Effect of topical prostaglandin analogue therapy on central corneal thickness: a systematic review

Author: Kim JY, Yim HW.

Geographical coverage: United States of America (USA), Switzerland, Brazil, Korea, Australia, India, Turkey, Iran, Canada, China, Japan, and Greece.

Sector: Treatment

Sub–sector: Prostaglandin analogues

Equity focus: Not explicitly stated

Study population: Adult patients with glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Prostaglandin analogues (PGAs) are commonly prescribed first‑line eye‑drop therapy to lower intra‑ocular pressure (IOP) in people with open‑angle glaucoma (OAG) or ocular hypertension (OHT), providing an average 24–33 % IOP reduction and outperforming most alternative medications. Central corneal thickness (CCT) is an important parameter in glaucoma care because it influences applanation tonometry readings and has prognostic value: the Ocular Hypertension Treatment Study reported that each 40 µm decrease in CCT raised the risk of developing glaucoma by 71 %. Long‑term PGA use has been linked to CCT thinning, which could confound diagnosis or progression monitoring. This review synthesises evidence on how topical PGAs affect CCT and whether routine CCT surveillance is warranted.

Objectives

To determine whether topical PGA eye drops produce a significant change in central corneal thickness.

Main findings

Prolonged PGA therapy was associated with a small but statistically significant reduction in CCT. Twenty‑two prospective primary studies (seven randomised controlled trials and 15 non‑randomised studies, including two secondary analyses of trials) encompassing 3 880 participants from 12 countries met the inclusion criteria. The pooled single‑arm meta‑analysis showed a modest CCT decrease, but heterogeneity was high (I² = 95 %). Subgroup analysis of studies with treatment duration ≥ 6 months lowered heterogeneity and confirmed the direction of effect. Severe CCT thinning (≥ 25 µm) was uncommon, reported in two non‑randomised studies and affecting 3.8 %–14.8 % of participants.

Methodology

English‑language studies published between 1 January 2000 and 14 June 2021 were searched in PubMed, Embase, Cochrane CENTRAL and supplemented by Google searches and reference lists. Eligible designs were randomised controlled trials, prospective observational studies, case–control, cross‑sectional studies, and case series reporting CCT change after PGA monotherapy (latanoprost, travoprost, bimatoprost or tafluprost) in adults (≥ 18 years) with OAG or OHT. Two reviewers independently screened records, extracted data and assessed methodological quality with the McMaster Quality Assessment Scale of Harms (McHarm). A single‑arm random‑effects meta‑analysis pooled mean CCT change; heterogeneity was explored with the I² statistic, and publication bias with funnel plots.

Applicability/external validity

Substantial clinical and methodological heterogeneity, absence of concurrent control groups and reliance on short‑ to medium‑term data limit generalisability. Findings chiefly apply to adults with OAG or OHT receiving PGA monotherapy for up to two years; extrapolation to other populations or longer treatment durations should be cautious.

Geographic focus

The included studies were conducted in the USA, Switzerland, Brazil, Korea, Australia, India, Turkey, Iran, Canada, China, Japan and Greece.

Summary of quality assessment

We have medium confidence in the review’s conclusions. Inclusion/exclusion criteria were explicit and two‑reviewer processes were used for study selection, quality appraisal and data extraction. However, the search was restricted to English‑language publications, experts were not contacted, a list of excluded studies was not provided and results were not stratified by individual study risk of bias. High statistical heterogeneity further reduces certainty in the pooled estimate.