Application of umbilical cord serum eyedrops after laser epithelial keratomileusis

To evaluate the effect of topical cyclosporine A 0.05% after laser epithelial keratomileusis (LASEK). This retrospective nonrandomized comparative analysis was performed in 40 patients (80 eyes) with myopia who underwent flap-off LASEK. Twenty patients (group A) were treated with topical cyclosporine A 0.05% in combination with conventional treatment, and 20 patients (group B) received conventional treatment only. In each group, 10 patients had preoperative dry eye. Uncorrected visual acuity, refractive error, corneal haze grade, symptom score, and ocular surface parameters were measured in both groups before LASEK and at 1, 2, 4, and 8 weeks postoperatively. There were no significant differences between the groups in postoperative uncorrected visual acuity, spherical equivalent, corneal haze grade, Schirmer test values, and keratoepitheliopathy scores. Group A had lower symptom scores (0.80 ± 0.52 vs.1.35 ± 0.49; P < 0.01) and higher tear film break-up time (BUT) (8.05 ± 1.39 vs. 6.55 ± 1.39 seconds; P < 0.01) compared with group B at 4 weeks after LASEK. In addition, in preoperative dry eye patients, symptom scores and tear film BUT returned to preoperative level at 4 weeks postoperatively in group A, whereas they returned to preoperative level at 8 weeks in group B. Treatment with topical cyclosporine A 0.05% can improve ocular discomfort and increase tear film BUT during the early postoperative period, especially in patients with preoperative dry eye.

Comparison of Corneal Nerve Regeneration and Sensitivity Between LASIK and Laser Epithelial Keratomileusis (LASEK)

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.

To determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in tears of patients with dry eye syndrome. IL-6 and TNF-alpha levels were measured by enzyme-linked immunosorbent assay in tear samples obtained from 18 patients with dry eye (8 patients with Sjögren syndrome and 10 patients with non-Sjögren syndrome) and 14 control subjects. The correlation between IL-6 and TNF-alpha levels and tear film and ocular surface parameters was analyzed. The relative expression of these cytokines was evaluated in conjunctival impression cytology and conjunctival biopsy specimens by using immunohistochemical staining. The mean levels of IL-6 and TNF-alpha were, respectively, 18.57 +/- 8.92 and 3.68 +/- 3.45 pg/mL in patients with dry eye and 3.59 +/- 3.38 (P < 0.01) and < 0.5 (P < 0.01) pg/mL in control subjects. IL-6 level was significantly increased in tears of patients with Sjögren syndrome compared with those with non-Sjögren syndrome (P < 0.01). IL-6 level correlated significantly with tear film breakup time (P = 0.04), Schirmer test (P < 0.01), tear clearance (P = 0.02), keratoepithelioplasty score (P < 0.01), and goblet cell density (P = 0.03), but not with corneal sensitivity (P = 0.08). There was no significant difference in TNF-alpha level between patients with non-Sjögren and Sjögren syndrome. TNF-alpha levels did not correlate with tear film and ocular surface parameters. Immunohistochemical staining showed positive staining for IL-6 in specimens from patients with dry eye, especially in specimens from patients with Sjögren syndrome. IL-6 and TNF-alpha levels are elevated in tears of patients with dry eye syndrome. IL-6 level, but not TNF-alpha level, is associated with the severity of the disease and correlates with various tear film and ocular surface parameters.

Corneal wound healing is a complex process: its mechanisms and the underlying genetic control are not fully understood. It involves the integrated actions of multiple growth factors, cytokines and proteases produced by epithelial cells, stromal keratocytes, inflammatory cells and lacrimal gland cells. Following an epithelial insult, multiple cytokines are released triggering a cascade of events that leads to repair the epithelial defect and remodelling of the stroma to minimize the loss of transparency and function. In this review, we examine the literature surrounding the genomics of corneal wound healing with respect to the following topics: epithelial and stromal wound healing (including inhibition); corneal neovascularisation; the role of corneal nerves in wound healing; the endothelium; the role of aquaporins and aptamers. We also examine the effect of ectasia on corneal wound healing with regard to keratoconus and following corneal surgery. A better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design treatments that selectively modulate key phases of the healing process resulting in scars that more closely resemble normal corneal architecture.

Purpose: To evaluate the clinical effectiveness of topical diquafosol tetrasodium (DQS) after laser epithelial keratomileusis (LASEK). Methods: This randomized prospective study included 97 eyes of 49 patients who were scheduled for LASEK. Patients in the DQS group used both 0.3% sodium hyaluronate and 3% DQS for 3 months after surgery while patients in the control group used only 0.3% sodium hyaluronate. Corneal staining score, tear film break-up time (TF-BUT), Schirmer test and ocular surface disease index (OSDI) were evaluated before surgery and 2, 4, 8, 12 and 16 weeks after surgery. Results: There was no significant difference in visual acuity, spherical equivalent and corneal haziness between the 2 groups after surgery. Corneal staining score was significantly lower in the DQS group than in the control group 2 weeks after LASEK (p < 0.01) and increased in the control group after LASEK compared with the preoperative value (2 weeks after LASEK, p < 0.01), but decreased in the DQS group (12 and 16 weeks after LASEK, p < 0.05). TF-BUT was significantly higher in the DQS group than in the control group 2 to 16 weeks after LASEK (p < 0.01) and increased values were observed in the DQS group after LASEK compared with the preoperative value (4 to 16 weeks after LASEK, p < 0.05). The mean OSDI was significantly higher 4 to 16 weeks after LASEK in the control group than in the DQS group (p < 0.01). Conclusions: Subjective dry eye symptoms and objective markers were worse for 4 weeks after LASEK. The use of 3% DQS for 12 weeks after surgery improved these symptoms and markers with the effect lasting 16 weeks after LASEK. J Korean Ophthalmol Soc 2015;56(9):1324-1330

Purpose To evaluate the efficacy and safety of umbilical cord serum (UCS) eye drops compared with intraoperative mitomycin-C (MMC) in enhancing corneal epithelial healing, reducing stromal haze, and improving early postoperative outcomes following photorefractive keratectomy (PRK). Patients and methods This prospective, randomized, case-control study included PRK patients with (−1.5 to −6 D) myopia and (≤−4 D) astigmatism. Participants were randomized into two groups: the study group received postoperative UCS eye drops (20% diluted with artificial tears), while control group received intraoperative MMC (0.02%) for up to 40 s. Both groups followed standard postoperative therapy. Outcomes measured included epithelial healing time, corneal haze (densitometry), uncorrected distance visual acuity, postoperative pain, and tear film stability. Results The study included 79 eyes from 40 patients. The mean age was 25.05±7.81 years in the UCS group and 29.14±5.48 years in the MMC group ( P =0.061). The mean spherical equivalent (SE) was −2.53±1.38 D in the UCS group and −2.55±1.49 D in the MMC group ( P =0.95). Epithelial healing was significantly faster in the UCS group (3.51±0.51 days vs. 4.67±1.3 days, P &lt;0.001). Postoperative haze was lower in the UCS group ( P &lt;0.05). Uncorrected distance visual acuity was significantly better at 1 and 2 weeks postoperatively ( P &lt;0.001), though long-term outcomes were similar. Pain scores were lower in the UCS group on postoperative day 2 ( P =0.012). Tear film stability remained unchanged, and no adverse events were observed. Conclusion UCS eye drops enhance epithelial healing, reduce corneal haze, and improve early visual recovery, with a comparable safety profile to MMC. UCS may serve as a promising biologic alternative to MMC in PRK postoperative management. Further large-scale studies are needed to validate these findings.

Purpose: To evaluate the clinical features of dry eye in thyroid-associated ophthalmopathy (TAO) according to disease activity and analyze the related factors. Methods: This study included 157 patients diagnosed with TAO and dry eye between March 2009 and March 2015. According to the clinical activity score (CAS), TAO patients were divided into inactive (CAS < 3) and active (CAS ≥ 3) groups. Clinical features included age, sex, visual acuity, proptosis, palpebral fissure width, orbital computed tomography (CT) findings, thyroid hormones, and ocular surface parameters including tear film break-up time (TFBUT), Schirmer tests, keratoepitheliopathy scores, and ocular surface disease index (OSDI) were obtained and compared between the groups. In addition, correlations between clinical features and ocular surface parameters were analyzed in both groups. Results: In the inactive and active TAO groups, CAS was 1.24 ± 0.69 and 4.23 ± 1.13, respectively (p = 0.001). Thyrotropin-binding inhibitory immunoglobulin was significantly higher in the active TAO group than in the inactive TAO group (p = 0.048). On orbital CT, extraocular muscle hypertrophy was more common in the active TAO group than the inactive TAO group (p = 0.020). No significant difference was found in age, sex, visual acuity, free T4, and thyroid-stimulating hormone between the two groups. During analysis of the tear film and ocular surface parameters, TFBUT (p = 0.006) was shorter and OSDI score (p = 0.028) was higher in the active TAO group than the inactive TAO group. TFBUT was negatively correlated with proptosis (r = -0.432, p = 0.001; r = -0.308, p = 0.032) and palpebral fissure width (r = -0.367 p = 0.012; r = -0.312, p = 0.031) in both groups. OSDI was positively correlated with proptosis in the active TAO group (r = 0.301, p = 0.033). Conclusions: TFBUT was shorter and OSDI score higher in dry eye patients with active TAO than in patients with inactive TAO. The TFBUT was negatively correlated with proptosis and palpebral fissure width in both groups. J Korean Ophthalmol Soc 2016;57(7):1037-1043

The purpose of this study was to compare corneal subbasal nerve morphology, corneal sensation, and tear film parameters after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). A prospective, randomized, single-masked, paired-eye design clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. In both techniques, an intrastromal lenticule was cut by a femtosecond laser and manually extracted. In FLEX, a LASIK-like flap allowed removal of the lenticule, whereas in SMILE, it was removed through a small incision. In-vivo confocal microscopy was used to acquire images of the central corneal subbasal nerve plexus, from which nerve density, total nerve number, and nerve tortuosity were analyzed. Corneal sensation was measured using Cochet-Bonnet esthesiometry. A visual analog scale, tear osmolarity, non-invasive tear film break-up time (keratograph) tear meniscus height (anterior segment OCT), Schirmer's test, and fluorescein tear film break-up time were used to evaluate tear film and ocular surface symptoms. Patients were examined before and 6 months after surgery. There were no statistically significant differences in baseline parameters between FLEX and SMILE (p > 0.050). With regard to changes from before to 6 months after surgery, mean reduction in subbasal nerve density was 14.22 ± 6.24 mm/mm(2) in FLEX eyes, and 9.21 ± 7.80 mm/mm(2) in SMILE eyes (p < 0.05). The total number of nerves decreased more in FLEX eyes than in SMILE eyes (p < 0.05). No change was found when comparing tortuosity (p > 0.05). Corneal sensation was reduced with 0.38 ± 0.49 cm in FLEX eyes, and 0.10 ± 0.34 cm in SMILE eyes (p < 0.01). No differences were found between FLEX and SMILE in tear film evaluation tests (p > 0.05). Significantly more patients felt postoperative foreign body sensation in the FLEX eye within the first days after surgery, as compared to the SMILE eye. Six months after surgery, the less invasive SMILE technique seemed better at sparing the central corneal nerves as compared to FLEX. Corneal sensation was only significantly reduced in FLEX eyes. There were no differences between FLEX and SMILE when comparing tear film evaluation tests 6 months after surgery.

ABSTRACTPurpose: To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease.Methods: The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry.Results: The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p < 0.01), and 13.32 ± 4.03 pmol/mg (p < 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p < 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients.Conclusions: The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

Objective: To compare the effectiveness of bromfenac sodium and fluorometholone eye drops on relieving corneal irritation and its safety in clinical applications after laser epithelial keratomileusis (LASEK) surgery. Methods: This was a prospective randomized, controlled study. A total of 60 patients (120 eyes) who underwent LASEK surgery from April 2017 to February 2018 in Tianjin Eye Hosptial were divided randomly into a bromfenac sodium group and a fluorometholone group according to the random number table, 30 patients (60 eyes) were included in each group. In the first week after the surgery, the bromfenac sodium group was given 0.1% bromfenac sodium eye drops twice a day, and then from the second week, this eye drops changed to 4 times per day for 1 month and 2 times per day in the following month. While the fluorometholone group was given 0.3% sodium hyaluronate eye drops twice a day in the first week after the surgery, then the eye drops changed to 0.1% fluorometholone by giving 4 times per day, which was gradually tapered in every month to the end. Corneal irritation and epithelial healing were evaluated at 1 d, 2 d, 3 d and 5 d after surgery. Examinations of uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, slit lamp, Schirmer Ⅰ test (SⅠT), tear film break-up time (BUT) and corneal epithelium integrity evaluation were performed 1 week, 1 month and 3 months after surgery. An intraocular pressure (IOP) examination was performed 1 week, 2 weeks, 1 month, 3 months and 4 months. The data were analyzed by repeated measures ANOVA, independent sample t-test and Mann-Whitney U test. Results: The scores for corneal irritation in the bromfenac sodium group were significantly lower than those in the fluorometholone group after surgery (Fgroups=7.8, P=0.018; Ftimes=121.7, P<0.001; Finteraction=273.4, P<0.001). At 1 month after surgery, the mean visual acuity of both groups recovered to 1.0 or better. There were no statistically significant differences in UCVA, BCVA or refraction between the two groups. At 1 month after surgery, there were 6 cases (10%) of corneal haze in the bromfenac sodium group while there were 2 cases (3%) in the fluorometholone group. The correction of IOP in the bromfenac sodium group after surgery were all below 21 mmHg, while there were 5 cases (9%) of high IOP at 2 weeks and 3 cases (5%) at 1 month in the fluorometholone group. After 3 months, both SⅠT and BUT in the two groups returned to normal levels, and the difference was not statistically significant. After 3 months, the corneal epithelium had totally recovered in most of the patients in the two groups. There was no statistically significant difference between the two groups. Conclusions: Bromfenac sodium eye drops can effectively alleviate corneal irritation after LASEK surgery. It is safe and effective for the recovery of vision and anti-inflammatory effects. Furthermore, bromfenac sodium can reduce the risk of postoperative high intraocular pressure caused by glucocorticoids. However, the incidence of corneal haze is slightly higher. Key words: bromfenac sodium; non-steroid anti-inflammatory drugs; glucocorticoids; laser epithelial keratomileusis; steroid-induced glaucoma

This study aimed to evaluate the efficacy of hyaluronic acid/trehalose drop for corneal epithelial and stromal healing after phacoemulsification surgery at Maltepe University, Department of Ophthalmology, Istanbul, Turkey. It is a retrospective randomized comparative study.The patients had phacoemulsification surgery divided into two groups. These patients received either a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®, Thea)(Group 1) or sodium hyaluronate 0.15% (Eye Still®; Teka) (Group 2) postoperatively. Effect on corneal epithelial and stromal healing was evaluated using Oxford staining and the vertical scar length measured by optic coherence tomography (OCT) respectively. Preoperative and postoperative findings for Oxford staining, Schirmer’s test, tear film break-uptime (TBUT) and ocular surface disease index(OSDI) scores were also evaluated. The correlation between scar length and tear film parameters was examined. The effect of trehalose on the epithelial healing and stromal scar formation was evaluated. Group 1 and 2 each had 30 eyes. The two groups were similar according to age and sex distribution. In terms of epithelial healing, it was faster in the trehalose group, although there was no statistical difference between the two groups. The length of the stromal scar was not significantly different between groups, though a smaller scar formation was observed in group 1 compared to those in group 2 at both 1 week and 1 month postoperatively. There was also no significant difference between the groups in tear film parameters. The stromal scar length was correlated with the Schirmer test on the 15th day. Although it was not statistically significant, the hyaluronic acid/trehalose may affect epithelial healing and stromal scar formation in a positive way after phacoemulsification surgery. Larger and longer studies are needed.

To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Thirty-three patients with dry eye (16 with and 17 without Sjögren's 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. 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 Sjögren's syndrome compared with those of the patients with non-Sjögren's 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 Sjögren's syndrome. Flow cytometry demonstrated an increased number of CXCR3(+) and CXCR3(+)CD4(+) cells in all the patients with dry eye. 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 Sjögren's syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.).

Effects of Prolonged Reading on Dry Eye

Refractive Surgery in Children: Treatment Options, Outcomes, and Controversies