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Purpose: To assess the risk factors for intraocular pressure (IOP) elevation during the early period post cataract surgery. Study design: Retrospective study. Methods: This study involved 1587 eyes that underwent cataract surgery at the Baptist Eye Institute, Kyoto, Japan between April 2020 and May 2021. In all subjects, risk factors for early postoperative IOP elevation (i.e., an increase of IOP of 10 mmHg or more at 1-day postoperative compared with that at baseline, or a postoperative IOP of 28 mmHg or more) were analyzed by multivariate logistic regression analysis. Results: Of the 1587 treated eyes in this study, 100 (6.3%) experienced early-postoperative IOP elevation. Of those 100 eyes, 78.0% were men, 27.0% had an axial length (AL) of ≥ 26.5 mm, 23.0% had a history of glaucoma treatment, 11.0% had poor mydriasis and 10.0% had intraoperative floppy iris syndrome (IFIS). Multivariate analysis findings revealed that male [odds ratio (OR) 4.36; 95% confidence interval (CI) 2.63–7.23; P < 0.001], AL of ≥ 26.5 mm (3.11; 1.83–5.30; P < 0.001), a history of glaucoma treatment (2.83; 1.63–4.91; P < 0.001), poorly mydriasis (2.63; 1.16–6.01; P = 0.02), IFIS (4.37; 1.78–10.74; P = 0.001) and baseline high IOP (1.09; 1.01–1.18; P = 0.03) were associated with increased IOP during the early period post cataract surgery. Conclusions: The findings in this study reveal that male sex, high myopia, a history of glaucoma treatment, poor mydriasis, IFIS and baseline high IOP are risk factors for IOP elevation during the early period post cataract surgery. [ABSTRACT FROM AUTHOR]

To investigate the differences in clinical and genetic characteristics between males and females with central serous chorioretinopathy (CSC). Consecutive 302 patients (mean age; 56.3 ± 11.7, male/female: 249/53) with CSC were evaluated on the initial presentation. All CSC patients underwent fluorescein angiography and indocyanine green angiography (FA/ICGA), swept-source or spectral-domain optical coherence tomography (OCT), and fundus autofluorescence (FAF) to confirm a diagnosis. All patients were genotyped for rs800292 and rs1329428 variants of CFH using TaqMan technology. On the initial presentation, female patients were significantly older (p = 2.1 × 10–4, female 61.6 ± 12.4 vs male 55.1 ± 11.3) and had thinner subfoveal choroidal thickness (p = 3.8 × 10–5) and higher central retinal thickness (p = 3.0 × 10–3) compared to males. A descending tract was more frequently seen in males than in females (p = 8.0 × 10–4, 18.1% vs 0%). Other clinical characteristics were comparable between the sexes. The risk allele frequency of both variants including CFH rs800292 and CFH rs1329428 was comparable between males and females (CFH rs800292 A allele male 51.2% vs female 47.2%, CFH rs1329428 T allele male 56.2% vs 52.8%). On the initial presentation, age, subfoveal choroidal thickness and central retinal thickness differ between males and females in eyes with CSC. A descending tract may be a strong male finding in CSC. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effects of a combination of two antifungal drugs against causative fungi of fungal keratitis in Japan. Study design: Multicenter prospective observational study. Methods: Eighteen isolates of yeast-like fungi and 22 isolates of filamentous fungi collected by the Multicenter Prospective Observational Study of Fungal Keratitis in Japan were studied. Specially manufactured minimum inhibitory concentration (MIC) measurement plates were used to test the effectiveness of 10 combinations of two antifungal drugs against the isolates. The combinations were pimaricin (PMR) + voriconazole (VRCZ), PMR + fluconazole (FLCZ), PMR + miconazole (MCZ), PMR + micafungin (MCFG), VRCZ + FLCZ, VRCZ + MCZ, VRCZ + MCFG, VRCZ + amphotericin–B (AMPH-B), MCZ + FLCZ, and MCZ + MCFG. The checkerboard microdilution method was used, and the fractional inhibitory concentration (FIC) index was calculated based on the guidelines of The Clinical & Laboratory Standards Institute (CLSI). Results: In yeast-like fungi, additive effects were observed between PMR and MCFG in 77.8% of the isolates, and they were also observed between the azoles. Synergistic effects were observed on 11.1% of the isolates for MCZ and FLCZ. On the other hand, antagonistic effects were present between PMR and azoles with 88.9% between PMR and VRCZ, 72.2% between PMR and FLCZ, and 94.4% between PMR and MCZ. In filamentous fungi, additive effects were observed between PMR and MCFG in 40.9% of the isolates, and between VRCZ and MCZ in 40.9% of the isolates. Antagonistic effects were observed for PMR and the azoles. Conclusions: The combination of drugs prescribed for fungal keratitis incurs a possibility of synergistic, additive, indifferent, or antagonistic effects, depending on drug combinations and fungal strains. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the localized expression of C1q/tumor necrosis factor related protein (CTRP) 6 in human age-related macular degeneration (AMD) retinal tissues. Experimental study design: 4 AMD and 3 non-AMD whole eyes of Caucasian donors were used. Eyecups were excised at Eye Bank CorneaGen, Inc. Methods: To elucidate the effects of CTRP6, C3b was measured by an enzyme-linked immunosorbent-like assay. CFB versus CTRP6 competitive binding assay was applied to clarify the inhibition by CTRP6 of C3bBb complex formation. The cornea, iris, lens, and vitreous were removed and the eyes were cut into a posterior eye-cup including the retina, choroid, and sclera. Six-µm-thick serial sections of frozen samples underwent hematoxylin-eosin (HE) staining and indirect immunohistochemical staining using primary antibodies, anti-CTRP6, -CTRP5, -CTRP10, -Complement factor H (CFH) and -Clusterin (CLU). Results The two in vitro studies confirmed that CTRP6 has an inhibitory effect on alternative pathways of complement (APC) function and that the molecular target of CTRP6 is the inhibition of the formation of C3bBb. Localized expression for CTRP6 and CFH was found in the drusen of the AMD eyes, both associated with APC inhibition, CLU associated with membrane-attack complex (MAC) inhibition, and CTRP5 associated with retinal degeneration. Conclusion: The localized expression of CTRP6 in the drusen of AMD eyes may open a new insight into the possible involvement of APC regulatory factors in the pathogenesis of AMD, together with the known CFH so far analyzed solely as an APC inhibitor. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical characteristics and causative fungi in patients with fungal keratitis in Japan, and to determine factors related to the prognosis. Study design: Multicenter prospective observational study. Methods: Eligible patients were enrolled from November 2011 to October 2013 at the 1st stage and from April 2015 to March 2016 at the 2nd stage. The corneal foci were scraped, and the scrapings were cultured in potato dextrose agar. The isolated fungi were identified by gene analyses. Data were collected from the clinical records and statistically analyzed by Cox and logistic regression analyses. Results: Ninety-four fungal strains were isolated from 93 cases, including 42 yeast-like fungi and 52 filamentous fungi. The fungi affected the deep layers of the cornea in 23 cases (24.7%) and the peripheral cornea in 29 cases (31.2%). The incidences of lid swelling/redness, ciliary injection, anterior chamber cells/flare, anterior chamber fibrin, and hyphate ulcer in cases of filamentous fungi were significantly higher than in yeast-like fungi. No history of topical steroids, absence of a main lesion in the peripheral cornea, and best-corrected visual acuity (BCVA) of more than 0.04 at the first visit were related to a shorter healing time. No history of ocular surgery, absence of lesion at one-third deep stromal layer and BCVA of more than 0.04 at the first visit were correlated with BCVA at 3 months after the initial examination. Conclusion: Fungal keratitis is caused by various species of fungi and can become refractory due to poor prognosis factors. [ABSTRACT FROM AUTHOR]

This study aimed to uncover the mechanism responsible for the clinical efficacy of cell injection therapy with fully differentiated cultured cells. Analysis of polarized expression of ion transporters on cultured human corneal endothelial cells (CECs) subpopulations (SPs) was performed. The intracellular pH (pHi) between two CEC SPs, distinct in the proportion of differentiated cells, was measured, and the association with mitochondrial respiration homeostasis was investigated. The effects of the ion transporter inhibition by their selective inhibitors or siRNA transfection were also explored. Na+/K+-ATPase, Aquaporin 1, SLC4A11, NBCe1, NHE1 as transporters, and ZO-1, were all selectively expressed in differentiated SPs, but were almost null in the cell-state-transitioned SPs. We also confirmed that the pHi of CEC SPs affected their mitochondrial respiration by modulating the expression of these ion transporters via inhibitors or siRNA transfection. Ion and water transporters might participate in the maintenance of pHi and mitochondria homeostasis in differentiated SPs, which may contribute, combined with integral barrier functions, to efficient water efflux. The differences in intracellular pH between the two SPs is attributed to variations in the expression profile of specific ion transporters and mitochondrial functions, which may associate with the efficacy of the SPs in cell injection therapy. [ABSTRACT FROM AUTHOR]

Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation. Retrospective case study. A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort. Two-sided Fisher exact test with an alpha level < 0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account. Primary analysis compared the incidence of blindness (defined as visual acuity [VA] < 0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation. The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7–20.2]; P < 0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4–11.4]; P < 0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P < 0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P < 0.001). Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation. [ABSTRACT FROM AUTHOR]

A relationship between ocular sarcoidosis (OcSar) and dry eye (DE) has previously been reported. Here we investigated the tear function in OcSar, and the other uveitis, Vogt–Koyanagi–Harada disease (VKH), to elucidate the association between OcSar and DE. This study involved 27 eyes of 27 female OcSar patients [mean age: 67.3 ± 13.5 (SD) years], 18 eyes of 18 female VKH patients (53.1 ± 14.1 years), and 17 eyes of 17 female healthy control subjects (59.7 ± 9.6 years). In all examined eyes, tear meniscus height (TMH, mm), fluorescein breakup time (FBUT, s), scoring of keratoconjunctival epithelial damage (ED), and the Schirmer 1 test (ST1, mm/5 min) were analyzed. In the OcSar patients, VKH patients, and control subjects, the respective TMH, FBUT, ED, and ST1 values (mean ± SD) were 0.26 ± 0.10, 0.24 ± 0.09, and 0.24 ± 0.08, 4.3 ± 2.5, 7.3 ± 2.9, and 6.3 ± 3.1, 1.1 ± 1.1, 0.7 ± 0.8, and 0.1 ± 0.3, and 12.9 ± 10.5, 21.5 ± 12.1, and 24.3 ± 10.5. Statistically, the ST1 values were significantly lower in the OcSar patients than in the VKH patients (P = 0.004) and control subjects (P = 0.001). ST1 findings revealed that the neural reflex arc and lacrimal gland system, which attenuate the vicious cycle between the tear film and ocular surface epithelium in DE, are significantly impaired in OcSar cases, thus indicating a possible association between OcSar and DE. [ABSTRACT FROM AUTHOR]

Mesectodermal leiomyoma of the ciliary body is a rare benign tumor, showing both neurogenic and myogenic characteristics. This tumor typically shows predilection for women of reproductive age. Because it is almost impossible to clinically distinguish this tumor from malignant melanoma, unnecessary eye enucleations have been unfortunately performed. Herein, we report a case of mesectodermal leiomyoma of the ciliary body in a young Japanese woman. She was referred to our hospital due to a slow-growing mass in her left iris. A malignant tumor could not be clinically ruled out and surgery with intraoperative pathology consultation was performed. Intraoperative frozen section diagnosis was a benign tumor with neurogenic features, and a simple excision of the tumor was performed. Histologically, the tumor was composed of diffuse growth of spindle cells with fibrillary indistinctive cytoplasm. Immunohistochemical examination showed diffuse positive staining of α-smooth muscle actin, h-caldesmon, calponin, and CD56. Scattered tumor cells were weakly positive for desmin. Neither melanocytic markers nor neural markers except for CD56 were positive. We diagnosed this tumor as mesectodermal leiomyoma. Mesectodermal leiomyoma is rare and often misdiagnosed as malignant melanoma. To avoid overtreatment, a correct preoperative diagnosis is essential. [ABSTRACT FROM AUTHOR]

Purpose: The study reports the correlation between surgical timing and postoperative ocular motility in orbital blowout fractures. Methods: This was a retrospective study of 191 patients that underwent surgical repair for unilateral orbital fractures. All patients included in the study had symptomatic diplopia from the fracture. Patients were classified into one of three groups according to the time of surgery after injury: (1) Early (within 14 days of surgery), (2) intermediate (between 15 and 30 days), and (3) late (greater than 30 days). Ocular motility was measured presurgery and at 3 and 6 months postsurgery by Hess chart with calculation of the Hess area ratio (HAR%). Results: Surgery was conducted at a mean of 24.7 ± 45.0 days (range: 1–283 days) postinjury. There were 120 patients in the early surgery group (surgery at 6.8 ± 3.8 days), 38 in the intermediate surgery group (20.7 ± 4.1 days), and 33 in the late surgery group (95.1 ± 75.0 days). Overall the HAR% improved significantly from a mean of 74.2% preoperatively to 90.8% at 6 months postoperatively (p < 0.01). In the early and intermediate groups, the postoperative HAR% improved significantly with all fracture regions (orbital floor, medial wall, and combined orbital medial wall and floor) (p < 0.05). However, in the late groups, the postoperative HAR% only improved significantly with orbital floor fractures. Conclusion: Pre- and postoperative the HAR% give objective evidence of ocular motility improvement with early orbital floor fracture repair surgery. However, observation can be deployed, as a significant improvement in ocular motility can also be achieved with reconstructive surgery conducted 30 days or more after depressed floor-fragment fractures. Early intervention should be prioritized for symptomatic medial wall fractures, as late surgery does not improve motility. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005–2007 and between 2008–2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances. [ABSTRACT FROM AUTHOR]

Proinflammatory cytokines, including interleukin-1 (IL-1) have been implicated in the inflammation that follows corneal alkali injury. The purpose of this series of experiments was to test whether topically applied interleukin-1 receptor antagonist (IL-1ra) could suppress corneal inflammation and promote transparency after alkali injury. Alkali injury was induced on day 0 by application of 1N NaOH to both eyes of Wistar rats (n=28). Immediately thereafter, eyes received either topical IL-1ra (20 mg ml−1) in 0·2% sodium hyaluronate or vehicle alone three times daily during days 0–14. Biomicroscopic features including corneal opacity and neovascularization were assessed using a standard grading scheme. Inflammation was quantified histologically. Corneas excised at day 3 and 7 (randomly selected six eyes in each group per time point studied) were homogenized, and levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, and RANTES were quantified by enzyme-linked immunosorbent assay. Epithelial wound healing was examined by computed analysis of fluorescein stained corneal photographs taken daily until day 14. According to these evaluations, eyes treated with IL-1ra maintained corneal transparency with minimal neovascular invasion. Additionally, corneal damage and cell infiltration were reduced on day 7 (infiltration cells were almost 40% decreased). All cytokine/chemokine levels in IL-1ra treated eyes were significantly lower at day 3, and IL-6 and IL-10 remained significantly lower at day 7 compared to vehicle-treated eyes. IL-1ra treatment retarded epithelial wound healing in the early stage (day 1–4); however, subsequently IL-1ra treated eyes had enhanced healing with full epithelial closure at nearly the same time point as vehicle-treated eyes (day 10). We conclude that local antagonism of IL-1 after alkali injury can significantly decrease corneal inflammation and lead to enhanced corneal transparency. [Copyright &y& Elsevier]

Purpose: To evaluate factors related to myopia progression in children wearing either orthokeratology (OK) lenses or single-vision spectacles (SVS) for 2 years. Study design: Pooled-analysis retrospective intervention study. Methods: This study involved 105 school-aged children wearing SVS who participated in the multi-center Myovision Study and 89 school-aged children wearing one of 3 OK lens types [Menicon Z Night (M, n = 27), αORTHO®-K (A, n = 32), and Emerald™ (E, n = 30)]. In the OK-lens patients, last examination was performed at ≥ 3-weeks post lens-wear discontinuation. Of the subjects, 102 SVS-Group and 79 OK-Group (M: n = 24, A: n = 28, and E: n = 27) children completed all examinations. A relationship between refractive error (RE) change and 7 factors (correction methods, baseline age, baseline RE, baseline axial length, gender, right or left eye, and follow-up period) was derived by multiple regression modeling. Via those same methods, we investigated the relationship between RE change and 7 factors including 3 OK-lens corrections. Results: Related influence factors were correction method (0.85 D myopia reduction in the OK Group, P < 0.001), baseline age (0.16 D myopia reduction in older-age patients, P < 0.001), and baseline RE (0.12 D myopia reduction per 1 D myopia, P = 0.01). No relationship was found between RE change and OK-lens type. No serious adverse events occurred. Conclusion: Regardless of OK lens design, myopia progression in school-aged children was suppressed. The effect was examined not only via axial-length elongation but also RE change, and the myopia control effect by OK lenses was found to be 0.85 D over the 2-year period. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the safety and efficacy of orthokeratology in myopic children in Japan. Study design: Prospective clinical trial. Methods: This study enrolled myopic children aged 6–16 years with a spherical equivalent of −1.00 D to −4.00 D and astigmatism of −1.5 D or lower, whose parents could manage contact lens use and could provide written informed consent. The children were treated with orthokeratology lenses (BREATH-O CORRECT R, Universal View Co., Ltd.) for 3 years. Slit-lamp findings, visual acuity, intraocular pressure, subjective refraction, corneal topography, corneal endothelial cell density, corneal thickness, and axial length were regularly assessed. Results: This study included 96 eyes of 48 patients (average age, 10.7 ± 2.08 years). The average baseline spherical equivalent was −2.46 ± 0.97 D. The average baseline uncorrected visual acuity was 0.74 ± 0.32 logMAR, with significant improvement to −0.08 ± 0.18 logMAR at 4 weeks and 0.02 ± 0.21 logMAR at 3 years (both p < 0.001, Dunnett's test). The average baseline corneal endothelial cell density was 3053 ± 181 cells/mm2 and 3028 ± 213 cells/mm2 at postoperative 3 years (p = 0.9933, Dunnett's test). The average axial length was 24.70 ± 0.78 mm at baseline, 24.77 ± 0.80 mm at 12 weeks, and 25.32 ± 0.85 mm at 36 months. Although mild corneal epithelial disorders occurred in 18% of eyes, they were successfully treated with eye drops, enabling resumption of lens usage. No serious adverse events were observed. Conclusion: Orthokeratology lens (BREATH-O CORRECT R) use in children demonstrated good efficacy and safety during 3 years of follow-up. [ABSTRACT FROM AUTHOR]

Purpose: To compare the commonly used formulas for intraocular lens (IOL) selection using IOLMaster®700 (Carl Zeiss Meditec) and to evaluate the Barrett Universal II (BU-II) formula accuracy when using the Vivinex™ iSert® XY1 IOL (Hoya Corporation Medical Division).Methods: A retrospective chart review was performed that included patients who underwent uneventful cataract surgery with in-the-bag insertion of Vivinex™ iSert® XY1 IOL. Prediction errors at 3 months postoperative of IOLMaster® 700 with Haigis, Holladay 1, SRK/T, and BU-II formulas were compared. As a subgroup analysis, we focused on the axial length (AL) and IOL power. AL subgroup analysis was based on the following AL subgroups: short (<22.5 mm), medium (22.5-25.5 mm), and long (>25.5 mm). IOL power subgroup analysis was based on the following IOL power subgroups: low (≤18.0 diopters [D]), medium (18.5-24.0 D), and high (≥24.5 D).Results: This study included 590 eyes of 590 patients. Overall, the four IOL calculation formulas appeared to be similarly accurate. In the long AL subgroup, the BU-II formula had a significantly lower absolute error (AE) than the Holladay 1 formula. In the low-power subgroup, the BU-II formula had a significantly lower AE than the Holladay 1 and SRK/T formulas. On the other hand, in the high-power subgroup, the BU-Ⅱ formula was significantly less accurate than the SRK/T formula and also appeared to be worse than the Holladay 1 formula (P = 0.052).Conclusion: The BU-II formula might be less accurate when using a Vivinex™ iSert® XY1 IOL of 24.5 D or greater. [ABSTRACT FROM AUTHOR]

To investigate the influence of age on prediction error (PE) after cataract surgery in very elderly (VE) patients aged more than 90 years. We retrospectively analyzed 66 eyes of patients aged ≥90 years (VE group) who underwent phacoemulsification and intraocular lens (IOL) implantation. As the control group (CG), we investigated 121 eyes of patients aged 70–89 years who underwent the same surgery. PE was calculated 1 month post-surgery as the actual postoperative spherical equivalent minus the target diopter, which was calculated using the Sanders–Retzlaff–Kraff/T formula. The absolute and arithmetic PE were compared between the two groups. The factors affecting absolute PE outside ±0.5 diopter (D) and ±1.0 D were determined through logistic regression analysis with the variables age, sex, axial length (AL), average corneal power, preoperative best-corrected visual acuity, target diopter, and coexisting pseudoexfoliation syndrome. The absolute PE was significantly larger in the VE group than that in the CG (0.60 ± 0.52 D and 0.34 ± 0.25 D, respectively; P <.001). There was no significant difference in terms of arithmetic PE between the two groups (−0.06 ± 0.79 D and −0.07 ± 0.42 D, respectively; P =.653). In the logistic regression analysis, age was significantly associated with absolute PE outside ±0.50 D (Odds ratio [OR]: 1.05). Age and AL were significantly associated with absolute PE outside ±1.0 D (OR: 1.24 and 0.20, respectively). Absolute PE tended to increase in the cataract surgery of VE patients. [ABSTRACT FROM AUTHOR]

Purpose: Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. Study design: Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. Methods: Participants were 171 Japanese schoolchildren aged 6 to 12 years, with progressive myopia, spherical equivalence (SE) of −1.00 to −6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24 months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. Results: Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, −1.26 D (95% confidence interval [CI]: −1.35, −1.17) and 0.63 mm (0.59, 0.67) for atropine and −1.48 D (− 1.57, −1.39) and 0.77 mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P < 0.001) for SE and − 0.14 mm (−0.20, −0.08; P < 0.001) for AL. Three patients experienced mild allergic conjunctivitis side effects, with no inter-group difference in incidence (atropine: 2.4%; 2/84 patients; placebo: 1.4%; 1/84 patients). Conclusion: With good compliance, 0.01% atropine is effective and safe for preventing the progression of childhood myopia. [ABSTRACT FROM AUTHOR]

To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. Prospective observational study. This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601–2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery. [ABSTRACT FROM AUTHOR]

Background: The efficacy of peripheral low add multifocal soft contact lenses (SCLs) for suppressing the progression of myopia is controversial. The aim of the on-going present clinical study is to investigate whether or not multifocal SCLs with + 0.50 diopters (D) addition suppress the progression of myopia in myopic elementary school children.Design: Prospective randomized controlled trial.Subjects and Methods: The study plans to include a total of 100 myopic school children. Target subjects are primary school male and female students with mild to moderate myopia. Children who have eye-related diseases other than myopia are excluded from the study, because they may affect the evaluation of the outcome. Subjects will be randomly assigned to wear daily disposable multifocal contact lenses with + 0.50D addition or daily disposable SCLs. Subjects will wear contact lenses on both eyes and will be observed for 2 years under a double-masked examination. Primary outcome is a change in the axial length over the 2-year period.Objectives: The purpose of this study is to identify whether or not multifocal SCLs with + 0.5D addition suppress the progression of myopia in myopic elementary school children as compared with standard SCLs.Trial Registration: 1. UMIN (University Hospital Medical Information Network) UMIN000027940. Registered on July 21, 2017 2. JRCT (Japan Registry of Clinical Trials) jRCTs052180172. Registered on March 26, 2019. [ABSTRACT FROM AUTHOR]

Microwave thermokeratoplasty (MTK) is a surgical procedure for the correction of pathologic corneal steepening. The purpose of this study was to examine the postoperative outcomes of eyes with advanced keratoconus that underwent femtosecond-laser zig-zag penetrating keratoplasty (z-PK) following MTK for reshaping of the central cornea. This study involved 32 eyes of 32 consecutive advanced keratoconus patients; i.e., 25 eyes of 25 patients who underwent MTK prior to z-PK (MTK + z-PK group), and 7 eyes of 7 patients who underwent z-PK alone (z-PK group). In all treated eyes, visual acuity (VA) and corneal topography were measured before surgery and at 6-months postoperative. At 6-months postoperative, the mean uncorrected distance VA (logarithm of the minimum angle of resolution) and surface regularity index (SRI) of the MTK + z-PK group was 0.62 ± 0.39 (mean ± standard deviation) and 1.26 ± 0.45, respectively, while that in the z-PK group was 1.02 ± 0.18 and 7.64 ± 3.22, respectively. Both variables were significantly better in the MTK + z-PK group than in the z-PK group (P < 0.05). The findings in this study reveal that MTK prior to z-PKP is effective for improving UDVA and reducing the irregularity of corneal topography in patients with advanced keratoconus. [ABSTRACT FROM AUTHOR]

To clarify the influence of tumor necrosis factor (TNF)-α on fibrotic phenotypes induced by transforming growth factor (TGF)-β in retinal pigment epithelial cells (RPECs) by epigenetic regulation. Human primary retinal pigment epithelial cells (RPECs including ARPE19) were used in cultures in the presence or absence of TNF-α and/or TGF-β2. RT2 Profiler™ (Qiagen) was used for PCR Array for fibrosis and epithelial mesenchymal transition (EMT). Microarray analysis by 3D gene DNA chip was outsourced to Toray Industries Inc. Quantification of histone acetyl transferase (HAT)-related and histone deacetylase (HDAC) related gene expression were also analyzed. HDAC and HAT activity was measured using an EpiQuik HDAC and HAT Activity/Inhibition Assay Kit (Epigentek). CD44, MMP-9, HAT, and HDAC in RPECs were analyzed by western blotting. Analysis of expression of the EMT/fibrosis related CD44 and MMP-9 phenotypes induced by TNF-α+TGF-β2 revealed four alterations in RPECs: 1) abolition of TGF-β2-induced α-SMA by TNF-α; 2) synergy between TNF-α+TGF-β2 for induction of CD44 and MMP-9 phenotypes 3) no inhibition of HDAC activity by either TNF-α or TGF-β2; and 4) significant inhibition of HAT activity by either TNF-α or TGF-β2, but no synergy. The HDAC activation through HAT inhibition by TNF-α+TGF-β was counteracted by HDAC inhibitors, leading to the inhibition of EMT/fibrosis. EMT/fibrotic CD44 and MMP-9 phenotypes were epigenetically upregulated by concerted action of TNF-α and TGF-β in RPECs. The intervention in epigenetic regulation may hold potential in preventing intraocular proliferative diseases. • TNF-α+TGF-β2 epigenetically upregulated CD44 and MMP-9 phenotypes in RPECs. • HAT activity was inhibited by either TNF-α or TGF-β2, but no synergy. • HAT inhibition by TNF-α+TGF-β was counteracted by HDAC inhibitors. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the therapeutic benefits of limbal-supported contact lens (CL) wear in patients with ocular sequelae due to Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).Methods: This interventional study enrolled 10 chronic SJS/TEN eyes with a spectacle best-corrected visual acuity (BCVA) of between 0.01 and 0.7 that were fitted with a limbal-supported CL. At baseline and at after 3-months CL use, CL-wear BCVA and the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) scores were measured, and then compared. Incidence rates and severities of adverse events were also analyzed.Results: At after 3-months CL use, BCVA with the fitted CL significantly improved compared to that with spectacle correction at baseline (LogMAR: 0.76-0.15) (P = 0.0039), all NEI VFQ-25 scores improved, however, only in ocular pain and mental health showed statistically significant improvement (P = 0.0078 and 0.0039). No serious adverse events were observed during the follow-up.Conclusion: Wearing of the limbal-supported CL improved vision compared to spectacles and reduced ocular pain in patients with ocular sequelae due to SJS/TEN. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term contrast sensitivity (CS) after laser in-situ keratomileusis (LASIK) for myopia.Methods: This retrospective, single-center, cohort study involved 190 eyes of 95 patients who underwent bilateral LASIK between January 2001 and October 2007. This study includes patients who underwent CS and higher-order aberration (HOA) measurements in a five-year postoperative period. For all enrolled patients, visual acuity, refractive error (RE) in diopters (D), CS at 3-, 6-, 12-, and 18-cycles per degree (cpd), and HOA in a 4 mm area of the dilated pupil were measured before surgery and 6 months, 1 year, and 5 years after it.Results: The mean RE measured before the surgery and after 6 months, 1 year, and 5 years after was -6.08 ± 2.50D, -0.26 ± 0.65D, -0.28 ± 0.65D, and -0.48 ± 0.80D, respectively. There were no clinically significant changes between preoperative results and the measures taken 6 months, 1 year, and 5 years after surgery. The slight increase in HOA had little effect on CS over the mid to long-term postoperative period.Conclusion: Our findings show that CS does not clinically change post LASIK. Although we were unable to identify the specific mechanism, we theorize that after LASIK there is a possibility for the compensation of HOA. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the microorganism detection and contamination rate of donor eyes. Study design: Retrospective study. Methods: In this retrospective study, we reviewed all donor cornea data collected from Kyoto Prefectural University of Medicine (KPUM) Eye Bank, Kyoto, Japan from April 2015 to June 2018, including microbiologic data obtained from conjunctival swabs and preservation medium and findings of postoperative infection from the medical records. Results: During the study period, 77 eyes from 44 deceased individuals (mean age at time of death: 75 ± 17.3 years [range, 30–102 years]) were donated to the KPUM Eye Bank after being harvested using standard safety precautions and disinfection procedures. In 49 of the 77 eyes (63.6%), the conjunctival-swab culture revealed microorganisms, with the 3 most commonly detected being methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-sensitive S aureus (MSSA), and methicillin-resistant S aureus (MRSA). The data revealed positive microorganism detection in only 4 (5.2%) of the 77 donor-cornea storage-medium cultures. Positive microorganism detection was found in all the age groups, with no statistical difference between the groups (P >.05). In the eyes enucleated ≥ 2.5 h postmortem, a higher positive microorganism detection occurred (P =.03). During the postoperative follow-up period, there was no record of corneal infection. Conclusions: The preenucleation conjunctival-swab-culture findings revealed that the rate of positive microorganism detection was similar for advanced-age and younger-age donors and that a shorter elapsed time from donor death to postmortem enucleation resulted in less donor-microorganism contamination. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the increase in refractive error (RE) and axial length (AL) in myopia patients in their 20s and 30s after laser-assisted in situ keratomileusis (LASIK) or epipolis-LASIK (epi-LASIK). Study design: Retrospective cohort study. Methods: This retrospective study involved 280 eyes of 140 myopia patients who underwent LASIK or epi-LASIK at the Baptist Eye Institute, Kyoto, Japan and who were followed for more than 5 years postoperatively. The patients were divided into 2 groups according to age: group A (age range, 20–29 years) and group B (age range, 30–39 years). In all patients, the RE and AL were measured at 1, 2, 3, 4, and 5 years postoperatively, and the 2 groups were compared in terms of each surgical method. Results: The patients' mean age at surgery was 30.6 ± 4.9 years. No significant difference was found between the 2 groups in terms of the preoperative mean spherical equivalent (SE) or AL. In the LASIK group, the mean changes in SE during the 4 years of study in groups A and B were + 0.054 ± 0.256 D and + 0.052 ± 0.327 D, respectively (P =.93, NS), and the postoperative increases in AL were 0.059 ± 0.134 mm and 0.027 ± 0.133 mm, respectively (P =.08, NS). In the epi-LASIK group, the mean change in SE during the 4 years of study in groups A and B were −0.438 ± 0.207 D and −0.259 ± 0.454 D, respectively (P =.41, NS), and the postoperative increases in AL were 0.124 ± 0.141 mm and 0.094 ± 0.166 mm, respectively (P =.46, NS). Conclusion: Our findings showed no significant difference in myopia progression in patients in their 20s and 30s during a 4-year period after either LASIK or epi-LASIK. [ABSTRACT FROM AUTHOR]

This study investigated corneal endothelial cell density (ECD) in pseudoexfoliation (PEX) syndrome patients and evaluated the clinical factors associated with ECD for 51 eyes of 41 phakic patients with pseudoexfoliation (PEX group) and 201 eyes of 117 patients with age-related cataracts (control group) as an age-matched control to the PEX group. Variable clinical factors, including ECD, central corneal thickness (CCT), anterior chamber depth (ACD), number of anti-glaucoma eye drops and severity of PEX, were examined using multivariate analyses. Severity of PEX was as follows: Mild in 28 eyes, Moderate in 16 eyes, and Severe in 7 eyes. The mean ECD was 2,548 ± 409 cells/mm2 in the PEX group and 2,757 ± 282 cells/mm2 in the control group, respectively, and ECD in the PEX group was significantly lower than that in the control group (P = 0.02). Multivariate analyses revealed that the severity of PEX [−176.8, 95% confidence interval (CI) (−244.5, −109.2), P < 0.01] was significantly associated with lower ECD. Accumulation of PEX materials contributed to early corneal endothelial decompensation. [ABSTRACT FROM AUTHOR]

Purpose: Rho-associated kinase-inhibitor ripasudil 0.4% eye drops are reportedly effective for the reduction of intraocular pressure (IOP) in glaucoma patients. However, the previous studies investigated the efficacy of IOP reduction for only about 1 year. Here, we evaluated the safety and efficacy of long-term ripasudil instillation in Japanese open-angle glaucoma (OAG) patients. Methods: This study involved 312 eyes of 312 Japanese OAG patients newly initiated with ripasudil treatment at Kyoto Prefectural University of Medicine and Oike-Ikeda Eye Clinic, Kyoto, Japan. In all patients, adverse events leading to discontinuation of ripasudil treatment were investigated. Of the 312 patients, 129 patients able to continue ripasudil administration for over 12-months post-treatment initiation were enrolled to investigate the long-term efficacy. IOP data at 0-, 1-, 3-, 6-, 12-, 18-, and 24-months post initiation of continuous ripasudil use were obtained, and the IOP values at each time point were then compared. The first period (from 1-6 months) and second period (from 12-24 months) IOP data were also compared based on the mixed model. Results: IOP at each time-point post-treatment initiation was significantly reduced compared with that at pre initiation (P < 0.05). Differences in IOP between the first and second periods of the study were not statistically significant (P = 0.058). Adverse events leading to discontinuation of treatment included blepharitis (15.7%) and conjunctival hyperemia (9.0%). Conclusions: We found that in Japanese OAG patients, 24-month ripasudil eye drop instillation is both safe and effective for lowering IOP and that blepharitis is the primary adverse event for discontinuation of use. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic ability of the ratio of anterior and posterior corneal surface areas (As/Ps) comparing with other keratoconus screening indices in distinguishing forme fruste keratoconus (FFKC) from normal eyes. Methods: In this comparative study, 13 eyes of 13 patients with FFKC, 29 eyes of 29 patients with keratoconus (KC) and 88 eyes of 88 patients with normal subjects were involved. The As/Ps measured by the anterior segment optical coherence tomography (AS-OCT) and other indices measured by AS-OCT and rotating Scheimpflug–based corneal tomography were evaluated. The area under receiver-operating-characteristics (AU-ROC) was calculated to assess the diagnostic ability in discriminating FFKC from normal eyes. Results: The As/Ps, the Belin/Ambrosio display enhanced ectasia total derivation value (BAD-D) and posterior and anterior elevation values showed the AU-ROC 0.9 or more in differentiating FFKC from normal eyes (0.980, 0.951, 0.924 and 0.903, respectively). The sensitivity and specificity were 0.92 and 0.96 for the As/Ps, 1.00 and 0.90 for BAD-D, 0.85 and 0.86 for posterior elevation value, and 0.85 and 0.96 for anterior elevation value, respectively. Conclusions: Among the several indices for keratoconus screening which we evaluated, the As/Ps obtained by AS-OCT had the large AU-ROC with high sensitivity and specificity in detecting FFKC, which was comparable with BAD-D obtained by rotating Scheimpflug–based corneal tomography. The As/Ps may provide information for improving the diagnostic accuracy of KC, even in the initial stage of the disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the safety of retrocorneal plaque aspiration in patients with fungal keratitis. Study design: Retrospective study. Methods: A retrospective case series of fungal keratitis seen at Kyoto Prefectural University of Medicine between November 2013 and September 2018. Patients with retrocorneal plaque who underwent retrocorneal plaque aspiration for the diagnosis and treatment of fungal keratitis were included. The retrocorneal plaques were either aspirated using a tuberculin syringe with a 27-gauge blunt needle or were directly pulled out using a forceps. The anterior chamber was carefully washed out using bimanual irrigation and aspiration (I/A). Diagnosis accuracy and treatment safety were evaluated. Results: Five eyes of five patients aged 68.4 ± 13.0 years old (range: 45–81 years) were included. Three of the five patients (60%) were positive for fungus obtained from corneal scrapings. Retrocorneal plaque aspiration improved the diagnosis accuracy to five out of five patients (100%), including two cases positive to Fungiflora Y® staining. Three of the five patients (60%) had good response rapidly after retrocorneal plaque aspiration, and two patients received therapeutic keratoplasty. All cases were finally stabilized without severe complications. Conclusion: Retrocorneal plaque aspiration may be useful for the precise diagnosis of fungal keratitis. [ABSTRACT FROM AUTHOR]

Nasolacrimal duct obstruction (NLDO) is thought to be due to inflammation and fibrosis of lacrimal duct epithelial cells (LDECs). Here we investigated the effect of rebamipide, a drug that is used for the protection of the mucosa and the treatment of gastritis and gastroduodenal ulcers, on LDECs, both in vitro and in vivo. In this study, LDECs were cultured from rabbit lacrimal duct tissues, and the barrier function of LEDCs was examined in vitro via transepithelial electrical resistance (TER) measurement, with or without interleukin (IL)-6 and/or rebamipide. For the in vivo examination, benzalkonium chloride (BAC) was injected into the rabbit lacrimal ducts, followed by the application of rebamipide or a placebo vehicle alone. The results of the in vitro examination revealed a significant decrease in TER in the group treated with IL-6 alone compared with the placebo-vehicle group (p < 0.05) and the group treated with IL-6 and rebamipide (p < 0.01). The results of the in vivo examination revealed that the infiltration of neutrophils under the basement membrane and the disruption of tight junction proteins with BAC injection and rebamipide attenuates the disturbance of tissue construction. These results suggest that rebamipide protects LDECs via an anti-inflammatory effect and preserves the barrier function of those cells. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the surgical outcomes of the 27-gauge (G) vitrectomy system for the treatment of primary rhegmatogenous retinal detachment (RRD). Methods: This retrospective consecutive series multicenter study involved a total of 410 eyes of 406 patients who underwent 3-port transconjunctival 27G pars plana vitrectomy (PPV) for RRD between November 2014 and December 2016 and who were followed for a minimum of 3 months postoperative. The main outcome measure was primary reattachment, with the secondary outcome measures being final reattachment, improvement of visual acuity (VA), intraocular pressure (IOP), intraoperative and postoperative complications, and surgery time. Results: Of the 410 treated eyes, primary reattachment was achieved in 392 (95.6%) and final reattachment was achieved in 410 (100%). In 226 eyes (55.1%) with macula-on RRD, the mean logarithm of the minimum angle of resolution (logMAR) VA improved from 0.16 ± 0.51 pre-surgery to 0.02 ± 0.14 post-surgery (P = 0.11). In 184 eyes (44.9%) with macula-off RRD, logMAR VA improved from 1.06 ± 0.77 pre-surgery to 0.26 ± 0.35 post-surgery (P < 0.001). Following surgery, the mean IOP was highest at 1 day (15.7 ± 7.0 mmHg) postoperative. In all eyes, surgery was concluded without the use of sutures or the need of conversion to a larger-gauge instrument. Although hypotony was observed in 14 (3.4%) of the 410 treated eyes at 1 day postoperative, it spontaneously resolved within 1 week without additional surgical intervention. No postoperative complications such as infectious endophthalmitis were observed throughout the follow-up period. Conclusion: Our findings show that 27G PPV is both safe and effective for the treatment of primary RRD. [ABSTRACT FROM AUTHOR]

A healthy corneal epithelium, which is essential for proper vision and protection from external pathogens, is continuously replenished throughout life by stem cells located at the limbus. In diseased or injured eyes, however, in which stem cells are deficient, severe ocular problems manifest themselves. These are notoriously difficult to manage and as a result the last 20 or so years has seen a number of therapeutic strategies emerge that aim to recover the ocular surface and restore vision in limbal stem cell deficient eyes. The dominant concept involves the generation of laboratory cultivated epithelial cell sheets expanded from small biopsies of the epithelial limbus (for patient or donors) or another non-corneal epithelial tissue such as the oral mucosa. Typically, cells are grown on sterilised human amniotic membrane as a substrate, which then forms part of the graft, or specially formulated plastic culture dishes from which cells sheets can be released by lowering the temperature, and thus the adherence of the plastic to the cells. Overall, clinical results are promising, as is discussed, with new cultivation methodologies and different cell lineages currently being investigated to augment the treatment options for visual disturbance caused by a corneal epithelial limbal stem cell deficiency. [ABSTRACT FROM AUTHOR]

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute inflammatory diseases of the skin and mucous membranes such as the ocular surface. This study aimed to evaluate the backgrounds, clinical symptoms, and disease course of SJS/TEN patients in our hospital. We retrospectively collected the data of the medical history, clinical symptoms, examinations, and treatments in patients with SJS or TEN, which were diagnosed in the Department of Dermatology, Kyoto Prefectural University of Medicine Hospital between April 2007 and March 2017. The subjects were 15 patients with SJS and five with TEN. All five children had cold symptoms and took cold medications. On the other hand, 15 adult patients took various types of drugs, such as antibiotics, cold medications, or anticonvulsants. Interestingly, all pediatric patients did not have large skin lesions but suffered from severe eye symptoms, while the severity of their skin and mucous lesions was various in adult patients. All patients were treated with oral corticosteroid therapy. Furthermore, 18 patients were treated with corticosteroid pulse therapy, six with high‐dose immunoglobulin therapy, and one with plasmapheresis. Our findings imply that cold symptoms and cold medicines may be associated with severe ocular involvement in SJS/TEN patients. We retrospectively collected the data of the medical history, clinical symptoms, examinations, and treatments of patients in whom SJS or TEN was diagnosed in the Department of Dermatology, Kyoto Prefectural University of Medicine Hospital between April 2007 and March 2017. All children's patients did not have large skin lesions but suffered from severe eye symptoms, while the severity of their skin and mucous lesions was various in adult patients. Our findings imply that cold symptoms and cold medicines may be associated with severe ocular involvement in SJS/TEN patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular edema (CME) post Descemet’s stripping automated endothelial keratoplasty (DSAEK).Study design: Retrospective observational studyMethods: In this study of 334 patients who underwent DSAEK at the Baptist Eye Institute, Kyoto, Japan between July 2011 and December 2015, 18 patients with postoperative CME (determined by optical coherence tomography) treated with topical NSAIDs after the onset of CME were included.Results: At CME onset, 17 of the 18 patients were treated with bromfenac eye drops and 1 was treated with nepafenac eye drops. Post initiation of treatment with topical NSAIDs, CME in 17 (94.4%) of the 18 patients improved at 1 month and all cases completely recovered within 3 months. At 12-months post initiation of treatment, 61.1% (n = 11) of patients achieved a visual acuity (VA) of 20/40 or better, and there was no significant difference of VA between the patients with or without an episode of postoperative CME (P = 0.55).Conclusion: The administration of topical NSAID eye drops was found to be effective in treating patients with CME post DSAEK. [ABSTRACT FROM AUTHOR]

CD3-negative and CD20-negative cells (red square) were positive for CD2, CD7, CD45, CD56, and HLA-DR, indicating the presence of NK lymphoma cells. Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group. [Extracted from the article]

Objective: To retrospectively identify epidemiological trends of infection on the ocular surface and investigate trends of resistance to bacterial antibiotics compared with 10-years previous for Staphylococcus aureus, coagulase-negative staphylococci (CNS), and Corynebacterium in Japan. Materials and methods: Bacterial isolate samples were collected from the conjunctival sacs of eyes afflicted with conjunctivitis, keratitis, dacryocystitis, and hordeolum from September 2004 through November 2005 (n = 145 isolates) and September 2014 through November 2015 (n = 195 isolates) at the Baptist Eye Institute, Kyoto, Japan. The prevalence of methicillin-resistant S. aureus (MRSA), methicillin-resistant CNS (MR-CNS), and fluoroquinolone-resistant Corynebacterium were examined, and susceptibility of isolated bacteria to levofloxacin (LVFX), cefmenoxime (CMX), chloramphenicol (CP), erythromycin (EM), vancomycin (VCM), and arbekacin (ABK) were compared between both time periods using the disc susceptibility method. Results: Over the 10-year period from initial to final examination, the prevalence of MRSA and MR-CNS significantly decreased from 52% to 22% (P < 0.05) and from 47% to 25% (P < 0.05), respectively, yet there was no change in the prevalence of fluoroquinolone-resistant Corynebacterium (60% and 54%; P = 0.38). Antibiotic-resistance trend analysis revealed that susceptibility to antibiotics in 2014–2015 was similar to that in 2004–2005. MRSA and MR-CNS were susceptible to CP (88%), VCM (100%), and ABK (100%), while fluoroquinolone-resistant Corynebacterium was susceptible to CMX (100%), VCM (100%), and ABK (96%). Conclusion: The prevalence of MRSA and MR-CNS significantly decreased between the two time periods, yet more than 50% of the Corynebacterium isolates were still resistant to LVFX. Although no increase in bacterial resistance to antibiotics was found, a cautionary use of fluoroquinolone eye drops should be considered. [ABSTRACT FROM AUTHOR]

Purpose: To assess corneal endothelial cell loss after penetrating keratoplasty (PK) treatment for laser iridotomy (LI)-induced bullous keratopathy (BK).Methods: A retrospective study conducted on consecutive patients who underwent PK between March 2000 and December 2011. Patients who had undergone more than 24 months of follow-up were included. Patients who underwent PK were subcategorized into two groups based on their diagnosis of BK prior to PK; PK was performed to treat either LI-BK or non LI-BK. The cell density of the central corneal endothelium and the graft survival were evaluated during follow-up.Results: Corneal endothelial cell density decreased in a similar fashion in both the LI-BK and non LI-BK patients, though the cell density decreased significantly faster in the LI-BK group than in the non LI-BK group throughout the 108 months of the study (p = 0.026). The mean cell loss at 36 months for the LI-BK group was 57.7% vs. 63.2% for the non LI-BK, 76.9% vs. 70.1% at 72 months, and 85.6% vs. 72.0% at 108 months. No eye among 21 eyes in the LI-BK group (0%) had failed grafts, whereas 4 of 25 eyes in the non LI-BK group (16.0%) had failed grafts at 60 months (p = 0.114).Conclusions: The outcome of PK for BK secondary to LI was no worse than the outcome of PK for other types of BK. However, our long-term follow-up after PK showed that cell density decreased faster in the LI-BK group than in the non LI-BK, suggesting that cell loss might be involved in the existence of LI prior to PK. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the possible role of the filtration bleb in the continuous decrease in corneal endothelial cell (CEC) density observed following trabeculectomy.Methods: This study involved 51 eyes of 37 glaucoma patients who underwent trabeculectomy. The CEC density was determined by contact specular microscopy in three areas: (1) the cornea center, (2) near the trabeculectomy filtration bleb, and (3) the opposite side of the bleb. The eyes were grouped according to post-surgical follow-up years: 0-1 (Group 1), 1-2 (Group 2), 2-3 (Group 3), 3-4, (Group 4), and 4+ years (Group 5).Results: The mean CEC densities at the opposite side of the bleb, in the cornea center, and near the bleb were 2210 ± 487, 1930 ± 528, and 1519 ± 507 cells/mm2, respectively, in all eyes. The CEC density was significantly lower near the bleb than at the other two sites. The coefficient of variation was significantly higher near the bleb than at the other two sites. The CEC densities at the cornea center and at the opposite side of the bleb showed no significant differences. However, the CEC densities near the bleb showed time-dependent decreases to 1790, 1601, 1407, 1339, and 1224 cells/mm2 for Groups 1, 2, 3, 4, and 5, respectively.Conclusions: CEC density following trabeculectomy decreased near the bleb, but not at the cornea center, suggesting that the involvement of the filtration bleb in CEC density loss should be further examined to elucidate the pathology of CEC loss following trabeculectomy. [ABSTRACT FROM AUTHOR]

It is well known that myogenic regulatory factors encoded by the Myod1 family of genes have pivotal roles in myogenesis, with partially overlapping functions, as demonstrated for the mouse embryo. Myogenin-mutant mice, however, exhibit severe myogenic defects without compensation by other myogenic factors. MYOGENIN might be expected to have an analogous function in human myogenic cells. To verify this hypothesis, we generated MYOGENIN-mutated human iPS cells by using CRISPR/Cas9 genome-editing technology. Our results suggest that MYOD1-independent or MYOD1-dependent mechanisms can compensate for the loss of MYOGENIN and that these mechanisms are likely to be crucial for regulating skeletal muscle differentiation and formation. [ABSTRACT FROM AUTHOR]

The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL) reporter human induced pluripotent stem cells (hiPS) by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021. We found that all SOX10-NL-positive cells expressed an early neural crest marker NGFR, however SOX10-NL-positive cells purified from differentiated hiPS cells progressively attenuate their NL-expression under proliferation. We therefore attempted to maintain SOX10-NL-positive cells with additional signaling on the plane and sphere culture conditions. These SOX10-NL cells provide us to investigate mass culture with neural crest cells for stem cell research. [ABSTRACT FROM AUTHOR]

PAX6, a paired box transcription factor, is necessary for eye development. However, how it regulates the cell identity of human corneal epithelial cells (CECs) is not well understood. We aimed to clarify the function of PAX6 in human CECs using gene knockout via the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) system. We designed guide RNAs for different targets in PAX6. PAX6-depleted CECs maintained the epithelial morphology, but became larger. Global analyses using microarray revealed that down-regulated genes were primarily CEC-specific and included keratin 12, keratin 3, clusterin (CLU), aldehyde dehydrogenase 3 family member A1 (ALDH3A1), angiopoietin-like 7 (ANGPTL7) and transketolase (TKT), while up-regulated genes were primarily epidermis-related and included keratin 10, keratin 1, involucrin (IVL), filaggrin (FLG). These findings suggest that PAX6 maintains CEC identity by regulating differentiation. [ABSTRACT FROM AUTHOR]

To investigate the response to polyinosinic:polycytidylic acid [poly(I:C)], a double-stranded RNA Toll-like receptor 3 agonist that mimics viral infection, in the barrier function of two established human telomerase reverse transcriptase-immortalized cell lines, termed HCLE for the human corneal-limbal epithelial line and HCjE for the human conjunctival-epithelial line. In this study, HCLE and HCjE cells were used to evaluate the underlying mechanism of epithelial-cell barrier function regulation. Briefly, HCLE and HCjE cells were first cultured on 12-well Transwell® (Corning®) filter-plates, and reverse transcription-polymerase chain reaction, western blotting, and immunohistochemical examinations were then performed to assess tight junction (TJ)-related protein expression and cellular distribution. Next, the barrier function of the cells was measured via transepithelial electrical resistance (TEER) and paracellular molecular flux. The cells were then stimulated with poly(I:C) and the TEER and TJ-related protein expressions were analyzed. Similar to that in in vivo epithelium, the expression of claudin (CLDN) subtypes CLDN-1, -4, and -7 was observed in the HCLE and HCjE cells, and the barrier function in the HCLE cells was tighter than that in the HCjE cells. Post stimulation with poly(I:C), TEER of the HCLE and HCjE cells increased in a dose- and time-dependent manner, the production of TJ-related protein mRNA and CLDN-4 protein were elevated, and the barrier function of the HCLE and HCjE cells increased, thus possibly indicating that the increased barrier function is a defense mechanism against viral infection. • Poly(I:C) is a synthetic analog of double-stranded RNA. • Poly(I:C) increases the barrier of hTERT immortalized corneal and conjunctival epithelia in a dose- and time-dependent manner. • Production of TJ-related protein mRNA and claudin-4 protein are elevated post stimulation with poly(I:C). • Most viruses synthesize dsRNA during their replication, and poly(I:C) stimulation mimics a viral infection. • Thus, we theorize that the increased barrier function must be a type of host defense reaction against viral infections. [ABSTRACT FROM AUTHOR]

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are drug-induced acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface. Even after recovery from skin symptoms, some SJS/TEN patients continue to suffer with severe ocular complications (SOCs). Therefore, this study aims to understand the pathophysiology of chronic SOCs. Because plasma lipid profiling has emerged as a useful tool to understand pathophysiological alterations in the body, we performed plasma lipid profiling of 17 patients who suffered from SJS/TEN-associated chronic SOCs. A lipidomics approach yielded 386 lipid molecules and demonstrated that plasma levels of inflammatory oxylipins increased in patients with SJS/TEN-associated chronic SOCs. In addition, oxidized phosphatidylcholines and ether-type diacylglycerols increased in the patients with chronic SOCs, while phosphoglycerolipids decreased. When we compared these lipidomic profiles with those of patients with atopic dermatitis, we found that patients with chronic SOCs, specifically, had decreased levels of ether-type phosphatidylcholines (ePCs) containing arachidonic acid (AA), such as PC(18:0e/20:4) and PC(20:0e/20:4). To confirm our finding, we recruited additional patients, who suffered from SOC associated with SJS/TEN (up to 51 patients), and validated the decreased plasma levels of AA-containing ePCs. Our study provides insight into the alterations of plasma lipidomic profiles in chronic SOCs and into the pathophysiology of SJS/TEN-associated chronic SOCs. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relation between visual function, clinical findings, and visual symptoms in Stevens-Johnson syndrome (SJS) and to compare the results with Sjögren syndrome (SS) patients and normal subjects. Design: Cross-sectional comparative study. Methods: One hundred fifteen eyes of 59 consecutive patients with SJS and toxic epidermal necrolysis (TEN), 208 eyes of 104 healthy normal subjects, and 132 eyes of 66 SS patients were investigated in this multicenter study. All study subjects underwent tear function and ocular surface examinations, Landolt and functional visual acuity examinations, and the Japanese version of the NEI VFQ-25 (National Eye Institute Visual Function Questionnaire). Results: The mean ocular surface grading scores were significantly higher and the mean score of all 12 NEI VFQ subscales was significantly lower in the SJS patients compared to the SS patients and the normal subjects (P < .05). The conventional and functional logarithm of minimal angle of resolution (logMAR) visual acuities in SJS patients with minimal corneal complications were significantly higher and the mean total composite NEI VFQ scores were lower compared to SS patients. The conventional and functional logMAR visual acuities and the mean ocular surface grading scores in SJS with aqueous deficiency were significantly higher and the mean total composite NEI VFQ scores were lower compared to SS patients. Strong correlations between best-corrected logMAR functional visual acuities and either ocular surface grading scores or the composite NEI VFQ-25 scores were observed. Conclusions: The functional visual acuity examination reflects the severity of clinical ocular surface findings and vision-related quality of life more than the standard conventional visual acuity in SJS. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the correlation of functional visual acuity (FVA) measurement with ocular surface findings in patients with Stevens-Johnson syndrome (SJS). Design: Prospective comparative study. Methods: Sixty-nine eyes of 38 patients with chronic SJS assessed at the Tokyo Dental College, Tokyo Medical Center, and the Kyoto Prefectural University of Medicine, Department of Ophthalmology, Kyoto, Japan, were studied. Twenty eyes of 10 normal subjects and 40 eyes of 20 patients with Sjögren syndrome (SS) were also studied. Conventional Landolt visual acuity (VA) and FVA examinations and slit-lamp examinations were performed. FVA was measured continuously by the FVA measurement system during a 30-second blink-free period in one eye. The visual maintenance ratio (VMR) was calculated as follows: VMR = [(2.7 − FVA)/(2.7 − baseline VA)], where logarithm of minimal angle of resolution values of FVA were entered into the formula and 2.7 represented the lowest visual acuity in this series. Slit-lamp examinations, Schirmer test, and fluorescein vital stainings were also performed in all subjects. Results: VMR was markedly lower in patients with SJS compared with patients with SS and controls. FVA values showed a relation with the presence of corneal opacity and vascularization. Conclusions: The FVA measurement system is not only a useful tool in the evaluation of dynamic VA changes, but also reflects the ocular surface clinical findings in SJS. [Copyright &y& Elsevier]

Purpose: To perform a midterm assessment of the integrity and reproducibility of cultivated autologous oral mucosal epithelial sheets, and to evaluate the clinical efficacy of their transplantation in ocular surface. Design: Observational case series. Methods: Cultivated autologous oral mucosal epithelial sheets were created using amniotic membrane and buccal mucosal epithelium from 12 patients with Stevens-Johnson syndrome, chemical and thermal injury, pseudo-ocular cicatricial pemphigoid, and idiopathic ocular surface disorder. They were transplanted onto 15 eyes from these patients who were then followed up for a mean of 20 months; with the longest follow-up being 34 months. We assessed their clinical outcomes with special reference to neovascularization. Results: Cultivated autologous oral mucosal epithelial sheets could be generated from all patients. On the second postoperative day, 14 of 15 sheets transplanted demonstrated total re-epithelialization on the cornea. During the follow-up, the ocular surface was stable and transparent without any major complications in 10 of 15 eyes (67%), and the transplanted epithelium survived for at least 34 months. There were five eyes (33%) with small but long-standing epithelial defects, three of these healed spontaneously, and two (13%) required reoperation. In 10 eyes, postoperative visual acuity was improved by more than 2 lines. All eyes manifested some peripheral corneal vascularization. Conclusions: We established a successful tissue-engineering technique to generate cultivated autologous oral mucosal epithelial sheets and succeeded in reconstructing the ocular surface. We suggest that this surgical modality may be both safe and useful, especially in younger patients with the most severe ocular surface disorders. [Copyright &y& Elsevier]

To explore new molecular targets for therapy in human model systems by discerning the role of extracellular vesicle (EV) microRNAs (miRs) secreted by human retinal pigment epithelium (hRPE) cells and their cellular interplay with macrophages (Mps). Human Mps differentiated from THP-1 cells stimulated by phorbol myristate acetate were co-cultured with induced pluripotent stem cell-derived differentiated hRPE (iPS-hRPE) cells in Transwell® system separated by 0.40 μm or 0.03 μm filters. EV-associated CD63+ proteins (CD63+ EV) were detected by western blotting, and secreted EVs were analyzed by Nanosight tracking. The miR profiles of the secreted EVs were determined using 3D-gene human microRNA chips (Toray Industries, Inc.). Levels of CD63+ EV were increased in co-cultures concomitantly with the increased production of EV particles (50–150 nm). The increased production of EVs was associated with higher production of MCP-1, IL-6, IL-8 from hRPE cells, and VEGF and repressed production of TNF-α from Mps and pigment epithelium-derived factor (PEDF) from RPE cells. Ultracentrifugation of semi-purified EVs increased the secretion of these pro-inflammatory cytokines and EV particles from hRPE cells, but this effect was eliminated in transwells equipped with 0.03 μm filters, whereas no repression of PEDF and TNF-α secretion occurred. 3D-gene miR analysis revealed a selective increase in secretion of miR494-3p in EVs from iPS-hRPE cells during the interplay with Mps. The miRs in EVs secreted by hRPE cells may have a critical role in the vicious inflammatory cycle, whereas repression of TNF-α and PEDF require cell-to-cell contact that is independent of EVs or exosomes. MiR494-3p may be a candidate molecular target of diagnosis and therapy for age-related macular degeneration. • CD63+EV was increased in co-cultures of iPS derived hRPE cells with macrophages from THP-1. • The increase of EVs was associated with the production of MCP-1, IL-6, IL-8, and VEGF from hRPE. • EV-miRNAs aggravate inflammatory cycles, while TNF-α and PEDF was repressed independent of EV. • MiRNA494-3p was found in EV secreted by hRPE through the interplay with macrophages. [ABSTRACT FROM AUTHOR]