Purpose To evaluate dry eye manifestations following photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and determine the incidence and predictive factors of chronic dry eye using a set of dry eye criteria. Setting Walter Reed Army Medical Center, Washington, DC, USA Methods This is a prospective non-randomized clinical study of 143 active duty U.S. Army personnel aged 29.9±5.2 years with myopia or myopic astigmatism (manifest spherical equivalent −3.83±1.96 diopters) undergoing either PRK or LASIK. Dry eye evaluation was performed pre- and postoperatively. Main outcome measures included dry eye manifestations, incidence, and predictive factors of chronic dry eye. Results Schirmer scores, corneal sensitivity, ocular surface staining, surface regularity index (SRI), and responses to dry eye questionnaire significantly changed over time after PRK. After LASIK, significant changes were observed in tear breakup time, corneal sensitivity, ocular surface staining, and responses to questionnaire. At twelve months postoperatively, 5.0% of PRK and 0.8% of LASIK participants developed chronic dry eye. Regression analysis showed preoperatively lower Schirmer score will significantly influence development of chronic dry eye after PRK whereas preoperatively lower Schirmer score or higher ocular surface staining score will significantly influence the occurrence of chronic dry eye after LASIK. Conclusions Chronic dry eye is uncommon after PRK and LASIK. Ocular surface and tear film characteristics during preoperative examination may help predict chronic dry eye development in PRK and LASIK.

Purpose To determine the association of single nucleotide polymorphisms (SNPs) of the thrombospondin 1 (THBS1) gene with development of chronic ocular surface inflammation (keratoconjunctivitis) after refractive surgery. Design Retrospective cohort study. Participants Active duty U.S. Army soldiers (n = 143) who opted for refractive surgery. Methods Conjunctival impression cytology samples collected from participants before the surgery were used to harvest DNA for genotyping 5 THBS1 SNPs (rs1478604, rs2228262, rs2292305, rs2228262, and rs3743125) using the Sequenom iPLEX Gold platform (Sequenom, San Diego, CA). Samples collected after surgery were used to harvest RNA for gene expression analysis by real-time polymerase chain reaction (PCR). Participants were followed for 1 year after surgery to monitor the status of keratoconjunctivitis. Main Outcome Measures Genetic basis of the development of chronic keratoconjunctivitis after refractive surgery. Results Carriers of minor alleles of 3 SNPs each were found to be more susceptible to developing chronic keratoconjunctivitis (rs1478604: odds ratio [OR], 2.5; 95% confidence interval [CI], 1.41–4.47; P = 2.5×10−3; rs2228262 and rs2292305: OR, 1.9; 95% CI, 1.05–3.51; P = 4.8×10−2). Carriers of the rs1478604 minor allele expressed significantly reduced levels of thrombospondin 1 (TSP1) (P = 0.042) and increased levels of an inflammatory cytokine associated with keratoconjunctivitis, interleukin-1 β (P = 0.025), in their ocular surface epithelial cells compared with homozygous major allele controls. Conclusions Genetic variation in the THBS1 gene that results in decreased expression of the encoded glycoprotein TSP1 in ocular surface epithelial cells significantly increases the susceptibility to develop chronic ocular surface inflammation after refractive surgery. Further investigation of THBS1 SNPs in a larger sample size is warranted.

Background:The wet visual surface of the eye is essentially a sterile environment. Results: Proteolytic processing of the prosecretory mitogen lacritin in tears releases a fragment that is required for much of the bactericidal activity of tears. Conclusion:The protease-released C terminus of lacritin is bactericidal under physiological conditions. Significance: All known lacritin activities are bundled within the same C-terminal region, although at different dose optimum.

PURPOSE. Molar accounting of bioactive fluids can expose new regulatory mechanisms in the growing proteomic focus on epithelial biology. Essential for the viability of the surface epithelium of the eye and for normal vision is the thin, but protein-rich, tear film in which the small tear glycoprotein lacritin appears to play a prominent prosecretory, cytoprotective, and mitogenic role. Although optimal bioactive levels in cell culture are 1 to 10 nM over a biphasic dose optimum, ELISA suggests a sustained tear lacritin concentration in the midmicromolar range in healthy adults. Here we identify a reconciling mechanism.METHODS. Monoclonal anti-lacritin 1F5 antibody was generated, and applied together with a new anti-C-terminal polyclonal antibody to tear and tissue Western blotting. In vitro tissue transglutaminase (Tgm2) cross-linking was monitored and characterized by mass spectrometry.RESULTS. Blotting for lacritin in human tears or saliva surprisingly detected immunoreactive material with a higher molecular weight and prominence equal or exceeding the~23 to 25 kDa band of monomeric glycosylated lacritin. Exogenous Tgm2 initiated lacritin cross-linking within 1 minute and was complete by 90 minutes-even with as little as 0.1 nM lacritin, and involved the donors lysine 82 and 85 and the acceptor glutamine 106 in the syndecan-1 binding domain. Lacritin spiked into lacritin-depleted tears formed multimers, in keeping with~0.6 lM TGM2 in tears. Cross-linking was absent when Tgm2 was inactive, and cross-linked lacritin, unlike recombinant monomer, bound syndecan-1 poorly. Enhanced TGM2 expression correlates with reduced cell viability, caspase activation, TNF receptor clustering, 7 and mitochondrial dysfunction 8 associated with hyperosmolar stress in dry eye. 9 Transglutaminases encompass a multifunctional family of enzymes involved in high-fidelity posttranslational modifications that catalyze Ca 2þ -dependent covalent bond formation between primary amines or e-amino groups of lysine and c-carboxamide groups of glutamine. Cross-linking affects function, both negatively and positively. TGM2 crosslinked collagen is resistant to metalloproteinase digestion and less mitogenic 10 ; and cross-linked IL-2 (unlike IL-2 monomer) is cytotoxic for oligodendrocytes. 11 TGM2 also positively regulates the activity of midkine, a small heparin binding growth factor, 12 and is required for the activation of latent TGF-b 13 and S100A11.14 Could TGM2 in tears regulate ocular surface biology?Lacritin is a 12.3 kDa tear prosecretory mitogen 15 with glutamine and lysine residues suitable for TGM2 catalyzed cross-linking. Lacritin promotes corneal epithelial cell survival (Zimmerman K, et al. IOVS 2012;53:ARVO E-Abstract 4231) and proliferation, 16 and basal tear protein secretion by lacrimal acinar cells. 15 When topically applied to rabbit eyes, lacritin acutely increases basal tear flow. 17 Lacritin is largely restricted to tears and to a lesser extent saliva, through its lacrimal acinar cell, 15