Search

Purpose To investigate the clinical courses of patients with corneal endothelial dysfunction due to Gomphocarpus physocarpus milky latex-induced injury. Patients and methods In this retrospective case series, we included consecutive patients who visited Miyata Eye Hospital or Kagoshima Miyata Eye Clinic between October 2010 and August 2017 and had corneal edema caused by G. physocarpus milky latex-induced injury. Patient information and data on central corneal thickness (CCT), corneal endothelial cell density (ECD), best-corrected visual acuity (BCVA), and treatment were retrospectively reviewed. Results Five eyes of four patients were included. The mean age was 79.0 ± 7.1 years. All patients complaining of symptoms visited the hospital 1 or 2 days after the injury. All patients had corneal edema; two of the five eyes showed hyperemia, whereas none showed corneal epithelial defect or blepharitis. The mean CCT was 699.8 ± 95.9 μm at the first visit and decreased to 563.2 ± 74.0 μm 1 week after the injury with treatment with topical steroids and antibiotics. The mean ECD and BCVA were 2695.8 ± 191.3 cells/mm2 and 0.22 ± 0.19 at the first visit and 2826.0 ± 132.9 cells/mm2 and 0.10 ± 0.09 one week after the injury, respectively. Conclusion G. physocarpus caused transient dysfunction of the corneal endothelium and thereby, corneal edema. Accurate diagnosis with history taking is important to ascertain the types of plants the patient has touched and to exclude other possible diagnoses.

To examine the effects of topical steroid instillation on central corneal thickness in eyes with bullous keratopathy (BK).Retrospective case series METHODS: Consecutive patients with BK who did not wish to receive corneal transplantation and were treated with 0.1% betamethasone eyedrops were included. Patients with BK treated with 5% sodium chloride (hypertonic saline) eyedrops served as controls. Central corneal thickness (CCT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), BK etiology, and clinical courses from medical records were retrospectively reviewed. We compared the two groups for differences in CCT, BCVA and IOP before treatment and 2 weeks, 1 month, and 3 months after treatment.Eighteen eyes of 18 patients who were treated with betamethasone and 18 eyes of 18 patients who were treated with hypertonic saline were included. There was no significant difference in CCT between the two groups before treatment. The reduction of CCT in the betamethasone group was significantly larger than in the hypertonic saline group at 2 weeks (p = 0.002), 1 month (p = 0.02), and 3 months (p = 0.001) after treatment. Complications such as infectious keratitis and IOP rise did not occur during the observation period.Topical steroid instillation reduced central corneal thickness in eyes with BK.

To compare the outcomes of ocular injuries of hornets and paper wasps’ stings. Retrospective case series. Patients diagnosed with ocular injuries sustained by bee stings at Miyata Eye Hospital (Miyazaki, Japan) between August 2000 and July 2016 were enrolled. Retrospective data regarding type of bee, visual acuity, and treatment were collected from medical records. Outcomes of the hornet and wasp groups were compared. Five eyes of 5 patients (3 men, 2 women; mean age 44.6±21.2 years [range 9–62 years]) were enrolled. The mean follow-up period was 50.6 ± 57.6 months (range 4 days to 121 months). The causative bee was hornet in 3 cases and wasp in 2. The anterior chamber was irrigated in 2 patients, both from the hornet group. The best-corrected visual acuity at the final visit was no light perception, light perception, and (0.02) in the hornet group, (1.5) and (1.2) in the wasp group. The hornet group exhibited significantly worse prognosis than the wasp group. Identifying the type of bee is important in establishing prognosis.

PURPOSE To estimate the prevalence of meibomian gland dysfunction (MGD) in the Japanese population using new diagnostic criteria, including lid margin abnormalities and signs of occlusion of the meibomian gland orifices as essential signs. METHODS The participants were consecutive patients scheduled for cataract surgery at Inouye Eye Hospital. All participants were aged 50 years or older. The participants completed a symptoms questionnaire and underwent a comprehensive slit-lamp examination. MGD was diagnosed when both of the following 2 factors were positive: lid margin abnormalities and signs of occlusion of the meibomian gland orifices. RESULTS The study included 510 participants (205 men, 305 women) of mean age 71.1 ± 8.5 (range 50-93) years. The prevalence rates of symptomatic MGD and total (symptomatic + asymptomatic) MGD were 18.0% and 47.5%, respectively. The prevalence of total MGD increased significantly with increasing patient age (P < 0.0001). The ratio of men to women and the prevalence of systemic disease did not differ between participants who were positive or negative for MGD. For the total MGD group, slit-lamp findings (lid margin abnormality, shift of the mucocutaneous junction, telangiectasia, and plugging) were more frequent; tear film breakup time was shorter; and the meiboscore was higher than in participants without MGD. CONCLUSIONS The prevalence of MGD is high in the Japanese population aged 50 years or older.

PURPOSE To propose a grading system of pterygium severity based on corneal higher-order irregularity (HOI) and to evaluate postoperative changes in corneal irregularity of the graded pterygia. METHODS In 268 eyes of 226 patients undergoing excision surgery of primary nasal pterygium, Placido corneal topography images were taken before and until 6 months after surgery. The best-corrected visual acuity (BCVA) and pterygium size with respect to the corneal diameter were also measured. HOI components within 1.0-, 3.0-, and 5.0-mm diameters were obtained using Fourier harmonic analysis of corneal topography data. With threshold levels when the HOIs for 3 diameters steeply increased, 4 levels of grading from 0 (mild) to 3 (severe) were determined. Associations of the grades with the preoperative surface regularity index (SRI), irregular components (IRRs) obtained from the 3.0-mm diameter Fourier analysis, and BCVA were examined. Time-course changes in the indexes after surgery were evaluated for each grade. RESULTS There were 62, 65, 41, and 100 eyes in grades 0 to 3, respectively. Preoperatively, the SRI in grade 3 was significantly higher than in the other grades (P < 0.001), and the IRR and BCVA varied with the grade (P < 0.001). Between 1 and 6 months postoperatively, grade 3 pterygia showed significant changes in the SRI and IRR (P = 0.013 and 0.017, respectively), whereas there was no change after 3 months postoperatively in the SRI, IRR, and BCVA for all other grades. CONCLUSIONS The proposed grading effectively classified the severity of pterygia and evaluated postoperative restoration of corneal irregularity. Using corneal topographic data allowed for objective evaluation of pterygium severity.

Purpose To compare the long-term outcomes of visual function and endothelial cell survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). Methods The cohort included 108 eyes from 97 patients who underwent primary PK and 85 eyes from 78 patients who underwent primary DSAEK at Miyata Eye Hospital in Japan. Uncorrected visual acuity, best spectacle-corrected visual acuity (BSCVA), endothelial cell density, and four components from Fourier harmonic analysis of topography data (spherical component, regular astigmatism component, asymmetry component, and higher-order irregularity component) were retrospectively compared between PK and DSAEK at each time point for 5 years using mixed-effects models. Subgroup analyses were performed to compare the effect of PK and DSAEK on visual acuity. Results Average BSCVA was significantly better in the DSAEK group compared with that in the PK group both preoperatively and postoperatively. Subgroup analyses revealed that average changes in BSCVA from preoperative baseline in eyes with preoperative logarithm of the minimum angle of resolution BSCVA between 0.39 and 1.0 and between 1.3 and 2.0 were not significantly different between the PK and DSAEK groups at all postoperative time points. All components from Fourier harmonic analysis were significantly higher after PK than DSAEK at almost all postoperative time points. There were no significant differences in endothelial cell density between PK and DSAEK after 3 years. Conclusions PK and DSAEK provide similar recovery of BSCVA and endothelial cell survival at 5 years after surgery.

To investigate the effect of topical prostaglandin (PG) eyedrops on the biomechanics and shape of the cornea. Consecutive patients with primary open-angle glaucoma who had been treated with the same anti-glaucoma PG (114 eyes, 57 patients) or β-blocker (36 eyes, 18 patients) eyedrops in 1 eye alone for more than 3 months at Inouye Eye Hospital or Miyata Eye Hospital. The biomechanical properties of the cornea were measured using a Corvis ST device (Oculus, Wetzlar, Germany). Corneal tomography was measured with a Casia 1 or 2 (Tomey Corp., Nagoya, Japan). The biomechanical parameters and tomographic features of the cornea were compared between PG-treated eyes, β-blocker-treated eyes, and contralateral eyes using a mixed-effect model adjusted for intraocular pressure and corneal thickness and a linear model adjusted for age, sex, intraocular pressure, and corneal thickness. The PG-treated eyes had a significantly smaller applanation 1 time, the highest concavity radius, and a larger deformation amplitude than the contralateral eyes. Also, the PG-treated eyes had a significantly smaller applanation 1 time and applanation 2 velocity but a larger peak distance than the β-blocker-treated eyes. There were no significant differences in any of the Casia parameters between the PG-treated eyes and the contralateral eyes. The results of this study suggest that topical PG makes biochemical changes to the cornea but does not alter its shape.

MicroRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. We reported that levels of microRNA (miR)-29 family are decreased in corneas of patients with Fuchs endothelial corneal dystrophy (FECD). The miR-29 family regulates the production of extracellular matrix (ECM) proteins. Accumulation of ECM proteins in Descemet membrane is an important pathologic change in FECD. In this study, we transfected miR-29b into human corneal endothelial cells and tissues and evaluated ECM protein expression levels.An immortalized Fuchs human corneal endothelial cell line (iFECD) was established by infection of corneal endothelial cells from patients with FECD with hTERT lentivirus. MiR-29b was transfected into iFECD, and the expression levels of ECMs collagen type 1 alpha 1 (COL1A1), collagen type 4 alpha 1 (COL4A1), and laminin gamma 1 (LAMC1) were evaluated with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Expression level of LAMC1 protein in miR-29b-transfected donor corneal endothelium was also evaluated by Western blot.Compared with control, miR-29b expression level after transfection of iFECD was increased to 335.6% (±91.0%), and ECM expression levels were significantly decreased. Compared with control, qRT-PCR demonstrated reduction of ECM to the following levels: COL1A1: 1.9% (±0.4%); COL4A1: 7.1% (±1.7%); and LAMC1: 21.5% (±2.7%). Western blot showed reduced protein expression: COL1A1: 4.8% (±3.2%); COL4A1: 42.5% (±25.0%); and LAMC1: 44.8% (±3.1%). In miR-29b-transfected corneal tissue, LAMC1 protein expression level was decreased to 14.4% (±20.5%).Overexpression of miR-29b decreased ECM protein production in human corneal endothelial cells. Thus, miR-29 replacement therapy might be a new treatment strategy for FECD aimed at reducing pathologic production of ECM proteins in Descemet membrane.

To conduct a long-term follow-up study evaluating the efficacy and safety of transplantation of preserved limbal allograft and amniotic membrane for recurrent pterygium. This was a retrospective, non-comparative, interventional case series conducted at a private eye hospital. Eighty-four eyes of 80 patients with recurrent pterygium were included in the study. The mean number of previous surgeries for pterygium was 1.36 ± 0.98 (range, 1–8). All subjects received transplantation of preserved limbal allograft and amniotic membrane. The mean follow-up period was 73.0 ± 38.1 months (range, 12–154 months). Pterygium recurred in 10 eyes (11.9 %). The mean period to recurrence was 16.3 ± 11.3 months (range, 5–33 months). Symblepharon was cured in 21 eyes, persisted in 2 eyes, and newly occurred in 3 eyes. Diplopia was cured in eight eyes, persisted in five eyes, and newly occurred in one eye. As for complications, intraocular pressure elevations over 21 mmHg were recognized in ten eyes of nine cases, in which the intraocular pressure was controlled by reduction of topical steroid in four eyes and by addition of topical prostaglandin derivatives in six eyes. Twenty-four eyes (28.6 %) gained two lines or more of Landolt best spectacle-corrected visual acuity (BSCVA), 56 eyes (66.7 %) stayed within one line from preoperation, and four eyes (4.8 %) lost two lines or more. There were no major complications and no graft rejection. Transplantation of preserved limbal allograft and amniotic membrane is a safe and effective procedure for recurrent pterygium.

Purpose To investigate the efficacy of hyperopic photorefractive keratectomy (HPRK) that was performed simultaneously with phototherapeutic keratectomy (PTK) with regard to decreasing hyperopic shift. Methods A total of 63 eyes of 47 consecutive patients with granular corneal dystrophy (GCD) or band-shaped keratopathy (BSK) underwent PTK or PTK + HPRK. PTK alone was performed in 40 eyes (20 GCD and 20 BSK), and PTK + HPRK was performed in 23 eyes (15 GCD and 8 BSK). All patients underwent examinations including uncorrected distance visual acuity, corrected distance visual acuity, refractometry, and keratometry before and at 1, 3, and 6 months after PTK. Medical charts were reviewed retrospectively. Results Superficial corneal opacity was successfully removed from all eyes, and uneventful reepithelialization was completed within 7 days after PTK or PTK + HPRK. The average uncorrected distance visual acuity was significantly better in the PTK + HPRK group than in the PTK group preoperatively and at 1, 3, and 6 months postoperatively. The corrected distance visual acuities were similar in both groups preoperatively and postoperatively. The hyperopic change in the PTK group was approximately 1.5 diopters, and that in the PTK + HPRK group was almost zero. There were significant differences in the average changes of the spherical equivalent from preoperation between the PTK and PTK + HPRK groups at all postoperative time points. Conclusions Simultaneous performance of PTK and HPRK can effectively reduce hyperopic shift after PTK and is as safe as PTK alone. It is recommended that HPRK be added to PTK to treat eyes in which hyperopic shift is undesirable.

Granular corneal dystrophy (GCD) is an autosomal dominant hereditary disease in which multiple discrete and irregularly shaped granular opacities are deposited in the corneal stroma. GCD is caused by a point mutation in the transforming growth factor-β-induced (TGFBI) gene, located on chromosome 5q31. Here, we report the first successful application of CRISPR-Cas9-mediated genome editing for the correction of a TGFBI mutation in GCD patient-derived primary corneal keratocytes via homology-directed repair (HDR). To correct genetic defects in GCD patient cells, we designed a disease-specific guide RNA (gRNA) targeting the R124H mutation of TGFBI, which causes GCD type 2 (GCD2). An R124H mutation in primary human corneal keratocytes derived from a GCD2 patient was corrected by delivering a CRISPR plasmid expressing Cas9/gRNA and a single-stranded oligodeoxynucleotide HDR donor template in vitro. The gene correction efficiency was 20.6% in heterozygous cells and 41.3% in homozygous cells. No off-target effects were detected. These results reveal a new therapeutic strategy for GCD2; this method may also be applicable to other heredity corneal diseases.

Purpose To evaluate the effects of commercially available eyelid warming devices on ocular temperatures, tear film function, and meibomian glands in normal subjects and patients with meibomian gland dysfunction (MGD). Methods Ten healthy volunteers were enrolled to evaluate the effects of a single warming and of repeated warming for 2 weeks. Ten MGD patients were enrolled for evaluation of repeated warming over 1 month. Two non-wet (Azuki no Chikara, Eye Hot R) and three wet (hot towel, Hot Eye Mask, Memoto Este) devices were compared in a masked manner. Visual analog scale (VAS) score for ocular symptoms, tear film breakup time (TFBUT), meibum grade, temperatures (eyelid skin, tarsal conjunctiva, central cornea), Schirmer test value, and meibomian gland area were measured before and after warming application. Results The single application of the five warming devices improved the VAS score, TFBUT, and ocular temperatures. In the repeated warming application, Azuki no Chikara as a representative non-wet warming device induced a stable and significant improvement in TFBUT and increased the tarsal conjunctival temperature and meibomian gland area in both normal subjects and MGD patients. It also improved meibum grade in MGD patients. Conclusion Our results suggest that repeated eyelid warming with a non-wet device improves tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.

Purpose The purpose of the present study was to investigate the role of glutathione peroxidase 4 (GPx4) in conjunctival epithelial cells. Methods An immortalized human conjunctival epithelial cell line was used. Cells were transfected with catalase, GPx1, GPx4, SOD1, SOD2, or control siRNA. Knockdown was confirmed by RT-PCR and immunoblotting. The cytotoxicity induced by knockdown of these antioxidant enzymes was examined by assay of LDH activity. Furthermore, evaluations of lipid peroxidation, cellular levels of reactive oxygen species, cell proliferation, and apoptosis were conducted in cells treated with GPx4 or control siRNA. In oxidative stress study, cells treated with GPx4 or control siRNA were applied with hydrogen peroxide or ferric sulfide, and their cytotoxicity was evaluated by assay of LDH activity. Results Small interfering RNA of catalase, GPx1, GPx4, SOD1, and SOD2 siRNA remarkably inhibited the mRNA and protein expression of each gene. Knockdown of GPx4 and SOD1 but not catalase, GPx1, and SOD2 significantly induced cytotoxicity. Glutathione peroxidase 4 knockdown increased lipid oxidation and reactive oxygen species. The proliferation of GPx4 siRNA-treated cells was reduced compared with control siRNA-treated cells. Moreover, cell death in GPx4 siRNA-treated cells was characterized by positive staining for annexin V. In an oxidation stress study, GPx4 siRNA knockdown enhanced the cytotoxicity induced by hydrogen peroxide or ferric sulfide. Conclusion These results suggest that GPx4 is essential for maintaining oxidative homeostasis and keeping defense against oxidative stress in conjunctival epithelial cells.

Purpose: Prolonged use of topical antifungal agents may compromise corneal epithelial integrity. Here, we used an in vitro model of human stratified corneal epithelium to compare the ocular toxicity profiles of 4 different antifungal eye drops. Methods: Human corneal epithelial cell sheets were cultured in a serum-free medium containing 0.1% micafungin, 1% voriconazole, 5% pimaricin, 0.1% amphotericin B, or controls (saline or 5% glucose). Cell viability and barrier function were measured by WST-1 assay and carboxyfluorescein permeability assay, respectively. Cell migration was measured on a wound healing assay. Results: WST-1 assay and carboxyfluorescein permeability assay revealed that amphotericin B was the most toxic drug, followed by pimaricin, micafungin, and voriconazole. Cell migration on a wound healing assay was decreased in the following order, amphotericin B, pimaricin, micafungin, and voriconazole. Conclusions: Topical micafungin and voriconazole appeared to be the least toxic to the corneal epithelium. Drug prescription should consider not only fungal species and susceptibility but also ocular toxicity and stage of treatment.

To evaluate the effect of transplanting bioengineered corneal endothelial grafts in a rabbit model of corneal endothelial failure.Human corneal endothelial cells (HCECs) were seeded on a vitrigel carrier. After Descemet's membrane was removed from the eyes of rabbits, transplantation was done with a vitrigel/HCEC graft or vitrigel alone without cells, or the eyes were left untreated. Slit lamp examinations and measurement of the central corneal thickness (CCT) were performed for 14 days postoperatively.HCECs cultured on vitrigel were strongly positive for ZO-1 and Na+/K+ ATPase. On day 14, the cornea showed mild edema and the pupil margins were visible through the grafts in the vitrigel/HCEC graft group. HCECs completely covered the grafts on day 14. In contrast, there was severe corneal edema and the pupil margins were undetectable on day 14 after transplantation of the vitrigel carrier alone or no transplantation. Proliferation of host cells was not observed in these groups. On day 14, the mean CCT was significantly thinner in the vitrigel/HCEC graft group than in the other two groups (p = 0.0008).Transplantation of a vitrigel/HCEC graft was effective for reducing the corneal thickness and restoring corneal transparency, suggesting the usefulness of vitrigel as a carrier for corneal endothelial cells.

Shiro Amano, Kenji Inoue Inouye Eye Hospital, Chiyoda-ku, Tokyo, Japan Purpose: To prospectively evaluate the effect of topical diquafosol sodium on eyes with dry eye disease (DED) and meibomian gland dysfunction (MGD).Patients and methods: The subjects were consecutive patients diagnosed with both DED and MGD at Inouye Eye Hospital between March and September of 2016. The subjects were administered topical 3% diquafosol sodium ophthalmic solution six times a day for 3 months. At each study visit, subjects underwent slit-lamp examination and completed MGD symptoms and dry eye-related quality of life score (DEQS) questionnaires. Meibum quality (meibum score) and meibomian gland loss (meiboscore) were evaluated. Tear lipid layer thickness was measured in both eyes with an ocular surface interferometer immediately after clinic arrival and 20 minutes after instillation of one drop of topical diquafosol.Results: Thirteen patients (3 men, 10 women) with a mean age of 69.5±8.3 years completed the 3-month study. The number of telangiectasia and plugged meibomian gland orifices significantly decreased from baseline after 1 month of diquafosol use. The meibum score and the meiboscore significantly decreased from baseline at 3 months. Also, the lipid layer thickness was greater after diquafosol administration than before administration at baseline and 1, 2, and 3 months by 12.2, 11.5, 9.5, and 17.0 nm, respectively, but this difference was only significant at 3 months (p=0.039). The DEQS ocular symptom (p=0.065) and MGD questionnaire (p=0.081) scores tended to be lower than baseline at 3 months.Conclusion: Diquafosol sodium ophthalmic solution improves DED- and MGD-related signs in eyes with MGD. Keywords: diquafosol, meibomian gland dysfunction, dry eye&nbsp

To determine steep increase of corneal irregularity induced by advancement of pterygium. A total of 456 eyes from 456 consecutive patients with primary pterygia were examined for corneal topography and advancement of pterygium with respect to the corneal diameter. Corneal irregularity induced by the pterygium advancement was evaluated by Fourier harmonic analyses of the topographic data that were modified for a series of analysis diameters from 1 mm to 6 mm. Incidences of steep increases in the asymmetry or higher-order irregularity components (inflection points) were determined by using segmented regression analysis for each analysis diameter. The pterygium advancement ranged from 2% to 57%, with a mean of 22.0%. Both components showed steep increases from the inflection points. The inflection points in the higher-order irregularity component altered with the analysis diameter (14.0%–30.6%), while there was no alternation in the asymmetry components (35.5%–36.8%). For the former component, the values at the inflection points were obtained in a range of 0.16 to 0.25 D. The Fourier harmonic analyses for a series of analysis diameters revealed that the higher-order irregularity component increased with the pterygium advancement. The analysis results confirmed the precedence of corneal irregularity due to pterygium advancement.

Purpose To estimate the prevalence of meibomian gland dysfunction (MGD) in the Japanese population. Methods We undertook a clinical study on the prevalence of MGD in Japan using the same diagnostic criteria as a previous population-based study conducted in Spanish Caucasians. The participants were consecutive patients scheduled for cataract surgery at Inouye Eye Hospital. All participants were aged 50 years or older. Patients completed a symptoms questionnaire and underwent a comprehensive slit-lamp examination. Meibomian gland dysfunction was diagnosed when one or more of the following was present in at least in one eye: absent, viscous, or waxy white secretion upon digital expression; presence of two or more lid margin telangiectases; and/or plugging of two or more gland orifices. Results The study included 510 patients (205 men and 305 women). Mean participant age was 71.1 ± 8.5 years (range, 50-93 years). The prevalences of symptomatic and total MGD (symptomatic MGD + asymptomatic MGD) were 11.2% and 74.5%, respectively. The prevalence of total MGD increased significantly as participant age increased (P < 0.0001). The ratio of males to females and the prevalence of any systemic disease did not differ between patients who were positive or negative for MGD. For the total MGD group, all slit-lamp findings were more frequent, fluorescein score was higher, tear film breakup time was shorter, and meibo-score was larger, compared to non-MGD patients. Conclusions Based on the present diagnostic criteria, prevalence of MGD is higher in Tokyo, compared to the Spanish population.

To evaluate the effect of diquafosol tetrasodium (DQS) for the treatment of persistent dry eye after laser in situ keratomileusis (LASIK).Miyata Eye Hospital, Miyazaki, Japan.Noncomparative case series.This prospective study included 30 eyes of 15 patients in whom dry eye had persisted for over 12 months after LASIK, and the symptoms had not improved with artificial tears and sodium hyaluronate treatment. In addition, treatment with DQS 3% eye drops, 6 times a day, was performed for 12 weeks. Best-corrected visual acuity, tear secretion with the Schirmer test, tear break-up time, and fluorescein and lissamine green staining scores on the cornea and conjunctiva were examined before and at 1, 4, and 12 weeks after the addition. A subjective questionnaire of 14 symptoms was also assessed before and 12 weeks after treatment.The fluorescein and lissamine green staining scores significantly improved over 12 weeks; however, the best-corrected visual acuity and tear secretion did not change. The symptoms of fatigue, dryness, grittiness, discomfort, difficulty in reading, and discomfort within the area of dryness improved after the additional DQS treatment.The DQS treatment improved the subjective and objective symptoms of persistent dry eye after LASIK. Increased mucin production because of the addition of DQS probably improved the tear film stability and reduced the symptoms of dry eye in patients who had persistent dry eye after LASIK.

We report a rapid liquid chromatography/quadrupole Orbitrap Fourier transform mass spectrometry (LC–FTMS) method for identifying free fatty acids (FAs) and (O-acyl)-ω-hydroxyFAs (OAHFAs) in human meibum without derivatization. Meibum is a lipid-rich secretion and an important component of the tear film lipid layer. FAs are commonly detected by gas chromatography (GC) or GC/MS after methyl ester derivatization. We developed high-throughput lipid profiling using LC–FTMS and lipid identification software, Lipid Search, without derivatization and applied the method to human meibum. Chromatographic separation was performed on a C18 column. We selected negative electrospray ionization [M−H]−, and applied high-resolution full scan mode to FA analysis and data-dependent MS2 mode to OAHFA analysis. High-resolution Orbitrap MS proved to be an excellent tool for the rapid analysis of lipids from meibum, and 100 FA and 61 OAHFA molecular species were detected. The analysis times were 12 and 16.5 min, respectively. Very long chain FAs (up to C37) and OAHFAs (up to C56) were also detected. The results clearly showed that retention time correlates with the number of double bonds and carbon chains. This LC/MS method can be applied to the identification of FAs and OAHFAs in human meibum.

PURPOSE The aim of this study was to introduce a newly developed graft inserter for Descemet stripping automated endothelial keratoplasty, which can be readily used with 1 hand, and to examine endothelial cell loss (ECL) after graft insertion using this new inserter in an ex vivo rabbit model. METHODS Rabbit corneal grafts (∼150 μm) were prepared by using a femtosecond laser. The grafts were inserted into an artificial anterior chamber by the pull-through technique using a Busin glide or the push-out technique using our new inserter. ECL was evaluated by means of trypan blue and alizarin red S staining. Grafts that were not injected served as a control group. RESULTS The mean percentages of ECL area in the control, Busin glide, and new inserter groups were 18.7 ± 1.79%, 25.4 ± 2.32%, and 24.7 ± 1.56%, respectively. The mean percentages of the ECL area in both the Busin glide group and new inserter groups were significantly greater than that in the control group (P = 0.001). There was no statistically significant difference between the Busin glide group and the new inserter group. CONCLUSIONS Our new inserter may provide a favorable option for donor tissue insertion in Descemet stripping automated endothelial keratoplasty procedures.

To evaluate central corneal thickness (CCT) and corneal volume (CV) in healthy eyes using swept source anterior segment optical coherence tomography (SS-AS-OCT) and other devices.Thirty-three healthy right eyes of 33 subjects were investigated. CCT was measured with SS-AS-OCT, rotating Scheimpflug camera, ultrasonic pachymetry and specular microscopy. CV was determined within a diameter of 10 mm at the center using SS-AS-OCT and Scheimpflug camera.Mean CCT was 523.5 ± 25.2 μm by SS-AS-OCT, 523.9 ± 26.1 μm by Scheimpflug camera, 532.1 ± 26.6 μm by ultrasonic pachymetry, and 525.5 ± 33.5 μm by specular microscopy. The CCTs measured with SS-AS-OCT, Scheimpflug camera and specular microscopy were significantly thinner than those measured with ultrasonic pachymeter (p0.001). The mean CV within a diameter of 10 mm at the center was 57.2 ± 3.0 mm(3) by SS-AS-OCT and 59.4 ± 2.9 mm(3) by Scheimpflug camera. Scheimpflug measurements of CV were statistically larger than SS-AS-OCT measurements (p = 0.0008). Statistically significant correlation was found between the CCT and CV measurements of each imaging devices (p0.0001, r = 0.527, and p0.0001, r = 0.749, respectively).SS-AS-OCT enables the measurements of CCT and CV, demonstrating agreement with other devices. CV in addition to CCT measurement may serve as a practical parameter of the corneal endothelial pump function.

To evaluate the long-term outcomes of penetrating keratoplasty (PKP) according to the corneal disease diagnosis and the number of PKP procedures performed. Five-hundred-and-nine eyes from 403 patients who underwent PKP at Miyata Eye Hospital in Japan from 1998 through 2014, were included in this study. Medical charts were retrospectively examined to ascertain the corneal disease diagnosis and the period of graft survival. Graft survival rates were compared among various corneal disease diagnoses and among the number of PKP procedures performed. Changes in corneal endothelial cell density (ECD) were analyzed using a mixed-effects model. The presence/absence of various risk factors was compared between transparent grafts and failed grafts. The overall rate of graft survival at 12 years was 60.4%. The rates of graft survival in keratoconus was 100%, in corneal dystrophy 100%, in leukoma 70.8%, and in bullous keratopathy 51.7%. The rates of graft survival at 12 years for the first PKP was 65.4% and for the second PKP, 43.4% (p

To elucidate the factors affecting visual acuity after Descemet stripping automated endothelial keratoplasty (DSAEK). We reviewed consecutive patients who underwent primary DSAEK for corneal endothelial dysfunction at Inouye Eye Hospital from January 2010 through January 2015 and who had a follow-up of at least 6 months. Fifty-four eyes of 49 patients (24 men and 25 women) were enrolled; the mean age was 72.5 ± 8.7 years. Medical charts were retrospectively examined for best spectacle-corrected visual acuity (BSCVA), intraocular pressure, keratometric value, keratometric cylinder, grade of preoperative corneal edema, preoperative graft thickness, and endothelial cell density (ECD) before and at 1, 3, 6, 12, and 24 months after surgery. A multiple regression analysis was used to evaluate the factors associated with BSCVA at 3, 6 months, and 1 year after surgery. Explanatory variables included age, sex, preoperative factors (BSCVA, degree of corneal edema, donor ECD, and graft thickness), and factors at each time point (keratometric value, keratometric cylinder, and intraocular pressure). The mean logarithms of the minimum angle of resolution (logMAR) BSCVA preoperatively and at 1, 3, 6, and 12 months after surgery were 1.03 ± 0.49, 0.42 ± 0.26, 0.29 ± 0.21, 0.24 ± 0.20, and 0.22 ± 0.20, respectively. Multiple regression analysis showed that preoperative BSCVA alone was significantly associated with BSCVA at 3, 6, and 12 months. A better preoperative BSCVA was associated with a better BSCVA after DSAEK, which suggests that DSAEK should be considered earlier than stromal changes such as subepithelial fibrosis occurrence.

Measurement of total tear immunoglobulin E (IgE) is useful for the diagnosis of allergic conjunctivitis, but it is still unknown whether measurement of total tear IgE is useful for assessment of the severity of allergic conjunctivitis. We evaluated the relation between the total IgE level in tears and objective signs of allergic conjunctivitis.A prospective, nonrandomized, and cross-sectional study was conducted in 84 patients with allergic conjunctivitis (allergic group) and 80 age- and sex-matched healthy control subjects (control group). The total tear IgE score was obtained with the Allerwatch(®) test (0, 1, and 2), and ten severity scores (0, 1, 2, 3) were determined for objective ocular findings of the palpebral and bulbar conjunctiva, as well as limbal and corneal lesions.The scores for total tear IgE and each of the objective ocular findings were higher in the allergic group than in the control group (all p0.01). The total tear IgE score was correlated with the severity of each clinical feature of allergic conjunctivitis (p0.01), except for corneal epithelial damage in the allergic group. Multivariate analysis revealed that the severity of giant papillae was the most important indicator of the total tear IgE score (odds ratio = 1.33, p0.00001).The total tear IgE score was correlated with the scores for objective signs of allergic conjunctivitis. This rapid test for total IgE in tear fluid is easy to perform and could be used to assess the severity of allergic conjunctivitis on an outpatient basis.

Dystroglycan (DG) is a key component of the dystrophin–glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specificDGconditional knock-out (DGCKO) mice. We found that theDGCKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in theDGCKO retina. In theDGCKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in thePikachurin−/−retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG–pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG–pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.

PURPOSE To examine iridotrabecular contact (ITC) as a peripheral anterior synechia (PAS) of patients who underwent penetrating keratoplasty (PKP) using anterior segment Fourier-domain optical coherence tomography (OCT). METHODS Retrospective, observational case series. ITC, ITC index, and ITC area of 60 eyes of 52 patients who underwent PKP at the Department of Ophthalmology in the University of Tokyo Hospital (mean follow-up time 102.8 ± 116.1 months postoperation) were calculated using the angle analysis mode of a commercially available anterior segment Fourier-domain OCT system (CASIA; TOMEY, Nagoya, Japan). We analyzed the occurrence of ITC, ITC index, and ITC area with preoperative diagnosis, lens status, operation method, operation frequency, graft size, and intraocular pressure elevation. RESULTS ITC was observed in 28 (46.7%) of 60 eyes. Average ITC index was 14.0%, and average ITC area was 5.97 mm. ITC was significantly associated with eyes with bullous keratopathy, infectious keratitis, pseudophakia, PKP with cataract operation, several PKP operations, and large graft size. CONCLUSIONS Anterior segment Fourier-domain OCT is a useful and innovative tool that enables us to observe the anterior chamber angle and examine ITC as PAS of eyes with corneal opacity, even after PKP.

Recently, a new commercial test for total tear immunoglobulin E (IgE), based on immunochromatography (Allerwatch), was developed. We examined the relation between the total IgE level in tears and specific serum IgE.A prospective, nonrandomized, cross-sectional study was conducted in 35 patients with allergic conjunctivitis (allergic group), 30 age- and sex-matched healthy control subjects (control group), and 8 patients with epidemic keratoconjunctivitis. In all subjects, the total tear IgE score was determined with the Allerwatch test (0, 1, and 2), and serum levels of total IgE and specific IgE for 12 inhaled allergens were measured with the Phadezym PRIST and CAP-RAST systems, respectively.The total tear IgE-positive rate was significantly higher in the allergic group than in the control and epidemic keratoconjunctivitis groups (100.0% vs. 0.0% vs. 0.0%; P0.00001). In the allergic group, the total tear IgE score was significantly correlated with the log-transformed total serum IgE level (r = 0.61) and with the serum levels of IgE for cedar pollen (r = 0.35), house dust (r = 0.46), Dermatophagoides pteronyssinus (r = 0.49), and acarus (r = 0.36). Multivariate logistic regression analysis showed that the log-transformed total serum IgE level was the only significant predictor of the total tear IgE score (odds ratio = 1.85, P = 0.00008).The total tear IgE score, determined with the Allerwatch test, was correlated with the total and specific serum IgE levels. This rapid test is easy to perform, sensitive, and highly specific for the detection of ocular allergy on an outpatient basis.

Pinguecula is a relatively frequent disease; however, there have been no reports about the grade of pinguecula. We investigated the relationship between age and the prevalence and severity of pinguecula by using a grading system and compared the grade of pinguecula between men and women and between the nasal and temporal halves of the conjunctiva.This was a prospective, randomized study of 1,040 patients aged 1 to 95 years, including 520 men and 520 age-matched women. The age, gender, medical history, ocular history, and grade of pingueculae located on the nasal and temporal conjunctiva were determined in all subjects.The prevalence of pinguecula increased dramatically with age. The mean grade was higher in male patients than in female patients for pingueculae located on both the nasal conjunctiva (P = 0.00072) and the temporal conjunctiva (P = 0.00035). However, there was no significant difference in the grade of pinguecula between the nasal and temporal conjunctiva.This was the first assessment of the grade of pinguecula in a large series of patients. Our findings strongly suggest that pinguecula is an age-dependent lesion that occurs from young adulthood onward. The present grading system should also be useful for future clinical studies of pinguecula.

In this review, the importance of Japanese research on meibomian gland dysfunction (MGD) is discussed from the perspective of global academic and clinical research on this topic. Many Japanese physicians and researchers have contributed to recent worldwide progress in various fields of MGD research, including pathophysiology, epidemiology, diagnosis, and therapy. In Japan, recent studies in the field of pathophysiology have provided direct evidence for the hypothesis that lipid composition and reactive oxygen species play a crucial role in the development and worsening of MGD. In the field of diagnosis, slit-lamp examination, in vivo confocal microscopy, and meibography have been widely used in studies from Japan. On the basis of the results of these studies, the MGD working group in Japan has proposed new diagnostic criteria for obstructive MGD. According to these criteria, obstructive MGD is considered present when ocular symptoms, anatomic abnormalities, and meibomian gland obstruction are present. In the field of therapy, devices and drugs newly developed in Japan have been shown to enhance the efficacy of lid hygiene and warm compression. Moreover, diquafosol and vitamin D3 have been shown to be effective for MGD. In conclusion, standardization of the diagnosis and treatment of MGD is necessary to enable all patients with MGD to receive appropriate treatment, and specific diagnostic criteria with cutoff values for each parameter are necessary to standardize the diagnosis of MGD.

Measurement of total immunoglobulin E (IgE) is clinically important for the diagnosis of allergic diseases. The total serum IgE level is normally measured because of its widespread use and convenience, but little attention has been paid to the measurement of local IgE concentrations. We evaluated whether the measurement of local production of IgE in tears, saliva, and nasal mucus was useful for the diagnosis of allergic rhinoconjunctivitis.A prospective, nonrandomized, cross-sectional study was conducted in 33 consecutive patients with seasonal allergic rhinoconjunctivitis (allergic group) and in 30 age- and sex-matched healthy control subjects (control group). The total IgE level was measured in tears, saliva, and nasal mucus from all subjects. Using a 4- or 5-point scale, symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and total symptom score for allergic conjunctivitis.Total IgE could be assayed within 10 minutes of collection in all samples. The scores for all symptoms were higher in the allergic group than in the control group (p.00001). The IgE scores for tear fluid samples (p.00001) and undiluted saliva (p = .00003) were significantly higher in the allergic group than in the control group. The total IgE score of tear fluid samples was strongly correlated with the severity of symptoms of allergic conjunctivitis, including ocular itching (r = 0.769, p.00001), tearing (r = 0.560, p = .00035), and ocular symptom score (r = 0.329, p = .03452). On the contrary, the total IgE scores for both saliva and nasal mucus were correlated with the severity of rhinitis-related symptoms, including sneezing (saliva r = 0.897, p.00001; nasal mucus r = 0.871, p = .00024), nose blowing (saliva r = 0.764, p.00001; nasal mucus r = 0.829, p = .00080), and nasal obstruction (saliva r = 0.519, p = .00099; nasal mucus r = 0.745, p = .00429). The ADL score was correlated with the total IgE level in each specimen (tear r = 0.705, p.00001; saliva r = 0.468, p = .00301; nasal mucus r = 0.479, p = .06816).These results suggest that local production of IgE is closely correlated with local allergic symptoms. This rapid test for the measurement of local IgE is easy to perform on an outpatient basis and may be helpful in the diagnosis of allergic rhinitis and conjunctivitis.

To compare clinical findings between patients with seborrheic meibomian gland dysfunction (MGD) and normal controls and to propose diagnostic criteria for seborrheic MGD.Thirty eyes of 30 patients [13 men and 17 women; age (mean +/- SD) 73.9 +/- 9.9 years] diagnosed with seborrheic MGD and 60 eyes of 60 healthy volunteers (22 men and 38 women; age: 71.0 +/- 9.3 years) as a control group were included in this study. Ocular symptoms were scored from 0 to 14 according to the number of symptoms present. Lid margin abnormality was scored from 0 to 4 depending on the number of abnormalities present. Meibomian gland changes were scored from 0 to 6 on the basis of noncontact meibography (meiboscore). Superficial punctate keratopathy was scored from 0 to 3. Tear film production was evaluated by Schirmer test. Receiver operating characteristic curves with calculations of the area under the curve were used to describe the accuracy of each parameter to differentiate patients with seborrheic MGD from normal eyes.Ocular symptom score and lid margin abnormality score were significantly higher in the seborrheic MGD group than in the control group (P0.0001 for both scores). Area under the curve values indicated that the lid margin abnormality score had the highest diagnostic power as a single parameter followed by the ocular symptom score. When the diagnosis for seborrheic MGD was made on the basis of the 2 scores (ocular symptom score and lid margin abnormality score) being abnormal, the sensitivity was 100% and the specificity was 98.3%.On the basis of these findings, we recommend that physicians use ocular symptom score and lid margin abnormality score in the diagnosis of seborrheic MGD. Seborrheic MGD should be considered very likely when both of the 2 scores are abnormal.

To evaluate diagnostic criteria for obstructive meibomian gland dysfunction (MGD) using three parameters (symptom score, lid margin abnormality score, and meibomian gland morphologic change scores) for differentiating obstructive MGD from aqueous deficiency dry eye (ADDE).Twenty-five eyes of 25 patients (mean age, 66.6 years) diagnosed with obstructive MGD and 15 eyes of 15 patients (mean age, 61.3 years) diagnosed with ADDE were analyzed. Ocular symptoms were scored from 0 to 14 according to the number of symptoms. Lid margin abnormality was scored from 0 to 4 according to the number of abnormalities. Meibomian gland changes were scored from 0 to 6 using noncontact meibography (meibo-score). Superficial punctate keratopathy was scored from 0 to 3. Meibum was graded from 0 to 3 according to volume and quality. Tear film break-up time was measured consecutively three times after instillation of fluorescein, and the median value was adopted. Tear film production was evaluated using the Schirmer test.Ocular symptom and lid margin abnormality scores and tear film break-up time did not differ significantly between the obstructive MGD and ADDE groups. The meibum score and meibo-score were significantly higher in the obstructive MGD group than in the ADDE group. The Schirmer value was significantly lower in the ADDE group than in the obstructive MGD group. When obstructive MGD was diagnosed on the basis of three scores (ocular symptom score, lid margin abnormality score, and meibo-score) all being abnormal, the sensitivity and specificity for differentiating between obstructive MGD and ADDE were 68.0% and 80%, respectively.Although the criteria were moderately reliable for differentiating patients with obstructive MGD from those with ADDE when the diagnosis of obstructive MGD was made on the basis of three abnormal scores, they do not provide comprehensive diagnostic tools for differentiating MGD, ADDE, and healthy individuals. We need to add other parameters such as the Schirmer test value and the meibum score to the diagnostic criteria to enhance their reliability for differentiating MGD and ADDE.

Subconjunctival hemorrhage (SCH) is a relatively common disease, but there have been no reports concerning the relationship between SCH and conjunctivochalasis (CCh). We compared the grade of CCh between patients with SCH and control patients.Prospective, nonrandomized study.A total of 104 patients with SCH aged 41 to 94 years and 120 age- and gender-matched controls aged 41 to 94 years were enrolled.The conjunctiva was divided into the following 8 equal areas: superior, superior/nasal, nasal, inferior/nasal, inferior, inferior/temporal, temporal, and superior/temporal. The age, gender, medical history, ocular history, site of hemorrhage, grade of CCh at 3 locations (nasal, middle, and temporal), and other parameters of CCh were determined in all subjects.Grade of each CCh parameter and location of SCH.The mean grade of CCh was higher in patients with SCH than in control patients at the nasal (P0.00001), middle (P0.00001), and temporal areas (P0.00001). The downward gaze- or digital pressure-dependent changes of CCh and the frequency of superficial punctate keratitis were all increased in SCH patients compared with control patients (P0.00001, P0.00001, and P = 0.00106, respectively). The number of areas involved by SCH and the presence of SCH in each area were positively correlated with the grade of each CCh-related parameter (P0.05).This was the first assessment of the grade of CCh in a large series of consecutive patients with SCH. Our results strongly suggest that CCh may have an important role in the pathogenesis of SCH.

This article reviews our data on secondary localized corneal amyloidosis after chronic ocular inflammation including trichiasis and keratoconus. Previous findings have suggested that lactoferrin is a precursor protein in secondary corneal amyloidosis. The clinical finding that amyloidosis i

Purpose: Various exogenous allergens can cause allergic conjunctivitis, whereas refractive errors are also related (as an endogenous factor) to the pathogenesis of allergic conjunctivitis. However, little is known about the interaction between exogenous and endogenous factors in patients with allergic conjunctivitis. We investigated the relationship between refractive errors and exogenous allergens in patients with allergic conjunctivitis. Methods: Sixty patients with allergic conjunctivitis and 60 healthy subjects (non-allergy patients) were enrolled. Refraction was carried out in all subjects. In addition, total immunoglobulin E (IgE) and specific IgE levels for 12 inhaled allergens were measured by the capsulated hydrolic carrier polymer system. Results: The patients who were positive for-specific IgE to indoor allergens had higher myopia than those who were negative, including those positive for house dust IgE (−3.66 ± 2.95 vs. −1.05 ± 3.39, P = 0.0015), Dermatophagoides pteronyssinus (D. pteronyssinus) IgE (−3.50 ± 2.91 vs. −1.01 ± 3.46, P = 0.0021), and acarus IgE (−3.45 ± 2.21 vs. −1.51 ± 3.73, P = 0.0087), whereas antibody-positive and antibody-negative patients for outdoor allergens showed no significant differences of refraction. Refractions in indoor group (−3.58 ± 3.42) and indoor/outdoor (−3.70 ± 2.64) group were higher than those in outdoor group (−0.84 ± 2.30, P = 0.0047 and P = 0.0032) and the non-allergy group (−1.30 ± 1.48, P = 0.0082 and P = 0.0054) [-refraction] was significantly correlated with total IgE (r = 0.333, P = 0.0093), house dust (r = 0.355, P = 0.0054) and D. pteronyssinus (r = 0.379, P = 0.0028), while no correlation between refractive error and outdoor allergens was proven. Conclusion: These results suggest that specific IgE levels for indoor allergens, such as house dust, might be associated with refractive errors.