Profiling ocular surface responses to preserved and non‐preserved topical glaucoma medications: A 2‐year randomized evaluation study

Abstract

Background: Use of topical glaucoma medications has been reported to cause ocular surface (OS) discomfort and inflammation. This study explores the profile of inflammatory cytokines and OS symptoms induced in response to preserved and non-preserved drops. Methods: Prospective, randomized evaluation on 36 treatment-naïve patients over 24 months of three differently preserved glaucoma drop preparations: Preservative-free (PF), polyquad (PQ) and benzalkonium chloride (BAK). Study participants were evaluated at baseline and then at 1, 3, 6, 12 and 24 months while on medication. At each visit, participants completed the OS disease index (OSDI) questionnaire, had basal tear sampling and impression cytology (IC) of the conjunctival epithelium. Quantitative polymerase chain reaction was performed to measure the gene expression of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-10, IL-12A, IL-12B, IL-17A, IL-1β and tumour necrosis factor-α] in the IC samples. Corresponding protein expression of cytokines in tear samples was assessed by the Becton-Dickinson cytometric bead arrays. Results: Compared to PF and PQ groups, mRNA and protein expression of IL-6, IL-8 and IL-1β increased in samples from the BAK group in a time-dependent fashion, whereas all other cytokines showed a non-significant increase. In the BAK group, there was a strong correlation between OSDI and the levels of IC/IL-1β (r = .832, R 2 = .692 and P = .040); IC/IL-10 (r = .925, R 2 = .856 and P = .008) and tear/IL-1β (r = .899, R 2 = .808 and P = .014). Conclusions: BAK-preserved topical drops stimulate a sterile inflammatory response on the OS within 3 months which is maintained thereafter, whereas PF-drops and PQ-preserved drops showed no significant OS inflammation.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: UK and Ireland Results from the VISIONARY Study

“…Fixed-dose combinations of PGAs and beta blockers are often used as they minimise drop requirement and improve adherence [ 4 , 5 ]. Preservative-free therapies are increasingly being adopted as they are associated with a lower risk of ocular surface disease (OSD) [ 6 , 7 ] than preserved drops, which further promotes adherence. Preservative-free tafluprost (0.0015%)/timolol (0.5%) fixed combination (PF Taf-T FC) is a preservative-free PGA/beta blocker fixed combination treatment approved for the treatment of OAG [ 8 ].…”

Toll-Like Receptor Signalling Pathways Regulate Hypoxic Stress Induced Fibroblast Growth Factor but Not Vascular Endothelial Growth Factor-A in Human Microvascular Endothelial Cells

“…The concentrations of VEGF-A and FGF-2 protein in the conditioned culture media was determined using ELISA as previously described [22]. Human VEGF-A and FGF2 DuoSet ELISA kits were supplied by R&D Systems (Minneapolis, MN, USA).…”

Impact of dorzolamide, benzalkonium-preserved dorzolamide and benzalkonium-preserved brinzolamide on selected biomarkers of oxidative stress in the tear film

“…Moreover, the tear hyperosmolarity, enhanced by BAC, also intensifies the secretion of inflammatory mediators and potentiates the inflammatory cascade [ 29 ]. There is a strong positive correlation between the level of cytokines in the tear film and the OSDI score [ 30 ]. It is worth noting, that also among asymptomatic patients an increase in inflammatory biomarkers in ocular surface cells can be observed [ 31 ].…”