Diagnosis Of Limbal Stem Cell Deficiency Research Articles

Autologous Serum Eye Drops in the Management of Limbal Stem Cell Deficiency Associated With Glaucoma Surgery.

To evaluate safety and efficacy of autologous serum eye drops (AS) in the treatment of limbal stem cell deficiency (LSCD) associated with glaucoma surgery. Retrospective case series of eyes with glaucoma surgery-induced LSCD treated with AS. Diagnosis of LSCD was confirmed by anterior segment optical coherence tomography, in vivo confocal microscopy, and/or impression cytology. Limbal stem cell deficiency severity was staged using a clinical scoring system (2-10 points). Outcome measures were changes (≥2 points) of the LSCD score and best-corrected visual acuity (BCVA) from the baseline to the last follow-up. Thirteen eyes of 12 consecutive patients treated with 50% AS for at least 3 months were included. The mean age was 78.9±7.5 years and the mean duration of AS use was 20.9±16.8 months. Indications of AS included LSCD progression in eight eyes (61.5%) and visual axis threatening in five eyes (38.5%). The mean LSCD score at baseline (6.7±1.6) was similar to that at last follow-up (6.5±2.2, P =0.625). Two eyes (15.4%) showed improvement, nine eyes (69.2%) were stable, and two eyes (15.4%) worsened. The mean baseline BCVA (0.89±0.64 logMAR) was similar to the mean final BCVA (1.05±0.63 logMAR, P =0.173). There were no serious adverse complications related to AS. AS appears to be well tolerated and may stabilize the progression of LSCD with limited effects. A larger study is necessary to confirm the findings.

A Review of the Diagnosis and Treatment of Limbal Stem Cell Deficiency.

Limbal stem cell deficiency (LSCD) can cause significant corneal vascularization and scarring and often results in serious visual morbidity. An early and accurate diagnosis can help prevent the same with a timely and appropriate intervention. This review aims to provide an understanding of the different diagnostic tools and presents an algorithmic approach to the management based on a comprehensive clinical examination. Although the diagnosis of LSCD usually relies on the clinical findings, they can be subjective and non-specific. In such cases, using an investigative modality offers an objective method of confirming the diagnosis. Several diagnostic tools have been described in literature, each having its own advantages and limitations. Impression cytology and in vivo confocal microscopy (IVCM) aid in the diagnosis of LSCD by detecting the presence of goblet cells. With immunohistochemistry, impression cytology can help in confirming the corneal or conjunctival source of epithelium. Both IVCM and anterior segment optical coherence tomography can help supplement the diagnosis of LSCD by characterizing the corneal and limbal epithelial changes. Once the diagnosis is established, one of various surgical techniques can be adopted for the treatment of LSCD. These surgeries aim to provide a new source of corneal epithelial stem cells and help in restoring the stability of the ocular surface. The choice of procedure depends on several factors including the involvement of the ocular adnexa, presence of systemic co-morbidities, status of the fellow eye and the comfort level of the surgeon. In LSCD with wet ocular surfaces, autologous and allogeneic limbal stem cell transplantation is preferred in unilateral and bilateral cases, respectively. Another approach in bilateral LSCD with wet ocular surfaces is the use of an autologous stem cell source of a different epithelial lineage, like oral or nasal mucosa. In eyes with bilateral LSCD with significant adnexal issues, a keratoprosthesis is the only viable option. This review provides an overview on the diagnosis and treatment of LSCD, which will help the clinician choose the best option amongst all the therapeutic modalities currently available and gives a clinical perspective on customizing the treatment for each individual case.

Diagnosis of corneal limbal stem cell deficiency.

A state of limbal stem cell deficiency (LSCD) can be secondary to a number of etiologies, resulting in either a reduction in the total number of limbal stem cells or an abnormality in stem cell function. Initially, the epithelium becomes irregular and hazy; however, this condition may progress to persistent corneal epithelial defects, stromal scarring, ulceration, and even perforation. Since LSCD secondary to a variety of etiologies may be reversible, and various factors are prognostic of disease progression, timely diagnosis is important. This review will describe current knowledge of diagnostic techniques for LSCD and understanding of epithelial stem cell function. Conjunctivalization, regarded as the most reliable clinical finding diagnostically, can be identified as late staining of epithelium with fluorescein. While identifying loss of the palisades of Vogt by slit-lamp examination, can provide a high suspicion of LSCD, but this is not diagnostic. Impression cytology is a simple, noninvasive technique that aids in the diagnosis of LSCD, but a negative result also cannot rule out the diagnosis. Recent findings have also shown that imaging techniques including in-vivo confocal microscope and optical coherent tomography can also aid in diagnosing LSCD; however, several challenges remain before these techniques become standard diagnostic methods in clinical practice. Meanwhile, determination of the absence of limbal epithelial crypts and focal stromal projections using image reconstruction techniques may assist in the diagnosis of LSCD. Furthermore, histologic markers may help not only to improve sensitivity and specificity of conventional techniques in diagnosis of LSCD, but also to identify human limbal stem cells and determine their number and function in LSCD. Efforts to develop and improve techniques for diagnosing LSCD are ongoing. Increased knowledge of limbal stem cells and components of their niches may not only help in understanding the pathogenesis of LSCD but may improve its diagnosis, thereby ameliorating the prognosis of patients with this devastating disease.

Diagnostic criteria for limbal stem cell deficiency—a systematic literature review

The diagnosis of limbal stem cell deficiency (LSCD) is often based on clinical manifestations with or without the use of tests to demonstrate the presence of goblet cells or of specific epithelial markers on the corneolimbal surface. This systematic review looks at the various diagnostic methods used in the diagnosis of LSCD in published interventional studies. The design is a systematic literature review. We did a systematic search on MEDLINE and PUBMED for articles published in English between January 1, 2003, and December 31, 2013. We collected data on diagnostic methods used to diagnose LSCD (clinical findings, impression cytology, immunohistochemistry for various epithelial markers, or in vivo confocal microscopy). Forty-six studies (mostly retrospective/interventional case series) met the inclusion criteria. All of the studies used clinical features as evidence of LSCD: discomfort, impaired vision, irregular epithelium, unstable tear film, persistent epithelial defects, scarring, fibrovascular pannus, neovascularization, keratinization, calcification, and opacification of the cornea. Eighteen studies (39.1%) used an additional test for the diagnosis; 17 studies (37.0%) used impression cytology for goblet cells, 4 studies (8.7%) used immunohistochemistry for epithelial markers, and 2 studies (4.3%) use in vivo confocal microscopy. The diagnosis of LSCD was made in most cases on clinical grounds alone. In some studies, diagnostic tests were used, but these varied considerably from study to study. Comparison of effectiveness of various interventions requires standardized diagnostic methods. Consensus on the diagnostic criteria for LSCD is essential and needs to be reached by the interested care providers.

The Role of Limbal Stem Cells in Corneal Epithelial Maintenance: Testing the Dogma

To study and characterize the epithelial cells in patients with a central "island" of normal epithelial cells surrounded with 360 degrees of clinically apparent limbal stem cell (SC) deficiency with conjunctivalization of the limbus and peripheral cornea. Observational, prospective, consecutive case series. Five human subjects (8 eyes) who presented with total limbal SC deficiency in 1 or both eyes with a central area of normal corneal epithelial cells. Clinical slit-lamp examination, aided with fluorescein staining, for evidence of conjunctivalization and in vivo confocal microscopy (IVCM) of the conjunctivalized limbus and peripheral cornea and the normal central corneal epithelium. Long term survival of normal stratified corneal epithelial cell sheet in the presence of total limbal SC deficiency. In all 8 eyes the diagnosis of limbal SC deficiency was confirmed by clinical and IVCM examination. The conjunctivalized area extended circumferentially along the entire limbus, seen clinically by the presence of fluorescein staining cells, epithelial irregularity, and vascularization and by IVCM showing bright conjunctival epithelial cells, superficial and deep blood vessels, and goblet cells. The central corneal epithelial cells had a normal appearance with polygonal superficial cells, well-defined wing cells, and smaller basal cells. The central "islands" of normal epithelial cells remained unchanged over the mean follow-up period of 60 months (range, 8-12 years). The existence and survival of a healthy sheet of corneal epithelial cells over the follow-up period, in the presence of clinically apparent total limbal SC deficiency, suggests a limited role of limbal epithelial SC in physiologic homeostasis of the corneal epithelium. The authors have no proprietary or commercial interest in any materials discussed on this article.