OSD). As treatment strategies, medications and devices for the treatment of OSD as well as glaucoma surgical approaches evolve rapidly, it is important to consider their application to these patients. RECENT FINDINGS: OSD in glaucoma patients may lead to reduced reliability of diagnostic tests, decreased medication compliance, poor surgical outcomes, and overall decreased quality of life. Chronic use of topical glaucoma medications has been linked to the development of limbal stem cell deficiency, and the role of preservatives in OSD continues to be demonstrated. Preservative free glaucoma medications as well as new anti-inflammatory agents for the treatment of OSD are now available. Omega-3 fatty acid supplementation and punctal plugs have been shown to benefit glaucoma patients with OSD. Drop burden may be reduced through the use of the new sustained-release delivery systems, selective laser trabeculoplasty, and minimally invasive glaucoma surgery. SUMMARY: There are multiple emerging strategies for managing OSD that may be applied to patients with glaucoma. With continued research and clinical experiences, we hope to better understand the multifaceted relationship between glaucoma and OSD and develop evidence-based algorithms for the management of these complex patients.

Tear neuromediators in eyes on chronic topical antiglaucoma therapy with and without BAK preservatives.

PURPOSE: To evaluate tear neuropeptides (NPs) (vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP), nerve growth factor (NGF)) in chronic ocular topical hypotensive therapy with and without benzalkonium chloride (BAK) preservative. METHODS: A comparative, open label, cross-sectional study of patients using antiglaucoma medications for >6 months with BAK (group I), without BAK (group II) and controls was done. Tear NPs (ELISA), ocular surface evaluation tests (tear breakup time (TBUT), Schirmer's test, corneal and conjunctival staining score) and confocal central corneal subbasal nerve fibre layer (SBNFL) imaging was done. RESULTS: Of 153 eyes evaluated, group 1 (82 eyes (41 patients; mean age 48±14.5 years)) and group 2 (71 eyes (36 patients; mean age 43.11±15 years)) were on therapy for a mean duration of 10.05±2.0 and 9.67±2.3 months, respectively. Tear analysis showed elevated SP and NGF (p<0.01); decreased CGRP (p=0.03), VIP and NPY (p<0.01) compared with controls (n=30, mean age 29.33±5.7 years). Tear NP levels (SP (p=0.1), NGF (p=0.33), CGRP (p=1), VIP (p=0.87), NPY (p=0.83)) and SBNFL (p=0.09) were comparable in both groups. There was no correlation seen between tear NP levels and clinical tests and SBNFL. CONCLUSION: Our study analysis points towards altered tear NP levels in eyes on chronic topical hypotensive therapy in comparison with controls with no significant difference in tear NP levels and central corneal SBNFL density between the BAK preservative and BAK-free antiglaucoma therapy.

Correlation of Ocular Surface Disease and Quality of Life in Indian Glaucoma Patients: BAC-preserved versus BAC-free Travoprost.

Objectives: The use of benzalkonium chloride (BAC)-preserved medications is associated with ocular surface disease (OSD) that can negatively affect quality of life (QoL) in glaucoma patients. This study aimed to compare QoL and correlate it with OSD in glaucoma patients receiving BAC-preserved and BAC-free travoprost. Materials and Methods: A total of 110 subjects were divided into 3 groups: 40 primary open-angle glaucoma (POAG) patients using BAC-preserved travoprost, 40 POAG patients using BAC-free travoprost, and 30 age-matched controls. All patients were assessed using a single interviewer-administered format of the Ocular Surface Disease index (OSDI) and Glaucoma Quality of Life-15 (GQL-15) questionnaires. Results: Mean GQL-15 score in the BAC group was significantly higher than in the BAC-free group (24.71±7.42 vs. 17.58±3.06; p<0.05). The mean difference in GQL-15 scores between controls and the BAC-free group (1.24) was insignificant (p>0.05). There was a strong positive correlation between OSDI scores and GQL-15 scores in all the groups (r values: BAC: 0.63, BAC-free: 0.23, controls: 0.29), with higher OSDI scores (severe OSD) associated with higher GQL-15 scores (worse QoL). Cronbach's alpha was 0.84 for GQL-15 and 0.75 for OSDI. Conclusion: BAC-preserved travoprost leads to higher OSDI scores, which correlate strongly with poor QoL scores as compared to BAC-free travoprost. The use of BAC-free formulations should be encouraged to reduce the onset or worsening of OSD and impaired QoL in glaucoma patients.

Efficacy and safety evaluation of benzalkonium chloride preserved eye-drops compared with alternatively preserved and preservative-free eye-drops in the treatment of glaucoma: a systematic review and meta-analysis.

BACKGROUND/AIMS: This systematic review compared the efficacy and safety of benzalkonium chloride (BAK)-preserved eye-drops with alternatively preserved (AP) and preservative-free (PF) eye-drops. METHODS: PubMed, EMBASE and MEDLINE were searched for randomised controlled trials in June and October 2019. Study selection, data extraction and risk of bias assessment were made by two independent reviewers using the Cochrane Handbook. Studies on prostaglandin analogue or beta-blocker eye-drops and patients with glaucoma or ocular hypertension were included. Primary outcome was change in intraocular pressure (IOP). Secondary outcomes were safety measures as assessed in original study. RESULTS: Of 433 articles screened, 16 studies were included. IOP meta-analysis was conducted on 13 studies (4201 patients) ranging from 15 days to 6 months. No significant differences between BAK versus PF and AP were identified (95% CI -0.00 to 0.30 mm Hg, p=0.05). Meta-analyses revealed no differences between BAK versus AP and PF with regards to conjunctival hyperaemia (risk ratio (RR) 1.05, 95% CI 0.91 to 1.22, 3800 patients, 9 studies), ocular hyperaemia (RR 1.31, 95% CI 0.96 to 1.78, 2268 patients, 5 studies), total ocular adverse events (RR 1.03, 95% CI 0.88 to 1.20, 1906 patients, 5 studies) or tear break-up time (mean difference 0.89, 95% CI -0.03 to 1.81, 130 patients, 3 studies). Diverse reporting on safety measures made comparison challenging. Risk of bias was assessed as high or unclear in many relevant domains, suggesting potential selective reporting or under-reporting. CONCLUSION: No clinically significant differences on efficacy or safety could be determined between BAK versus AP and PF. However, there were substantial uncertainties on safety.PROSPERO registration numberCRD42019139692.

Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review / Eficácia do uso de colírios sem preservativos comparados com colírios com preservativos no tratamento do olho seco: uma revisão sistemática

ABSTRACT This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.

RESUMO Esta revisão sistemática teve como objetivo avaliar a eficácia do uso de lágrimas artificiais sem conservantes em comparação com lubrificantes preservados no tratamento do olho seco na Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). As bases de dados online foram pesquisadas (LILACS, EMBASE, MEDLINE e CENTRAL) desde o início até abril de 2018; referências de artigos incluídos também foram pesquisadas. Foram utilizados os seguintes descritores: lubrificantes OU lágrimas artificiais OU lágrimas artificiais, lubrificantes E olho seco OU síndrome do olho seco OU síndromes, olho seco OU olhos secos. Dos 2028 resultados de busca eletrônica, 29 artigos completos foram recuperados, e quatro foram considerados relevantes. O número de participantes desses estudos variou de 15 e 76. A meta-análise foi possível para as seguintes variáveis: escore de desfecho dos sintomas de acordo com o Índice de Doença da Superfície Ocular - Allergan (OSDI), taxa de secreção lacrimal pelo teste de Schirmer, taxa de evaporação lacrimal usando o teste de tempo de ruptura do filme lacrimal, queimação, sensação de corpo estranho e fotofobia. Nenhuma diferença estatisticamente significativa foi observada entre os dois grupos, e nenhum efeito adverso foi atribuído às intervenções. Evidências provando que as lágrimas artificiais sem conservantes são mais eficazes do que as lágrimas artificiais preservadas estão faltando.

Effects of Preservative-free 3% Diquafosol in Patients with Pre-existing Dry Eye Disease after Cataract Surgery: A Randomized Clinical Trial.

Dry eye disease (DED) after cataract surgery has become a critical concern, and various therapeutic options have been developed. Recently, preservative-free diquafosol ophthalmic solution has been introduced; however, its therapeutic effect on DED after cataract surgery has not been reported. We investigated the efficacy of preservative-free diquafosol in patients with pre-existing DED after cataract surgery. We divided subjects who were diagnosed with DED and scheduled to undergo cataract surgery, into 3 groups (preservative-free diquafosol, group 1; preservative-containing diquafosol, group 2; preservative-free hyaluronate, group 3), and each eye drops was administered 6 times daily after surgery. Tear break up time (TBUT), Ocular Surface Disease Index (OSDI), corneal staining score, lid margin abnormality, and meibum quality improved over time in group 1. Groups 1 and 2 had significantly superior TBUT, meibomian gland dysfunction grade, and meibomian gland expressibility throughout the study period than group 3. Meibum quality of group 1 was significantly better than group 2 at 1 and 3 months after surgery. Preservative-free diquafosol showed better efficacy in treating DED after cataract surgery than preservative-containing diquafosol or preservative-free hyaluronate. Preservative-free diquafosol may serve as a reliable option for the management of patients with pre-existing DED after phacoemulsification.

Effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes: a systematic review.

This systematic review aimed to assess the effectiveness of using preservative-free artificial tears versus preserved lubricants for the treatment of dry eyes in Universidade Federal de Alagoas (PROSPERO 2018 CRD42018089933). Online databases were searched (LILACS, EMBASE, MEDLINE, and CENTRAL) from inception to April 2018; references from included papers were also searched. The following keywords were used: lubricants OR artificial tears OR artificial tears, lubricants AND dry eye OR dry eye syndrome OR syndromes, dry eye OR dry eyes. Among the 2028 electronic search results, 29 full papers were retrieved and four were considered relevant. The number of participants from these studies ranged from 15 to 76. Meta-analysis was possible for the following outcomes: score of symptoms according to the Ocular Surface Disease Index - Allergan (OSDI), tear secretion rate using the Schirmer test, tear evaporation rate using the tear film breakup time test, burning, foreign body sensation, and photophobia. No statistically significant difference was observed between the two groups, and no side effects were attributed to the interventions. Evidence proving that preservative-free artificial tears are more effective than preserved artificial tears is lacking.

Patient-Reported Nonadherence with Glaucoma Therapy.

Purpose: Effective glaucoma therapy relies to a great extent on the patients' ability to regularly self-administer eye drops. This study aimed to assess self-reported nonadherence and to identify potential barriers to adherence in glaucoma patients. Methods: Participants completed a 16-item questionnaire, designed to examine nonadherence rate and assess the therapy experience. Inclusion criteria stipulated treatment duration of at least 1 year. Nonadherence was defined as missing ≥5% of the prescribed pressure-lowering eye drops doses. Results: In total, 201 glaucoma patients aged 24-88 years were included. Mean treatment duration was 9.4 years. Nonadherence was reported by 30.3% of participants and 69.7% were reported to be adherent. Individuals who experienced side effects reported higher levels of nonadherence than those who did not (37.6% vs. 18.4%; P = 0.004). Eye drops with preservatives were used by 84.1% of participants, 11.9% were on combined preservative and preservative-free treatment, and 4.0% on preservative-free medication only. Self-reported nonadherence levels were 32.0%, 25.0%, and 12.5%, respectively, for each of these groups. Men reported higher rates of nonadherence than women (36.8% vs. 24.5%; P = 0.066). Age, social status, history of migration, severity of disease, and fear of blindness were not associated with significant differences in nonadherence levels. Conclusions: Nonadherence with glaucoma therapy is a significant barrier to therapeutic success for approximately one-third of patients. Nonadherence may be reduced if side effects are avoided. Preservative-free products may provide adherence benefits. The patient experience should be a key consideration when selecting appropriate treatments, to reduce nonadherence and optimize outcomes.

Conjunctival Goblet Cells, the Overlooked Cells in Glaucoma Treatment.

Glaucoma is the leading cause of irreversible blindness worldwide. Although no definitive cure exists, lowering of the intraocular pressure decreases the rate of progression in the majority of patients with glaucoma. Antiglaucomatous treatment modalities consist predominantly of chronic use of eye drops. It has become increasingly evident that long-term exposure to eye drops has a significant impact on the ocular surface, and thereby on patient compliance and quality of life. Maintenance of the ocular surface is highly dependent on a stable tear film. Conjunctival goblet cells (GCs) of the ocular surface play an important role in providing the innermost mucin layer of the tear film and are essential for maintaining the ocular surface homeostasis. Recent studies have reported severe side effects of antiglaucomatous drops on GCs. In particular, a preservative containing antiglaucomatous drops have been shown to affect the viability and functions of the GCs. Furthermore, GC density has been suggested as a potential predictor of surgical outcome after filtration surgery. The present review provides an overview of the current literature on the impact of antiglaucomatous eye drops on GCs as well as the impact on the ocular surface. Moreover, the existing evidence of a possible association between GC density and glaucoma filtration surgery outcome is summarized. We conclude that prostaglandin analogs spare the conjunctival GCs more compared with other antiglaucomatous drops and that GCs may be a good predictor of surgical outcome after filtration surgery. Overall, given the multiple functions of GCs in the ocular surface homeostasis, dedicated strategies should be adopted to preserve this cell population during the course of glaucoma.

Objective ocular surface tolerance in patients with glaucoma treated with topical preserved or unpreserved prostaglandin analogues.

PURPOSE: Preservatives in glaucoma medications have been associated with ocular toxicity. We compared ocular signs and symptoms in patients with open-angle glaucoma or ocular hypertension treated in monotherapy with preserved or preservative-free prostaglandin analogues. METHODS: Observational cross-sectional clinical study in real life. 82 patients treated for at least 6 months with prostaglandin analogue were assessed for intraocular pressure, ocular symptoms and ocular signs including conjunctival hyperaemia, tear break-up time and tear meniscus height measured using objective and non-invasive methods (OCULUS Keratograph 5M). Patients presenting with symptoms of ocular toxicity with preserved prostaglandin analogues were switched to preservative-free latanoprost, and a second assessment was processed 6 months after. RESULTS: At inclusion, 30 (36.6%) patients were treated with preservative-free latanoprost, 25 (30.5%) with preserved latanoprost, 16 (19.5%) with preserved travoprost and 11 (13.4%) with preserved bimatoprost. Patients treated with preservative-free latanoprost reported significantly less ocular symptoms upon instillation (mainly burning) and between instillations than patients treated with preserved prostaglandin analogues. The mean conjunctival hyperaemia (limbal + bulbar) was significantly lower with preservative-free latanoprost (2.08 ± 0.55) compared to preserved latanoprost (2.50 ± 0.7, p = 0.0085), preserved travoprost (2.67 ± 0.82, p = 0.0083) and preserved bimatoprost (2.68 ± 0.67, p = 0.0041). There were no relevant between-group differences in mean tear meniscus height and break-up time. Ocular symptoms and conjunctival hyperaemia improved when preserved prostaglandin analogues were switched to preservative-free latanoprost for 6 months while intraocular pressure reduction was maintained. CONCLUSION: Overall, this study suggests a better subjective and objective ocular tolerance when patients were treated with preservative-free latanoprost than with other preserved prostaglandin analogues monotherapy. Switching to preservative-free latanoprost maintained intraocular pressure at the same level as preservative prostaglandin analogue, but improved ocular surface tolerance.

Cytokine expression in tears of patients with glaucoma or dry eye disease: A prospective, observational cohort study.

BACKGROUND: The aim of this study was to assess the expression of cytokines/chemokines in tears from patients with non-advanced primary open-angle glaucoma and patients with non-severe dry eye disease versus healthy controls. METHODS: This prospective, observational cohort study enrolled patients with confirmed or suspected non-advanced primary open-angle glaucoma who received any prostaglandin analogue monotherapy for longer than 6 months, patients with non-severe dry eye disease, and healthy controls. Expression of interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, and interleukin-12; tumor necrosis factor α; vascular endothelial growth factor; granulocyte-macrophage colony-stimulating factor; and interferon γ was assessed. RESULTS: 107 participants were enrolled (primary open-angle glaucoma, n = 41; dry eye disease, n = 30; and healthy controls, n = 36). Compared with healthy controls, interleukin-6 was significantly higher (p = 0.0001) in patients with primary open-angle glaucoma and interleukin-1ß (p = 0.0144), interleukin-6 (p < 0.0001), and interleukin-10 (p = 0.0392) were higher in patients with dry eye disease. Compared with patients with dry eye disease, patients with primary open-angle glaucoma had significantly lower levels of interleukin-4 (21.79 vs 20.18 pg/mL; p = 0.0012) and significantly higher levels of vascular endothelial growth factor (367.75 vs 609.28 pg/mL; p = 0.0058), tumor necrosis factor α (14.27 vs 17.93 pg/mL; p = 0.0048), and interleukin-6 (17.95 vs 27.48 pg/mL; p = 0.0145). In patients with primary open-angle glaucoma, interleukin-1ß expression (p = 0.0011) was lower than in those who received intraocular pressure-lowering eye drops without preservatives compared with those who received eye drops with preservatives. CONCLUSION: Different cytokine/chemokine expression profiles in tears of patients with primary open-angle glaucoma and dry eye disease strongly suggest the involvement of a variety of signaling pathways in the pathogenesis of these ophthalmic processes.