The purpose of the study is to evaluate the risk factors associated with exfoliation in a case-cohort setting and literature review. This single-center, prospective, case-cohort study was carried out from January 2010 to April 2020 on patients operated for cataract surgery by a single surgeon in Lebanon. Forty-nine consecutive patients with exfoliation syndrome (XFS) and 62 consecutive control patients were identified and further investigated for selected systemic (diabetes mellitus, systemic hypertension, asthma, or atopy) and ocular variables (baseline vision, severity of nuclear sclerosis, glaucoma, eye rubbing, history of dry eye, or allergic eye disease). The mean baseline Snellen visual acuity was 20/283 in XFS versus 20/145 in control cases ( = 0.012). XFS also demonstrated significantly denser nuclear sclerosis than controls ( = 0.00958). By univariate analysis, allergic conjunctivitis (15 [30.6%] vs. 2 [3.2%]; < 0.001), dry eye (20 [40.8%] vs. 13 [21.0%]; = 0.0133), and habitual rubbing of the eyes (33 [67.3%] vs. 19 [30.6%]; < 0.001) were associated with the presence of XFS. Habitual ocular rubbing was closely associated with allergic conjunctivitis (odds ratio [OR] = 13.0; 95% confidence interval [CI]: 2.8-58.8; = 0.032). After multivariable analysis, the following variables showed significant results: glaucoma (OR = 34.5; 95% CI: 4.4-250; = 0.010), duration of surgery (OR = 5.6; 95% CI 2.43-12.9; < 0.001), and habitual ocular rubbing (OR = 4.42; 95% CI: 1.97-9.90; = 0.029). This study shows a novel potential correlation between eye rubbing and XFS in a Lebanese cohort. Chronic eye rubbing induces or may exacerbate preexistent zonular damage in subjects with XFS, hence the need to better manage concurrent ocular surface disorder in these patients.