Recovering vision in corneal epithelial stem cell deficient eyes

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

Trans-ethnic study confirmed independent associations of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe ocular surface complications

Stevens-Johnson syndrome (SJS) and its severe variant, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes. Cold medicines including non-steroidal anti-inflammatory drugs and multi-ingredient cold medications are reported to be important inciting drugs. Recently, we reported that cold medicine related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement including severe ocular surface complications (SOC) is associated with HLA-A*02:06 and HLA-B*44:03 in the Japanese. in this study, to determine whether HLA-B*44:03 is a common risk factor for CM-SJS/TEN with SOC in different ethnic groups we used samples from Indian, Brazilian, and Korean patients with CM-SJS/TEN with SOC, and investigated the association between CM-SJS/TEN with SOC and HLA-B*44:03 and/or HLA-A*02:06. We found that HLA-B*44:03 was significantly associated with CM-SJS/TEN with SOC in the Indian and Brazilian but not the Korean population, and that HLA-A*02:06 might be weakly associated in the Korean-but not the Indian and Brazilian population.Ministry of Education, Culture, Sports, Science and Technology of the Japanese governmentJapanese Ministry of Health, Labour and WelfareKyoto Foundation for the Promotion of Medical ScienceIntramural Research Fund of Kyoto Prefectural University of MedicinePromotion Project of Knowledge-Based Industrial Clustering of Okinawa PrefectureKyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, JapanDoshisha Univ, Fac Life & Med Sci, Res Ctr Inflammat & Regenerat, Kyoto 602, JapanLV Prasad Eye Inst, Prof Brien Holden Eye Res Ctr, Hyderabad, Andhra Pradesh, IndiaUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilSeoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul, South KoreaChonnam Natl Univ, Dept Ophthalmol, Kwangju, South KoreaYonsei Univ, Coll Med, Severance Hosp, Inst Vis Res,Dept Ophthalmol, Seoul, South KoreaCatholic Univ Korea, Seoul St Marys Hosp, Coll Med, Dept Ophthalmol & Visual Sci, Seoul, South KoreaLV Prasad Eye Inst, Cornea & Anterior Segment Serv, Hyderabad, Andhra Pradesh, IndiaUniv Tokyo, Grad Sch Med, Dept Human Genet, Tokyo, JapanUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of Scienc

Japan: Diagnosis and Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis With Severe Ocular Complications

In 2005, the 'Japanese Research Committee on Severe Cutaneous Adverse Reaction' (J-SCAR) presented the official 'Diagnostic Criteria' for SJS/TEN, and the specific ocular findings are included in these very important criteria. In SJS/TEN cases involving ocular disorder, conjunctivitis often occurs prior to the onset of the high fever. In a Japanese survey, ocular involvement was observed in 77% of the cases, and the incidence of ocular sequelae increased depending on the score of the acute ocular severity findings. Pseudo-membrane formation and epithelial defects are considered to be high-risk signs of ocular sequelae. At the chronic stage, limbal stem cell deficiency, visual disturbance, and severe dryness of the ocular surface are the primary disease characteristics. In 2002, we started performing Cultivated Oral Mucosal Epithelial Transplantation (COMET) for the treatment of severe ocular disorders, including SJS/TEN. As an additional treatment method, we developed a new type of rigid contact lens (CL) that is 13 to 14.0-mm in diameter, known as the 'Limbal Rigid Contact Lens (Limbal CL).' Our Limbal Rigid CL greatly enhances the postoperative outcome of COMET. The detection rate of ocular surface bacteria is high in SJS/TEN cases. Thus, appropriate use of topical antibiotics reduces the risk of ocular surface inflammation. Moreover, rebamipide is an ophthalmic solution for dry eye that was developed in Japan, and it also has the effect of suppressing ocular surface inflammation. From disease onset until the chronic stage, the control of inflammation and stem cell loss is key to successfully treating eyes afflicted with SJS/TEN

Current Evidence for Corynebacterium on the Ocular Surface

Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species

Core Transcription Factors Promote Induction of PAX3-Positive Skeletal Muscle Stem Cells

The use of adult skeletal muscle stem cells (MuSCs) for cell therapy has been attempted for decades, but still encounters considerable difficulties. MuSCs derived from human induced pluripotent stem cells (hiPSCs) are promising candidates for stem cell therapy to treat Duchenne muscular dystrophy (DMD). Here we report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different MuSC populations, enhance the derivation of PAX3-positive myogenic progenitors from fibroblasts and hiPSCs, using medium that promotes the formation of presomitic mesoderm. These induced PAX3-positive cells contribute efficiently to the repair of DMD-damaged myofibers and also reconstitute the MuSC population. These studies demonstrate how a combination of core transcription factors can fine-tune the derivation of MuSCs capable of contributing to the repair of adult skeletal muscle

Dematiaceous fungal keratitis caused by Cladophialophora boppii — A case report

Purpose: To report a rare case of dematiaceous fungal keratitis caused by Cladophialophora boppii (C. boppii) in an immunocompromised patient. Observations: An 83-year-old male with chronic renal failure was referred to the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan due to persistent corneal epithelial defects (PEDs) in his left eye. Initial examination revealed decreased central corneal sensitivity and decreased tear secretion in that eye, both thought to be associated with herpetic keratitis. Permanent punctal-plug surgery combined with therapeutic soft contact lens wear was performed to treat the PED, which initially healed, yet recurred. Follow-up examination revealed a 1.0-mm-diameter black lesion consistent with the PED site, which subsequently increased in size, so treatment with miconazole solution eye drops, natamycin ophthalmic ointment, and systemic itraconazole was initially performed. Since the region of the lesion had progressed to corneal perforation, corneal transplantation surgery under general anesthesia was scheduled, yet the patient refused to undergo surgery. Mycological testing via DNA sequencing of the internal transcribed spacer of ribosomal DNA regions revealed that the isolate or pathogen was C. boppii. Mycotic keratitis caused by C. boppii was found to be resistant to antifungal drugs. Conclusion and importance: This is a rare case of fungal keratitis caused by C. boppii in an elderly immunocompromised patient