Tear Film hTERT Concentration and Corneal Nerve Architecture in Episodic Migraines in a Saudi Population: A Cross-Sectional Study

Background/Objectives: The human telomerase reverse transcriptase (hTERT) maintains mitochondrial DNA, modulates the release of reactive oxygen species, and contributes to axonal regeneration. Previous work reported that hTERT levels in the tear film may reflect stress and loss of homeostasis in dry eyes. This was accompanied by morphological changes in corneal nerves. In episodic migraines, oxidative stress, imbalance in antioxidant defense, and mitochondrial dysfunction play a major role in the pathogenesis, and changes in corneal nerves have been reported to occur. Against this, the current study primarily aimed to investigate tear film hTERT levels in individuals with episodic migraine. A secondary aim was to assess the relationship between tear film hTERT levels and morphological changes in corneal nerves. Methods: Flush tears were collected from 25 individuals with episodic migraine (18 females, 7 males), with a mean age of 26 ± 8 years, and from 18 healthy controls without migraine or dry eye disease (7 females, 11 males), with a mean age of 23 ± 5 years. Levels of tear film hTERT were measured using an enzyme-linked immunosorbent assay. Images of the sub-basal nerve plexus were captured at the central cornea and the inferior whorl region using confocal microscopy. Characteristics of corneal nerves were analyzed using ACCMetrics Software version June 2015 (University of Manchester, Manchester, UK). Results: No significant difference was found in tear film hTERT levels between individuals with episodic migraine (median (interquartile range): 604 (317–800) ng/mL and healthy controls 670 (550–858) ng/mL, p = 0.362). Reductions in mean ± SD values of nerve fiber length 14.0 ± 3.8 mm/mm2 vs. 16.9 ± 3.1 mm/mm2, unadjusted p = 0.012, total number of branches 42.1 ± 21.9 no./mm2 vs. 56.4 ± 20.7 no./mm2, unadjusted p = 0.039, nerve fiber area 0.0055 ± 0.0017 mm2/mm2 vs. 0.0071 ± 0.0018 mm2/mm2, unadjusted p = 0.005, and in fractal dimension 1.4770 ± 0.0359 vs. 1.5049 ± 0.0292, unadjusted p = 0.011, were observed in episodic migraine compared to healthy controls at the central cornea, respectively. These differences remained significant even after adjusting for dry eyes and sex discrepancy (p < 0.05, ANCOVA). No significant differences were observed in other nerve parameters (p > 0.05). However, these reductions were nominal, as after Bonferroni correction, only NFA at central corneal remained statistically significant in the unadjusted comparisons (p = 0.035) and none remained significant after adjustment for dry eyes and sex. Conclusions: Tear film hTERT levels did not differ significantly between healthy controls and individuals with episodic migraine. In contrast, nominally significant morphological reductions were found in corneal nerve parameters and persisted, even after adjusting for dry eyes and sex discrepancy. This may reflect trigeminal activation due to episodic migraine although causality cannot be established in a cross-sectional study. Only nerve fiber area survived Bonferroni correction, and none did for adjusted comparison; these findings should be considered exploratory and further studies are needed. Whether hTERT behavior differs during the ictal phase remains to be elucidated.