To investigate the association between subjective symptoms and severity in patients with Fuchs endothelial corneal dystrophy (FECD). Observational case series. This study included patients with FECD registered in the Japanese National FECD registry with recorded subjective symptoms, including morning blur, ocular pain, visual disturbance, and glare. Severity assessments included central corneal thickness (CCT) and modified Krachmer grading using the more severely affected eye with greater CCT for each patient. The area under the curve (AUC) was used to evaluate the predictive ability of subjective symptoms based on disease severity. This study included 137 cases (mean age: 69±11 years; men, n=32) with subjective symptom records. The threshold values of CCT for predicting subjective symptoms based on the Youden index were 623 µm for morning blur compared to that at night (AUC, 0.76), 653 µm for ocular pain (AUC, 0.79), 623 µm for visual disturbance (AUC, 0.69), and 581 µm for glare (AUC, 0.60). The threshold values of the modified Krachmer grading for predicting subjective symptoms were grade 5 for morning blur compared to that at night (AUC, 0.85), and grade 6 for ocular pain (AUC, 0.79), grade 5 for visual disturbance (AUC, 0.72), and grade 4 for glare (AUC, 0.70). The predictive ability of subjective symptoms based on disease severity in patients with FECD was relatively high using the modified Krachmer grading. The severity threshold for each subjective symptom was considered helpful in deciding on interventional treatment.

[This corrects the article DOI: 10.1371/journal.pone.0258688.].

PURPOSE:To report the results of a national survey on corneal transplantation in Japan. METHODS:The Japan Cornea Society and the Keratoplasty Society of Japan conducted a national survey on corneal transplantation performed from 2017 to 2019. Data from various institutions were collected through an online database and subsequently analyzed. RESULTS:In total, 4951 cases from 44 facilities were documented. The leading cause of corneal transplantation was corneal edema (CE), which accounted for 39.3% of cases, followed by repeat keratoplasty at 27.7%. Among CE cases, postcataract surgery was the most prevalent (25.1%), followed by postglaucoma surgery (20.8%) and laser iridotomy-induced CE (18.2%). Fuchs endothelial corneal dystrophy was the fourth most common cause (10.9%). Regarding surgical methods, Descemet stripping automated endothelial keratoplasty was the most common, used in 41.3% of procedures, followed by penetrating keratoplasty at 37.1%. Deep anterior lamellar keratoplasty and Descemet membrane endothelial keratoplasty were used in 8.1% and 2.6% of cases, respectively. One year after transplantation, graft clarity was maintained in 80.5% of cases, and regrafting was necessary in 15.2% of instances. CONCLUSIONS:The national survey reveals that CE is the most frequent indication for corneal transplantation in Japan. Increases in cases from glaucoma surgery and Fuchs endothelial corneal dystrophy were noted among patients with CE. Endothelial keratoplasty, especially Descemet stripping automated endothelial keratoplasty, is now the preferred surgical technique for these transplants.

This study investigated corneal epithelial thickness and its distribution in keratoconus (KC) and forme fruste keratoconus (FFK). A total of 35 KC eyes, 25 FFK eyes, and 35 control eyes underwent anterior segment-optical coherence tomography for corneal epithelial evaluation. Sixty KC eyes were included for the assessment of epithelial changes according to KC severity. Epithelial thickness in the central, paracentral, and peripheral areas-each subdivided into eight zones-was statistically analysed. Minimum, maximum, and average epithelial thicknesses were reduced in KC eyes, especially in the inferior and inferior-temporal zones. Standard deviations were greater in KC eyes across nearly all zones. In FFK and KC eyes, the differences between superior and inferior epithelial thickness were significantly altered compared to control eyes. According to the Amsler-Krumeich classification, more advanced KC stages were associated with greater corneal thinning. Epithelial heterogeneity decreased in the central and paracentral area as a result of superior epithelial thinning, whereas it increased in the peripheral area with KC progression. Epithelial thickness and distribution were altered in KC and even in FFK eyes with normal topography. Different stages of KC may exhibit distinct epithelial remodelling patterns.

Keratoconus is a condition that causes progressive thinning and anterior protrusion of the cornea. Because of its irregular astigmatism, mild to moderate keratoconus is corrected with hard contact lenses (HCL), but blepharoptosis due to long-term wear is often a problem. In this study, we investigated blepharoptosis in hard contact lens wearers with keratoconus. Thirty seven keratoconic eyes were enrolled and divided into several groups according to their wearing history or age. Eyelid margin distance (EMD), margin light reflex distance-1 (MRD-1) and eyelid elevator muscle function were measured by ruler or anterior segment optical coherence tomography. EMD decreased with years of HCL wear but showed no correlation with age; MRD-1 decreased with years of wear and with older age; LF showed no relationship with either years of wear or age. In the classification of ptosis, there was no severe ptosis in the present sample. Long-term wear of HCLs is likely to cause blepharoptosis even in keratoconic eyes, but its degree may be mild.

To investigate the associations of tomographic parameters in anterior segment optical coherence tomography (AS-OCT) with sex and age in a cohort study. A cohort design. AS-OCT data from 391 Japanese participants aged ≥ 35 years were obtained using swept-source OCT. In the cornea, the keratometric power at the flat (Kf) and steep (Ks) meridians, maximum keratometric power (Kmax), keratometric cylinder, spherical power, regular astigmatism, asymmetry, higher-order irregularity (HOI) from the anterior and posterior surfaces, and the central and thinnest corneal thicknesses were evaluated. Also, anterior chamber depth (ACD), lens thickness, crystalline lens rise (CLR), and nasal and temporal angle opening distances at 500 μm from the scleral spur (AOD500) were assessed. Sex differences and age-related changes were analyzed. Women exhibited higher anterior Kf, Ks, and Kmax and lower posterior Kf, Ks, and Kmax than men. The ACD and nasal/temporal AOD500 were shorter in women than in men. The CLR was higher in women, whereas the lens thickness did not differ between the sexes, indicating a more anteriorly positioned lens in women. Age-related changes included increased anterior/posterior HOI, increased lens thickness and CLR resulting in decreased ACD and AOD500. This study reveals sex-related differences in corneal shape, anterior chamber conformation, and lens position, as well as age-related changes in tomographic parameters. ACD, CLR, nasal and temporal AOD500 showed significant sex differences in the 50–70 s, whereas lens thickness showed no difference.

Conclusion:Our data, demonstrating the eradication of bacteria and the prevention of resistance by the combination of ciprofloxacin and phages, call for in vivo experiments to probe their clinical translation.These results constitute a proof-of-concept for innovative therapeutic strategies against Gram-negative pathogens in veterinary medicine, combining phages and veterinary antimicrobials.

Purpose: The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography. Methods: We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors. Results: In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side. Conclusions: Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal.

Descemet's membrane endothelial keratoplasty (DMEK) for patients with corneal endothelial loss rarely results in graft rejection. Herein, we report a rare case of graft rejection following DMEK, in which peripheral anterior synechiae were observed postoperatively. A 66-year-old woman was referred to our hospital after complaints of decreased visual acuity of her right eye after laser iridotomy for primary angle closure 3 years earlier. Her right cornea had bullous keratopathy with mild cataract, and her best-corrected visual acuity (BCVA) was 20/40. After cataract surgery, DMEK was successfully performed, except for development of peripheral anterior synechiae at the temporal cornea. Her BCVA recovered to 20/20. However, when topical instillation was changed to 0.1% fluorometholone from 0.1% betamethasone once a day, corneal edema reappeared with hyperemia, mutton fat keratic precipitates (KPs), and cells in the anterior chamber. The BCVA worsened to 20/32. Graft rejection was diagnosed, and subconjunctival injection of dexamethasone was performed 3 times, once every few days, with 0.1% topical betamethasone instillation. Subsequently, the hyperemia, mutton fat KPs, and cells in the anterior chamber disappeared with a recovered BCVA of 20/20 after 2 weeks. Ten months after graft rejection, there was no recurrence of intraocular inflammation, and only topical betamethasone was administered twice daily. It is important to exercise caution in cases with peripheral anterior synechiae after DMEK. Long-term steroid administration is necessary to prevent graft rejection.

The purpose of this study was to evaluate corneal irregular astigmatism of patients with granular and lattice corneal dystrophy (GCD and LCD). 70 GCD, 35 LCD, and 81 control eyes were included. Anterior and posterior corneal topographic data obtained from anterior segment optical coherence tomography were expanded into four components via Fourier harmonic analysis. These components were compared with healthy eyes and the association between each component and best-corrected visual acuity (BCVA) was investigated. Anterior and posterior components increased in both GCD and LCD eyes. Anterior and posterior components of GCD2, anterior of LCD type 1 (LCD1), posterior of LCD type IIIA (LCD 3A), and type IV (LCD4) significantly increased. BCVA was significantly associated with anterior and posterior components in LCD eyes but not in GCD. The anterior components of LCD1, anterior and posterior of LCD3A, and posterior of LCD4 , were positively correlated with BCVA. As conclusions, in GCD eyes, anterior and posterior components differed from those of the control but BCVA was not significantly associated with them. In LCD eyes, the anterior and posterior components increased, and BCVA was significantly associated with the anterior and posterior components.

Graft detachment after Descemet stripping automated endothelial keratoplasty (DSAEK) is usually managed with air-bubbling. However, it is an invasive procedure, which can cause corneal endothelial reduction, and requires hospitalization and supine position maintenance. Only few case reports on graft reattachment in the prone position exist, and this is the first report from Japan. An 87-year-old woman presented with sudden pain in her left eye. Examination of her left eye showed a best-corrected vision of 20/50, shallow anterior chamber, cataractous lens, central corneal thickness (CCT) of 630 μm, and corneal endothelial cell count of 467 cells/mm2. She was diagnosed with left-eye bullous keratopathy due to primary angle closure, and DSAEK was performed after cataract surgery. Post-surgery, she touched her left eye due to agitation. Graft adhesion was good until postoperative day 4; however, a partial detachment was observed on day 12. She was instructed to remain in a prone position for as long as possible; on day 22, the graft was reattached, and the CCT improved to 555 μm. Since then, the graft adhesion has been maintained, and her best-corrected vision has improved to 20/30. To date, 5 cases of graft reattachment in the prone position have been reported, with reattachment observed in all cases within 10 days from the onset of detachment, including this case. Re-bubbling is an effective technique; however, it is invasive and may cause additional corneal endothelial loss. Therefore, it may be beneficial to have the patient initially attempt the prone position for reattachment.

Purpose: Irregular corneal epithelium in limbal stem cell disease can cause visual acuity to deteriorate substantially when it reaches the pupil. In this case series, we assessed the effectiveness of simple corneal epithelial superficial keratectomy in improving visual acuity in patients with irregular corneal epithelium in focal limbal stem cell disease covering the visual axis. Observations: We performed simple corneal epithelial superficial keratectomy in four patients (five eyes) with irregular corneal epithelium covering the visual axis. The main outcome measures were best-corrected visual acuity, slit lamp findings with fluorescein staining, anterior segment optical coherence tomography and histopathology. In all five eyes, slit lamp findings showed uneven fluorescein staining in a spiral pattern, with impaired corneal epithelial smoothness and visual disturbance. We removed the irregular epithelium in all five eyes. Visual acuity in all the eyes was improved immediately after surgery, and good visual acuity and stable epithelium were maintained for the duration of the observation periods. Hematoxylin and eosin staining showed, normal squamous and columnar epithelial cells. Goblet cells were not detected. Conclusionsand Importance: Corneal epithelial superficial keratectomy can lead to a pathological diagnosis by examining the removed epithelial tissues, and result in excellent therapeutic outcomes in focal limbal stem cell disease reaching the pupil.

Objective To assess the long-term efficacy and safety of accelerated transepithelial corneal cross-linking (ATE-CXL) with 30 mW/cm2 × 3 min. Methods and Analysis Thirty-four eyes of 23 patients with progressive keratoconus (KCN) recruited within a single centre were enrolled in this prospective interventional study. Exclusion criteria included: history of Descemet’s membrane rupture, glaucoma, uveitis, severe dry eye, concurrent corneal infections, and systemic disease that could affect corneal healing. ATE-CXL was performed with 3 min of ultraviolet-A continuous irradiation (30 mW/cm2). Follow-up examinations were scheduled on postoperative day 1; 1 and 2 weeks; 1, 3 and 6 months; and 1, 2 and 3 years. Main outcome measures were maximum corneal power (Kmax), average corneal power (AvgK), steepest corneal power (Ks), central corneal thickness, thinnest corneal thickness, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA) and endothelial cell density. Results Mean Kmax, AvgK, Ks, UCVA, BCVA and endothelial cell density did not significantly change over 3 years. The speed of progression obtained by linear regression analysis on corneal parameters (Kmax, AvgK, Ks) improved after ATE-CXL. All baseline parameters correlated with the postoperative Kmax slope. Two eyes underwent ATE-CXL redo because of continued progression after the primary CXL. Conclusion This is the first report of 3-year results of ATE-CXL with 30 mW/cm2 × 3 min. ATE-CXL (30 mW/cm2 × 3 min) was safe and effective for slowing down KCN progression. Trial registration number This study was registered with ID UMIN000009372 in UMIN-Clinical Trials Registry.

Peripheral ulcerative keratitis (PUK) is a non-infectious ulcer at the peripheral corneal stroma. Autoimmune diseases can cause PUK, but PUK caused by large vessel vasculitis (LVV) has rarely been reported. We report the case of a 71-year-old woman with complaints of low-grade fever and left eye pain. Ophthalmologic examination revealed PUK in the left eye, and we diagnosed LVV by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) findings. The patient was treated with topical betamethasone eye drops for PUK and oral prednisolone for LVV. This case suggests that LVV can cause PUK.