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Patient stratification in clinical glaucoma trials using the individual tear proteome.

ABSTRACT: Glaucoma patients are prone to concomitant ocular surface diseases; however, switching from preserved to preservative-free medication can often alleviate these symptoms. The objective of this study was to examine how the adverse effects and tear proteome change for glaucoma patients (n?=?28) during a 12-month drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost (Taflotan). We hypothesized that patient stratification could help identify novel recovery patterns in both tear proteomics and clinical data. In order to accomplish patient stratification, we implemented sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) as a tool for quantitative analysis of individual tear protein profiles. During each visit (baseline and four follow-up visits), the patients' tears were sampled and the state of their ocular surface was evaluated clinically. Altogether 785 proteins were quantified from each tear sample using SWATH strategy and as these protein expression levels were compared between baseline and 12-month follow-up, three distinct patient groups were identified. We evaluated how these patient groups differed in their protein expression levels at baseline and discovered that the patients with increased levels of pro-inflammatory proteins and decreased levels of protective proteins benefitted most from the medication switch.

SUBMITTER: Nattinen J

PROVIDER: S-EPMC6089987 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Patient stratification in clinical glaucoma trials using the individual tear proteome.

Nättinen Janika J Jylhä Antti A Aapola Ulla U Parkkari Minna M Mikhailova Alexandra A Beuerman Roger W RW Uusitalo Hannu H

Scientific reports 20180813 1

Glaucoma patients are prone to concomitant ocular surface diseases; however, switching from preserved to preservative-free medication can often alleviate these symptoms. The objective of this study was to examine how the adverse effects and tear proteome change for glaucoma patients (n = 28) during a 12-month drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost (Taflotan). We hypothesized that patient stratification could help identify novel recovery patterns in both ...[more]

PMID: 30104599

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Project description:PurposeThere have been concerns that short-term clinical trials for evaluating new treatments in glaucoma would require prohibitively large sample sizes when using visual field endpoints, given that glaucoma is often a slowly progressive disease. This study sought to determine the required sample size for such trials using event-based analyses, and whether it can be reduced using trend-based analyses.DesignLongitudinal, observational study.Participants321 eyes of 240 glaucoma participants followed under routine clinical care using 242 visual field for an average of 10 years.MethodsSample size requirements were derived using computer simulations that reconstructed "real-world" visual fields by combining estimates of point-wise variability according to different threshold levels and rates of change obtained from the clinical glaucoma cohort. A clinical trial lasting 2 years with testing every 3 months was simulated, assuming that the new treatment halted visual field change in various percentages of participants (or "responders"). Treatment efficacy was evaluated by: (a) Difference in incidence of point-wise event-based progression (similar to the commercially available Guided Progression Analysis), and (b) Difference in rate of visual field mean deviation (MD) change between groups using linear mixed models (LMMs).Main outcome measuresSample size to detect a statistically significance difference between groups.ResultsBetween-group trend-based analyses using LMMs reduced sample size requirements by 85-90% across the range of new treatment effects when compared to the conventional point-wise event-based analysis. To detect the effect of a new treatment that halted progression in 30% of the participants under routine clinical care (equal to a 30% reduction in average rate of MD change) with 90% power, for example, 1924 participants would be required per group using event-based analysis, but only 277 participants per group if LMMs were used.ConclusionsThe feasibility of future glaucoma clinical trials can be substantially improved by evaluating differences in the rate of visual field change between groups.

Dataset Information

Patient stratification in clinical glaucoma trials using the individual tear proteome.

Publications

Patient stratification in clinical glaucoma trials using the individual tear proteome.

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