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.
Review Article

Amniotic membrane transplantation: an updated clinical review for the ophthalmologist

:22-56
 
Although amniotic membrane transplantation (AMT) has long been used as an essential surgical technique for ocular surface reconstruction, its role continues to evolve and expand. In the management of numerous ocular surface disorders, ranging from inflammatory to infectious, traumatic to neoplastic, the ability to perform AMT is a valuable addition to the skillset of any ophthalmologist. The purpose of this paper is to provide ophthalmologists with an updated, evidence-based review of the clinical indications for AMT in corneal and conjunctival reconstruction, reviewing its common and even experimental applications known to date. The methods of amniotic membrane preservation, the available commercial amniotic membrane products to date, and future directions for amniotic membrane use, including amniotic membrane extract eye drops (AMEED), are also discussed. It is paramount for ophthalmologists to stay up-to-date on the applications of AMT so as to effectively incorporate this versatile treatment modality into their practice,both in the operating room and in the clinic. By familiarizing the general ophthalmologist with its diverse applications, we hope to motivate general ophthalmologists to incorporate the use of AMT into their clinical practice, or provide guidance on how to recognize when referral to a corneal specialist for amniotic membrane application is prudent.
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

Conjunctival flaps for the treatment of advanced ocular surface disease—looking back and beyond

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Conjunctival flaps have previously proven to be effective in preserving the globe for individuals with severe ocular surface disease. Infectious keratitis, neurotrophic keratitis, nontraumatic corneal melts, descemetoceles, perforations, and corneal burns are all indications for this procedure. The flaps promote nutrition, metabolism, structure, and vascularity, as well as reduce pain, irritation, inflammation, and infection. Furthermore, patients avoid the emotional and psychological repercussions of enucleation or evisceration, while requiring fewer postoperative medications and office visits. Currently, fewer flaps are performed due to the emergence of additional therapeutic techniques, such as serum tears, bandage lenses, corneal grafting, Oxervate, amniotic membrane, and umbilical cord grafting. However, despite newer conservative medical methods, conjunctival flaps have been demonstrated to be useful and advantageous. Moreover, future technologies and approaches for globe preservation and sight restoration after prior conjunctival flaps are anticipated. Herein, we review the history, advantages, and disadvantages of various surgical techniques: Gundersen’s bipedicle flap, partial limbal advancement flap, selective pedunculated conjunctival flap with or without Tenon’s capsule, and Mekonnen’s modified inferior palpebral-bulbar conjunctival flap. The surgical pearls and recommendations offered by the innovators are also reviewed, including restrictions and potential complications. Procedures for visual rehabilitation in selective cases after conjunctival flap are reviewed as well.
Case report

Case report: simultaneous femtosecond laser astigmatic keratotomy and toric intraocular lens implantation in femtosecond laser-assisted cataract surgery in a patient with surgically induced high corneal astigmatism

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Background: Femtosecond laser astigmatic keratotomy (FSAK) and toric intraocular lens (IOL) implantation have been studied individually for comparison to treat astigmatism at cataract surgery. We report a case of surgically induced high corneal astigmatism by laser thermal keratoplasty (LTK) in a patient with cataract who was successfully treated with simultaneous combination of FSAK and toric IOL implantation with femtosecond laser-assisted cataract surgery (FLACS). This is the first report of both procedures combined simultaneously, with or without history of LTK.

Case Description: A 68-year-old male presented with a history of LTK with two enhancements each eye in 2004, with subsequent surgically induced high corneal astigmatism, and with age-related nuclear cataract of both eyes. IOL master demonstrated +7.71 diopters of astigmatism at 163 degree right eye and +3.29 diopters of astigmatism at 4 degree left eye. After extensive discussion of the risks and benefits, the patient agreed to undergo FLACS with FSAK with two 61 degrees of relaxation incisions (RIs) and toric IOL (Alcon SN6AT9) right eye; FLACS with toric IOL (Alcon SN6AT7) alone left eye. At 2-year follow-up, uncorrected visual acuity was 20/30 right eye, 20/25 left eye. His best corrected visual acuity was 20/25 (+0.25 +1.00 axis 21) right eye and 20/20 (plano +0.25 axis 90) left eye; his best corrected near visual acuity was J1+ with add +2.50 diopters right eye and left eye.

Conclusions: Patients with age-related cataract and LTK induced high corneal astigmatism can hardly be sufficiently treated with FSAK or toric IOL alone at the time of cataract surgery. An effective way is to combine large FSAK and toric IOL of the highest cylindrical power of T9, in our case, simultaneously, which can achieve an excellent long term visual outcome.

Technical Note

Allogeneic sclera graft combined autologous conjunctival flap for repairing the emergent corneal perforation

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Abstract: To report a palliative and alternative surgical procedure, allogeneic sclera graft combined with autologous conjunctival flap (ASGACF), employing to repair the large emergent corneal perforation. The detail protocol of the surgical procedure was characterized and four representative cases were reviewed. An allogeneic sclera graft and recipient bed were prepared as the traditional penetrating keratoplasty (PK). And then sutured the sclera graft to the bed with 10-0 nylon suture and covered with a pedicled autologous conjunctival flap in half size. In the follow-up, the ASGACF repaired all of the corneal perforations and restored the integral walls of eyeballs, in spite of one who underwent a second surgery. This surgical procedure provided a palliative method to repair the large emergent corneal perforation while there is the lack of a corneal graft.

Review Article
Theme 3: Emerging Technologies

AB011. A collagen-alginate-based cell-encapsulation intraocular implant for retinal disease therapy

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Abstract: Encapsulated-cell therapy (ECT) is an attractive approach for continuously delivering freshly synthesized therapeutics to treat sight-threatening posterior eye diseases, circumventing repeated invasive intravitreal injections and improving local drug availability clinically. Composite collagen-alginate (CAC) scaffold in ECT contains an interpenetrating network that integrates the physical and biological merits of its constituents, including biocompatibility, mild gelling properties and availability. An injectable CAC system that supported the growth of HEK293 cells with sustainable glial-derived neurotrophic factor (GDNF) delivery has been developed. Continuous GDNF delivery was detected in culture and in healthy rat eyes for at least 14 days. The gels were well tolerated with no host tissue attachment and contained living cell colonies. Most importantly, gel implantation in dystrophic Royal College of Surgeons rat eyes for 28 days retained photoreceptors while those gels containing higher initial cell number yielded better photoreceptor rescue effect. This rescue effect is clinically relevant as photoreceptor death is a common pathology in many retinal diseases. Moreover, since cells including autologous cells can be genetically engineered to secrete various therapeutic agents, CAC gel offers a flexible system design and is a potential treatment option for other chronic neurodegenerative diseases.

Commentary
其他期刊
  • 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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