Abstract
Purpose:
Chronic topical glaucoma medication is an important risk for the ocular surface disease and for the failure in glaucoma surgery. Benzalkonium chloride (BAK), the preservative still used in many glaucoma drops, has been shown to be toxic to the anterior surface of the eye. In the present study, we evaluated the changes in tear fluid proteome after the switch from preserved latanoprost to preservative tafluprost and correlated the change with the clinical signs and tear fluid dynamics.
Methods:
30 patients that have been using preserved latanoprost monotherapy for their glaucoma at least two years and have symptoms and signs of ocular surface disease were recruited in the study. Patient’s clinical condition and their symptoms were carefully evaluated at baseline and 6 weeks, 3, 6, 12 months after the switch. At each visit tear samples were collected using Schirmer's strips. Relative concentration of proteins in each sample analysis was done by NanoLC-TripleTOF using iTRAQ method. A mixed-effects regression model was used for statistical analysis and it was implemented in R software using ‘lme4’ and ‘nlme’ packages. Multiple testing correction was applied by computing the FDRs (Benjamini-Hochberg procedure) for all p-values resulting from multiple testing.
Results:
The symptoms and signs of the the pati0ents were significantly reduced after the switch: symptom scores 8,5 vs 5,6; conjunctival hyperemia 1,75 vs 0,79; corneal staining 0,61 vs 0,21; conjunctival staining 3,0 vs 2,4. Schirmer’s test was significantly increased with time (0.310 0.128, p = 0.015). The proteomic data was then tested against the clinical findings. Schirmer’s test results for patients were increased significantly by an increase in LYZ (β ̂=1.857±0.539,p=0.001), LACRT (β ̂=1.874±0.608,p=0.005) and PIP (β ̂=2.294±0.625,p=0.001) expression level ratios (log2). Further on, Schirmer’s test results were significantly lowered by increased levels of S100A6 (β ̂=-3.848±1.280,p=0.006), S100A11 (β ̂=-1.921±0.728,p=0.014) and ENO1 (β ̂=-4.670±1.470,p=0.004) expression level ratios (log2).
Conclusions:
The switch from the preserved latanoprost to preservative free tafluprost reduced the symptoms and signs of OSD of the patients. The concomitant change in tear fluid proteome of indicates improved tear function and reduced inflammation of the anterior surfaces of the eye.