The role of inflammation and antiinflammation therapies in keratoconjunctivitis sicca

Koray Gumus1, Dwight H Cavanagh21Department of Ophthalmology, Erciyes University School of Medicine, Kayseri, Turkey; 2Department of Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas, USAPurpose: To review and integrate recent advances in identifying the role of inflammation in the pathogenesis of dry eye conditions and the biological rationale and practical clinical aspects of newer, antiinflammatory theories.Methods: A comprehensive literature survey. Results and conclusion: Keratoconjunctivitis Sicca (KCS) is a multifactorial and complex disorder in which ocular surface infl ammations play a central role. Identification of specific CD4-T-Cell pathways and the recent recognition of targeting of alpha-fodrin suggest a case for novel new therapeutic aspects such as anti-CD4 monoclonal antibodies, systemic linoleic and gamma-linolenic acids, and omega-6 essential fatty acids. Replacement of tear volume with nonpreserved wetting agents and standard typical antiinflammatory corticosteroid and/or cyclosporine A continues to be central current conventional therapy for KCS.Keywords: dry eye, keratoconjunctivitis sicca, antiinflammatory therap

The clinical and cellular basis of contact lens-related corneal infections

Microbial keratitis (MK) is the most visually devastating complication associated with contact lens wear. Pseudomonas aeruginosa (PA) is highly invasive in the corneal epithelium and is responsible for more than half of the reported cases of contact lens-related MK. To protect against Pseudomonas-mediated MK, the corneal epithelium has evolved overlapping defense mechanisms that function to protect the ocular surface from microbial invasion. Research has shown that contact lens wear disrupts these protective mechanisms through breakdown of normal homeostatic surface renewal as well as damaging the corneal surface, exposing underlying cell membrane receptors that bind and internalize PA through the formation of lipid rafts. Human clinical trials have shown that initial adherence of PA with resulting increased risk for microbial infection is mediated in part by contact lens oxygen transmissibility. Recently, chemical preserved multipurpose solutions (MPS) have been implicated in increasing PA adherence to corneal epithelial cells, in addition to inducing significant levels of toxic staining when used in conjunction with specific silicone hydrogel lenses. This review summarizes what is currently known about the relationship between contact lenses, the corneal epithelium, MPS, and infection

The Effect of Nonpreserved Care Solutions on 12 Months of Daily and Extended Silicone Hydrogel Contact Lens Wear

PURPOSE. To determine the effects of nonpreserved care solutions on human corneal epithelium in long-term daily wear (DW) compared with overnight (extended) wear (EW) of hyper-oxygen-permeable silicone hydrogel contact lenses. METHODS. This was a prospective, randomized, double-masked, single-center, parallel treatment group clinical trial (NCT 00344643). One hundred twenty-one patients completed the 13 month study: (1) Lotrafilcon A (30 night EW, n ϭ 29; DW, n ϭ 32); (2) Galyfilcon A (DW, n ϭ 20); and (3) Lotrafilcon B (6 night EW, n ϭ 20; DW, n ϭ 21). Irrigation chamber collection of corneal surface cells (OD) and confocal microscopy (OS) were performed at baseline, 1 week; and 1, 3, 6, 9, and 12 months of EW. The main outcome measures were: (1) Pseudomonas aeruginosa (PA) binding to exfoliated corneal surface cells; (2) central epithelial thickness (CET); and (3) epithelial surface cell exfoliation rate (desquamation). RESULTS. DW had no significant effect on CET; there was a decrease in CET with EW that recovered (adapted) over 1 year (Lotrafilcon B, P Ͻ 0.05). All lens wear (DW, EW) decreased desquamation with adaptive effects over 1 year (P Ͻ 0.001). There was no significant difference in PA binding between lenses or modality of wear. CONCLUSIONS. PA binding to corneal epithelial cells is a prerequisite for infection, and no binding indicates no lensenhanced risk of infection. In contrast to prior studies of preserved lens-care products, the absence of a change in the PA binding data results predict that the risk for PA CTLkeratitis should be similar for daily and extended silicone hydrogel lens wear over 1 year when preservative-free care solutions are used. (ClinicalTrials.gov number, NCT00344643.) (Invest Ophthalmol Vis Sci. 2008;49:7-15

Corneal Pseudodendritic Lesions Masquerading as Herpetic Keratitis in a Patient With Tyrosinemia Type I

Objective: To describe the clinical findings of a patient with tyrosinemia type I with noncompliance to a protein-restricted diet, treated with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)

Vertical movement of epithelial basal cells toward the corneal surface during use of extended-wear contact lenses." Invest Ophthalmol Vis Sci 44(3

PURPOSE. To study the effects of extended contact lens wear (EW) on the movement of basal epithelial cells toward the corneal surface. METHODS. Rabbits (n ϭ 32) were injected with 5-bromo-2-deoxyuridine (BrdU) to label a group of proliferating basal epithelial cells, and, 24 hours later, one randomly chosen eye was fitted with a low-or medium-oxygen-transmissible (Dk/t) rigid gas permeable (RGP) contact lens, while the other eye served as the control (n ϭ 28). Four rabbits were not fitted with any contact lens. Rabbits were euthanatized at different time points and the corneal epithelium was immunocytochemically stained for BrdU and/or Ki-67 and counterstained with propidium iodide or Syto 59. Corneal flatmount tissues were examined three dimensionally under a laser confocal microscope and the location of each BrdU-labeled cell in the corneal epithelium (basal or suprabasal) was determined. RESULTS. Four days after injection of BrdU, both low-(P Ͻ 0.001) and medium-Dk/t RGP (P Ͻ 0.001) lens groups showed significantly more BrdU-labeled cells in the basal cell layer than in the control eyes. Six days after injection of BrdU, a small percentage of BrdU-labeled cells (Ͻ0.5%) were Ki-67 positive. CONCLUSIONS. Within 6 days, the majority (80%) of BrdU-labeled basal cells became terminally differentiated and rarely divided secondarily in the central epithelium. Short-term use of lowand medium-Dk/t RGP EW contact lenses slows the normal movement of basal epithelial cells toward the surface in the central cornea. This is consistent with known EW-lens-induced decreases in corneal epithelial basal cell proliferation and surface cell exfoliation. Overall, the data suggest that EW lenses significantly inhibit the normal homeostatic turnover rate of the corneal epithelium. (Invest Ophthalmol Vis Sci. 2003;44:1056 -1063) DOI:10.1167/iovs.02-0725 E xtended-wear (EW) contact lens users are exposed to a significantly higher risk of development of an infectious corneal ulcer than daytime lens wearers and non-contact lens users. 1,2 One of the important components of the ocular surface's defense against infection is the intact corneal epithelium, which forms a strong barrier against the penetration of infectious organisms. Increasing evidence in humans and rabbits suggests that EW contact lens use produces a decrease in basal cell proliferation and surface cell exfoliation of the corneal epithelium, causing an apparent stagnant ocular surface. There are, however, currently no reports on the effect(s) of contact lens wear on the movement of epithelial basal cells toward the surface of the cornea. Based on previous studies, we have proposed that in the central corneal epithelium, continuous contact lens wear slows down the movement of basal epithelial cells toward the corneal surface. Epithelial cells in the cornea are continuously in motion. There are two principal directions for the migration of epithelial cells: centripetal and vertical. Early observations with pigment and ink tracers have revealed the existence of centripetal movement in the corneal epithelium from the periphery to the center. 6 By contrast, vertical or upward cell movement occurs when basal cells leave the basal lamina and move toward the surface of the corneal epithelium, ultimately ending in apoptotic exfoliation. 7-10 Using tritiated thymidine labeling to track the movement of basal cells toward the corneal surface, Hanna and O'Brien 11 estimated the turnover rate of the epithelium to be 3.5 to 4 days in the rat and 6 to 7 days in the mouse. Beebe and Masters 12 demonstrated that after a single-pulse injection of 5-bromo-2-deoxyuridine (BrdU), the first BrdU-labeled cells reach the rat corneal epithelial surface by days 3 to 4; however, some BrdUlabeled cells remain in the basal cell layer for up to 14 days. Overall, these findings suggest that the complete homeostatic turnover rate of the normal epithelium may be longer than previously suspected. In this study, the proliferation marker BrdU was selected to label a group of basal epithelial cells in both corneas of each rabbit before application of a contact lens. Once a cell takes up BrdU, the label remains detectable in the nucleus over time, even if the cell exits the cell cycle or is not actively undergoing cell division. BrdU-labeled cells can then be monitored over time as they move upward toward the surface of the corneal epithelium

Topical Cyclosporine A as a Steroid-Sparing Agent in Steroid-Dependent Idiopathic Ocular Myositis With Scleritis: A Case Report and Review of the Literature

Objective: To report on a case of idiopathic orbital myositis with scleritis that was effectively controlled with topical 0.05% cyclosporine A and to provide a review of the literature on the treatment of ocular myositis with scleritis

C-Terminal Cleavage of ΔNp63α Is Associated with TSA-Induced Apoptosis in Immortalized Corneal Epithelial Cells

ΔNp63α is the dominant interacting isoform in corneal epithelial cells and undergoes proteolytic cleavage during apoptotic-directed cell death in the corneal epithelium. The loss of ΔNp63α during apoptosis appears to be correlated with loss of the classic tumor suppressor p53

Corneal Endothelial Characteristics and Central Corneal Thickness in a Population of Turkish Cataract Patients

Objectives: The aim was to assess corneal endothelial characteristics and central corneal thickness (CCT) in a population of Turkish cataract patients and to define the impact of age and gender on these parameters