Background and Objective: Limbal stem cell deficiency (LSCD) describes the clinical condition when there is dysfunction of the corneal epithelial stem/progenitor cells and the inability to sustain the normal homeostasis of the corneal epithelium. The limbal stem cells are located in a specialized area of the eye called the palisades of Vogt (POV). There have been significant advances in the diagnosis and management of LSCD over the past decade and this review focuses on the pathophysiology of LSCD, its clinical manifestations, diagnosis, and causes.

Methods: Papers regarding LSCD were searched using PubMed to identify the current state of diagnosis and causes of LSCD published through to June 2022. 
Key Content and Findings: LSCD is clinically demonstrated by a whorl-epitheliopathy, loss of the POV, and conjunctivalization of the cornea. The diagnosis of this condition is based on clinical examination and aided by the use of impression cytology, in vivo confocal microscopy, and anterior segment optical coherence tomography (asOCT). There are many causes of LSCD, but those which are most common include chemical injuries, aniridia, contact lens wear, and Stevens-Johnson syndrome (SJS).

Conclusions: While this condition is most commonly encountered by corneal specialists, it is important that other ophthalmologists recognize the possibility of LSCD as it may arise in other co-morbid eye conditions.

Abstract: Myopia and astigmatism, two common refractive errors frequently co-exist, are degrading vision at all working distances in populations worldwide. Eyeballs having high degrees of myopia and astigmatism are known to exhibit abnormal eye shape at the anterior and posterior eye segments, but whether the outer coats of these abnormal eyeballs, cornea anteriorly and sclera posteriorly, are regulated by region-specific molecular mechanism remains unclear. Here we presented the changes in eye shape and mRNA expression levels of three genes (MMP2, TIMP2, and TGFB2), all known to participate in extracellular matrix organization, at five regions of the cornea and sclera in chickens developing high myopia and astigmatism induced by form deprivation. Our results showed that, compared to normal chicks, the highly myopic-astigmatic chicks had significantly astigmatic cornea, deeper anterior chamber, longer axial length, and higher expressions of all three genes in the superior sclera. These results imply that local molecular mechanism may manipulate the eye’s structural remodeling across the globe during refractive eye growth.

Abstract: Blinding diseases such as photoreceptor degenerations are debilitating conditions that severely impair daily lives of affected patients. This group of diseases are amenable to photoreceptor replacement therapies and recent transplantation studies provided proof-of-principle for functional recovery at the retinal and behavioral level, though the actual mechanism of repair still needs further investigations. The immune system responds in several ways upon photoreceptor engraftment, resulting in T-cell and macrophage infiltrations and, consequently, decrease in graft survival. Most studies on the role of the immune system suggest a detrimental effect in a therapeutic setting. Conversely, the opposite idea wherein the immune system can be activated towards a protective state was also explored in other experimental paradigms. Here, Neves and colleagues explored the potential of cross-species studies and, to a certain extent, the concept of a protective immune system in retinal degeneration and therapy. Mesencephalic astrocyte-derived neurotrophic factor (MANF) was identified in this study as a novel factor that, by modulating the immune system, can slow down photoreceptor degeneration and improve transplantation outcome.

Abstract: Diabetic retinopathy (DR) is the most common microvascular complication in patients with diabetes mellitus (DM), and remains the single greatest cause of blindness in working age adults around the world. In this article, we review the evolution of pharmacotherapies for both diabetic macular edema (DME) and DR such as anti-vascular endothelial growth factor inhibitors and various steroid formulations, as well as other emerging pharmacotherapies currently in late stage clinical testing for this disease.

Background: The neovascular aged-related macular degeneration (AMD) is the leading cause of legal blindness in the elderly. It is presently treated by anti-VEGF intravitreal injection in order to stop the neovascularization. In seeking of more efficient treatments to prevent retinal damage, it has been proposed that the kinin-kallikrein system (KKS), a key player in inflammation, could be involved in AMD etiology. However, the role of kinin receptors and their interaction with VEGF in AMD is poorly understood.

Methods: In order to address this question, choroidal neovascularization (CNV) was induced in the left eye of Long-Evans rat. After laser induction, anti-VEGF or IgG control were injected into the vitreal cavity. Gene expression was measured by qRT-PCR, retinal adherent leukocytes were labelled with FITC-Concanavalin A lectin, vascular leakage by the method of Evans blue and cellular localisation by immunohistochemistry.

Results: The number of labelled adherent leucocytes was significantly increased in laser-induced CNV compared to the control eye. This was significantly reversed by one single injection of anti-VEGF. Extravasation of Evans blue dye was significantly increased in laser-induced CNV eyes compared to control eyes and partially reversed by one single injection of anti-VEGF or by R954 treatment. The mRNA expression of inflammatory mediators was significantly increased in the retina of CNV rats. Immunodetection of B1R was significantly increased in CNV eyes. B1R immunolabeling was detected on endothelial and ganglion cells.

Conclusions: This study is the first to highlight an effect of the kinin/kallikrein system in a model of CNV that could be reduced by both anti-VEGF therapy and topically administered B1R antagonist R-954.

Abstract: The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.