Seong-Kyu Im

Expression of CXCL9, -10, -11, and CXCR3 in the Tear Film and Ocular Surface of Patients with Dry Eye Syndrome

PURPOSE To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. METHODS Thirty-three patients with dry eye (16 with and 17 without Sjögrens syndrome) and 15 control subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were measured with enzyme-linked immunosorbent assays. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. The expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by using immunohistochemistry. Flow cytometry was performed to count CXCR3(+) cells and CXCR3(+)CD4(+) cells in the conjunctiva. RESULTS The concentrations of CXCL9, -10, and -11 were 1,148 +/- 1,088, 24,338 +/- 8,706, and 853 +/- 334 pg/mL, in the patients with dry eye, and 272 +/- 269 (P = 0.01), 18,149 +/- 5,266 (P = 0.02), and 486 +/- 175 (P < 0.01) pg/mL in the control subjects, respectively. The concentrations significantly increased in tears of the patients with Sjögrens syndrome compared with those of the patients with non-Sjögrens dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P < 0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry eye, especially in the patients with Sjögrens syndrome. Flow cytometry demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the patients with dry eye. CONCLUSIONS Expression of CXCL9, -10, -11, and CXCR3 increased in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögrens syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.).

Application of umbilical cord serum eyedrops for the treatment of dry eye syndrome

Purpose: To investigate the efficacy of umbilical cord serum eyedrops for the treatment of severe dry eye syndrome. Methods: Fifty-five eyes of 31 patients with severe dry eye syndrome were treated with umbilical cord serum eyedrops. Symptom scoring, tear film break-up time (BUT), Schirmer test, corneal sensitivity test, and corneal fluorescein staining were performed before and 1 and 2 months after treatment, and conjunctival impression cytology was performed before and 2 months after treatment. The concentrations of epidermal growth factor (EGF), vitamin A, and transforming growth factor-&bgr; (TGF-&bgr;) in umbilical cord serum and normal peripheral blood serum were measured. Results: Two months after treatment, significant improvement was observed in symptom score (from 3.07 ± 0.54 to 0.96 ± 0. 58), BUT (from 3.96 ± 1.56 to 5.45 ± 2.54 seconds), and keratoepitheliopathy score (from 4.87 ± 3.22 to 1.71 ± 1.84) (P < 0.01). There was no statistically significant change in Schirmer and corneal sensitivity tests. In impression cytology, the grade of squamous metaplasia (from 2.35 ± 0.72 to 1.44 ± 0.69) and goblet cell density (from 80.91 ± 31.53 to 154.68 ± 43.06 cell/mm2) improved significantly (P < 0.01). The mean concentrations of EGF, TGF-&bgr;, and vitamin A were 0.48 ± 0.09, 57.14 ± 18.98, and 230.85 ± 13.39 ng/mL in umbilical cord serum and 0.14 ± 0.03, 31.30 ± 12.86, and 372.34 ± 22.32 ng/mL in peripheral blood serum, respectively. Conclusion: Umbilical cord serum contains essential tear components, and umbilical cord serum eyedrops are effective and safe for the treatment of severe dry eye syndrome.

Therapeutic effect of intracameral amphotericin B injection in the treatment of fungal keratitis.

Purpose: To study the therapeutic efficacy of intracameral amphotericin B (ICAMB) injection in the treatment of fungal keratitis. Methods: Fourteen patients with fungal keratitis received ICAMB, 10 μg/0.1 mL (group A), and 17 patients received conventional treatment only (group B). Visual acuity, time to hypopyon disappearance, time to epithelial defect closure, time to final improvement, and final outcome were analyzed and compared between the 2 groups. The concentration of amphotericin B in the aqueous humor after injection was measured using high-performance liquid chromatography. Results: The mean final visual acuity (log MAR) was 1.6 ± 1.1 in group A and 1.3 ± 1.4 in group B (P = 0.24). The mean time to disappearance of hypopyon, epithelial defect closure, and final improvement was 9.4 ± 9.4, 19.8 ± 10.4, and 26.6 ± 9.2 days in group A and 26.7 ± 21.3 (P = 0.03), 32.6 ± 22.8 (P = 0.08), and 52.8 ± 38.2 days (P = 0.04) in group B, respectively. At the last follow-up, treatment success was achieved in 92.9% of group A and 82.4% of group B (P = 0.38). The mean concentration of intracameral amphotericin B was 601.6 ± 51.3 ng/mL at 6 hours, 98.8 ± 43.1 ng/mL at 1 day, 57.0 ± 11.6 ng/mL at 3 days, and 52.3 ± 8.3 ng/mL at 7 days after injection. Conclusions: ICAMB seems to be effective in reducing time to disappearance of hypopyon and final improvement in the treatment of fungal keratitis.

Usefulness of double vital staining with 1% fluorescein and 1% lissamine green in patients with dry eye syndrome.

Purpose: To determine the relative staining characteristics of the nasal and temporal conjunctiva as compared with other measures of dry eye and evaluate the qualitative clinical impression of the utility of the double vital staining with fluorescein and lissamine green. Methods: Ocular surface staining was performed with a mixture of 1% fluorescein and 1% lissamine green in 50 patients with dry eye (12 patients with Sjögren syndrome and 38 patients with non-Sjögren syndrome). Ocular surface disease index (OSDI), tear breakup time (BUT), and Schirmer test were evaluated. Digital photographs were taken after vital staining on the ocular surface, and the grade of staining in various areas was assessed. Correlation among the degrees of staining, OSDI, and ocular surface parameters was analyzed. Results: The nasal conjunctiva evidenced greater staining compared with the temporal conjunctiva and cornea (P = 0.04). Staining of the nasal conjunctiva showed significant correlation with OSDI (P < 0.01) and BUT (P = 0.03). Staining of the temporal conjunctiva correlated significantly with OSDI (P = 0.01), and staining of the cornea correlated with BUT (P = 0.02). Conclusions: Double vital staining with 1% fluorescein and 1% lissamine green correlates with symptoms and some ocular surface parameters in patients with dry eye and helps to identify ocular surface changes easily. It may be a useful method for the diagnosis of dry eye and the assessment of the therapeutic effect in patients with dry eye syndrome.

Expression of CCR5 and its ligands CCL3, -4, and -5 in the tear film and ocular surface of patients with dry eye disease.

Purpose: To evaluate the expression of CCR5 and its ligands CCL3, CCL4, and CCL5 in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. Materials and Methods: The concentrations of CCL3, CCL4, and CCL5 were measured using enzyme-linked immunosorbent assay in tear samples obtained from forty-three patients with dry eye (17 SS and 26 non-SS patients) and 20 control subjects. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. Expression of the chemokines and their receptor in the conjunctiva was evaluated using immunohistochemistry. Flow cytometry was performed to detect CCR4+CD4+, CCR5+CD4+, and CCR6+CD4+ cells in the conjunctiva. Results: The concentrations of CCL3, CCL4, and CCL5 were 25.3 ± 24.2, 4.65 ± 3.21, and 93.12 ± 26.31 pg/mL in control subjects, 92.33 ± 13.23, 263.13 ± 116.13, and 253.64 ± 46.29 pg/mL in patients with non-SS, and 215.56 ± 36.1, 697.85 ± 185.65, and 456.12 ± 92.82 pg/mL in patients with SS. The concentrations showed a significant increase in tears of SS patients compared with those of non-SS patients and control subjects (p < 0.05). CCL5 levels showed significant correlation with tear film break-up time, basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (p < 0.01). Staining for the chemokines and their receptor increased in dry eye patients, especially in those with SS patients. Flow cytometry demonstrated increased numbers of CCR5+CD4+, and CCR6+CD4+ cells in dry eye patients in contrast to CCR4+CD4+ cells. Conclusions: Expression of CCR5 and its ligands CCL3, CCL4, and CCL5 increase in the tear film and ocular surface of patients with dry eye syndrome, especially in those with SS. CCL5 levels correlate significantly with various tear film and ocular surface parameters.

Experimental Inhibition of Corneal Neovascularization by Photodynamic Therapy with Verteporfin

Purpose: To investigate the anti-angiogenic effects of photodynamic therapy with verteporfin in a rabbit model of corneal neovascularization. Methods: One week after suturing, the localization of verteporfin in the neovascularized cornea was examined through fluorescent microscopy 1 hr after administration. Rabbits were treated with one or two times of photodynamic therapy with verteporfin at 1-week intervals. Analysis of corneal neovascularization was performed by biomicroscopic and histological examinations. Results: Fluorescent microscopy showed green fluorescence in the vascular walls and interstitial tissue of the corneal stroma. The mean percentages of neovascularized corneal area at 3 days, 1 week, and 2 weeks after one time of photodynamic therapy were 90.3% ± 3.5%, 71.6% ± 6.2%, and 43.6% ± 15.1% in treated eyes and 96.4% ± 1.9% (p = 0.10), 88.6% ± 4.6% (p = 0.01), and 76.8% ± 4.4% (p < 0.01) in control eyes, respectively. The mean percentages 3 days, 1 week, and 2 weeks after two times of photodynamic therapy were also significantly lower in treated eyes compared with control eyes. In quantitative histological examination at 1 and 2 weeks after therapy, treated eyes showed significantly less neovascular area and number of vessels than control eyes. Conclusions: Photodynamic therapy with verteporfin is a safe and useful procedure to reduce experimental corneal neovascularization and can be used to inhibit angiogenesis in the cornea.

Photodynamic therapy with verteporfin combined with subconjunctival injection of bevacizumab for corneal neovascularization.

Purpose: To investigate the efficacy of combined photodynamic therapy with verteporfin and subconjunctival injection of bevacizumab for the treatment of patients with corneal neovascularization. Methods: Twelve eyes of 12 patients with stable corneal neovascularization who were refractory to conventional treatment were treated with photodynamic therapy with verteporfin (6 mg/m2) and subconjunctival injection of bevacizumab (2.5 mg/0.1 mL). Anterior segment photography was performed before and after treatment. Best-corrected visual acuity, cumulative length of corneal blood vessels, and area of corneal neovascularization were measured. Results: From 1 week to 1 month after treatment, all eyes showed a notable decrease in corneal neovascularization and evidence of vascular thrombosis. At the 6-month and 1-year follow-ups, complete vascular occlusion was achieved in 8 eyes (66.7%) and partial occlusion was achieved in 3 eyes (25.0%). One eye (8.3%) showed revascularization after temporary occlusion. No ocular complications or systemic events developed. Conclusions: Photodynamic therapy with verteporfin combined with subconjunctival injection of bevacizumab seems to be effective for the treatment of corneal neovascularization.

Recurrent herpes simplex keratitis after verteporfin photodynamic therapy for corneal neovascularization.

Purpose: To report a case of recurrent herpes simplex keratitis after verteporfin photodynamic therapy for corneal neovascularization. Methods: A 69-year-old man who had lipid keratopathy with corneal neovascularization secondary to herpes simplex keratitis in the right eye and who was treated with topical steroid received photodynamic therapy with verteporfin. Six neovascular areas in the cornea were treated consecutively to occlude new vessels and reduce the risk of allograft rejection after subsequent keratoplasty. Results: Three days after verteporfin photodynamic therapy, there was evidence of vascular occlusion. However, a herpetic epithelial ulcer was detected in the cornea. Ten days after treatment, the lesion progressed to a geographic ulcer. After topical and systemic acyclovir treatment, the lesion healed. Five months after treatment, penetrating keratoplasty and postoperative antiviral prophylaxis were performed. During a follow-up period of 12 months, the graft remained clear with visual acuity of 20/40. Conclusion: Herpes simplex keratitis can recur after verteporfin photodynamic therapy for corneal neovascularization.

Prognosis of paraquat-induced ocular surface injury: therapeutic effect of amniotic membrane transplantation.

Purpose: To investigate the prognosis of paraquat-induced ocular surface injury and the therapeutic efficacy of amniotic membrane transplantation for the treatment of ocular surface damage. Methods: Twenty patients (26 eyes) with ocular surface injury caused by paraquat were studied. Twelve patients (14 eyes) underwent amniotic membrane transplantation combined with medical treatment (group A), and 8 patients (12 eyes) received medical treatment only (group B). Visual acuity, time to epithelial defect closure, stromal haze, and complications were analyzed. Results: The grade of the ocular surface injury was mild in 19 eyes (73.1%). Visual acuity improved in 20 eyes (76.9%). The epithelial defect healed completely in 25 eyes (96.2%), with a mean healing time of 16.04 ± 6.22 days. At the final visit, 80.8% of cases had no stromal haze. The mean time to epithelial defect closure was 13.43 ± 3.55 days in group A and 19.18 ± 7.25 days in group B (P = 0.03). Complications included punctal stenosis (2 eyes) and pannus (1 eye) in group A and conjunctivalization (1 eye) and symblepharon (1 eye) in group B. Conclusions: Paraquat-induced ocular surface injury had a relatively good prognosis. Amniotic membrane transplantation was helpful in shortening the time to closure of the epithelial defect.

Combined Ethylenediaminetetraacetic Acid Chelation, Phototherapeutic Keratectomy and Amniotic Membrane Transplantation for Treatment of Band Keratopathy

Purpose The objective of this study is to evaluate the therapeutic efficacy of ethylenediaminetetraacetic acid (EDTA) chelation and excimer laser phototherapeutic keratectomy (PTK) combined with amniotic membrane transplantation (AMT) for the treatment of band keratopathy (BK). Methods Eleven eyes in ten patients with BK received combined PTK (ablation zone of central 7.0-7.5 mm, depth of 50 µm), EDTA chelation (0.05 M, 3 minutes), and amniotic membrane transplantation using fibrin glue. Preand postoperative best corrected visual acuities, symptom changes, reepithelialization time, cosmesis, recurrence, and complications were analyzed. Results Visual acuity improved in three eyes (27.3%) and did not change in eight eyes (72.7%). Symptoms improved in all patients, and the mean reepithelialization time was 10.6±5.3 days. The cosmetic results were good in eight eyes (72.7%) and were fair in three eyes (27.3%). During the mean follow-up period of 11.4±6.1 months (range, 6 to 23 months), no postoperative complications or recurrences were observed. Conclusions The combination of EDTA chelation, PTK, and AMT is safe and effective for the treatment of band keratopathy.