Age-Related Conjunctival P2Y2 Receptor Alterations in the Cu, Zn-Superoxide Dismutase-1 (Sod1)-Knockout Dry Eye Model Mice.

PURPOSE: To investigate the effects of aging on the conjunctival P2Y2 receptors, tear functions, and corneal epithelial status from 10 to 50 weeks in the Sod1 in comparison with the wild-type mice. METHODS: Eight eyes of 4 Sod1 male mice and 8 eyes of 4 C57BL6 strain wild-type male mice were examined at 10 and 50 weeks in this study. Tear film breakup time (BUT) and corneal epithelial damage by fluorescein staining were evaluated. Phenol red-impregnated cotton threads were performed without topical anesthesia to measure aqueous tear quantity. Anterior segment photography was also performed at 10 and 50 weeks. Conjunctival specimens underwent immunohistochemistry stainings with anti P2Y2 antibodies. P2Y2 receptor mRNA expression in the bulbar conjunctiva was investigated by using quantitative real-time polymerase chain reaction. RESULTS: The mean tear quantity and BUT scores significantly declined, and the mean fluorescein staining scores significantly increased in both strains of mice from 10 to 50 weeks. % mRNA expression for P2Y2 receptors significantly increased in both mice strains from 10 to 50 weeks. CONCLUSION: The tear stability, quantity, and ocular surface health decline with aging as evidenced by the decrease in tear BUT, tear quantity, and the increase in ocular surface staining. Conjunctival P2Y2 receptor mRNA was upregulated from 10 to 50 weeks, which we believe is a compensation for the decline of tear functions with aging.

Efficacy of Plate Expression of Meibum on Tear Function and Ocular Surface Findings in Meibomian Gland Disease.

PURPOSE: To evaluate the clinical effectiveness of expression treatment on meibomian gland disease (MGD). METHODS: Seventeen right eyes of 17 patients with MGD were divided into 3 groups in this randomized prospective clinical study: no expression group: routine treatment with no expression (five patients, five eyes); digital expression group: routine treatment with digital expression (five patients, five eyes); and plate expression group: routine treatment with plate expression (seven patients, seven eyes). All groups received the same routine treatment for 1 month. Tear film break-up time (TBUT), vital staining scores, meibum expressibility, and the dry eye-related quality of life score (DEQS) questionnaire results were assessed before and 1 month after treatment. RESULTS: There was a statistically significant difference of posttreatment TBUT among groups as determined by one-way analysis of variance (P<0.05). A post hoc test revealed that TBUT was statistically significantly higher in plate expression group compared with digital expression group. The fluorescein staining score did not show a statistically significant difference among the groups. Meibum expressibility and the DEQS scores improved in all groups. CONCLUSION: Plate expression when used as an adjunct to routine medical management of MGD has been found to be a comparatively effective treatment in terms of improvement of tear film stability compared with no expression or digital expression.

Application of CASIA SS-1000 Optical Coherence Tomography Tear Meniscus Imaging in Testing the Efficacy of New Strip Meniscometry in Dry Eye Diagnosis.

PURPOSE: To investigate the applicability of CASIA SS-1000 anterior-segment optical coherence tomography (AS-OCT) imaging parameters in testing the efficacy of the new strip meniscometry (SM) namely "Strip Meniscometry Tube" (SMTube) in the diagnosis of dry eyes. METHODS: Forty-three eyes of 22 patients (4 men and 18 women) with definite dry eye disease (DED) and 49 eyes of 28 normal controls (6 men and 22 women) were studied. All subjects underwent symptom questionnaires, SMTube, the Schirmer-1 test, tear film break-up time measurement, vital staining examinations, as well as tear meniscus height (TMH) and TM area (TMA) measurements using an AS-OCT system. We evaluated the cutoff values for the diagnosis of DED, looked into the correlations between TMH, TMA, and SMTube scores and checked the sensitivity and specificity of these parameters in the diagnosis of DED. RESULTS: The mean values of TMH, TMA, and SMTube scores in the patient group were 0.138±0.102 mm, 0.013±0.015 mm and 1.4±2.3 mm, whereas those for the control group were 0.27±0.10 mm, 0.033±0.025 mm and 5.8±2.8 mm, respectively. The differences between both groups were significant (P<0.001). The cutoff values of TMH, TMA, and SMTube for DED were 0.197 mm, 0.020 mm and 3.8 mm, respectively. SMTube had significant correlations with TMH (r=0.82, P<0.001) and TMA (r=0.86, P<0.001). CONCLUSIONS: The SMTube was useful in DED diagnosis, the validity of which could be effectively evaluated by the CASIA SS-1000 AS-OCT TM parameters.

Caruncular and Pericaruncular Sebaceous Gland Hyperplasia: A Report of 2 Cases and Literature Review.

PURPOSE: To report the clinical and histopathological features of two patients with caruncular and pericaruncular sebaceous gland hyperplasia (SGH) with a literature review. METHODS: We performed a retrospective pathology database search of 1195 ophthalmic specimens receiving the clinical diagnosis of SGH for caruncular/pericaruncular lesions during 2004 to 2014 at Tokyo Dental College, Ichikawa General Hospital. Paraffin sections were stained with hematoxylin and eosin. A retrospective patient record and literature review was also performed. RESULTS: Database search disclosed 2 male patients with SGH of 1195 specimens (0.15%). Pathological specimens revealed neither any cellular/nuclear atypia nor any mitotic figures and invasive features. No recurrences were observed in these 2 cases 12 to 18 months after excision. CONCLUSIONS: Caruncle and pericaruncular SGH is an uncommon lesion which needs careful histopathological evaluation for differentiation especially from caruncular neoplasias.

Epidermal Fatty Acid-Binding Protein: A Novel Marker in the Diagnosis of Dry Eye Disease in Sjögren Syndrome.

PURPOSE: Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease of the lacrimal and salivary glands. This study compared the concentrations of epidermal fatty-acid binding protein (E-FABP) in the saliva, serum, and tears of SS patients with dry eye and dry mouth, with those of healthy adults to investigate the usefulness of E-FABP as a diagnostic marker for SS. DESIGN: Prospective, observational case series. PARTICIPANTS: The subjects were 11 new patients with untreated Sjogren syndrome and 12 healthy control individuals. METHODS: The diagnosis of SS was in accordance with the Ministry of Health, Labour and Welfare (Japan) Diagnostic Criteria (1999). Saliva, serum, and tear specimens were collected during internal medicine, dental, and ophthalmological examinations. The ophthalmological tests included the Dry Eye-related Quality of life Score (DEQS), tear break-up time (BUT), vital staining with fluorescein (FS) and lissamine green (LG), and the Schirmer test-1. The E-FABP concentration in the tears, saliva, and serum was measured by enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOME MEASURE: The E-FABP concentrations were compared between patients and controls. RESULTS: There were significant differences between the patient and healthy control groups in all ophthalmological test results. There were no significant differences between the groups in the E-FABP concentrations in the saliva (p = 0.1513) or the serum (p = 0.4799), but the E-FABP concentration in the tears significantly differed between groups. The E-FABP concentration in tears tended to be significantly lower in patients with SS (mean, 323.5 ± 325.6 pg/mL) than healthy control subjects (mean, 4076 pg/mL; p = 0.0136). The E-FABP concentration in tears significantly correlated with the results of dry eye parameters. CONCLUSION: The E-FABP concentration in tears appears to be related to ocular surface epithelial damage and tear stability and may be a promising novel biomarker in the diagnosis of SS.

The Application of Strip Meniscometry to the Evaluation of Tear Volume in Mice.

Purpose: Strip meniscometry quantitatively measures the volume of tears in the tear meniscus and has been reported to diagnose dry eyes in clinical settings conveniently, easily, and rapidly. In this study, we used a modified strip meniscometry to assess the applicability of measuring the tear volume in mice in experimental settings. Methods: Dry eye was induced in 11 9-week-old C57BL/6J wild-type male mice (11 right eyes) by exposing them to an air fan inside a small compartment for 5 hours for 2 consecutive days. Tear function tests, including the SMTube for mice (SMTM) for tear volume evaluation, break-up time, fluorescein staining score, and lissamine green staining score, were performed. The correlation between SMTM and other tear function parameters was assessed. Results: The mean SMTM value was 3.89 ± 0.603 mm before and 3.09 ± 0.625 mm after dry environment exposure (P = 0.0078*). The Spearman's correlation by rank test showed a strong positive correlation between SMTM and tear film break-up time and a strong linear negative correlation with fluorescein and lissamine green values. Conclusions: The SMTM was capable of rapidly measuring the minimum tear volume in mice and correlated well with tear function parameters and appears to be a promising new modality in the evaluation of dry eyes in mice.

Corneal cross-linking for keratoconus caused by compulsive eye rubbing in patients with Tourette syndrome: Three case reports.

RATIONALE: Eye rubbing is an important risk factor for keratoconus progression. Tourette syndrome (TS) is a neurological disorder, and approximately 50% of individuals with TS exhibit obsessive-compulsive behaviors including eye rubbing. We report the effects of corneal cross-linking (CXL) on the progression of keratoconus combined with psychiatric treatment for 3 patients with TS. PATIENTS' CONCERNS: Three cases, 24-year-old male, 14-year-old male, and 17-year-old male, were all referred to our institute, due to decreased visual acuity. DIAGNOSIS: All 3 patients were diagnosed with progressive keratoconus. They were found to rub their eyes, and were also diagnosed with TS by psychiatrists. INTERVENTION: Upon diagnosis of keratoconus, we performed CXL on 1 eye of each patient. OUTCOMES: After CXL, there was no further progression. Psychiatric medication was also required. LESSONS: For patients with keratoconus caused by eye rubbing due to TS, CXL seems to be effective when done in association with psychiatric treatment.

A prospective, randomized clinical study comparing accelerated corneal collagen crosslinking with 5% NaCl hypertonic saline for bullous keratopathy in Asian eyes.

BACKGROUND: We compared the clinical outcomes of accelerated corneal collagen crosslinking (CXL) and 5% NaCl hypertonic saline (HS) for the treatment of symptomatic bullous keratopathy (BK). METHODS: A randomized controlled trial was held at Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan. Twenty-three eyes of 23 consecutive patients with symptomatic BK were enrolled. The etiology of BK included pseudophakic BK, previous keratoplasty, previous endotheliitis, previous glaucoma surgery, trauma, herpes infection, as well as unknown causes. Eleven eyes received epi-off accelerated CXL (with epithelial abrasion and 18 mW/cm ultraviolet A irradiation for 5 minutes) and 12 eyes received HS instillation. In addition to the usual ophthalmic examination, the best-corrected visual acuity (BCVA) and central corneal thickness (CCT) were determined. The CCT was measured using anterior segment optical coherence tomography before and up to 6 months after treatments. Subjective symptoms of pain, blurred vision, photophobia, and irritation were also recorded. RESULTS: The follow-up was completed for all patients in the CXL group. However, 6 patients in the HS group requested CXL treatments after 3 months. The BCVA was not significantly changed during the study periods in both groups. The CCT was significantly thinner in the CXL group compared to the HS group at 1 and 6 months (P = .015 and 0.144, respectively). Among the subjective symptoms recorded, irritation was significantly lower in the CXL group at 1 month (P = .013). CONCLUSIONS: Accelerated CXL may produce transient improvement in pain and corneal edema in patients with BK.

The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet-Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from in vivo confocal microscopy images before and 3 months after treatment were performed. Results: The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (P < 0.01). The mean squamous metaplasia grade also showed a significant improvement (1.2 ± 0.1 → 0.3 ± 0.1) 3 months after treatment (P = 0.004). There were similar significant improvements in the mean corneal epithelial cell density (660.1 ± 62.6 → 1015.5 ± 43.5 cells/mm2) (P = 0.002) and nucleocytoplasmic ratios (0.1 ± 0.0 → 0.2 ± 0.0) (P = 0.0042) after treatment. Conclusions: Topical use of 2% rebamipide for 3 months was associated with improvements in ocular surface differentiation due to changes of mucosal functions at the cellular level. These alterations may explain objective and subjective improvements in dry eye disease.

Corneal crosslinking for keratoconus in Japanese populations: one year outcomes and a comparison between conventional and accelerated procedures.

PURPOSE: We retrospectively investigated the efficacy of corneal crosslinking (CXL) on progressive keratoconus in a Japanese population and compared the outcomes of conventional and accelerated CXL. STUDY DESIGN: A retrospective cohort study METHODS: A total of 108 consecutive eyes in 95 patients (75 men; 21.9 ± 6.2 years) with progressive keratoconus were enrolled. The epithelium was ablated in all eyes. After presoaking the corneal stroma in riboflavin, UV-A was irradiated at 3.0 mW/cm2 (conventional CXL) for 30 min on 23 eyes and 18.0 mW/cm2 for 5 min (accelerated CXL) on 85 eyes. Best spectacle-corrected visual acuity (BSCVA), manifest refraction, keratometric value, corneal thickness, corneal endothelial cell density (ECD), intraocular pressure, and complications were evaluated at 1, 3, 6, and 12 months after the procedure. RESULTS: BSCVA, manifest refraction, ECD, and corneal thickness did not change significantly after both procedures. The keratometric value was significantly decreased from the preoperative value at 12 months (p < 0.001). Progression to more than 1.0 D after CXL was observed in 10 eyes (9.3%). The ΔKmax was negatively associated with preoperative Kmax (p < 0.001) and positively associated with preoperative thinnest corneal thickness (p < 0.001). Both treatment modules showed no significant difference in all parameters. CONCLUSION: CXL was as effective in treating keratoconus in Japanese patients as in individuals of other ethnicities. Overall, CXL could be performed using either the conventional or accelerated approach to halt the progression of keratoconus in Japanese populations.

Flattening effect of corneal cross-linking depends on the preoperative severity of keratoconus.

A retrospective observational study was conducted to validate the effect of corneal cross-linking (CXL) on eyes with progressing keratoconus, depending on severity.In total, 45 eyes of 33 patients (age: 23.9 ±â€Š6.8 years, range: 14-42 years) with progressive keratoconus who underwent CXL were enrolled. Examinations were performed at pre-, 1, 3, 6, and 12 months after surgery. In addition to a slit lamp microscopy, measurement of visual acuity, the steepest keratometric value (Kmax), the thinnest corneal thickness (TCT), and the corneal endothelial cell density (ECD) were assessed. Change in Kmax (ΔKmax) was calculated by subtracting the preoperative Kmax from the 12-month postoperative Kmax.CDVA, TCT, and ECD did not change significantly throughout the follow-up period. Kmax was 56.4 ±â€Š7.2 D preoperatively and 54.3 ±â€Š5.6 D at 12 months after CXL (P = .174). The average value of ΔKmax was -2.23 ±â€Š4.31 D at 12 months after CXL. ΔKmax was negatively correlated with preoperative Kmax (ρ = -0.5517, P = .0001), and positively correlated with preoperative TCT (ρ = 0.4791, P = .0012). However, no correlation was observed between Kmax and patient age or the decrease ratio of ECD.The more flattening was obtained after CXL in cases with the more advanced keratoconus. No complication, including corneal endothelial damage, was observed even in advanced cases.

How Much Progress Has Been Made in Corneal Transplantation?

To assess the benefits of component lamellar corneal surgery, we investigated the surgical outcomes of deep anterior lamellar keratoplasty (DALK) for keratoconus and Descemet stripping automated endothelial keratoplasty (DSAEK) for laser iridotomy-induced bullous keratopathy (LI-BK). The results were compared with the surgical outcomes of penetrating keratoplasty (PKP). Seventy-nine eyes with keratoconus treated with DALK and 81 eyes with LI-BK treated with DSAEK were studied, and the graft clarity rate, best spectacle-corrected visual acuity, endothelial cell density (ECD), and surgical complications were compared with 273 eyes with keratoconus and 98 eyes with LI-BK all treated with PKP. Keratoconus eyes showed excellent visual outcomes with DALK and PKP, but graft survival was higher for PKP (100%, 98.9%, and 96.3% vs. 98.6%, 90.6%, and 86.1%, at 1, 3, and 5 years after surgery, respectively; P < 0.0001). There were no significant differences in the ECD up to 1 year after surgery. Greater ECD decline was observed for PKP at 3 and 5 years after surgery. Descemet membrane microperforation was observed in 49 eyes treated with DALK. Postoperative complications in eyes treated with PKP were increased incidence of immunological rejection and secondary glaucoma compared with eyes treated with DALK. LI-BK graft survival rates were excellent in both groups (DSAEK: 89.6% and 86.1%; PKP: 100% and 98.6%, 1- and 2-year rates, respectively; P = 0.17). Best spectacle-corrected visual acuity was better in the DSAEK group, and ECD showed a higher rate of decrease with DSAEK than with PKP. DALK and DSAEK considerably improved surgical outcomes in eyes with keratoconus and those with LI-BK, respectively. However, several key areas require further work, including development of safe surgical methods in DALK and prevention of early postoperative ECD loss in DSAEK.