Case of Primary Isolated Subconjunctival IgG4-Related Disease.

PURPOSE: To report a case of isolated subconjunctival ocular adnexal IgG4-related disease that met the diagnostic criteria according to the Japanese Ministry of Health, Labour and Welfare's 2011 guidelines. METHODS: We report a case of a 56-year-old woman with a left subconjunctival mass for 3 months. Excisional biopsy was performed. Postoperatively, the patient underwent systemic and radiologic evaluations for IgG4-related disease. RESULTS: The clinicopathologic study revealed storiform fibrosis and lymphoplasmacytic infiltration, with increased IgG4-positive plasma cells and an IgG4/IgG-positive plasma cell ratio of 40%. Serum IgG4 and IgG levels were slightly elevated. Systemic involvement was not detected. CONCLUSIONS: IgG4-related disease is well known in the orbit and ocular adnexa, particularly the lacrimal gland. However, subconjunctival involvement should be recognized as a possible presentation for this entity.

Manifestation of meibomian gland dysfunction in patients with Sjögren's syndrome, non-Sjögren's dry eye, and non-dry eye controls.

PURPOSE: To evaluate the manifestation of meibomian gland dysfunction in patients with Sjögren's syndrome (SS), non-Sjögren's syndrome dry eye (non-SS) patients, and non-dry eye controls. METHODS: We recruited 31 participants with SS dry eye, 30 participants with non-SS dry eye, and 35 healthy controls without dry eye symptoms. Noninvasive tear breakup time (NITBUT) and meibomian gland dropout score (meiboscore) were measured using the Oculus Keratograph 5 M. Meibomian gland expressibility and secretion quality were evaluated via slit lamp biomicroscopy. The correlation between measurements was analyzed. RESULTS: NITBUT was lower, and the meiboscore, meibomian gland expressibility, and secretion quality scores were significantly higher in the SS and non-SS groups than in the control group (p < 0.001). NITBUT was lower, and the meiboscore and meibomian gland expressibility were higher in the SS group than in the non-SS group. NITBUT correlated negatively with the meiboscore in both SS and non-SS groups and with meibomian gland expressibility in the SS group. A positive correlation was obtained between meiboscore and meibomian gland expressibility in both the SS and the non-SS groups. CONCLUSION: Patients in both SS and non-SS groups exhibited greater impairment in meibomian gland function than the non-dry eye controls. SS patients had more severe meibomian gland dysfunction with poorer mean meiboscore and meibomian gland expressibility than non-SS patients.

Effect of diquafosol tetrasodium 3% on the conjunctival surface and clinical findings after cataract surgery in patients with dry eye.

PURPOSE: To investigate the effects of diquafosol tetrasodium (DT) 3% on conjunctival impression cytologic findings in addition to clinical symptoms and signs after cataract surgery in patients with preexisting dry eye disease (DED). METHODS: Ninety-four eyes of 94 patients with DED who underwent uneventful cataract surgery were included. In total, 50 patients were treated with DT 3% (group A), while 44 patients were treated with sodium hyaluronate 0.1% (group B) postoperatively, along with topical antibiotics and steroids. Conjunctival impression cytology was performed at baseline and at 4 and 12 weeks after surgery. Visual acuity, ocular surface disease index (OSDI), tear film breakup time (TBUT), keratoepitheliopathy score, Schirmer's test, and tear clearance rate were measured at baseline and at 1, 4, and 12 weeks, and corneal aberration was analyzed at baseline and at 4 and 12 weeks. RESULTS: The grade of conjunctival squamous metaplasia was lower at 12 weeks, and goblet cell density was higher at 4 and 12 weeks in group A than in group B (P < 0.05). Compared with group B, group A showed significantly lower OSDI scores at 4 and 12 weeks, longer TBUT at 1, 4, and 12 weeks, lower keratoepitheliopathy scores at 1 and 12 weeks, and lower total root-mean-square score and spherical aberrations at 4 weeks after surgery (P < 0.05). CONCLUSIONS: DT 3% eye drops application after cataract surgery was effective in improving conjunctival epithelial morphology and goblet cell density as well as clinical findings in patients with DED.

Effectiveness of Combined Tear Film Therapy in Patients with Evaporative Dry Eye with Short Tear Film Breakup Time.

PURPOSE: The aim of this study was to evaluate the effectiveness of combined tear film therapy targeted to aqueous, mucin, and lipid layers in patients with refractory evaporative dry eye (EDE) with short tear film breakup time (TBUT). METHODS: The patients who had EDE with short TBUT and severe symptoms refractory to artificial tears were treated with hyaluronic acid (HA) 0.15% and diquafosol tetrasodium (DQS) 3% (Group 1), HA and carbomer-based lipid-containing eyedrops (Liposic EDO Gel, LPO) (Group 2), or HA, DQS, and LPO (Group 3). Ocular Surface Disease Index (OSDI) score, visual analog scale (VAS) symptom score, TBUT, Schirmer score, and corneal and conjunctival staining scores were evaluated, and noninvasive tear film breakup time (NIBUT) and tear meniscus height were measured using Keratograph® 5 M before and 1 and 3 months after treatment. RESULTS: OSDI scores, VAS scores, TBUT, and NIBUT were improved at 1 and 3 months after treatment in all groups (all P < 0.05). At each follow-up visit, the total OSDI, OSDI symptom, and all VAS scores were significantly lower in group 3 compared with groups 1 and 2 (all P < 0.05). In addition, TBUT and NIBUT were significantly higher in group 3 compared with groups 1 and 2 (all P < 0.05). No significant adverse effects were noted in the groups during treatment. CONCLUSIONS: Mucin or lipid-targeting agents combined with aqueous supplements in patients with refractory EDE with short TBUT might improve subjective symptoms and TBUT. Of this, targeting whole tear film layers was most effective in improving ocular symptoms and tear film quality.

A novel TRPM8 agonist relieves dry eye discomfort.

BACKGROUND: Physical cooling of the eye surface relieves ocular discomfort, but translating this event to drug treatment of dry eye discomfort not been studied. Here, we synthesized a water-soluble TRPM8 receptor agonist called cryosim-3 (C3, 1-diisopropylphosphorylnonane) which selectively activates TRPM8 (linked to cooling) but not TRPV1 or TRPA1 (linked to nociception) and tested C3 in subjects with mild forms of dry eye disease. METHODS: A set of 1-dialkylphosphoryalkanes were tested for activation of TRPM8, TRPV1 and TRPA1 receptors in transfected cells. The bioactivity profiles were compared by perioral, topical, and intravenous delivery to anesthetized rats. The selected lead candidate C3 or vehicle (water) was applied with a cotton gauze pad to upper eyelids of patients with dry eye disease (n = 30). Cooling sensation, tear film break-up time (TBUT), basal tear secretion, and corneal staining were evaluated. C3 was then applied four times daily for 2 weeks to patients using a pre-loaded single unit applicator containing 2 mg/mL of C3 in water (n = 20) or water only. TBUT, basal tear secretion, and corneal staining, and three questionnaires surveys of ocular discomfort (VAS scale, OSDI, and CVS symptoms) were analyzed before and at 1 and 2 weeks thereafter. RESULTS: C3 was a selective and potent TRPM8 agonist without TRPV1 or TRPA1 activity. In test animals, the absence of shaking behavior after C3 perioral administration made it the first choice for further study. C3 increased tear secretion in an animal model of dry eye disease and did not irritate when wiped on eyes of volunteers. C3 singly applied (2 mg/ml) produced significant cooling in <5 min, an effecting lasting 46 min with an increase in tear secretion for 60 min. C3 applied for 2 weeks also significantly increased basal tear secretion with questionnaire surveys of ocular discomfort indices clearly showing improvement of symptoms at 1 and 2 weeks. No complaints of irritation or pain were reported by any subject. CONCLUSIONS: C3 is a promising candidate for study of TRPM8 function on the eye surface and for relief of dry eye discomfort. TRIAL REGISTRATION: ISRCTN24802609 and ISRCTN13359367 . Registered 23 March 2015 and 2 September 2015.

Comparison of 0.3% Hypotonic and Isotonic Sodium Hyaluronate Eye Drops in the Treatment of Experimental Dry Eye.

PURPOSE: To compare the efficacy of 0.3% hypotonic and isotonic sodium hyaluronate (SH) eye drops in the treatment of experimental dry eye. METHODS: Experimental dry eye was established in female C57BL/6 mice by subcutaneous scopolamine injection and an air draft. The mice were divided into three groups (n = 15): control, preservative-free 0.3% isotonic SH, and preservative-free 0.3% hypotonic SH. The tear volume, tear film break-up time, and corneal fluorescein staining scores were measured 5 and 10 days after treatment. After conjunctival tissues were excised at 10 days, the levels of interleukin (IL)-6, IL-17, interferon (IFN)-γ, and IFN-γ inducible protein-10 were determined using the multiplex immunobead assay. In addition, PAS staining and flow cytometry were performed to evaluate the counts of conjunctival goblet cells and CD4+ IFN-γ+ T cells. RESULTS: Mice treated with 0.3% hypotonic SH showed a significant decrease in corneal staining scores (P = 0.04) and the levels of IL-6 (16.7 ± 1.4 pg/mL, P = 0.02) and IFN-γ (46.5 ± 11.5 pg/mL, P = 0.02) compared to mice treated with 0.3% isotonic SH (IL-6; 32.5 ± 8.8 pg/mL, IFN-γ; 92.0 ± 16.0 pg/mL) at day 10. Although no significant difference in CD4+ IFN-γ+ T cell numbers was observed, goblet cell counts were higher in the hyopotonic SH group than in the isotonic SH group (P = 0.02). CONCLUSIONS: When compared to 0.3% isotonic SH eye drops, 0.3% hypotonic SH eye drops can be more effective by improving corneal staining scores, decreasing inflammatory molecules, and increasing goblet cell counts for experimental dry eye. These data suggest that hypotonic artificial tears may be useful as an adjunctive treatment for inflammatory dry eye.

Anti-Inflammatory and Antioxidative Effects of Camellia japonica on Human Corneal Epithelial Cells and Experimental Dry Eye: In Vivo and In Vitro Study.

Purpose: To analyze the anti-inflammatory and antioxidative effects of Camellia japonica (CJ) on human corneal epithelial (HCE) cells and its therapeutic effects in a mouse model of experimental dry eye (EDE). Methods: Camellia japonica extracts of varying concentrations (0.001%, 0.01%, and 0.1%) were used to treat HCE cells. Dichlorofluorescein diacetate (DCF-DA) and dihydroethidium (DHE) assays were performed. The production of peroxiredoxin (PRX) 1-6 and manganese-dependent superoxide dismutase (MnSOD) in HCE cells was assessed using Western blot analysis. Furthermore, eye drops containing 0.001%, 0.01%, or 0.1% CJ extract or a balanced salt solution (BSS) were applied to the EDE. Clinical parameters were measured 7 days after treatment. The levels of inflammatory markers and intracellular reactive oxygen species (ROS) were measured. Results: Treatment with 0.01% and 0.1% CJ extracts decreased apoptosis in HCE cells. In addition, band intensities of PRX 1, 4, and 5, as well as MnSOD, after hydrogen peroxide (H2O2) treatment showed a significant improvement after pretreatment with 0.01% and 0.1% CJ extracts. Mice treated with 0.1% CJ extract showed significantly improved clinical parameters when compared to those of the EDE control and BSS groups. A significant decrease in the levels of inflammatory markers and intracellular ROS was observed in the 0.01% and 0.1% CJ extract groups. Conclusions: Camellia japonica extracts promoted antioxidative protein expression and suppressed apoptosis in HCE cells. Furthermore, CJ extracts improved clinical signs of dry eye and reduced oxidative stress and the expression of inflammatory markers, suggesting that eye drops containing CJ extract could be used as an adjunctive treatment for dry eye.

Experimental and Clinical Applications of Chamaecyparis obtusa Extracts in Dry Eye Disease.

PURPOSE: To investigate the effects of Chamaecyparis obtusa (CO) on human corneal epithelial (HCE) cells, a murine experimental dry eye (EDE) model, and the efficacy of antioxidant eye mask in dry eye disease (DED) patients. METHODS: 0.001%, 0.01%, and 0.1% CO extracts were used to treat HCE cells, cell viability, and production of antioxidative enzymes, and reactive oxygen species (ROS) were assessed. Afterwards, CO extracts or balanced salt solution (BSS) was applied in EDE. Clinical and experimental parameters were measured at 7 days after treatment. In addition, DED patients were randomly assigned to wear either an eye mask containing CO extracts or a placebo. Clinical parameters were evaluated. RESULTS: The viability of HCE cells and antioxidative enzyme expression significantly improved after treatment with 0.1% CO extracts. Mice treated with 0.1% CO extracts showed significant improvement in clinical parameters. During the trial, the clinical parameters significantly improved in the treatment group at 4 weeks after application. CONCLUSIONS: 0.1% CO extracts could promote the expression of antioxidative proteins and ROS production. In addition, an eye mask containing CO extracts could improve DED clinical parameters. These suggest that CO extracts may be useful as an adjunctive option for the DED treatment.

Correction: Influence of Light Emitting Diode-Derived Blue Light Overexposure on Mouse Ocular Surface.

[This corrects the article DOI: 10.1371/journal.pone.0161041.].

Bilateral Corneal Epithelial Lesions Associated with Paclitaxel.

PURPOSE: An antineoplastic drug, paclitaxel, is widely used in small cell lung cancer, breast cancer, and ovarian cancer. We report a case of bilateral, vision-impairing corneal epithelial lesions that developed in a patient receiving paclitaxel monotherapy for breast cancer. CASE REPORT: A 45-year-old woman presented with a 1-month history of bilateral visual disturbances. She had been receiving paclitaxel chemotherapy after modified radical mastectomy for invasive ductal carcinoma in her left breast. Best-corrected visual acuity was 20/100 in the right eye and 20/40 in the left eye. Slit-lamp examination revealed irregular triangular corneal lesions in both eyes. The lesions extended to the center of the cornea involving the visual axis and showed late staining with fluorescein dye. The lesions resolved 5 months after discontinuation of paclitaxel chemotherapy, and best-corrected visual acuity was restored to 20/20 in both eyes. CONCLUSIONS: Microtubule-stabilizing chemotherapeutic drugs such as paclitaxel can cause visually significant corneal lesions, and these lesions appear to be reversible with discontinuation of the drug. This case highlights the need for regular ophthalmologic examinations for the detection of this reversible adverse ocular reaction.