OBJECTIVE: To evaluate limbal graft transplantation success in pediatric patients with chemical injury-induced limbal stem cell deficiency (LSCD) using the \'LSCD Working Group\' staging system.
METHODS: Medical records of 11 eyes of 11 children who underwent limbal graft transplantation (limbal autograft/limbal allograft) were included. Surgical success was defined as improvement in the post-operative 1st year LSCD stage.
RESULTS: The mean age was 12 ± 5 (4-17) years. Causative agent was alkaline in 4(36.4%) and acid in 3(27.2%) patients. Limbal autograft was performed in 9 (81.8%) eyes with unilateral LSCD, and allograft transplantation was performed in 2 (18.2%) eyes with bilateral LSCD. The mean follow-up time was 33.89 ± 30.73 (12-102.33) months. The overall limbal graft transplantation success rate was 72.7%. Among 9 patients who receive limbal autograft, 8 had improvement in post-operative LSCD stage, 1 had stable LSCD stage. Of the 2 patients who receive limbal allograft, post-operative LSCD stage remained the same in 1 and worsened in 1 patient. The mean time between injury and the surgery was 30.47 ± 30.08 (7-108.47) months. Penetrating keratoplasty was performed in 3 (27.2%) of 11 patients following limbal graft transplantation.
CONCLUSIONS: Management of LSCD in children is challenging and appears to be somewhat different from that of adults. Limited data in the literature indicate that cultivated or simple limbal epithelial transplantations (CLET/SLET) are primarily preferred in children. Although the tendency to take small tissue from the healthy eye is noteworthy, conventional limbal allograft and autograft transplantations also show promising results without any further complications in at least 1 year follow-up period.

UNASSIGNED: Oral epithelial cells were recently shown to be able to differentiate into corneal epithelium, and the efficacy of cultured autologous oral mucosal epithelial cells (CAOMEC) has been suggested by the presence of epithelium replacement. Therefore, the aim of this study was to evaluate the treatment outcome in limbal stem cell deficiency (LSCD) by adding CAOMEC to regular amniotic membrane (AM) treatment.
UNASSIGNED: Eyes with LSCD were randomized to two groups to undergo either autologous oral mucosal epithelial cell sheet (CAOMECS) combined with AM transplantation (A group) or AM transplantation alone (B group). Clinical outcome measures were corneal epithelium healing, best corrected visual acuity, symblepharon, corneal transparency, corneal neovascularization and ocular surface inflammation.
UNASSIGNED: The normal corneal epithelialization rate in group A (73.33%) was higher than that in group B (35.48%), and the average healing time was shorter (3.45 ±2.12 weeks vs. 4.64 ±1.63 weeks). The symblepharon in the above two groups was improved in the first 3 months after surgery, but after 6 months, part of the B group had recurrence. In improving corneal transparency, group A has obvious advantages. Corneal neovascularization (CNV) was improved to some extent in the first 3 months after surgery, but group A (1.47 ±0.64) was better than group B (1.94 ±0.85) after 6 months. Both groups can improve the inflammatory state to some extent.
UNASSIGNED: The transplantation of CAOMECS offers a viable and safe alternative in the reconstruction of a stable ocular surface. The effect is better than that of traditional AM transplantation, mainly in promoting corneal epithelialization, improving ocular surface structure, and reducing fiber and vascular infiltration.

UNASSIGNED: To evaluate the prevalence and clinical characteristics of limbal stem cell deficiency (LSCD) in the setting of a tertiary referral cornea practice at an academic center.
UNASSIGNED: A retrospective chart review was performed to identify all unique medical record numbers (MRNs) presenting to a single cornea specialist (JHH) at the University of Minnesota during calendar years 2019 and 2020. Records were queried and confirmed for a diagnosis of LSCD. Clinical characteristics of identified patients, including demographics, etiology of LSCD, severity of LSCD, treatment, and best corrected visual acuity (BCVA) at final follow-up, were documented.
UNASSIGNED: In total 1436 unique MRNs were identified over the study period. There were 61 individuals (91 eyes) diagnosed with LSCD, resulting in a prevalence of 4.25% (95% CI, 3.33-5.42). Of 91 eyes, 60 eyes were bilateral (65.9%). Among all eyes, ocular surface burns were the most common etiology (18.7%) followed by iatrogenic or medicamentosa (15.4%). There were 51 eyes (56.0%) that underwent some form of transplantation. The median BCVA at final follow-up was Snellen 20/80 (range 20/20 to no light perception).
UNASSIGNED: The prevalence of LSCD found at a cornea subspecialty tertiary referral center in our study was much higher than previously reported prevalence rates. This may reflect referral bias and potential underdiagnosis of LSCD in practices outside of subspecialty referral centers. The high prevalence rate in our study also suggests that LSCD patients are concentrated in subspecialty referral practices, with many having high morbidity disease. This constitutes a major health burden for these practices.

UNASSIGNED: We report a patient with bilateral limbal stem cell deficiency (LSCD) like clinical manifestations and secondary corneal perforation presumably induced by durvalumab following its use for the treatment of non-small cell lung carcinoma.
UNASSIGNED: A 65-year-old male diagnosed with non-small cell lung carcinoma was treated with monthly durvalumab infusions. Two months after starting durvalumab, the patient was found to have bilateral severe keratoconjunctivitis and LSCD-like clinical findings. Despite topical management and oral prednisone for presumed ocular cicatricial pemphigoid, the patient continued to worsen clinically. The patient was transferred to our institution about one year later with persistent inflammation. The patient eventually developed a corneal perforation of the left eye, which required the application of cyanoacrylic tissue adhesive. Due to the lack of response to oral prednisone, durvalumab was discontinued with the approval of the patient\'s oncologist. Several months following the discontinuation of durvalumab, the conjunctival inflammation subsided, and corneal epithelial breakdown and ulceration resolved.
UNASSIGNED: We report an association between durvalumab and the development of bilateral LSCD-like clinical findings with subsequent corneal perforation. We hope this case reinforces the importance of routine ophthalmologic follow-up after starting any cancer treatment, especially in patients with symptoms and signs suggesting ocular surface disease or inflammation.

Limbal stem cell deficiency (LSCD) is a clinically challenging eye disease caused by damage to limbal stem cells (LSCs). Currently, the international consensus classifies LSCD into three clinical stages based on the disease severity. However, no existing animal models attempt to replicate the varying degrees of LSCD observed in clinical cases. The present study demonstrates an easy-to-create, reproducible, and reliable mouse model of graded LSCD. To achieve mild, moderate, or severe LSCD, filter paper rings with a variety of central angles (90°, 180°, or 270°) are utilized to deliver alkali burns to different sizes of the limbal area (1, 2, or 3 quarters). The animal model has successfully resulted in the development of clinical signs and pathological manifestations in escalating severity that are similarly observed in the three clinical stages of LSCD. Our study thus provides new insights into distinct pathological features underlying different grades of LSCD and serves as a new tool for further exploring the disease mechanisms and developing new effective therapeutics for repairing damaged LSCs.

The mammalian cornea is decorated with stem cells bestowed with the life-long task of renewing the epithelium, provided they remain healthy, functional, and in sufficient numbers. If not, a debilitating disease known as limbal stem cell deficiency (LSCD) can develop causing blindness. Decades after the first stem cell (SC) therapy is devised to treat this condition, patients continue to suffer unacceptable failures. During this time, improvements to therapeutics have included identifying better markers to isolate robust SC populations and nurturing them on crudely modified biological or biomaterial scaffolds including human amniotic membrane, fibrin, and contact lenses, prior to their delivery. Researchers are now gathering information about the biomolecular and biomechanical properties of the corneal SC niche to decipher what biological and/or synthetic materials can be incorporated into these carriers. Advances in biomedical engineering including electrospinning and 3D bioprinting with surface functionalization and micropatterning, and self-assembly models, have generated a wealth of biocompatible, biodegradable, integrating scaffolds to choose from, some of which are being tested for their SC delivery capacity in the hope of improving clinical outcomes for patients with LSCD.

Limbal stem cell deficiency (LSCD) is one of the leading factors negatively affecting the success of keratoplasty, and its treatment remains an urgent problem in ophthalmology. With the development of regenerative medicine, one of the promising approaches is the transplantation of tissue-engineered constructs from cultured limbal stem cells (LSCs) in biopolymer carriers.
OBJECTIVE: This study was conducted to develop an experimental model of LSCD and evaluate the effectiveness of transplantation of a tissue-engineered construct consisting of cultured cells containing a population of LSCs and a collagen carrier.
METHODS: The study was performed on 12 rabbits and included several stages. At the first stage, the physiological effects of collagen matrix implantation into the limbal zone were studied. At the second stage, tissue-engineered constructs consisting of LSCs on a collagen matrix were formed and their effect on the regeneration processes in the experimental LSCD model was analyzed. The animals were divided into 2 groups: surgical treatment (transplantation of the tissue-engineered construct) was used in the experimental group, and conservative treatment was used in the control group. Slit-lamp biomicroscopy with photo-registration, fluorescein corneal staining, optical coherence tomography of the anterior segment of the eye, and impression cytology were used to assess the results.
RESULTS: No side reactions were observed after implantation of the collagen matrix into the limbal zone. One month after surgical treatment of the LSCD model in the experimental group, complete epithelization with minor manifestations of epitheliopathy was observed. In the control group, erosion of the corneal epithelium was noted. The time of corneal epithelization in the experimental and control groups was 9.2±2.95 and 46.20±12.07 days, respectively (p=0.139). According to the data of impression cytology, in the experimental group there were no goblet cells in the central part of the cornea, which indicates the restoration of corneal type epithelial cells, in contrast to the control group.
CONCLUSIONS: Transplantation of a tissue-engineered construct from cultured limbal cells on a collagen membrane should be considered as a promising method for the treatment of limbal stem cell deficiency.
UNASSIGNED: Одним из ведущих факторов, негативно влияющих на успешность кератопластики, является лимбальная недостаточность (ЛН), лечение которой остается актуальной проблемой в офтальмологии. С развитием регенеративной медицины одним из перспективных подходов является трансплантация тканеинженерных конструкций из культивированных лимбальных стволовых клеток (ЛСК) в составе биополимерных носителей.
UNASSIGNED: Разработка экспериментальной модели ЛН и оценка эффективности трансплантации тканеинженерной конструкции, состоящей из культивированных клеток, которые содержат популяцию ЛСК и коллагенового носителя.
UNASSIGNED: Исследование выполнено на 12 кроликах и включало несколько этапов. На первом этапе изучали физиологические эффекты имплантации коллагенового матрикса в зону лимба. На втором — формировали тканеинженерные конструкции, состоящие из ЛСК на коллагеновом матриксе, и изучали их влияние на процессы регенерации экспериментальной модели ЛН. Животные были разделены на 2 группы: в опытной группе применяли хирургическое лечение (трансплантация тканеинженерной конструкции), в контрольной — консервативное лечение. Для оценки результатов использовали биомикроскопию с фоторегистрацией, окрашивание роговицы флюоресцеином, оптическую когерентную томографию переднего сегмента глаза и импрессионную цитологию.
UNASSIGNED: После имплантации коллагенового матрикса в лимбальную зону побочные реакции отсутствовали. Через 1 мес после хирургического лечения экспериментальной модели ЛН в опытной группе наблюдали полную эпителизацию с незначительными проявлениям эпителиопатии. В контрольной группе отметили эрозию эпителия. Время эпителизации роговицы в опытной и контрольной группах составило 9,2±2,95 и 46,20±12,07 сут соответственно (p=0,139). По данным импрессионной цитологии в опытной группе отсутствовали бокаловидные клетки в центральной части роговицы, что свидетельствует о восстановлении эпителиальных клеток по роговичному типу, в отличие от контрольной группы.
UNASSIGNED: Трансплантацию тканеинженерной конструкции из культивированных клеток лимба на коллагеновой мембране следует рассматривать как перспективный метод лечения ЛН.

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OBJECTIVE: To investigate the correlation between the opening and closing states of anterior chamber angle (ACA) and the density of limbal epithelial basal cells (LEBCs) in subjects with primary angle-closure glaucoma (PACG).
METHODS: Cross-sectional observational study.
METHODS: A total of 54 eyes of 29 patients diagnosed with PACG were included in the study. Fifty-four eyes from normal subjects were included as control. Automatic evaluation system for ultrasound biomicroscopy images of anterior chamber angle was used to assist ophthalmologists in identifying the opening or closing state of ACA, and the in vivo confocal microscopy (IVCM) was used to evaluate the density of LEBCs in different directions.
RESULTS: (1) The average density of LEBCs in the superior, inferior, nasal, and temporal limbus of the eyes in the PACG group was lower than that in the control group, and this pattern did not align with the density distribution observed in the control group. (2) In the early, moderate and advanced PACG, the density of LEBCs corresponding to the closed angle was lower than that in the control group (P < .05). Compared with the density of LEBCs corresponding to the closed angle and the open angle, the closed angle of PACG in the early, moderate and advanced stages was less than that in the open angle (P < .05 in the early and moderate stages; advanced stage P > .05). (3) The basal cell density was processed by dimensionless analysis. In the data calculated by averaging and minimizing, both closed angle dimensionless values were smaller than the open angle (P < .05). (4) Comparative analysis was conducted among the normal, open-angle, and closed-angle conditions in the superior, inferior, nasal, and temporal limbus. In the early stage of PACG, significant differences were observed in 4 limbal regions (P < .05), while in the moderate PACG stage, this difference was noted in 3 limbal regions (P < .05). In advanced PACG, 2 limbal regions exhibited significant differences (P < .05). These findings suggest that during the early PACG stage, angle closure is the predominant influencing factor on LEBCs density, while in the advanced stage, the decrease in density is attributed to a combination of angle closure and the natural progression of the disease.
CONCLUSIONS: There is a significant correlation between anterior chamber angle status and LEBCs. Advanced PACG and angle closure should be highly suspected of the occurrence of limbal stem cell deficiency (LSCD).