Vivek Singh

Mesenchymal stem cell therapy for corneal diseases

ABSTRACT Introduction: The transparency of human cornea is critical for normal vision. It is maintained by a small population of stem cells present in the corneal limbus. Corneal diseases are a major cause of global blindness, second only to cataract in overall importance. They are usually treated by medications and surgical modalities that sometimes include expensive and potentially toxic medications with long-term side effects, particularly to prevent rejection of the corneal allograft. Therefore, cell based therapies may provide a promising alternative to overcome these limitations for the treatment of corneal diseases. Areas covered: This review article covers major sources, properties, and applications of mesenchymal stem cells in corneal reconstruction. This also includes a brief description of the structure, function, and immune privilege of the cornea; corneal stem cells, corneal diseases, available treatments, and potential of MSC-based cell therapy for corneal diseases. Expert opinion: Technical advancements in corneal transplantation and development of explant culture techniques like cultivated limbal epithelial transplantation, cultivated oral mucosal epithelial transplantation, and simple limbal epithelial transplantation have resulted in improved outcomes for treating corneal diseases; however, the treatment for bilateral corneal diseases still remains elusive. The increased risk of allograft rejection and long term side-effects of immunosuppressive medications, calls for alternative cell based therapies. Mesenchymal stem cells, with their unique dual property of multipotency and immunomodulation, offer a promising approach towards treatment of bilateral corneal disorders. However, the parameters including mechanism of homing, transdifferentiation, immunomodulation, and the risk of rejection, the cell source and the number of cells, the time of injection, and the mode of delivery must be studied before translating the possible benefits of MSCs in corneal transplants to clinical practice.

The effect of glutaraldehyde cross-linker on structural and biocompatibility properties of collagen-chondroitin sulfate electrospun mat

Abstract The collagen with glycosaminoglycans such as chondroitin sulfate can potentially be used in many soft tissue engineering applications since the scaffolds mimic the structure and biological function of native extracellular matrix (ECM). In this study, we designed woven and aligned collagen-chondroitin sulfate mats by electrospinning method. The electrospun mats cross-linked with glutaraldehyde vapor at different times, the cross-linked mats became more biostable and were resistant to collagenase degradation. Cellular results with corneal epithelial cells showed that bioviability was reduced in cross-linked mats with glutaraldehyde. Characteristics such as high surface area of nanofibers, biodegradability, and orientation of fibers may maximize cell-ECM interaction and promote tissue regeneration faster than other conventional scaffolds. The cross-linked collagen-chondroitin sulfate electrospun mats can be used in tissue engineering, especially in soft tissue regeneration.

Papilledema revisiting after sinus angioplasty of chronic cerebral venous sinus thrombosis

This case series aimed to review the significance of revisiting papilledema after successful cerebral venous sinus thrombosis (CVST) management with sinus angioplasty. Four patients presented with blurring and transient obscuration of vision with papilledema, headache, tinnitus, and vomiting. On magnetic resonance venography and digital subtraction angiography, chronic transverse sinus thrombosis was diagnosed for which patients underwent endovascular intervention (stenting). After the resolution of CVST, patients developed the recurrence of symptoms which on digital subtraction angiography revealed dural arteriovenous malformation (DAVM). DAVM and papilledema resolved with endovascular embolization. This case series highlights a need of constant monitoring of CVST cases after the endovascular intervention.

Simple limbal epithelial transplantation: Impactful innovation

The first major scientific advancement in the field of ocular surface diseases was made by Kenyon and Tseng in 1989,[1] whose seminal work provided clinical evidence for the existence of corneal epithelial stem cells at the limbus. They elegantly demonstrated that by transplanting healthy limbal tissue from a donor eye, one could successfully reverse the blinding conjunctival overgrowth seen in burn‐injured corneas. Following that breakthrough, both clinicians and stem cell biologists had focused their time and energy on developing techniques aimed at minimizing the amount of limbal tissue required for successful corneal regeneration and thereby limiting the risk to the donor eye. While ex vivo expansion of cells from a tiny limbal biopsy in a laboratory emerged as an alternative,[2] this technology was not only inaccessible to most corneal surgeons but also remained beyond the reach of most patients because of the astronomical costs involved in the process. This ideal balance between minimal donor tissue and minimal risks and costs seemed practically unattainable until the development of simple limbal epithelial transplantation (SLET) by Sangwan et al. in 2010.[3] The innovative new technique turned existing paradigms on their heads by introducing the concept of in vivo stem cell cultivation, completely eliminating the need for expensive laboratories, using the ocular surface as a biological incubator and making stem cell technology accessible to every ophthalmic surgeon and patient. To use a more relatable metaphor, SLET as an innovation breathed new life into limbal stem cell transplantation just as the development of phacoemulsification, capsulorhexis, viscosurgical devices, and foldable intraocular lenses together had changed the future course of cataract surgery many decades ago.

Simple limbal epithelial transplantation (SLET) in failed cultivated limbal epithelial transplantation (CLET) for unilateral chronic ocular burns

Aims Cultivated limbal epithelial transplantation (CLET) fails in around 20%–30% of cases. This study aimed to report the clinical outcomes of autologous simple limbal epithelial transplantation (SLET) in eyes with recurrent unilateral limbal stem cell deficiency (LSCD) due to failure of CLET. Methods This was a prospective case series which included 30 eyes of 30 patients who underwent SLET between 2010 and 2016 after failure of one (n=24) or two (n=6) previous CLET procedures for chronic unilateral ocular burns. The primary outcome measure was success of SLET defined on the basis of relative improvement in five objective criteria: best corrected visual acuity (BCVA), and grades of symblepharon, corneal conjunctivalisation, vascularisation and opacification. Results At a mean follow-up of 2.3 years, 24 (80%) of the 30 eyes maintained a successful outcome. Kaplan-Meier analysis showed a 5-year survival probability of 77%±8%. At 1 year postoperatively statistically significant improvement was noted in BCVA (logarithm of the minimum angle of resolution of 3 to 1) and in the median grades of corneal conjunctivalisation (2 to 0), vascularisation (2 to 0) and opacification (2 to 1) (P≤0.0026). In 62.5% of successful cases, BCVA improved to 20/200 or better. The success rate of SLET in failed CLET was better than that of repeat CLET (53.5%, P=0.011). None of the donor eyes developed any complications. Conclusion SLET is an effective alternative to CLET in eyes with recurrence of LSCD after previously failed CLET procedures. Since SLET is single-staged and less expensive, it is probably preferable to repeating CLET.

Corneal Regeneration: Current Status and Future Prospective

The human cornea is an avascular and transparent tissue which is responsible for the three-fourths of the total refractive power of the eye. It undergoes continuous stress due to the dust, pollution, infection and other environmental insults which may lead to dryness and abrasion injuries. Diseases of the cornea show wide spectrum of manifestations including corneal opacity, conjunctivalization, scarring, limbal stem cell deficiency and immune disorders and may result in blindness. The field of regenerative medicine has shown a great promise in the last two decades. Almost 30 years have been passed since the corneal epithelial stem cells were first reported to be localized in the limbus, a transition zone between the transparent cornea and opaque sclera. During these years, various efforts have been made for the corneal regeneration, including the cell and tissue engineering-based approaches and development of surgical modalities. However, a successful therapy for bilateral corneal diseases remains elusive. We put in here our perspective about the past, the present and the foreseeable future of regeneration and reconstruction of the human cornea.