Artificial Cornea: Past, Current, and Future Directions

Abstract

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.

Application of Bioprinting in Ophthalmology

“…However, printing multilayers of the cornea and maintaining the physiological and mechanical properties and functions is still an immense challenge. Using natural macromolecules in the ECM, rather than synthetic materials, can reduce the risk of corneal transplantation, but the degree of immune response elicited by these constructs remains to be investigated[ 12 , 80 ].…”

Advanced surgeries, medicines and materials for corneal regeneration

“…Keratoprostheses (KPros) or artificial corneas are defined as ¨laboratory-made constructs, with or without the help of biological material but typically consisting of manmade materials, designed principally to replace the function of the native human cornea¨ 63 . The history of KPros began in the second world war when Poly (methyl methacrylate) (PMMA) splinters from crashed Perspex® canopies were found in the cornea of a pilot's eye without causing any adverse events.…”

“…The ideal biomaterial for engineering a corneal stromal substitute needs to be transparent with adequate refractive index, strong enough to allow surgical manipulation and allow permeability of oxygen and nutrient while acting as a barrier for toxins and microorganisms. It should allow cell adhesion and migration of host epithelium and stromal cells but at the same time resist vascularization and opacification [63][64][65][66] . Natural polymers offer the advantage of biocompatibility while synthetic polymers can meet individual needs by adjusting chemical and mechanical properties 63 .…”

“…It should allow cell adhesion and migration of host epithelium and stromal cells but at the same time resist vascularization and opacification [63][64][65][66] . Natural polymers offer the advantage of biocompatibility while synthetic polymers can meet individual needs by adjusting chemical and mechanical properties 63 .…”

Ultra-wide field imaging to assess the optic nerve and retina in Boston type I and II keratoprosthesis patients

“…Artificial corneal transplantation was developed to treat severe ocular surface disease and corneal blindness in cases of poor prognosis with traditional penetrating keratoplasty. The Boston type I keratoprosthesis (Kpro) is the most used artificial corneal design worldwide [ 1 ]. The less commonly used Boston type II Kpro is indicated in patients with severe, end-stage corneal disease and implanted through surgically closed eyelids [ 2 , 3 ].…”