Prognostic factors associated with progression of open-angle glaucoma in adults

Background: Glaucoma is the leading cause of irreversible blindness globally, and the second leading cause of blindness in high-income countries. It is a chronic optic nerve disease that can lead to loss of vision, although it is usually asymptomatic until it progresses (worsens) to an advanced stage. Primary open angle glaucoma (POAG) is the most common type of glaucoma, and it is recognized as a multifactorial disorder. Pseudoexfoliative glaucoma (PXFG) is a common form of secondary open-angle glaucoma and has a higher rate of progression.The understanding of prognostic factors is useful for clinicians to estimate the risk of disease progression and to identify those who are at risk of losing sight early.

Objectives:To identify risk factors associated with disease progression, defined as worsening or deterioration of functional visual outcomes and/or structural outcomes, amongst adults with POAG and PXFG.

Search methods: We searched CENTRAL, Ovid MEDLINE, Ovid Embase, and two trial registries on 15 August 2024. The search was supplemented by checking reference lists of eligible articles. We did not apply any restrictions on language or year of publication.

Selection criteria: We included randomized controlled trials, cohort, and case-control study designs. We excluded any study with less than two years of followup and a sample size of < 200. The targeted population consisted of adults M 18 years of age of any sex with glaucoma type restricted to POAG, normal-tension glaucoma (NTG), and PXFG and no previous glaucoma surgery. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility. The discrepancies were resolved through discussion with a third reviewer. The time points for the evaluation of outcomes were at a minimum of two years of follow-up..

Data collection and analysis: Two review authors independently extracted data from included studies using pre-piloted data extraction forms in Covidence, SRDR+ and MicrosoO Excel. We used the Quality in Prognosis Studies (QUIPS) tool to assess the risk of bias in Covidence. We conducted meta-analyses where homogeneous outcomes were reported, using a random-ePects, generic inverse variance model. We reported hazard ratios (HR), odds ratio (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by diPerent time points and multivariable or univariable prognostic estimates, where possible. We evaluated and reported the certainty of evidence using the GRADE guidelines.

Main results: We screened 16,188 titles and abstracts and retrieved 487 full-text reports from 239 studies for assessment. AOer full-text screening, we included 123 reports of 22 studies in this review. The 22 studies included 6082 participants. The mean ages of participants ranged from 50 to 78 years across studies. Sixteen of the included studies used visual field (VF) deterioration alone to detect and measure glaucoma progression. In six studies, disease progression was assessed by both functional and structural outcomes (e.g. retinal nerve fiber layer thickness changes by spectral-domain optical coherence tomography). We judged 19 of the 22 (86%) included studies to be at a high risk of bias overall. We found some prognostic factors had consistent evidence of a relationship with progression. Specifically, presence of disc hemorrhage (adjusted HR 2.03, 95% CI 1.55 to 2.67, 1068 participants, 3 studies; unadjusted HR 1.51, 95% CI 1.12 to 2.02, 961 participants, 3 studies; low certainty), presence of bilateral disease (adjusted HR 1.77, 95% CI 1.35 to 2.32, 771 participants, 2 studies; moderate certainty), and treatment for glaucoma (adjusted HR 0.44, 95% CI 0.31 to 0.61, 961 participants, 3 studies; unadjusted HR 0.56, 95% CI 0.44 to 0.72, 771, 2 studies; low certainty). The remaining factors had mixed evidence as to their prognostic associations with glaucoma progression, including a few factors that were expected to be important based on other literature. With regard to intraocular pressure (IOP) at baseline, our meta-analysis of the HR had suPicient evidence for an ePect (adjusted HR 1.08, 95% CI 1.03 to 1.13, 913 participants, 3 studies, low certainty) while the OR did not (adjusted OR 0.96, 95% CI 0.84 to 1.10, 458 participants, 2 studies, low certainty) and more than half the studies reporting IOP found no evidence of an ePect. Similarly, the pooled adjusted HR per 1-year increase in age at baseline was 1.01 (95% CI 0.97 to 1.05; 865 participants, 4 studies) with very low certainty of evidence, and studies had mixed results for its association with progression. Regarding sex, the combined adjusted analyses of two studies suggest females may have a 64% greater hazard of progression than males (HR 1.64, 95% CI 1.15 to 2.34; 961, 3 studies; low certainty). However, other study estimates for sexes that could not be combined were mixed in their directions of ePect. We did not find consistent evidence to suggest that central corneal thickness (adjusted HR 1.13, 95% CI 0.85 to 1.51, 425 participants, 2 studies; unadjusted HR 1.00, 95% CI 1.00 to 1.00, 706 participants, 2 studies, very low certainty), systemic hypertension (adjusted HR 1.33, 95% CI 0.68 to 2.60, 731 participants, 3 studies; unadjusted HR 0.89, 95% CI 0.67 to 1.17, 771 participants, 2 studies; very low certainty), cardiovascular disease (adjusted HR 1.06, 95% CI 0.75 to 1.49, 771 participants, 2 studies; low certainty), migraine (unadjusted HR 1.06, 95% CI 0.75 to 1.49, 961 participants, 3 studies; very low certainty), or Raynaud’s syndrome (unadjusted HR 1.21, 95% CI 0.85 to 1.73, 961 participants, 3 studies; very low certainty), have an ePect on visual field progression.

Authors' conclusions: There is moderate-certainty evidence to support the finding that bilateral disease is a prognostic factor associated with VF progression in people with glaucoma. There is low-certainty evidence that female sex and the presence of disc hemorrhage are associated with progression, while treatment with pharmacologics is protective of progression. The evidence is uncertain about the associations between progression and all other prognostic factors that we identified. Properly designed prognostic factor research studies are required in the future.

Authors: Piyasena MP, Daka Q, Qureshi R, Roberti G, Michelessi M, Liu SH, Li T, Takwoingi Y, Azuara-Blanco A, Virgili G, supported by the Cochrane Eyes and Vision Group.

Link: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015436.pub2/abstract

Doi: 10.1002/14651858.CD015436.pub2

NGP Papers Manager: Carlo Cutolo