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IMPORTANCE: Whether guttae in Fuchs endothelial corneal dystrophy (FECD) can be removed by polishing without Descemet stripping and whether postoperative maintenance of reduced guttae can be achieved through cultured corneal endothelial cell (CEC) transplant therapy are critical issues to be addressed. OBJECTIVE: To investigate the decrease of guttae through polishing degenerated CECs and abnormal extracellular matrix (ECM) without Descemet stripping and to observe the behavior of guttae following cultured CEC transplant. DESIGN, SETTING, AND PARTICIPANTS: This case series prospective observational study was conducted in a hospital outpatient clinic setting. Between December 2013 and January 2019, 22 eyes with corneal endothelial failure caused by FECD received cultured CEC transplant therapy at Kyoto Prefectural University Hospital. Of these, 15 eyes were consistently monitored at the same central corneal area during the preoperative phase, as well as in the early (within 1 year) and late (after 3 years) postoperative phases. The images from these phases were categorized into 3 groups: typical guttae, atypical guttae, and no guttae. EXPOSURES: Cultured CEC transplant therapy. MAIN OUTCOMES: Proportion of guttae in the observable area was measured, comparing the early and late postoperative phases for each group. RESULTS: The mean age of the patients at the time of surgery was 69 years (range, 49-79 years). All 15 eyes exhibited the presence of confluent guttae preoperatively (100%). Among these, 3 of 15 eyes belonged to male patients. The early postoperative phase of guttae morphologies was classified into 3 groups: 5 eyes with typical guttae, 7 with atypical guttae, and 3 with no guttae. The decrease in the number of these guttae was achieved by surgical procedures. The median percentage of guttae in the typical guttae, atypical guttae, and no guttae groups was 41.8%, 44.4%, and 16.2%, respectively, in the early phase, and 42.2%, 38.2%, and 18.8%, respectively, in the late phase. CONCLUSIONS AND RELEVANCE: The findings demonstrate that in some cases of FECD, guttae can be removed by scraping and polishing abnormal ECM and degenerated CECs, while preserving the Descemet membrane. Furthermore, cultured CEC transplant resulted in no increase in guttae for up to 3 years, providing insights into surgically eliminating guttae.

PurposeTo provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy.DesignRetrospective cohort.MethodsIn 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively.ResultsThis study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed.ConclusionIn patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation.

Brief summary: In the new classification system using central serous chorioretinopathy international group criteria, the complex type has distinct genetic and clinical characteristics compared with the simple type.

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Recently, the prescription of large-diameter rigid gas-permeable contact lenses (CLs), also known as “scleral lenses,” “corneoscleral lenses,” and “limbal-rigid CLs,” is on the rise for the treatment of both moderate and severe ocular surface disorders (OSDs). Compared with scleral lenses, the diameter of limbal-rigid CLs is generally smaller, that is, a diameter ranging from 13.0 to 14.0 mm, and they are designed so that the peripheral edge bears on the limbus. The Suncon Kyoto-CS (Sun Contact Lens Co., Ltd.) is a novel limbal-rigid CL design with multistep curves on the peripheral edge for easy tear exchange during blinking that removes debris and prevents lens clouding or fogging, thus allowing patients to enjoy a longer daily duration of CL wear. In severe OSD cases, limbal-rigid CL wear after surgery is a noninvasive therapeutic approach that can neutralize corneal irregularities, decrease dry eye symptoms, prevent the progression or recurrence of symblepharon, and improve the patient's visual acuity and overall quality of life. Thus, surgeries such as amniotic membrane transplantation and cultivated oral mucosal epithelial transplantation, as well as limbal-rigid CL wear, which is noninvasive, are valuable and effective treatment strategies that can now be applied for the management of patients afflicted with severe OSDs.

Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED.

Corneal epithelial stem cells (CEpSCs) mostly reside at the limbal area and are responsible for tissue homeostasis throughout life. Once complete CEpSC deficiency occurs, regenerative medicine cell-based therapy using CEpSCs or their alternatives can provide successful clinical outcomes. Due to an improved understanding of CEpSCs and mucosal epithelial stem cells, major advancements have been made over the past few decades in in vivo and ex vivo cell-based ocular surface reconstruction therapies for the treatment of severe ocular surface diseases. New therapeutic concepts and clinical strategies are emerging for the treatment of corneal endothelial dysfunction. For example, unlike corneal epithelial cells, in vivo corneal endothelial cells (CECs) stop proliferating and are arrested in the G1 phase of the cell cycle due to cell-to-cell contact inhibition and exposure to a high concentration of transforming growth factor-beta in the aqueous humor. Thus, the production of CECs with good functionality in culture has consistently been difficult. To solve this problem, Rho-associated protein kinase inhibition has taken center stage, as it not only makes the production of human CECs in culture closely mimic the functional characteristics of in vivo healthy CECs possible but also helps sustain those biological properties. Thus, cultured human CEC injection therapy is now moving to the forefront for the treatment of corneal endothelial failure. Herein, we summarize key historical discoveries in corneal cell–based regenerative medicine and illustrate the concept of corneal cell therapy for the treatment of refractory corneal epithelial and endothelial diseases.

Background/aimsTo investigate the long-term outcomes of cultivated oral mucosal epithelial transplantation (COMET) for fornix reconstruction in eyes with chronic cicatrising disease.MethodsThis retrospective cohort study involved 16 eyes of 15 patients who underwent COMET for symblepharon release and fornix reconstruction between June 2002 and December 2008. The mean postoperative follow-up period was 102.1±46.0 months (range: 32–183 months). The treated cicatrising disorders included ocular cicatricial pemphigoid (OCP, five eyes), thermal/chemical injury (three eyes) and other chronic diseases (seven eyes; including recurrent pterygium (two eyes), Stevens-Johnson syndrome (one eye) and graft-versus-host disease (one eye)). Ocular-surface appearance was evaluated before surgery, at 1, 4, 12 and 24 weeks postoperative, and then annually based on the previously reported scoring system. Main outcome measures included overall and disease-specific fornix-reconstruction success probabilities analysed by the Kaplan-Meier survival curve. Symblepharon/fornix-shortening recurrence at 24 weeks postoperative, and its relationship to long-term surgical success was also examined.ResultsAt 5 years postoperative, the mean±SD overall fornix-reconstruction success probability was 79.6%±10.7%, and success probability for thermal/chemical injury and OCP was 100% and 53.3%±24.8%, respectively (p=0.53, log-rank test). The 3-year success probability was significantly higher in the no-disease-recurrence group at 24 weeks postoperative (13 eyes) than in the disease-recurrence group (three eyes) (100% and 33.3%±27.2%, respectively) (p=0.0073, log-rank test).ConclusionCOMET was found to be safe and effective for symblepharon release and long-term fornix reconstruction in eyes with chronic cicatrisation. Although the 5-year success probability differed depend on the underlying disease, ocular-surface appearance at 24 weeks postoperative is a factor for predicting long-term outcome.

Background/AimsTo investigate the time-dependent change of corneal endothelial cell (CEC) morphology and density (CECD) in patients with glaucoma post instillation of rho-associated protein kinase inhibitor ripasudil (Rip) 0.4% eye drops.MethodsThis observational study involved 163 eyes of 163 patients with glaucoma in whom CEC morphological change was evaluated by CECD calculated via non-contact specular microscopy (NCSM) before and at 1 or 3 months post-Rip instillation. The change of CECD was plotted along with elapsed time from last instillation of Rip. The patients were divided into the following three groups based on the elapsed time post-Rip instillation: Early Group (<2 hours), Middle Group (≥2 hours, yet <6 hours) and Late Group (≥6 hours). The rate of CECD change was then analysed and compared among the three groups. An additional eight eyes of four patients with glaucoma were enrolled for a time-dependent study, with NCSM images evaluated before and at 1, 2, 3, 4 and 6 hours post-Rip instillation.ResultsMorphological changes in the CECs appeared within 1 hour and recovered to normal within 6 hours post instillation. In the Early, Middle and Late Group, the median rate of CECD change as calculated by the NCSM automated software was −5.68%, −4.95% and −0.07%, respectively. The CEC images showed the same morphological changes with observational study in all four cases.ConclusionDue to transient morphological changes, the NCSM software produced misleading data for determining CECD within 1 hour post-Rip instillation, yet revealed that CEC morphology gradually recovered to normal within 6 hours.

Nasal screening is performed to avoid the complications of postoperative surgical site infections (SSI), especially those due to antimicrobial-resistant species such as methicillin-resistant Staphylococcus aureus(MRSA). This study examined the relationship between bacterial isolates from the conjunctiva and the nasal cavity.

Background/aimsTo evaluate the axial length (AL) and refractive status in central serous chorioretinopathy (CSC).MethodsThis retrospective observational case series involved 140 patients with CSC (180 eyes) and 78 age-matched and gender-matched control subjects. A detailed ophthalmic examination was performed, including an interferometer measurement of AL. Multimodal imaging comprised colour fundus photography, fluorescein angiography, indocyanine green angiography, fundus autofluorescence photography and spectral domain optical coherence tomography.ResultsEighty eyes of 40 patients were categorised into the bilateral-CSC (b-CSC) group and 100 eyes of 100 patients were categorised into the unilateral-CSC (u-CSC) group. AL of the b-CSC (23.19 mm) and u-CSC (23.75 mm) groups was significantly shorter than that of the control (24.85 mm) group (p<0.001 for both). Moreover, AL was significantly shorter in the b-CSC group than in the u-CSC group (p=0.020). Spherical equivalent (SE) in the b-CSC (0.25 D) group was significantly greater than in the u-CSC (−0.81 D) and control (−1.38 D) groups (p<0.001 for both). Gender (male; OR 4.55; 95% CI 1.13 to 18.40; p=0.033), AL (OR 0.38; 95% CI 0.23 to 0.63; p<0.001), area of choroidal vascular hyperpermeability (OR 1.08; 95% CI 1.03 to 1.13; p=0.002) and presence of descending tract (OR 7.22; 95% CI 1.86 to 28.00; p=0.004) were the variables found to be significantly associated with b-CSC via multiple regression analyses.ConclusionAnatomical features, such as shorter AL and greater SE, may be associated with the pathogenesis of CSC.

Background/aimsIn a previous genome-wide association study of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) patients we reported the association between SJS/TEN and the prostaglandin E receptor 3 (PTGER3) gene, and that its protein PGE2receptor 3 (EP3) was markedly downregulated in the conjunctival epithelium of SJS/TEN patients. Here we examined EP3 expression of the eyelid epidermis in SJS/TEN patients with severe ocular complications and investigated the function of EP3.MethodsFor the immunohistochemical study, we obtained eyelid samples from five SJS/TEN patients and five patients without SJS/TEN (control subjects) who were undergoing surgery to treat trichiasis, and investigated the expression of EP3 protein in the epidermis of those samples. To investigate the EP3 function in the human epidermal keratinocytes, we performed ELISA and quantitative reverse transcription polymerase chain reaction, since it is reported that PGE2suppresses cytokine production via EP3 in human conjunctival epithelium.ResultsThe results of the immunohistochemical study revealed that EP3 expression in the eyelid epidermis of the SJS/TEN patients was the same as that in the controls. PGE2and a selective EP3 agonist suppressed cytokine production and expression induced by polyinosine-polycytidylic acid stimulation, such as chemokine ligand 5 and chemokine motif ligand 10.ConclusionOur findings revealed that in chronic-phase SJS/TEN, EP3 protein was expressed in the eyelid epidermis and was not downregulated, unlike in conjunctival epithelium, and that PGE2could suppress cytokine production via EP3 in human epidermal keratinocytes. Thus, EP3 expression in the epidermis might contribute to a silencing of skin inflammation in chronic-phase SJS/TEN.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, severe mucocutaneous adverse reactions. Severity prediction at early onset is urgently required for treatment. However, previous prediction scores have been based on data of blood tests.

PurposeTo investigate spontaneous resolution of congenital nasolacrimal duct obstruction (CNLDO) beyond 12 months of age in Japanese infants.MethodsRetrospective, observational case series. We retrospectively reviewed the clinical records of patients diagnosed with CNLDO beyond 12 months of age at Kyoto Prefectural University Hospital, Kyoto, Japan. This study involved 155 cases of CNLDO in 133 Japanese infants diagnosed with CNLDO. All patients chose intervention with either dacryoendoscopic guided probing and stenting or conservative management. The proportion and age of patients who had spontaneous CLNDO resolution were analysed.ResultsThe patients were divided into two groups: (1) 62 patients with 70 obstructed nasolacrimal ducts (45%) in whom spontaneous resolution occurred and (2) 71 patients with 85 obstructed nasolacrimal ducts (55%) who underwent dacryoendoscopic guided probing and stenting. The mean age of spontaneous resolution was 17.8±5.3 months (range: 12.0–35.4 months). Dacryoendoscopic guided probing and stenting were successful in 83/85 (97.6%) of cases.ConclusionsSpontaneous resolution of CNLDO can occur in 45% of infants over the age of 12 months. Dacryoendoscopic guided stenting also has high success rates in this patient group, and both treatment options can be proposed to caregivers.

Background/aimsTo investigate the efficacy of topical ganciclovir (GCV) for preventing disease recurrence and improving the surgical outcome post-Descemet’s stripping automated endothelial keratoplasty (DSAEK) in patients with cytomegalovirus (CMV) endotheliitis.MethodsThis prospective, non-comparative case series study involved six eyes of six patients with endothelial decompensation due to CMV endotheliitis who underwent DSAEK, followed by a continuous, four to six times daily, topical administration of 0.5% GCV. Patient demographics, clinical history, and preoperative and postoperative examination (including any recurrence of CMV endotheliitis post-DSAEK), best corrected visual acuity (BCVA), intraocular pressure (IOP), graft survival rate and endothelial cell density (ECD) were examined.ResultsNo recurrence of CMV endotheliitis was detected post-DSAEK. The mean follow-up period was 40 months (range, 12–60 months). The mean preoperative BCVA was 1.52±0.68 LogMAR (range, 0.52–2.40 LogMAR), yet it had significantly improved to 0.15±0.16 LogMAR (range: −0.08 to 0.30 LogMAR) by 1 year postoperative (P<0.01). In all patients, IOP was well controlled (10–20 mm Hg) postsurgery. The mean preoperative donor ECD was 2692±177 cells/mm2, and the mean postoperative ECD was 1974, 1771 and 1174 cells/mm2for the ECD loss of 26%, 33% and 54% at 6, 12 and 36 months, respectively. No adverse effects were observed associated with the long-term topical administration of GCV.ConclusionThe continuous topical application of 0.5% GCV was found to be effective for preventing the recurrence of CMV endotheliitis, and it provided the optimal mid-term clinical outcomes post-DSAEK in patients with CMV endotheliitis.Trial registration numberUMIN000026746

PurposeTo investigate the surgical timing postinjury in regard to ocular motility in patients with orbital-floor blowout fractures.MethodsThis study involved 197 eyes (92 right eyes and 105 left eyes) of 197 patients (154 males and 43 females, mean age: 29.0 years, range: 7–85 years) with pure orbital blowout fractures. All patients underwent surgical repair within 30 days postinjury and were followed up for 3 months or more postoperative (mean follow-up period: 8.4 months, range: 3–59 months). Orbital blowout fractures were classified into one of three shapes: (1) trap-door fracture with muscle entrapment, (2) trap-door fracture with incarcerated tissue and (3) depressed fragment fracture. Ocular motility was estimated by percentage of Hess area ratio (HAR%) on the Hess chart at the final follow-up examination. In addition, correlations between postinjury surgical timing and HAR% were analysed.ResultsThe mean postinjury surgical timing was 10.7±7.8 days (range: 0–30 days). The mean postoperative HAR% (92.9%±10.5%) was significantly improved compared with preoperative HAR% (73.5%±21.7%) (p<0.01). The mean postoperative HAR% (98.3%±4.4%) of the orbital-floor trap-door fracture patients with incarcerated tissue who underwent surgical repair within 8 days postinjury was significantly better than that of the patients who underwent surgical repair after 8 days (94.2%±5.8%) (p<0.01).ConclusionsPatients with orbital-floor trap-door blowout fractures with incarcerated tissue that were repaired within 8 days postinjury had better outcomes than those repaired after 8 days, and HAR% is a useful method to record orbital fracture surgical outcomes.

Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10−14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

IMPORTANCE: Describing the association with human leukocyte antigen (HLA) alleles could facilitate the understanding of increased risk factors for development of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with severe ocular complications (SOCs). OBJECTIVE: To investigate the association between HLA class I genes and cold medicine (CM)–associated SJS/TEN with SOCs. DESIGN, SETTING, AND PARTICIPANTS: This case-control study was conducted between February 8, 2013, and August 29, 2014. Thirty-nine Brazilian patients with CM-SJS/TEN of 74 patients with SJS/TEN with SOCs and 133 healthy Brazilian volunteers were enrolled. Human leukocyte antigen class I genes (HLA-A, HLA-B, and HLA-C) were examined to determine whether there was a genetic predisposition for CM-SJS/TEN with SOC. Patients were interviewed to identify possible etiologic factors. Data analysis was performed from April 14, 2013, to August 29, 2014. MAIN OUTCOMES AND MEASURES: Genetic predisposition for CM-SJS/TEN with SOCs by analysis of HLA class I genes. RESULTS: Of 74 patients included in the analysis, 32 (43%) were male; mean (SD) age was 36.01 [15.42] years. HLA-A*66:01 (odds ratio [OR], 24.0; 95% CI, 2.79-206.0; P &lt; .001), HLA-B*44:03 (OR, 2.71; 95% CI, 1.11-6.65; P = .04), and HLA-C*12:03 (OR, 5.6; 95% CI, 1.67-18.80; P = .006) were associated with Brazilian CM-SJS/TEN with SOCs, and HLA-A*11:01 (OR, 0.074; 95% CI, 0.004-1.26; P = .008), HLA-B*08:01 (OR, 0.15; 95% CI, 0.02-1.15; P = .048), and HLA-B*51:01 (OR, 0.23; 95% CI, 0.05-1.03; P = .045) were inversely associated with Brazilian CM-SJS/TEN with SOCs (39 cases: 19 Pardo and 16 European ancestry; 14 males and 25 females; age, 35.2 [14.4] years; and 133 controls: 66 Pardo and 61 European ancestry; 55 males and 78 females; age, 41.2 [12.9] years). When multiple test correction within the HLA locus, HLA-A*66:01 and HLA-C*12:03 demonstrated associations. When participants were segregated into Pardo and locus is considered, HLA-A*66:01 was associated with CM-SJS/TEN with SOC among individuals of both ethnic groups (Pardo: OR, 12.2; 95% CI, 1.19-125.0; P = .03; and European: OR, 21.2; 95% CI, 0.97-465.0; P = .04). An association was observed only in the European cohort for HLA-B*44:03 (OR, 5.50; 95% CI, 1.47-20.50; P = .01) and HLA-C*12:03 (OR, 8.79; 95% CI, 1.83-42.20; P = .008). CONCLUSIONS AND RELEVANCE: This study suggests that HLA-A*66:01 might be a marker for CM-SJS/TEN with SOCs in Brazilian individuals of Pardo and European ancestry and that HLA-B*44:03 and HLA-C*12:03 might be markers only in those of European ancestry. Moreover, HLA-A*11:01 might be a marker of resistance to CM-SJS/TEN with SOCs.

A genome-wide association study (GWAS) for cold medicine-related Stevens–Johnson syndrome (CM-SJS) with severe ocular complications (SOC) was performed in a Japanese population. A recently developed ethnicity-specific array with genome-wide imputation that was based on the whole-genome sequences of 1070 unrelated Japanese individuals was used. Validation analysis with additional samples from Japanese individuals and replication analysis using samples from Korean individuals identified two new susceptibility loci on chromosomes 15 and 16. This study might suggest the usefulness of GWAS using the ethnicity-specific array and genome-wide imputation based on large-scale whole-genome sequences. Our findings contribute to the understanding of genetic predisposition to CM-SJS with SOC.

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PurposeTo observe the most peripheral region of the corneal endothelial cell (CEC) layer as long as optically recordable by use of a prototype slit-scanning wide-field contact specular microscope and produce a panoramic image to evaluate the variation of CEC density with ageing.DesignObservational case series study.MethodsThis study involved 15 eyes of 15 normal healthy subjects divided into three groups according to age: A (20–40 years), B (41–60 years) and C (>60 years). The corneal endothelial layer of each eye was recorded in a horizontal direction, from nasal to temporal, with a slit-scanning wide-field contact specular microscope (Konan) and endothelial cell density (ECD) in three specific regions (central, mid-peripheral, and peripheral) was automatically calculated via built-in analysis software.ResultsCorneal endothelial images from near the surgical limbus to limbus in all eyes were clearly recorded and panoramic images were made by combining still images. ECD in groups A, B and C were 2809±186, 2717±91 and 2580±129 cells/mm2at the centre, 2902±242, 2772±97 and 2604±187 cells/mm2at the mid-periphery and 2893±308, 2691±99 and 2533±112 cells/mm2at the periphery. Significance differences in ECD was found between groups A and C in all regions and groups between B and C at mid-peripheral region.ConclusionsA prototype slit-scanning wide-field contact specular microscope enabled us to record the endothelial layer from the surgical limbus to limbus of the cornea and compare specific areas among subjects, and showed that ECD in each region of the cornea decreases with ageing.Trial registration numberUMIN000021264, Results.

Background/aimsThe aim of this study was to evaluate the therapeutic efficacy and drug transfer of topical application of 0.15% ganciclovir (GCV) gel on cytomegalovirus (CMV) corneal endotheliitis.MethodsThis study is a multicentre, prospective, interventional case series. Seven eyes of seven immunocompetent patients diagnosed with CMV corneal endotheliitis, based on clinical manifestations and qualitative PCR, were enrolled in this study. The patients were treated with topical applications of 0.15% GCV gel six times daily for 12 weeks without concomitant systemic GCV. Clinical evaluations and quantitative PCR of CMV were performed, and GCV concentrations in aqueous humour were measured by liquid chromatography/tandem mass spectrometry.ResultsClinical improvement of coin-shaped lesions, other types of keratic precipitates, corneal oedema, and anterior chamber inflammation was confirmed at the 4-week visit in all seven eyes. The GCV treatment significantly decreased the CMV copy numbers (p<0.0001). After 12 weeks of treatment, six eyes recovered clear corneas with good vision, and endothelial function was well maintained. Detectable levels of GCV were confirmed in the aqueous humour of all the eyes. The mean GCV concentration in the anterior chamber was 162.0±202.4 ng/mL. The re-emergence of CMV without symptoms was observed in one eye with lower drug transfer. No side effects were observed.ConclusionsClinical improvement and reduced CMV copy numbers in the aqueous humour were confirmed in the CMV corneal endotheliitis cases. Although the case numbers are limited and long-term follow-up is necessary, the topical application of 0.15% GCV gel appears to be a useful treatment option for CMV endotheliitis.Trial registration numberUMIN000012435.

AimTo investigate the viability of donor corneal endothelial cells (CECs) preserved in storage media by histological examination.MethodsTwenty-eight donor corneas were obtained from SightLife Eye Bank (Seattle, Washington), and redundant peripheral portions of those corneas were used for histological examination after removal of the centre corneal graft for transplantation. To assess cell viability in the corneal endothelium, biostaining experiments were performed using propidium iodide, calcein-AM, Hoechst 33 342, annexin V, anti-vimentin antibody and toluidine blue.ResultsHistological analysis of the endothelium showed that the cytoplasm of dead cells had low-intensity fluorescence and that their nuclei stained red, while almost all living cells had green cytoplasm and blue-stained nuclei. The mean dead cell rate in the 28 donor corneas was 4.9%±3.3% (mean ±SD) (range: 0.6%–10.5%). The propidium iodide-positive cells stained positive for annexin V, negative for vimentin and pale for toluidine blue. After the specimens were incubated in a culture medium, the red nucleus dead cells dropped off from the level of the blue nucleus living cells.ConclusionOur findings showed the existence of dead cells in storage-media-preserved donor corneal endothelium and that they dropped off after incubation, thus suggesting that the decrease of CECs following keratoplasty may be related to the presence of dead cells.

Descemet-stripping automated endothelial keratoplasty (DSAEK) combined with cataract surgery was performed in a 55-year-old man who had bilateral phakic intraocular lens (pIOL) implantation in Moscow, Russia, for high myopia when he was 26 years old. In 2015, he had DSAEK in Nagoya, Japan, after examinations showed the presence of bullous keratopathy in the right eye. In August 2017, he was referred to the Baptist Eye Institute in Kyoto, Japan, because the DSAEK graft had failed. The failed graft and the pIOL were extracted, after which lensectomy, IOL implantation, and anterior capsule staining were performed. A fresh DSAEK graft was attached to the posterior corneal surface via an air injection. By 6 months postoperatively, the corrected distance visual acuity had improved from 20/2000 to 20/20. These outcomes suggest that this surgical procedure would be safe, effective, and applicable in similar complicated cases.

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.

The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. Part I summarizes the epidemiology and immunopathogenesis of SJS/TEN and discusses systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN and enhance their care of patients with this complex and often debilitating disease. Part II (April 2016 issue) will focus on ophthalmic manifestations.

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AimsTo investigate the safety of anterior chamber (AC) paracentesis using a 30-gauge needle integrated with a specially designed disposable pipette.MethodsIn this retrospective observational case-series study, AC paracentesis was performed on 301 eyes of 301 patients between September 2009 and August 2016 at the Department of Ophthalmology, Kyoto Prefectural University of Medicine and the Baptist Eye Institute, Kyoto, Japan. AC paracentesis was performed with the patient placed in the supine position using a 30-gauge needle integrated with a disposable pipette with one hand, and the safety post procedure was then evaluated.ResultsThe indications for AC paracentesis were virus detection (ie, corneal endotheliitis, anterior infectious uveitis, cytomegalovirus retinitis and acute retinal necrosis) in 264 eyes, bacterial detection (ie, endophthalmitis) in 8 eyes and malignancy (ie, primary intraocular lymphoma, leukaemia and retinoblastoma) in 29 eyes. No serious complications such as infection, hyphema, lens trauma or severe inflammation including hypopyon and AC fibrin formation were observed.ConclusionsOur findings show that AC paracentesis with a disposable pipette is safe with no severe complications.

Rebamipide, a gastroprotective drug, has been reported to suppress gastric mucosal inflammation. In Japan, rebamipide eyedrops have recently been approved for the treatment of dry eye disease. Some patients with allergic conjunctival diseases such as vernal keratoconjunctivitis (VKC) or atopic keratoconjunctivitis (AKC) manifest dry eye with decreased tear break-up time only. We report patients with VKC/AKC refractory to anti-allergic treatments who responded to the combination of rebamipide eyedrops and conventional anti-allergic treatments with anti-allergic- and/or immunosuppressive/steroid eyedrops.

Severe ocular surface diseases are some of the most challenging entities currently facing ophthalmologists. The purpose of this review was to describe the recent advances, current developments, and future challenges related to ocular surface reconstruction from both the basic science and clinical aspects. To date, many candidate corneal epithelial stem-cell markers for tissue-engineered culture transplants have been proposed worldwide. Several groups have reported the long-term clinical results of cultivated epithelial transplantation for treating severe ocular surface disease. In an attempt to further develop the surgical procedures of ocular surface reconstruction, several groups recently reported using cells obtained from novel sources, surrounding cell substrates, and safer culture processes. As a result of the basic research and breakthroughs in the field of corneal regenerative medicine, great progress has been made in the basic understanding and development of new therapeutic tools.

ABSTRACTFor the past few years, we have been observing the dissemination of methicillin-resistant staphylococci in the community. From 2001 to 2003, an evaluation of nasal samples from 1,285 children in five day-care centers and two kindergartens in three districts in Japan revealed that methicillin-resistant coagulase-negative staphylococci (MRC-NS) have been widely disseminated in the Japanese community. Their prevalence is much greater than community-acquired methicillin-resistant Staphylococcus aureus(CA-MRSA). Forty-nine children (3.81%) were colonized with MRSA, whereas 390 children (30.35%) were colonized with MRC-NS. These MRC-NS strains predominantly harbored a pair of cassette chromosome recombinase types A2 and B2 (ccrAB2). Of these, 40.8% harbored type IVa staphylococcal cassette chromosome mec(SCCmec) elements, a distinct/characteristic type of SCCmecin pandemic clones of CA-MRSA. Interestingly, there was also a high frequency of nontypeable strains which possessed atypical structures compared to previous SCCmectypes. Among the MRC-NS, the majority of strains (63.59%) were methicillin-resistant Staphylococcus epidermidis(MRSE). Their genotypes, as judged from pulsed-field gel electrophoresis (PFGE), were highly diverse. They were so diverse that there was no sign of an immediate transmission of any MRSE clone among children in the same institutions. In a previous report, we expounded that a few CA-MRSA clones with distinct SCCmectypes were disseminated among children in the same institutions. Au contraire, with the case of CA-MRSE, there was no single genotype of CA-MRSE disseminated among children even in the same institution or class.