Application of Artificial Intelligence in the Diagnosis and Management of Corneal Diseases.

Diagnosis and treatment planning in ophthalmology heavily depend on clinical examination and advanced imaging modalities, which can be time-consuming and carry the risk of human error. Artificial intelligence (AI) and deep learning (DL) are being used in different fields of ophthalmology and in particular, when running diagnostics and predicting outcomes of anterior segment surgeries. This review will evaluate the recent developments in AI for diagnostics, surgical interventions, and prognosis of corneal diseases. It also provides a brief overview of the newer AI dependent modalities in corneal diseases.

Therapeutic approaches for induction of tolerance and immune quiescence in corneal allotransplantation.

The cornea is the most commonly transplanted tissue in the body. Corneal grafts in low-risk recipients enjoy high success rates, yet over 50% of high-risk grafts (with inflamed and vascularized host beds) are rejected. As our understanding of the cellular and molecular pathways that mediate rejection has deepened, a number of novel therapeutic strategies have been unveiled. This manuscript reviews therapeutic approaches to promote corneal transplant survival through targeting (1) corneal lymphangiogenesis and hemangiogenesis, (2) antigen presenting cells, (3) effector and regulatory T cells, and (4) mesenchymal stem cells.

Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation.

Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-ß1 (TGFß1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)+ effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+ cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.

Proangiogenic Function of T Cells in Corneal Transplantation.

BACKGROUND: Corneal neovascularization increases the risk of T cell-mediated allograft rejection. Here, we investigate whether T cells promote angiogenesis in transplantation. METHODS: Conventional effector T cells were collected from draining lymph nodes of allogeneic or syngeneic corneal transplanted BALB/c mice. T cells were either cocultured with vascular endothelial cells (VECs) to assess VEC proliferation or used in a mixed lymphocyte reaction assay. Messenger RNA (mRNA) expression of vascular endothelial growth factor (VEGF)-A, -C, and VEGF receptor 2 (VEGF-R2) in VECs was assessed by real-time PCR. VEGF-A protein expression was determined by enzyme-linked immunosorbent assay. Flow cytometry was used to analyze VEGF-R2 expression in corneal CD31 cells, and VEGF-A and IFNγ expression in corneal CD4 T cells. RESULTS: Allogeneic T cells from high-risk (HR) grafted mice induced more VEC proliferation than those from syngeneic transplant recipients (P = 0.03). Vascular endothelial growth factor-A mRNA and protein expression were higher in T cells from draining lymph nodes (P = 0.03 and P = 0.04, respectively) and cornea (protein; P = 0.04) of HR compared with low-risk (LR) grafted hosts. Vascular endothelial growth factor-A, VEGF-C, and VEGF-R2 mRNA expression were increased in VECs when cocultured with T cells from HR transplants compared with LR transplants and naive mice. In addition, IFNγ blockade in T cell/VEC coculture increased VEC proliferation and VEGF-A protein expression, whereas blocking VEGF-A significantly reduced VEC proliferation (P = 0.04). CONCLUSIONS: Allogeneic T cells from corneal transplant hosts promote VEC proliferation, probably via VEGF-A signaling, whereas IFNγ shows an antiangiogenic effect. Our data suggest that T cells are critical mediators of angiogenesis in transplantation.

Prevention of corneal neovascularization: comparison of different doses of subconjunctival bevacizumab with its topical form in experimental rats.

BACKGROUND: To compare the effect of different dosages of subconjunctival bevacizumab with its topical administration on preventing the development of corneal neovascularization (CNV) in a rat model of corneal chemical injury. METHODS: Neovascularization was induced by pressing a 2-mm diameter alkaline-coated applicator on the central cornea of the right eye of 50 anesthetized male rats. Immediately after cauterization, rats were divided randomly into 5 groups. Groups 1-4 received a subconjunctival injection of 0.02 ml of normal saline (control) or 1, 5 and 25 mg/ml of bevacizumab, respectively. In the fifth group, topical bevacizumab was instilled daily for 7 consecutive days. After 7 days, digital photographs of the cornea were taken and the area of the neovascularized cornea was calculated. RESULTS: Analysis of digital photographs showed that, compared with the controls, a single subconjunctival injection of at least 0.1 mg of bevacizumab (5 mg/ml) - immediately after corneal cauterization - effectively decreased CNV after 7 days. Injection of 25 mg/ml of bevacizumab in the fourth group increased the avascular area more than twofold, compared with the saline-treated group (32.2% compared with 15%, p < 0.001). This difference between groups 4 and 2 was statistically significant (p = 0.04). Although topical delivery of 25 mg/ml bevacizumab was effective to inhibit CNV (p = 0.004), the results were similar to those of the third group. Qualitative microscopic evaluation of the cornea was compatible with the gross findings, as bevacizumab-treated groups had less intense corneal vessel channels and inflammation. CONCLUSION: Both subconjunctival and topical bevacizumab can prevent CNV in rats.