PURPOSE: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A was determined using an experimental murine dry eye model. METHODS: The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered twice per day to dry eye induced murine corneas for 1 week. RESULTS: The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. CONCLUSIONS: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.
Animals ; Cornea/diagnostic imaging ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Dry Eye Syndromes/diagnosis/*drug therapy ; Female ; Mice ; Mice, Inbred C57BL ; Microscopy, Acoustic ; Ophthalmic Solutions/administration & dosage ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors

The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028).
Aged ; B-Cell Activating Factor/analysis/blood ; Blood Sedimentation ; Double-Blind Method ; Drug Administration Schedule ; Dry Eye Syndromes/complications/*drug therapy ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hydroxychloroquine/*therapeutic use ; Interleukin-16/analysis/blood ; Interleukin-17/analysis/blood ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Sjogren's Syndrome/*complications/diagnosis ; Th17 Cells/cytology/immunology ; Treatment Outcome

PURPOSE: To investigate the therapeutic effects of mineral oil (MO) and hyaluronic acid (HA) mixture eye drops on the tear film and ocular surface in a mouse model of experimental dry eye (EDE). METHODS: Eye drops consisting of 0.1% HA alone or mixed with 0.1%, 0.5%, or 5.0% MO were applied to desiccating stress-induced murine dry eyes. Tear volume, corneal irregularity score, tear film break-up time (TBUT), and corneal fluorescein staining scores were measured at 5 and 10 days after treatment. Ten days after treatment, goblet cells in the conjunctiva were counted after Periodic acid-Schiff staining. RESULTS: There was no significant difference in the tear volume between desiccating stress-induced groups. The corneal irregularity score was lower in the 0.5% MO group compared with the EDE and HA groups. The 0.5% and 5.0% MO groups showed a significant improvement in TBUT compared with the EDE group. Mice treated with 0.1% and 0.5% MO mixture eye drops showed a significant improvement in fluorescein staining scores compared with the EDE group and the HA group. The conjunctival goblet cell count was higher in the 0.5% MO group compared with the EDE group and HA group. CONCLUSIONS: The MO and HA mixture eye drops had a beneficial effect on the tear films and ocular surface of murine dry eye. The application of 0.5% MO and 0.1% HA mixture eye drops could improve corneal irregularity, the corneal fluorescein staining score, and conjunctival goblet cell count compared with 0.1% HA eye drops in the treatment of EDE.
Animals ; Conjunctiva/*drug effects/pathology ; Cornea/metabolism ; Disease Models, Animal ; Drug Combinations ; Dry Eye Syndromes/*drug therapy/metabolism ; Emollients/administration & dosage ; Female ; Goblet Cells/drug effects/metabolism/pathology ; Hyaluronic Acid/*administration & dosage ; Mice ; Mice, Inbred C57BL ; Mineral Oil/*administration & dosage ; Ophthalmic Solutions ; Tears/*metabolism ; Viscosupplements/administration & dosage

BACKGROUNDLong-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment.

METHODSFifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91.

RESULTSCompared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = -3.843, P < 0.001, and z = -3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = -10.994, P < 0.001) and aqueous tear production (t-test: t = -10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = -9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment.

CONCLUSIONSSH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.

Adolescent ; Adult ; Aged ; Benzalkonium Compounds ; adverse effects ; Dry Eye Syndromes ; chemically induced ; prevention & control ; Eye ; drug effects ; Eye Injuries ; chemically induced ; prevention & control ; Female ; Glaucoma ; drug therapy ; Humans ; Hyaluronic Acid ; therapeutic use ; Male ; Middle Aged ; Young Adult

PURPOSE: To assess current practice patterns for dry eye patients in South Korea and to evaluate the preference according to the ages and clinic types of physicians. METHODS: Dry eye patients (n = 1,612) were enrolled in this multicenter cross-sectional, observational study. The severity level of dry eye patients was classified based on the Korean guidelines for dry eye treatment. The medical records of the enrolled dry eye patients were evaluated, and the practice styles and the preferences were analyzed according to the ages and clinic types of physicians. RESULTS: Of all patients, dry eye level 1 was most common (47.5%), followed by level 2 (33.5%), level 3 (9.1%), and level 4 (1.1%). Topical anti-inflammatory agents were used in 70.7% of patients with dry eye level 2 and in 80.6% of patients at levels 3 and 4. Topical anti-inflammatory agents were also used in 48.7% of patients with dry eye level 1. Preservative-free artificial tears were preferred at all dry eye levels. The use of topical anti-inflammatory agents did not differ with investigator ages, but older physicians preferred preserved artificial tears more than younger ones. Physicians at referral hospitals also tended to use topical anti-inflammatory agents and preservative-free artificial tears earlier, beginning at dry eye level 1, than those who worked at private eye clinics. CONCLUSIONS: Topical anti-inflammatory agents were commonly prescribed for the treatment of dry eye patients in South Korea, even from dry eye level 1. Preservative-free artificial tears were preferred at all dry eye levels. Practice styles differed somewhat depending on the ages and clinic types of physicians.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents/*therapeutic use ; Attitude of Health Personnel ; Cross-Sectional Studies ; Cyclosporine/*therapeutic use ; Dry Eye Syndromes/*drug therapy ; Fatty Acids, Essential/therapeutic use ; Female ; Humans ; Lubricant Eye Drops/*therapeutic use ; Male ; Middle Aged ; Ointments/therapeutic use ; Ophthalmology/*standards ; Practice Guidelines as Topic ; *Professional Practice ; Referral and Consultation ; Republic of Korea ; Severity of Illness Index ; Young Adult

PURPOSE: To evaluate changes in clinical outcomes, inflammatory cytokine levels, and tear osmolarity in the tears of patients with moderate to severe dry eye syndrome before and after the application of topical 1% methylprednisolone. MATERIALS AND METHODS: Thirty-two patients with moderate to severe dry eye unresponsive to previous aqueous enhancement therapy were enrolled. Five patients were lost to follow up, and twenty-seven patients were eligible for analysis. Patients were instructed to apply topical 1% methylprednisolone four times per day, as well as to continue applying their current therapy of preservative-free 0.1% sodium hyaluronate four times per day. Corneal and conjunctival staining scores, tear film breakup time (TFBUT), Schirmer test, and tear osmolarity were assessed at baseline, 4 weeks, and 8 weeks. Tear samples were collected at every visit for cytokine analysis. RESULTS: Corneal and conjunctival staining scores and TFBUT showed significant improvement at 4 (p<0.001, <0.001, <0.001 respectively) and 8 (p<0.001, <0.001, <0.001 respectively) weeks. Tear osmolarity decreased significantly at 8 weeks (p=0.008). Interleukin (IL)-1beta, IL-8, and monocyte chemoattractant protein-1 were significantly decreased at 8 weeks compared with those at baseline (p=0.041, 0.001, 0.008 respectively). CONCLUSION: Short-term treatment with topical 1% methylprednisolone not only improved clinical outcomes, but also decreased tear osmolarity and cytokine levels. By measuring the changes in cytokine levels and tear osmolarity, we could objectively evaluate the anti-inflammatory effects of topical methylprednisolone applied in the treatment of patients with moderate to severe dry eye syndrome.
Adult ; Aged ; Cytokines/*metabolism ; Dry Eye Syndromes/*drug therapy/metabolism ; Female ; Humans ; Male ; Methylprednisolone/administration & dosage/*therapeutic use ; Middle Aged ; Osmolar Concentration ; Prospective Studies ; Tears/*chemistry/*metabolism

PURPOSE: To evaluate the clinical efficacy of newly developed guidelines for the diagnosis and management of dry eye. METHODS: This retrospective, multi-center, non-randomized, observational study included a total of 1,612 patients with dry eye disease who initially visited the clinics from March 2010 to August 2010. Korean guidelines for the diagnosis and management of dry eye were newly developed from concise, expert-consensus recommendations. Severity levels at initial and final visits were determined using the guidelines in patients with 90 +/- 7 days of follow-up visits (n = 526). Groups with different clinical outcomes were compared with respect to clinical parameters, treatment modalities, and guideline compliance. Main outcome measures were ocular and visual symptoms, ocular surface disease index, global assessment by patient and physician, tear film break-up time, Schirmer-1 test score, ocular surface staining score at initial and final visits, clinical outcome after three months of treatment, and guideline compliance. RESULTS: Severity level was reduced in 47.37% of patients treated as recommended by the guidelines. Younger age (odd ratio [OR], 0.984; p = 0.044), higher severity level at initial visit, compliance to treatment recommendation (OR, 1.832; p = 0.047), and use of topical cyclosporine (OR, 1.838; p = 0.011) were significantly associated with improved clinical outcomes. CONCLUSIONS: Korean guidelines for the diagnosis and management of dry eye can be used as a valid and effective tool for the treatment of dry eye disease.
Adult ; Aged ; Aged, 80 and over ; Diagnostic Techniques, Ophthalmological/*standards ; *Disease Management ; Dry Eye Syndromes/*diagnosis/*drug therapy/epidemiology ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents/*administration & dosage ; Male ; Middle Aged ; Morbidity/trends ; Ophthalmic Solutions ; *Practice Guidelines as Topic ; Republic of Korea/epidemiology ; Retrospective Studies ; Young Adult

BACKGROUNDDry eye is a multifactorial disease of the tears and the ocular surface. This study aimed to investigate the clinical efficacy of a non-steroidal anti-inflammatory drug, pranoprofen, in the treatment of dry eye.

METHODSIt is a prospective, multi-center, randomized, controlled, parallel group study. One hundred and fifteen patients with mild to moderate dry eye disease (55-60 in each treatment group) participated in this multi-center study. Patients were randomly administered with eyedrops containing 0.1% pranoprofen (PRA) plus 0.1% sodium hyaluronate (SH) or SH only, three times daily for 28 days, followed by a 1-week after treatment observation. Dry eye symptom score (DESS), fluorescein corneal staining (FLCS), tear break-up time (TBUT), and Shirmer 1 tear test (ST1, without anesthesia) were evaluated or conducted before treatment and at each study visit. Conjunctival impression cytology was taken from the patients treated with PRA plus SH before and after treatment and real-time polymerase chain reaction (RT-PCR) was performed to detect the changes of human leukocyte antigen DR (HLA-DR) and intercellular adhesion molecule 1 (ICAM-1).

RESULTSPatients treated with PRA plus SH showed gradual improvements of DESS, FLCS, and TBUT. Between-group comparisons of FLCS and TBUT have statistically significant differences from day 14. Good tolerance with no severe adverse events was found in both groups. Patients treated with PRA plus SH had a reduced expression level of HLA-DR and were statistically different after 28 days of therapy.

CONCLUSIONSThe application of PRA at a dose of 0.1% was well tolerated and benefited to the patients with mild to moderate dry eye disease. The underlying mechanism of its efficacy may be associated with the reduction of inflammatory factors of conjunctival epithelial cells.

Adult ; Benzopyrans ; therapeutic use ; Dry Eye Syndromes ; drug therapy ; Humans ; Middle Aged ; Ophthalmic Solutions ; therapeutic use ; Propionates ; therapeutic use

PURPOSE: To evaluate the effectiveness of cyclosporine 0.05% for dry eye after cataract surgery. METHODS: Thirty-two newly diagnosed patients with dry eye syndrome 1 week after cataract surgery received a twice-daily treatment of cyclosporine 0.05% for one eye and normal saline 0.9% for the other. Disease severity was measured at 2 weeks, 1 month, 2 months, and 3 months by Schirmer test I (ST-I), tear film break-up time (tBUT), corneal temperature and dry eye symptom questionnaire (Ocular Surface Disease Index). RESULTS: Both groups increased in ST-I and tBUT over time. ST-I in the cyclosporine 0.05% group showed a significant increase at 3 months and tBUT in the cyclosporine 0.05% group showed an increase at 2 and 3 months. The dry eye symptom score was significantly reduced in the cyclosporine 0.05% group. CONCLUSIONS: Cyclosporine 0.05% can also be an effective treatment for dry eye after cataract surgery.
Aged ; Aged, 80 and over ; *Cataract Extraction ; Cyclosporine/*administration & dosage ; Dry Eye Syndromes/*drug therapy ; Female ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Middle Aged ; Ophthalmic Solutions/*administration & dosage ; Postoperative Complications/*drug therapy ; Treatment Outcome

PURPOSE: To study the clinical features, pathophysiologic and radiologic characteristics, and prognostic factors in patients with orbital and adnexal lymphoma. METHODS: The medical records of patients who were diagnosed with orbital and adnexal lymphoma, and patients who were treated and observed, were retrospectively reviewed. Information regarding age, sex, initial symptoms and signs when visiting the hospital, mass location and features, histology and staging, response to treatment and side effects, and prognosis were collected. RESULTS: Fifty-four patients, with an equal number of men and women, were diagnosed with orbital and adnexal lymphoma. The average age was 50.9 years (14 to 82 years). The main symptom was orbital swelling, and the main site was conjunctiva. Histologically, Mucosa-Associated Lymphoid Tissue (MALT) lymphoma was the most observed. The major ocular complication was dry eye syndrome, which showed good response with ophthalmic treatment. Radiologic features did not have prognostic relevance. CONCLUSIONS: Most orbital and adnexal lymphomas were MALT lymphomas. Proper therapy according to stage can result in a good response and remission. In the present study, the therapy complications were well-controlled with medical treatment, and radiologic features of a mass could not be considered as a prognostic factor.
Conjunctiva ; Drug Therapy ; Dry Eye Syndromes ; Factor Analysis, Statistical* ; Female ; Humans ; Lymphoid Tissue ; Lymphoma* ; Lymphoma, B-Cell, Marginal Zone ; Male ; Medical Records ; Orbit* ; Prognosis ; Radiotherapy ; Retrospective Studies