Experimental interventions attenuate a conjunctival epidermal metaplasia model.

The conjunctiva is a non-keratinized, stratified columnar epithelium with characteristics different from the cornea and eyelid epidermis. From development to adulthood, a distinguishing feature of ocular versus epidermal epithelia is the expression of the master regulator PAX6. A conditionally immortalized conjunctival epithelial cell line (iHCjEC) devoid of stromal or immune cells established in our laboratory spontaneously manifested epidermal metaplasia and upregulated expression of the keratinization-related genes SPRR1A/B and the epidermal cytokeratins KRT1 and KRT10 at the expense of the conjunctival trait. In addition, iHCjEC indicated a significant decrease in PAX6 expression. Dry eye syndrome (DES) and severe ocular surface diseases, such as Sjögren's syndrome and Stevens-Johnson syndrome, cause the keratinization of the entire ocular surface epithelia. We used iHCjECs as a conjunctiva epidermal metaplasia model to test PAX6, serum, and glucocorticoid interventions. Reintroducing PAX6 to iHCjECs resulted in upregulating genes related to cell adhesion and tight junctions, including MIR200CHG and CLDN1. The administration of glucocorticoids or serum resulted in the downregulation of epidermal genes (DSG1, SPRR1A/B, and KRT1) and partially corrected epidermal metaplasia. Our results using an isolated conjunctival epidermal metaplasia model point toward the possibility of rationally "repurposing" clinical interventions, such as glucocorticoid, serum, or PAX6 administration, for treating epidermal metaplasia of the conjunctiva.

Clinical characteristics of lacrimal drainage pathway disease-associated keratopathy.

PURPOSE: To report the clinical characteristics of 13 cases of noninfectious corneal ulceration related to lacrimal drainage pathway disease. METHODS: Medical records of 13 patients with lacrimal drainage pathway disease-associated keratopathy who were examined at Ehime University Hospital between April 2007 and December 2021 were analyzed. RESULTS: The predisposing lacrimal drainage pathway diseases for corneal ulceration were chronic dacryocystitis in seven patients and lacrimal canaliculitis in six patients. The corneal ulcers were located at the peripheral cornea in 10 patients and the paracentral cornea in three patients. All patients indicated few cellular infiltrations of the ulcerated area at the slit-lamp examination. Corneal perforation was found in seven patients. The primary identified organisms were Streptococcus spp. in chronic dacryocystitis and Actinomycetes spp. in lacrimal canaliculitis. All patients showed rapid healing of the epithelial defects after treatment of the lacrimal drainage pathway disease. The mean time elapsed between treatment of the lacrimal drainage pathway disease and re-epithelialization of corneal ulcer was 14.5 ± 4.8 days. CONCLUSION: Lacrimal drainage pathway disease-associated keratopathy may be characterized by peripheral corneal ulcer with few cellular infiltrations, occasionally leading to corneal perforation. Treatment of the lacrimal drainage pathway disease could be the most effective treatment for lacrimal drainage pathway disease-associated keratopathy.

Observation of Retrocorneal Plaques in Patients With Infectious Keratitis Using Anterior Segment Optical Coherence Tomography.

PURPOSE: Endothelial plaques are a typical characteristic in patients with fungal keratitis. However, bacterial keratitis and herpetic keratouveitis are rarely associated with fibrin formation on the retrocorneal surface. This study was conducted to examine plaques attached to the endothelium in patients with infectious keratitis using anterior segment optical coherence tomography (AS-OCT). METHODS: Seventeen patients (10 women and 7 men; mean age, 75 ± 15.5 years) suspected to have infectious keratitis with retrocorneal plaques were included. AS-OCT was used to acquire a scan of the retrocorneal plaque at the patient's first visit. RESULTS: Based on the culture results and detection of viral DNA, the patients were diagnosed with fungal keratitis (6 patients), bacterial keratitis (8 patients), and herpetic keratouveitis (3 patients). Examination of the cornea using AS-OCT showed a clear boundary between the corneal endothelial surface and plaque in 8 patients with bacterial keratitis and in all patients with herpetic keratitis. Moreover, a space between the corneal endothelial surface and plaque was found in 3 patients with bacterial keratitis. In 5 patients with fungal keratitis, the AS-OCT images showed an unclear boundary between the corneal endothelial surface and plaque, and high reflection of the plaque was extended from the corneal lesion. CONCLUSIONS: Endothelial plaques in patients with fungal keratitis could continue from the corneal lesion. Observation of retrocorneal plaques using AS-OCT could be used in the diagnosis of infectious keratitis.

Effect of Mandarin Orange Yogurt on Allergic Conjunctivitis Induced by Conjunctival Allergen Challenge.

Purpose: To evaluate the effects of mandarin orange yogurt containing nobiletin and ß-lactoglobulin on the allergic conjunctivitis induced by a conjunctival allergen challenge (CAC). Methods: Experiment 1 was performed on 26 asymptomatic patients (age, 25.3 ± 5.3 years) with proven seasonal allergic conjunctivitis due to cedar pollen. We compared the degree of conjunctivitis induced by CAC before and after ingesting mandarin orange yogurt for 2 weeks. Experiment 2 was a double-blind, placebo-controlled trial performed on 31 patients (age, 32.5 ± 12.2 years). A diet containing mandarin orange yogurt was compared to a diet containing yogurt lacking the mandarin orange on the conjunctivitis induced by CAC. The temperature of the inferior bulbar conjunctiva was measured before and 20 minutes after the CAC with an ocular surface thermographer (OST). The degree of conjunctival injection and chemosis was graded by slit-lamp biomicroscopy. The changes in the symptoms were evaluated by a questionnaire. Results: In experiment 1, the scores of redness (3.07 ± 3.03 vs. 1.05 ± 1.70), chemosis (2.84 ± 2.27 vs. 0.81 ± 1.11), itching (4.34 ± 3.05 vs. 1.39 ± 2.12), and temperature (0.73 ± 0.42°C vs. 0.45 ± 0.43°C) were significantly lower (P < 0.001) after a diet of mandarin orange yogurt for 2 weeks. In experiment 2, the scores of redness (1.03 ± 0.18 vs. 1.28 ± 0.52; P = 0.0156), itching (1.93 ± 1.92 vs. 2.82 ± 2.21; P = 0.0133), and surface temperature (0.54 ± 0.21°C vs. 0.31 ± 0.25°C; P < 0.001) were significantly lower in the mandarin orange yogurt group than in the control yogurt group. Conclusions: Mandarin orange yogurt can be an effective nutritional intervention for allergic conjunctivitis.

Effectiveness of in vivo confocal microscopy in detecting filamentous fungi during clinical course of fungal keratitis.

PURPOSE: To determine the effectiveness of laser confocal microscopy in detecting filamentous fungi in the cornea of patients with fungal keratitis (FK) and in evaluating the effectiveness of the treatment. METHODS: The corneas of 6 patients clinically diagnosed with FK were examined with the Heidelberg Retina Tomograph II-Rostock Cornea Module (HRT II-RCM). Three of these patients were also monitored periodically with the HRT II-RCM after antifungal treatment. RESULTS: The HRT II-RCM examination showed interlocking and branching, white, septated, hyphae-like lines in the cornea of all patients. All 6 patients had positive corneal smears and/or laboratory cultures. Three patients were monitored with HRT II-RCM after antifungal treatment. One patient, whose initial smear was negative, was diagnosed by HRT II-RCM before the positive culture results. In another case, the epithelial regeneration was impaired even 3 weeks after the initial treatment and HRT II-RCM revealed a mass of hyphae in the corneal ulcerated lesion. These findings indicated the necessity of surgical debridement. After the surgical debridement, the corneal epithelial defect was healed. HRT II-RCM was able to detect the morphological changes of hyphae after antifungal treatment and helped in the treatment modifications during the clinical course in all 3 patients. CONCLUSIONS: These results indicate that HRT II-RCM can be used to diagnose FK and to monitor the effect of therapy on FK.