Diquafosol is known as a purinergic P2Y2 receptor (P2Y2R) agonist that stimulates water and mucin secretion from conjunctival epithelial cells and goblet cells, leading to tear film stability in dry eye. However, its effect on corneal epithelial healing has not yet been elucidated. The aim of the present study was to evaluate the effect of diquafosol on corneal epithelial healing in vivo and on P2Y2R-related downstream signaling pathways in vitro. We administered 3% diquafosol ophthalmic solution on 3 mm-diameter epithelial defects made in rat corneas and assessed the wound closure over time. Corneal epithelial healing was significantly accelerated in diquafosol-treated eyes compared to control eyes at 12 and 24 h. During wound healing, P2Y2R staining appeared stronger in the re-epithelized margin near the wound defect. To evaluate whether diquafosol stimulates epidermal growth factor receptor/extracellular-signal-regulated kinase (EGFR/ERK)-related cell proliferation and migration, simian virus 40-transfected human corneal epithelial (THCE) cells were used for in vitro experiments. Cell proliferation was accelerated by diquafosol at concentrations from 20 to 200 μM during 48 h, but inhibited at concentrations over 2000 μM. The intracellular calcium ([Ca(2+)]i) elevation was measured in diquafosol (100 μM)-stimulated cells using Fluo-4/AM ([Ca(2+)]i indicator). [Ca(2+)]i elevation was observed in diquafosol-stimulated cells regardless of the presence of calcium in media, and suramin pretreatment inhibited the calcium response. The effect of diquafosol on phosphorylation of EGFR, ERK and Akt, and cell migration was determined by western blotting and in vitro cell migration assay. Diquafosol induced phosphorylation of EGFR at 2 min post-stimulation, and phosphorylation of ERK at 5 min post-stimulation. Phosphorylation of ERK was attenuated in cells pretreated with suramin or BAPTA/AM ([Ca(2+)]i chelator), and partially with AG1478 (EGFR inhibitor). Likewise, diquafosol-treated cells showed acceleration of gap closure in cell migration assay, which was inhibited by suramin, BAPTA/AM, AG1478, and U0126 (MEK inhibitor). These studies demonstrate that diquafosol is effective in promoting corneal epithelial wound healing and that this effect may result from ERK-stimulated cell proliferation and migration via P2Y2R-mediated [Ca(2+)]i elevation.

Keratometric values with standard devices are a good choice for cataract surgery, whereas the corneal topography is not an appropriate method for the assessment of preoperative keratometric values.

PurposeTo investigate the effect of anterior chamber depth (ACD) on the refractive outcomes of the SRK/T, Holladay 1, Hoffer Q and Haigis formulae in short, normal, long and extremely long eyes.MethodsThis retrospective study involved patients who had uncomplicated cataract surgery. Preoperative axial length (AL) was divided into four subgroups: short (< 22.00 mm), normal (22.00–24.49 mm), long (24.50–25.99 mm), extremely long (≥ 26.00 mm). Preoperative ACD was divided into three subgroups: < 2.5, 2.50–3.49, and ≥ 3.5 mm. Median absolute errors (MedAEs) predicted by the SRK/T, Holladay 1, Hoffer Q and Haigis formulae were compared with the Friedman test. Post-hoc analysis involved the Wilcoxon signed rank test with a Bonferroni adjustment. Correlations between ACD and the predictive refractive errors of the four formulas were analyzed.ResultsIn short eyes with an ACD < 2.5 mm, the Haigis formula revealed the highest MedAE. The difference in MedAE with the Hoffer Q formula (which had the lowest MedAE) was statistically significant (P = 0.002). In normal eyes, the Haigis formula significantly differed from the Holladay 1 (P = 0.002) and Hoffer Q (P = 0.005) formulae in the ACD < 2.5 mm group. In long eyes and extremely long eyes with an ACD ≥ 3.5 mm, the differences in MedAEs were statistically significant (P = 0.018, P = 0.001, respectively) and the Haigis formula had the lowest MedAEs in both subgroups (0.29 D, 0.30 D, respectively). In the total of 1,123 eyes, refractive errors predicted by the Haigis formula showed a significant negative correlation with the ACD (R2 = 0.002, P = 0.047).ConclusionsThe Hoffer Q formula is preferred over other formulae in short eyes with an ACD shallower than 2.5 mm. In short and normal eyes with an ACD < 2.5 mm the Haigis formula might underestimate ELP. The Haigis formula is the preferred choice in eyes with an AL ≥ 24.5 mm and an ACD ≥ 3.5 mm.