Chi Kit Yan

Resident Doctor, Manchester Royal Eye Hospital

Introduction

Vision is inarguably the most vital sense, enabling individuals to navigate the world, connect with others, and experience life in vivid detail. At the forefront of maintaining clear vision is the cornea, the transparent, dome-shaped outer layer of the eye that focuses light onto the retina. However, injury, infection, or diseases such as keratoconus and corneal dystrophies can compromise its clarity, leading to significant visual impairment or blindness. For millions of people worldwide, corneal transplantation has offered a lifeline, restoring sight and improving quality of life. This remarkable procedure, first performed successfully over a century ago, has transformed from a rudimentary surgical endeavour into a sophisticated intervention supported by advances in technology, immunology, and bioengineering. As we look to the future, corneal transplantation continues to evolve, offering innovative solutions to the challenges of donor shortages, surgical precision, and accessibility. This article will explore a brief history, current techniques and future advancement in corneal transplantation.

Historical Perspective

The history of corneal transplantation traces back to the early 20th century, marked by Eduard Zirm’s pioneering achievement in 1905, performing the first successful human corneal transplant in Olomouc, Austria-Hungary (1). Despite this breakthrough, early attempts were fraught with challenges, including graft rejection, limited understanding of tissue compatibility, and rudimentary surgical techniques that hindered outcomes (2). Over subsequent decades, incremental milestones refined these procedures.

The mid-20th century seen transformative progress with the introduction of the operating microscope, which enabled surgeons to perform more precise and controlled interventions. Concurrent advancements in anaesthesia and sterilisation significantly improved patient safety and surgical outcomes (3,4).

The establishment of organised corneal donor programmes and the creation of eye banks, like first Eye Bank in the United Kingdom, established in 1952, provided a national service for storing and supplying corneas for hospitals throughout the UK. The improved technology in storage by organ culture, introduced by Corneal Transplant Service in Bristol (CTS Eye Bank), also extend the graft availability vastly (5). These breakthroughs addressed the critical issue of donor tissue availability, laying the foundation for modern corneal transplantation as a reliable therapeutic option.

Current State of Corneal Transplantation

Modern Techniques

A spectrum of advanced surgical techniques is made available with rapid advancement in the understanding graft rejection. These procedures vary based on the extent and nature of corneal damage.

Penetrating keratoplasty (PK), the traditional full-thickness replacement, remains widely used as the treatment to most causes of corneal blindness (6). Lamellar keratoplasty techniques, aimed at replacing the damaged layers of cornea and leaving healthy corneal tissue intact. For instance, Deep anterior lamellar keratoplasty (DALK) is used in stromal diseases, is favoured over the conventional PK without the risk of endothelial rejection. Endothelial keratoplasties focus on replacing the corneal endothelium have gained prominence due to their reduced rejection rates and faster recovery times. Common techniques include Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) (7,8).

In addition, ocular surface reconstruction and keratoprosthesis surgery are procedures that are advancing rapidly. Boston keratoprosthesis (BKPro) is the most widely used form of artificial cornea, serving a treatment option for corneal disease not amenable to standard penetrating keratoplasty (PKP) or corneal transplant. Continued advances in design and superior postoperative care have resulted in improved outcomes and an exponential increase in the use of the device in recent years (9).

Osteo-odonto-keratoprosthesis (OOKP) describes a longer lasting KPros using alveo-dental lamina of a single tooth, usually canine, creating an optical cylinder in its centre. A buccal mucosa membrane then provides protection and nourishment to the prosthesis. This is indicated for bilateral corneal blindness with severe visual loss (<6/60) and dry eye or lid damage, as well as poor keratoplasty prognosis. It is especially multiple failed corneal transplants and those with ocular surface disease such as mucous membrane pemphigoid and SJS (10,11).

The use of femtosecond lasers, and improved graft survival rates underscore the progress in surgical precision and efficacy (12).

Technological and Medical Innovations

The integration of cutting-edge imaging technologies, such as optical coherence tomography (OCT), has revolutionised pre- and post-surgical planning, enabling detailed visualisation of corneal layers and guiding surgical decisions. Recent study also revealed the use of intraoperative OCT guided surgeries, which showed the potential impact of real time imaging, paving ways for improved precision and better outcomes (13).

Meanwhile, innovations in corneal preservation, such as organ culture and enhanced hypothermic storage methods, have extended tissue viability (14).

The development of immunosuppressive therapies, including topical corticosteroids and calcineurin inhibitors, has further reduced rejection risks and complications.

Current challenges

Despite these advancements, significant challenges persist. The global scarcity of donor corneas, driven by logistical and cultural barriers remain one of the major challenges for many patients. Public education and increased awareness would be rudimental in streamlining the donation process.

Yule et al. reported centres exploring benefits and challenges faced in corneal splitting (15).Evidence suggested each cornea can be divided up to five patients by separating it into four quarter DMEKs and one DALK (16, 17).Utilising donor tissue in this way would optimise the utilisation of existing resources whilst bridging the demand-supply gap between available donor tissues and patients awaiting keratoplasties.

Furthermore, rejection and other complications remain critical concerns, particularly in complex cases (18).Disparities in access to transplantation services in low-resource settings exacerbate the global burden of corneal blindness, highlighting the need for scalable solutions to bridge these gaps.

The Future of Corneal Transplantation

Emerging Innovations

The future of corneal transplantation is shaped by groundbreaking innovations to address long-standing challenges and expand accessibility. Bioengineered corneas, including synthetic and lab-grown tissues, are at the forefront of this transformation (19). Recent successes in clinical trials have demonstrated the potential of lab-grown corneal implants to restore vision in patients with corneal blindness, offering an alternative to traditional donor tissues. Stem cell therapy is another promising avenue, with advances in regenerating damaged corneal tissues and treating conditions such as limbal stem cell deficiency (20, 21).

Similarly, the integration of game-changing 3D printing technology enables the creation of custom-designed corneas tailored to the individual needs (22, 23). These bespoke corneas offer a substitution to conventional human tissues, providing customisable structure, refractive ability. It is believed that these multi-material integration alternatives can offer improve structural strength, building complex structure with a diversity of cell types for different transplantation needs.

Advancement in Anti-rejection Medications

Advancements in anti-rejection medications have significantly improved outcomes in corneal transplantation, yet challenges remain due to the side effects and long-term risks associated with systemic immunosuppressive therapies. Current research, as highlighted by Armitage et al., explores innovative strategies to reduce dependency on these medications. One promising approach involves the potential use of oral anti-rejection drugs, similar to those employed in solid organ transplantation, which could offer a more convenient and targeted therapeutic option. Additionally, targeting specific pathways in the rejection mechanism, such as neovascularisation, as a key contributor to graft failure has gained attention. Anti-VEGF therapies, for instance, may inhibit corneal neovascularisation and improve graft survival. Furthermore, pre-treating donor corneas with locally injected anti-inflammatory cytokines to modulate antigen-presenting cells could create an “anti-rejection coating,” enhancing immune tolerance (24). These developments, alongside immune tolerance induction and targeted immunomodulatory therapies, represent a paradigm shift towards minimising systemic immunosuppression and improving long-term graft outcomes.

Gene Therapy and Genetic Engineering

Gene therapy and genetic engineering also hold immense potential. CRISPR-based approaches are being explored to prevent rejection and address hereditary corneal disorders, offering hope for long-term graft survival and improved outcomes (25). These technologies could revolutionize the treatment landscape, reducing the need for immunosuppressive therapies and enhancing the durability of corneal grafts (26).

Global Initiative and Accessibility

Addressing global accessibility remains a critical goal for the future of corneal transplantation. Strategies such as xenotransplantation and the development of artificial corneas are being explored to mitigate donor shortages. Simultaneously, global initiatives aim to make transplantation affordable and accessible in low-income regions, ensuring equitable access to life-changing care. Together, these advances herald a new era for corneal transplantation, where innovation and equity converge to tackle the global burden of corneal blindness.

Conclusion

Corneal transplantation has undergone remarkable evolution since Eduard Zirm’s pioneering surgery 120 years ago, transforming from an experimental procedure into a widely practiced intervention that restores sight to millions worldwide. Advances in surgical techniques, preservation methods, and immunosuppressive therapies have dramatically improved success rates and patient outcomes, underscoring its profound impact on global health. However, the transformative potential of emerging innovations, including bioengineered corneas, stem cell therapies, 3D printing, and gene editing, promises to further revolutionise the field, offering hope to those currently underserved by traditional approaches.

Achieving universal access to these vision-restoring solutions will require sustained investment in research and the fostering of international collaboration. Addressing challenges such as donor shortages, rejection risks, and healthcare disparities demands a concerted global effort, uniting scientific ingenuity with equitable policies. By building on the foundations of past achievements and embracing the possibilities of future advancements, corneal transplantation can continue to evolve as a beacon of hope for tackling the global burden of corneal blindness.

References

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