Objective: Pseudoexfoliation syndrome (PEX) is an age-related systemic disorder characterised by the deposition of extracellular fibrillar material in ocular tissues, particularly the lens capsule, pupillary margin, and trabecular meshwork. PEX is a major risk factor for glaucoma and elevated intraocular pressure (IOP), but its independent effect on corneal endothelial morphology remains uncertain. Previous studies have reported inconsistent findings regarding endothelial cell density (ECD), morphology, and central corneal thickness (CCT). This study aimed to evaluate the impact of PEX on endothelial morphology and CCT using non-contact specular microscopy in a Portuguese cohort. 

Material and methods: We conducted a retrospective cross-sectional study including 450 eyes: 250 with PEX and 200 age-matched controls without PEX. Eyes with pre-existing corneal disease, prior intraocular surgery, or contact lens wear were excluded. PEX was diagnosed by slit-lamp biomicroscopy, and IOP was measured by Goldmann applanation tonometry. Endothelial parameters were assessed with the EM-3000 specular microscope, including cell count, ECD, mean cell area, coefficient of variation (CV), hexagonality, and CCT. Group differences were analysed using parametric and non-parametric tests, with ANCOVA adjusting for age, sex, and IOP. 

Results: Baseline characteristics were comparable for age (PEX: 76.2 ± 6.9 years; controls: 75.9 ± 6.1 years; p = 0.289) and sex (female: 56.4% vs. 55.5%; p = 0.521). Glaucoma and ocular hypertension were more frequent in PEX (35.5% and 5.2%, respectively) compared with controls (3.9% and 0%; p < 0.001). On unadjusted analysis, ECD was lower in PEX eyes (2389.2 ± 305.7 vs. 2461.8 ± 274.1 cells/mm²; p = 0.042), though the difference attenuated after adjustment (p = 0.055). Mean cell area was larger in PEX (417.0 µm² [IQR 386.0–452.0] vs. 410.5 µm² [381.0–439.0]) and reached significance after adjustment (p = 0.036). CV was slightly lower in PEX (37.8% [35.0–42.5] vs. 40.9% [36.5–45.0]; p = 0.029), persisting after adjustment (p = 0.031). Hexagonality did not differ between groups. CCT was significantly greater in PEX (541.0 ± 35.9 vs. 530.2 ± 36.8 µm; p = 0.029), remaining significant after adjustment (p = 0.041). 

Conclusion: PEX was associated with subtle but clinically relevant corneal endothelial changes, including a trend toward reduced ECD, larger cell area, lower CV, and increased CCT. These alterations persisted for CCT, CV, and cell area after adjustment for age, sex, and IOP. The higher prevalence of glaucoma and ocular hypertension in PEX further reinforces the need for careful preoperative assessment. Specular microscopy should be considered routine in PEX patients to anticipate surgical risks and guide management.