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Purpose: To investigate the cell survival of human conjunctival goblet cells (CGs) when incubated with preserved and preservative-free (PF) artificial tears (AT) used against dry eye disease (DED). The following ATs were tested: 0.011% benzalkonium chloride (BAK)-preserved Viskøse Øjendråber, 0.006% BAK-preserved Oftagel, 0.005% BAK-preserved Oculac, 0.001% PolyQuad-preserved Systane Ultra, 0.01% Cetrimide-preserved Artelac, and PF ATs: Systane Ultra, Oculac, Oftagel, and Thealoz Duo. Method: Primary cultures of human conjunctival CGs were cultivated from donor conjunctiva. After incubation with said ATs for 2 hours, CG survival was analysed using a lactate dehydrogenase assay and calculated to a negative control. Results: AT preserved with 0.011% BAK reduced GC survival by 28% compared to negative control (p=0.001). The remaining ATs did not significantly alter the cell survival. Conclusion: BAK-preserved ATs cause GC death in a concentration-dependent manner. Reduction of the GC density may contribute to the development of DED. PF-ATs and PolyQuad- and Cetrimide-preserved ATs may thus be a better choice for treating DED than BAK-preserved ATs, as the latter may add to ocular surface disease., Aims/Purpose: To investigate the cell survival of human conjunctival goblet cells (CGs) when incubated with preserved and preservative-free (PF) artificial tears (AT) used against dry eye disease (DED). The following ATs were tested: 0.011% benzalkonium chloride (BAK)-preserved Viskøse® Øjendråber, 0.006% BAK-preserved Oftagel®, 0.005% BAK-preserved Oculac®, 0.001% PolyQuad™-preserved Systane® Ultra, 0.01% Cetrimide-preserved Artelac®, and PF ATs: Systane® Ultra, Oculac®, Oftagel®, and Thealoz® Duo. Methods: Primary cultures of human conjunctival CGs were cultivated from donor conjunctiva. After incubation with the above-mentioned ATs for 2 h, CG survival was analysed using a lactate dehydrogenase assay and calculated to a negative control. Results: AT preserved with 0.011% BAK reduced GC survival by 28% compared to negative control (p = 0.001). The remaining ATs did not significantly alter the cell survival. Conclusions: BAK-preserved ATs cause GC death in a concentration-dependent manner. Reduction of the GC density may contribute to development of DED. PF-ATs and PolyQuad- and Cetrimide-preserved ATs may thus be a better choice for treating DED than BAK preserved ATs, as the latter may add to the ocular surface disease.

Purpose The purpose of the study was to describe the rationale and design of Project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability). Design Project FOREVER will build a comprehensive database of clinical eye and vision data collected from ~280 000 adults at 100 optician stores across Denmark. The FOREVER database (FOREVERdb) includes detailed data from refraction, visual acuity, intraocular pressure, corneal thickness, visual field assessments and retinal fundus images. Linkage to the comprehensive Danish national registries with, that is diagnostic and prescribing data permits investigation of rare associations and risk factors. 30 000 individuals over 50 also provide a saliva sample for later genetic studies and blood pressure measurements. Of these 30 000, 10 000 will also get optical coherence tomography (OCT) nerve and retinal scans. This subpopulation data is reviewed by ophthalmologists for disease detection. All participants will be asked to complete a questionnaire assessing lifestyle, self-perceived eye health and general health. Enrolment of participants began in April 2022. Perspective The FOREVERdb is a powerful tool to answer a wide range of research questions that can pave the way for better eye health. This database will provide valuable insights for future studies investigating the correlations between eye and general health in a Danish population cohort, enabling research to identify potential risk factors for a range of diseases.

Purpose: To examine the physicochemical properties of five preservative-free (PF) 0.005% latanoprost ophthalmic products; Monoprost®, Latanest®, Gaap Ofteno®, Xalmono®, and Xaloptic® Free. Furthermore, the study investigated the mucin production and cell survival of primary cultured human conjunctival goblet cells when treated with PF eye drops. Method: The pH value, osmolality, and surface tension were examined. Cell survival was analyzed using lactate dehydrogenase and tetrazolium dye colorimetric assays. Mucin production was analyzed with immunohistochemical staining. Results: Monoprost® (pH value 6.84 ± 0.032) had a pH value closest to the pH value of tear fluid (pH value 7.4–7.6), whereas Gaap Ofteno® (pH value 6.34 ± 0.004) and Latanest® (pH value 6.33 ± 0.003) had the lowest pH values. Gaap Ofteno® (325.9 ± 2.9 mosmol/kg) showed iso-osmolar probabilities, whereas the other products were hypo-osmolar. Gaap Ofteno® (60.31 ± 0.35 mN/m) had a higher surface tension compared to the tear fluid (40 to 46 mN/m), as described in the literature. No significant differences in goblet cell survival or mucin release were observed between the treatments and control. Conclusion: Significant differences in pH value, osmolality, and surface tension were observed. However, this did not affect the viability of the goblet cells or the release of mucin. Clinical studies are required to evaluate the long-term effects of use on efficacy and safety.

Purpose To investigate the effect of polyquaternium-1 (PQ)-preserved and benzalkonium chloride (BAK)-preserved travoprost eye drops on viability of primary human conjunctival goblet cell (GC) cultures and on secretion of mucin and cytokines. Furthermore, to evaluate the physicochemical properties of the branded travoprost eye drop Travatan® and available generics. Methods The effect of travoprost eye drops was evaluated on GC cultures. Cell viability was assessed through lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin secretion was evaluated by immunohistochemical staining. Secretion of interleukin (IL)-6 and IL-8 was measured using BD Cytometric Bead Arrays. pH, viscosity, droplet mass, osmolality and surface tension were measured for all included eye drops. Results In the LDH assay, BAK travoprost caused significant GC loss after 2 hrs of incubation compared to the control. PQ travoprost caused no GC loss at any time point. Both PQ- and BAK travoprost caused secretion of mucin to the cytoplasma. No difference in IL-6 and IL-8 secretion was identified compared to controls. The pH values for the generics were lower (pH 6.0) than the pH value for Travatan (pH 6.7; p < 0.0001). The viscosity was lowest for Travatan, while the mean droplet mass was higher for Travatan (35 mg) than the generics (28–30 mg; p ≤ 0.0318). The osmolality and surface tension did not differ between the eye drops investigated. Conclusion BAK travoprost caused GC loss, indicating that PQ preservation may be preferable in treatment of glaucoma. Furthermore, physicochemical properties of branded and generic travoprost eye drops can not be assumed to be identical.

Purpose To investigate the impact on human conjunctival goblet cell (GC) survival and mucin release for benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties. Methods GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Mucin release was evaluated through mucin-specific immunostaining. pH-value, osmolality, drop mass and surface tension for all LT eye drops were measured. Results After application with PF-LT for 30 minutes (min), the GC survival was maintained (p = 0.7043), while all BAK-LT eye drops reduced survival to approximately 70% (p<0.0001). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH of the BAK-LT and PF-LT eye drops were 6.0-6.9 and 6.8, respectively. The osmolality was 258-288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drop. The mean drop mass was 26-31 mg for the BAK-LT eye drops and 30mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1-32.1 mN/m) compared to PF-LT (42 mN/m). Conclusions PF-LT compared to various branded and generic LT preparations containing BAK should be used to improve goblet cell tolerability and ocular surface health.

Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta-blockers, or combination using beta-blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow-up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow-up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative-free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07–0.51 mmHg, p = 0.010; moderate-certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break-up time (TBUT) was better with preservative-free drops (p < 0.001). Schirmer’s test was better in the preservative-free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative-free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative-free medications, more evidence is needed. The increasing use of preservative-free drops may b

BackgroundWe included randomized clinical trials examining commercially available ROKi‐based monotherapy or combination therapy compared with placebo or other IOP‐lowering medical treatments in people diagnosed with (P)OAG or OHT. We included trials where ROKi were administered according to official glaucoma guidelines. There were no restrictions regarding type, year or status of the publication.Data collectio

Objective To investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops' physicochemical properties.Methods and analysis Primary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured.Results After application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (pConclusion PF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.

Purpose: To investigate the trends and progresses in glaucoma research by searching two major clinical trial registries; clinicaltrials.gov, and Australianclinicaltrials.gov.au. Methods: All clinical trials with glaucoma covered by Clinicaltrials.gov, and Australianclinicaltrials.gov.au starting the study before 1 January 2021 were included. Trials evaluating glaucoma treatment were separated from non-treatment trials and divided into three major categories: “laser treatment,” “surgical treatment,” and “medical treatment.” In the category of “medical treatment,” new compounds and their individual targets were identified and subcategorized according to treatment strategy; intraocular pressure (IOP)-lowering, neuroprotective or vascular. The phase transition success rates were calculated. Results: One-thousand five hundred and thirty-seven trials were identified. Sixty-three percent (n = 971) evaluated glaucoma treatment, of which medical treatment accounted for the largest proportion (53%). The majority of medical trials evaluated IOP-lowering compounds, while trials with neuroprotective or vascular compounds accounted for only 5 and 3%, respectively. Eighty-eight new compounds were identified. Phase I, II, and III transition success rates were 63, 26, and 47%, respectively. Conclusion: The number of clinical trials in glaucoma research has increased significantly over the last 30 years. Among the most recently evaluated compounds, all three main treatment strategies were represented, but clinical trials in neuroprotection and vascular modalities are still sparse. In addition to traditional medicines, dietary supplements and growth factors are assessed for a potential anti-glaucomatous effect. Phase II and III success rates were below previously reported success rates for all diseases and ophthalmology in general. A stricter phenotyping of patients can improve the success rates in glaucoma and ophthalmological research and gain a better understanding of responders