Identifiable Historic and Observable Factors May Predict Progression to Exfoliation Glaucoma in Newly Diagnosed Exfoliation Patients

Abstract

To identify clinical factors associated with conversion to exfoliation glaucoma (XFG) in exfoliation syndrome (XFS) patients most at risk of progression to XFG within 3 years for increased surveillance and early preventive interventions. A retrospective patient cohort study design was employed. A source population of XFS patients 50 years and older was identified from electronic medical records in the Utah Population Database. From this, 487 study patients with one or more dilated eye exams prior to chart-confirmed XFS onset in 2011 or later, and three or more years of subsequent eye exams, were selected for study. We implemented a binomial linear mixed models with L1-penalized estimation to select variables associated with conversion. Models included a random intercept to account for within-patient correlation for eye-level data. Candidate demographic, lifestyle, systemic and ocular comorbidities data were obtained and diagnoses categorized as binary (history or no history). These potential factors between conversion and non-conversion patients were used in model selection of variables jointly predictive of conversion. Odds ratios and confidence intervals were calculated using the link logit. To determine the main outcome of conversion to XFG following an index diagnosis of XFS compared with nonconversion within 3 years, clinical records of each subject's left and right eyes were assessed to confirm XFS and date of onset and date of XFG onset, if conversion occurred. Clinical measurements, e.g. intraocular pressure (IOP), cup to disc ratio, provider notes and IOP-lowering procedures and medications were used to corroborate conversion status. Eighteen variables jointly predicted XFG conversion within 3 years correctly in 71% of patient eyes. Odds of conversion was highest for exudative age-related macular degeneration (AMD), 2.3-fold (P=0.004). Other predictive variables included nonexudative AMD (P=0.05), primary open angle glaucoma (P<0.001), obstructive sleep apnea (P=0.03), and ocular hypertension (P=0.003) diagnosed prior to XFS onset. We determined a set of clinically relevant factors that predicted which newly-diagnosed XFS patients progressed to XFG within 3 years. A planned validation will independently confirm if these prognostic indicators hold promise in other settings.