Review Article

Cell-based therapies for limbal stem cell deficiency: a literature review

:22-55
 
Background and Objective: Limbal stem cell deficiency (LSCD) is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium. Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue. Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants. In this review, we describe the success rates, and complications of different cell-based therapies for LSCD. We also discuss each therapy’s relative strengths and weaknesses, their history in animal and human studies, and their effectiveness compared to traditional transplants.
Methods: PubMed was searched for publications using the terms LSCD, cell-based therapy, cultivated limbal epithelial transplantation (CLET), cultivated oral mucosal epithelial transplantation (COMET),and mesenchymal stem cells from 1989 to August 2022. Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.
Key Content and Findings: current cell-based therapies for LSCD are CLET and non-limbal epithelial cells. Non-limbal epithelial cell methods include COMET, conjunctival epithelial autografts, and mesenchymal stem/stromal cells (MSCs). Moreover, several alternative potential sources of non-limbal cells have described, including induced pluripotent stem cells (iPSCs), human embryonic stem cells (hESCs),human dental pulp stem cells, hair follicle bulge-derived epithelial stem cells, amniotic membrane epithelial cells, and human umbilical cord lining epithelial cells.
Conclusions: Cell-based therapies are a promising treatment modality for LSCD. While CLET is currently the only approved cell-based therapy and is only approved in the European Union, more novel methods have also been shown to be effective in human or animal studies thus far. Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure. iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated. Lastly, cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study. Several potential sources of non-limbal cells are under investigation.
Original Article

Fundus photography, fundus fluorescein angiography, and optical coherence tomography of healthy cynomolgus monkey, New Zealand rabbit, Sprague Dawley rat, and BALB/c mouse retinas

:22-54
 
Background: A variety of experimental animal models are used in basic ophthalmological research to elucidate physiological mechanisms of vision and disease pathogenesis. The choice of animal model is based on the measurability of specific parameters or structures, the applicability of clinical measurement technologies, and the similarity to human eye function. Studies of eye pathology usually compare optical parameters between a healthy and altered state, so accurate baseline assessments are critical, but few reports have comprehensively examined the normal anatomical structures and physiological functions in these models.
Methods: Three cynomolgus monkeys, six New Zealand rabbits, ten Sprague Dawley (SD) rats, and BALB/c mice were examined by fundus photography (FP), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT).
Results: Most retinal structures of cynomolgus monkey were anatomically similar to the corresponding human structures as revealed by FP, FFA, and OCT. New Zealand rabbits have large eyeballs, but they have large optic disc and myelinated retinal nerve fibers in their retinas, and the growth pattern of retinal vessels were also different to the human retinas. Unlike monkeys and rabbits, the retinal vessels of SD rats and BALB/c mice were widely distributed and clear. The OCT performance of them were similar with human beings except the macular.
Conclusions: Monkey is a good model to study changes in retinal structure associated with fundus disease, rabbits are not suitable for studies on retinal vessel diseases and optic nerve diseases, and rats and mice are good models for retinal vascular diseases. These measures will help guide the choice of model and measurement technology and reduce the number of experimental animals required.
Review Article

A narrative review of limbal stem cell deficiency & severe ocular surface disease

:22-35
 
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.
Review Article

An updated narrative review of treatment for limbal epithelial stem cell deficiency

:22-51
 
Background and Objective: Nearly 30 years have passed since limbal stem cell deficiency (LSCD) was first identified by pioneers and given clinical attention. LSCD remains a difficult disease to treat. It can potentially lead to blinding. At present, understanding of limbal stem cells (LSCs) has deepened and various treatment options for LSCD have been devised. The objective of this review is to summarize basic knowledge of LSCD and current treatment strategies.
Methods: PubMed search was performed to find studies published in English on LSCs and LSCD including original reports and reviews. Literatures published from 1989 to 2022 were reviewed.
Key Content and Findings: LSCs are enigmatic stem cells for which no specific marker has been discovered yet. Although LSCD is not difficult to diagnose, it is still challenging to treat. An important advancement in the treatment of LSCD is the provision of guidelines for selecting systematic surgical treatment according to the patient’s condition. It is also encouraging that stem cell technologies are being actively investigated for their potential usefulness in the treatment of LSCD.
Conclusions: Although various treatment options for LSCD have been developed, it should be kept in mind that the best chance of treatment for LSCD is in the early stage of the disease. Every effort should be made to preserve as many LSCs as possible in the early treatment of LSCD.
Editorial
Review Article

Psychophysics in the ophthalmological practice—I. visual acuity

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Perception is the ability to see, hear, or become aware of external stimuli through the senses. Visual stimuli are electromagnetic waves that interact with the eye and elicit a sensation. Sensations, indeed, imply the detection, resolution, and recognition of objects and images, and their accuracy depends on the integrity of the visual system. In clinical practice, evaluating the integrity of the visual system relies greatly on the assessment of visual acuity, that is to say on the capacity to identify a signal. Visual acuity, indeed, is of utmost importance for diagnosing and monitoring ophthalmological diseases. Visual acuity is a function that detects the presence of a stimulation (a signal) and resolves its detail(s). This is the case of a symbol like “E”: the stimulus is detected, then it is resolved as three horizontal bars and a vertical bar. In fact, within the clinical setting visual acuity is usually measured with alphanumeric symbols and is a three-step process that involves not only detection and resolution, but, due to the semantic content of letters and numbers, their recognition. Along with subjective (psychophysical) procedures, objective methods that do not require the active participation of the observer have been proposed to estimate visual acuity in non-collaborating subjects, malingerers, or toddlers. This paper aims to explain the psychophysical rationale underlying the measurement of visual acuity and revise the most common procedures used for its assessment.
Editorial
Review Article
Review Article

Genetic epidemiology of diabetic retinopathy

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Abstract: The disease burden of diabetic retinopathy (DR) is tremendous around the world. While DR is correlated with hemoglobin A1c (HbA1c) and duration of diabetes, genetic differences likely account for variation in susceptibility to DR. DR is a polygenic disorder with demonstrated heritability. However, linkage and admixture analyses, candidate gene association studies, and genome-wide association studies (GWAS) have not identified many loci for DR that can be consistently replicated. Larger, collaborative, multi-ethnic GWAS are needed to identify common variants with small effects. Rigorous defining of controls groups as patients with a long duration of diabetes without DR, and case groups as patients with severe DR will also aid in finding genes associated with DR. Replication in independent cohorts will be key to establishing associated loci for DR. Investigations of mitochondrial DNA and epigenetics in DR are ongoing. Whole exome sequencing presents new opportunities to identify rare variants that might be implicated in DR development. Continued research in the genetic epidemiology of DR is needed, with the potential to elucidate pathogenesis and treatment of an important disease.

Review Article
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  • 眼科学报

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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  • Eye Science

    主管:中华人民共和国教育部
    主办:中山大学
    承办:中山大学中山眼科中心
    主编:林浩添
    主管:中华人民共和国教育部
    主办:中山大学
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