Artificial Cornea: Past, Current, and Future Directions

Corneal diseases are a leading cause of blindness with an estimated 10 million patients diagnosed with bilateral corneal blindness worldwide. Corneal transplantation is highly successful in low-risk patients with corneal blindness but often fails those with high-risk indications such as recurrent or chronic inflammatory disorders, history of glaucoma and herpetic infections, and those with neovascularisation of the host bed. Moreover, the need for donor corneas greatly exceeds the supply, especially in disadvantaged countries. Therefore, artificial and bio-mimetic corneas have been investigated for patients with indications that result in keratoplasty failure. Two long-lasting keratoprostheses with different indications, the Boston type-1 keratoprostheses and osteo-odonto-keratoprostheses have been adapted to minimise complications that have arisen over time. However, both utilise either autologous tissue or an allograft cornea to increase biointegration. To step away from the need for donor material, synthetic keratoprostheses with soft skirts have been introduced to increase biointegration between the device and native tissue. The AlphaCor™, a synthetic polymer (PHEMA) hydrogel, addressed certain complications of the previous versions of keratoprostheses but resulted in stromal melting and optic deposition. Efforts are being made towards creating synthetic keratoprostheses that emulate native corneas by the inclusion of biomolecules that support enhanced biointegration of the implant while reducing stromal melting and optic deposition. The field continues to shift towards more advanced bioengineering approaches to form replacement corneas. Certain biomolecules such as collagen are being investigated to create corneal substitutes, which can be used as the basis for bio-inks in 3D corneal bioprinting. Alternatively, decellularised corneas from mammalian sources have shown potential in replicating both the corneal composition and fibril architecture. This review will discuss the limitations of keratoplasty, milestones in the history of artificial corneal development, advancements in current artificial corneas, and future possibilities in this field.

Efficacy of Haridradwayadi Rasakriyanjana in Shushkakshipaka w.s.r to Dry Eye Syndrome- A Case Report

Tear secretion is an integral component of the ocular surface physiology; when compromised (quantitatively or qualitatively) lead to Dry eye syndrome with several ocular symptoms and ultimately the patient may end up in corneal blindness. The symptoms of Dry eye syndrome are similar to the disease Shushkakshipaka (ocular surface inflammatory syndrome) in Ayurveda. Vata & Pitta vitiation as per Ayurveda viewpoint are the major contributing pathological factors in its manifestation. Although a number of researches have been carried out and are still continuing, no curative treatment has been achieved yet. This paper aims to establish the efficacy of Haridradwayadi Rasakriyanjana during the clinical observation of a 55 years old female subject who was diagnosed with Shushkakshipaka. She was administered with the drug Haridradwayadi Ghrita in the form of Rasakriyanjana (semi-solid collyrium) drops topically for 30 days, by using subjective and objective assessment criteria which showed a significant result. After the treatment, majority of the symptoms reduced considerably and during the follow up concluded that there was no aggravation of the same.

Assessment of Clinical Outcome Following Therapeutic Penetrating Keratoplasty in Non-Healing Infective and Perforated Corneal Ulcer

BACKGROUND Corneal blindness has been a significant visual disability in developing countries like India. Corneal ulcer contributes mainly as the leading cause for monocular blindness. Considering the common condition, the studies and literature have been surprisingly less when it comes to corneal ulcer and their management. But with the advent of therapeutic penetrating keratoplasty (TPK), the scenario and prevalence of corneal blindness can be reduced. Hence this study was done to know the importance of therapeutic penetrating keratoplasty in case of non-healing infective and perforated corneal ulcers. The objectives were to assess the clinical outcome in a non-healing and perforated corneal ulcer, reduction in symptoms and signs of infection, anatomical or structural integrity of the globe and also evaluate the visual outcome following therapeutic penetrating keratoplasty. METHODS Data were obtained from 30 patients operated at our institute for therapeutic penetrating keratoplasty. Patients with less than one year of follow up, paediatric cases, PL negative cases were excluded. The outcome was assessed based on maintenance of structural integrity, reduction in infective load, improvement in visual acuity and graft survival and its correlation with corneal vascularisation, previously failed grafts, donor tissue quality, graft size and type of surgery. RESULTS Structural integrity was maintained in 93.3 % of the cases, reduction of infective load in 90 % of cases and optically clear grafts in 46.7 % of cases and vision was better than 6/60 in 30 % of cases. CONCLUSIONS The study proved that in the case of non-healing and perforated corneal ulcers, therapeutic penetrating keratoplasty had a good prognosis in reducing infective load, maintaining structural integrity without which eye could have been lost. KEYWORDS Therapeutic Penetrating keratoplasty, Perforated corneal ulcer, non-healing corneal ulcer, corneal blindness, TPK

Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.

In situ Tissue Regeneration in the Cornea from Bench to Bedside

Corneal blindness accounts for 5.1% of visual deficiency and is the fourth leading cause of blindness globally. An additional 1.5–2 million people develop corneal blindness each year, including many children born with or who later develop corneal infections. Over 90% of corneal blind people globally live in low- and middle-income regions (LMIRs), where corneal ulcers are approximately 10-fold higher compared to high-income countries. While corneal transplantation is an effective option for patients in high-income countries, there is a considerable global shortage of corneal graft tissue and limited corneal transplant programs in many LMIRs. In situ tissue regeneration aims to restore diseases or damaged tissues by inducing organ regeneration. This can be achieved in the cornea using biomaterials based on extracellular matrix (ECM) components like collagen, hyaluronic acid, and silk. Solid corneal implants based on recombinant human collagen type III were successfully implanted into patients resulting in regeneration of the corneal epithelium, stroma, and sub-basal nerve plexus. As ECM crosslinking and manufacturing methods improve, the focus of biomaterial development has shifted to injectable, in situ gelling formulations. Collagen, collagen-mimetic, and gelatin-based in situ gelling formulas have shown the ability to repair corneal wounds, surgical incisions, and perforations in in-vivo models. Biomaterial approaches may not be sufficient to treat inflammatory conditions, so other cell-free therapies such as treatment with tolerogenic exosomes and extracellular vesicles may improve treatment outcomes. Overall, many of the technologies described here show promise as future medical devices or combination products with cell or drug-based therapies. In situ tissue regeneration, particularly with liquid formulas, offers the ability to triage and treat corneal injuries and disease with a single regenerative solution, providing alternatives to organ transplantation and improving patient outcomes.

Effectiveness of eye donation orientation session in bridging the knowledge gap amongst undergraduate medical students in Delhi

Background: Corneal blindness may be curable by keratoplasty but the demand for eye donation is however, unmet due to a variety of factors including knowledge gap. The purpose of this study was to assess the awareness of the medical undergraduate students towards eye donation and to assess the effectiveness of an orientation program in bridging the knowledge gap. Methods: This was a cross-sectional study done on MBBS students of 2nd and 3rd professional years. A pretested questionnaire was used to assess the knowledge of medical students. Knowledge regarding the contraindications to eye donation, the procedure involved and common misconceptions were assessed. This was followed by a session on orientation regarding eye donation. A second assessment using the same questionnaire was done after the session to assess the effectiveness of the same. The data was analysed using EPIINFO version 3.5.4 using chi square test. Results: Less than 50% students were aware of contraindications and less than 10% students knew ideal cornea harvesting time and nearest eye bank to their homes. Less than one-fourth students knew common causes of corneal blindness. However, most (77%) students were aware that hospital staff must motivate deceased’s family for eye donation. Significant increase in awareness was observed post orientation regarding most issues.Conclusions: This study shows that there is a knowledge gap amongst undergraduate medical students regarding eye donation. It also suggests that orientation sessions may be helpful in bridging this gap.

Microbiological profile of infective keratitis in a tertiary care hospital in north Karnataka

Corneal blindness is seen worldwide with 1.5 to 2 million new cases reported every year and approximately there are 6.8 million cases of corneal blindness in India. The study constituted 109 clinically diagnosed infective keratitis cases. Aseptically collected corneal scrapings are subjected to Gram stain, KOH wet mount & Culture. Further identification done by study of Colony morphology, staining & biochemical tests. Antibiotic sensitivity was found using Kirby buer’s disc diffusion method following CLSI guidelines. Males affected more common than females. Common age group being 21-40 yrs. Infective keratitis is usually Bacterial(61.4%) in origin than fungal(22%). Trauma found to be the most common predisposing factor followed by diabetes, other ocular diseases, surgery & corticosteroid therapy. Trauma with vegetative material is most common. Streptococcus pneumonia & pseudomonas are most common bacterial cause while Fusarium & Aspergillus cause most fungal cases. Infective keratitis both bacterial & fungal are more common in working males, mainly agriculturists who are exposed to vegetative trauma. Early detection and treatment with proper antibacterial & antifungals is important to prevent ocular problems and scarring of cornea.

Preventing corneal blindness caused by keratitis using artificial intelligence

Keratitis is the main cause of corneal blindness worldwide. Most vision loss caused by keratitis can be avoidable via early detection and treatment. The diagnosis of keratitis often requires skilled ophthalmologists. However, the world is short of ophthalmologists, especially in resource-limited settings, making the early diagnosis of keratitis challenging. Here, we develop a deep learning system for the automated classification of keratitis, other cornea abnormalities, and normal cornea based on 6,567 slit-lamp images. Our system exhibits remarkable performance in cornea images captured by the different types of digital slit lamp cameras and a smartphone with the super macro mode (all AUCs>0.96). The comparable sensitivity and specificity in keratitis detection are observed between the system and experienced cornea specialists. Our system has the potential to be applied to both digital slit lamp cameras and smartphones to promote the early diagnosis and treatment of keratitis, preventing the corneal blindness caused by keratitis.

Cultivated autologous oral mucosal epithelial transplantation

According to the World Health Organization, corneal blindness is the fourth most common cause of blindness and visual impairment worldwide. In Russia, up to 18% of blindness is caused by corneal damage. Limbal stem cell deficiency (LSCD) is one of the causes of corneal blindness and visual impairment due to anterior epithelial replacement with fibrovascular pannus. Bilateral LSCD may develop in patients with aniridia, Steven-Jones syndrome, and severe corneal burns of both eyes, leading to severe decrease in visual acuity in both eyes and, as a consequence, physical disability associated with blindness. In such cases, cell therapy, based on autologous oral epithelial culture as an alternative to allogeneic limbus transplants, is proposed for reconstruction of the anterior corneal epithelium. This new treatment method promotes corneal reepithelization, better visual acuity, reduced nonspecific ocular complaints and improved quality of life of patients. The effectiveness and significant increase in the frequency of transparent engraftment of donor corneas after cell therapy drives huge interest in this topic all over the world. This review presents literature data on the features of histotopography and methods for obtaining a cultured autologous oral mucosal epithelium, on cell markers that are used to identify epithelial cells, and on methods for creating cell grafts for subsequent transplantation to the corneal surface in LSCD patients.