The cornea is remarkably strong and resilient; it can heal itself and even outlast the lifetime of its original owner. However, corneal injuries, diseases, or degeneration can lead to corneal fibrosis, scarring, clouding, or structural damage— which could potentially result in impaired vision, and in some cases, permanent damage. Second only to cataracts, corneal blindness is a leading cause of vision loss globally, resulting in 2 million new cases of unilateral blindness each year.
It is estimated that approximately 3% of all emergency room visits are due to eye trauma, with the majority of cases involving corneal injury. Sadly, the vast majority of these cases were preventable. Most corneal injuries can be categorized as either traumatic (abrasion, foreign bodies) or exposure-related (chemical, thermal, or radiation burns). Morbidities resulting from corneal trauma vary widely, ranging from minor or insignificant injuries to vision-threatening with life-long consequences.
Most often, in cases of minor corneal trauma caused by abrasions or foreign bodies, the approach involves managing symptoms using analgesia, removing the foreign object, and treating with topical non-steroidal anti-inflammatory drugs or topical antibiotics. When it comes to major trauma or injury, aggressive measures are required, with the most extreme option being corneal transplant.
The ultimate gift of sight
Corneal transplantation, the most commonly performed form of organ transplantation, can be a viable option for individuals who have suffered irreversible corneal damage due to disease or trauma.
Currently, over 10 million people worldwide are affected by corneal blindness. The unfortunate reality is that there is a much greater demand for corneal transplants than there are available corneas from donors. However, advancements have been made in reducing transplant rejection rates and enhancing our understanding of the procedure and wound-healing process, resulting in higher success rates for corneal transplants than ever before. This ensures that these valuable donations are put to good use.
In a 2016 study evaluating the status of global corneal transplants and eye banking, it was found that for every cornea donated, there was a demand for 70 more.1 They also found that 53% of the world’s population does not have access to corneal transplantation. The authors noted the need for ongoing efforts to encourage cornea donation in all countries.
However, public education programs still face significant challenges in dispelling myths and encouraging individuals to donate their corneas. Among the general public, there is a lack of awareness that only the corneas are donated, not the entire eye. It is important to know that corneal donation can take place within 24 hours of death, and corneal donation will not affect how someone looks at their funeral. Additionally, even if someone had cancer or poor vision during their lifetime, their corneas can still be extremely valuable to someone in need.
The evolution of corneal transplantation
Did you know that corneal transplantation has a history dating back almost 120 years? The first corneal transplant was performed by Dr. Eduard Zirm in 1905 on a patient who suffered an alkali chemical injury. Over the decades that followed, there has been an evolution in surgical techniques, suture materials, antibiotics, steroid and tissue storage, and preparation techniques.
Indeed, we have moved away from the era of full-thickness transplants, and there is now a shift towards more customized, disease-focused procedures. Nowadays, surgeons determine whether the deficits are in the endothelial layer, requiring endothelial keratoplasty, or if midlayer procedures such as anterior lamellar keratoplasty are required.
Endothelial keratoplasty represents a major advancement in corneal transplantation, allowing for the targeted replacement of the diseased corneal endothelium. There are several endothelial keratoplasty techniques that vary in the way the recipient’s endothelium is removed and how the donor tissue is prepared. These techniques include Descemet’s membrane endothelial keratoplasty (DMEK), Descemet stripping endothelial keratoplasty (DSEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane automated endothelial keratoplasty (DMAEK).
Keys to successful corneal transplantation
Prof. Vito Romano, a professor of ophthalmology at the University of Brescia in Italy and the head of Cornea and Ocular surface service at Spedali Civili di Brescia, is passionate about clinical and translational research. His research is primarily focused on lamellar corneal transplantation and strategies aimed at improving the success of corneal transplantation.
Prof. Romano shared the key to successful corneal transplantation. “It is well known that corneal endothelial cell viability is the main predictor for corneal graft survival. Currently, surgeons have no means to assess the endothelial status independently before transplantation,” he said.
One of the areas that Prof. Romano’s research focuses on is testing a method that could enhance the standardization of keratoplasty outcomes, improve graft survival, and offer eye banks and surgical teams an accessible tool for validating tissues before transplantation. This initiative aims to reinforce the overall quality of their services.
Prof. Romano and his colleagues have recently published the protocol for their viability study, which aims to validate a preoperative method of evaluating the endothelial health of donor corneal tissues. This method will enable surgeons to determine the proportion of tissues deemed suitable for transplantation and prospectively record clinical outcomes.2
Prof. Romano’s research is also focused on DMEK, recognizing the difficulty of the procedure and the importance of surgeon training. “Spreading knowledge about a surgical technique with a steep learning curve is of paramount importance,” he shared. “Such techniques often require years of practice and mentorship to master. Sharing expertise accelerates the learning process and reduces the risk of errors and complications associated with novices. Moreover, it promotes standardization and ensures that best practices are consistently applied.”
Prof. Romano and his colleagues have published a useful guide for DMEK learners in the Survey of Ophthalmology. This guide identifies potential limitations and offers alternative approaches and emerging technologies that can speed up the DMEK learning curve.3
Vision-threatening corneal diseases
Fuchs’ dystrophy and keratoconus are among the major corneal diseases that may require transplantation.
Fuchs’ endothelial corneal dystrophy is a progressive hereditary disease characterized by the dysfunction of the corneal endothelium. It can be classified based on the time of onset— with early-onset cases manifesting in early childhood and progressing into the patient’s 30s, while lateonset cases typically begin in their 40s and 50s.
In Fuchs’ dystrophy, the corneal endothelium is unable to properly regulate fluid absorption, resulting in stromal edema, which, in turn, causes hazy or cloudy vision. In addition, there is a progressive loss of endothelium, contributing to an increase in stromal and Descemet’s membrane thickness. This aggravates stromal and epithelial edema, and in severe cases, can result in the development of epithelial bullae.
Patients with Fuchs’ dystrophy often experience fluctuating blurriness in their vision throughout the day, with mornings typically being the worst. One of the most telling clinical signs is the formation of excrescences, known as “guttae,” on the Descemet’s membrane.
Navigating keratoconus
Keratoconus, on the other hand, is a devastating, slowly progressive, noninflammatory ectatic corneal disease that affects the corneal collagen structure and organization.
Dr. Ashraful Huq Ridoy, a consultant ophthalmologist currently practicing at Bangladesh Eye Hospital and Institute in Dhanmondi and Bangladesh Eye Care Hospital in Zigatola, shared his expertise in diagnosing and managing patients with keratoconus.
Dr. Huq explained the features of keratoconus that eye care professionals should take into account, noting that the origins of the condition are not well understood.
“Though the exact reason for keratoconus is still unclear, it usually appears at early puberty and might be progressive until the 3rd or 4th decade of life. Keratoconus is usually bilateral, but progression could be asymmetrical. Ocular allergies and eye rubbing secondary to atopy are believed to have a higher incidence of association with keratoconus, along with other few systemic and ocular disease conditions,” he said.
He added that awareness is key to timely diagnosis. “In South Asian countries, it is important to prioritize awareness and logistics of keratoconus diagnosis because not all patients exhibit the classical signs of the condition,” he continued.
Dr. Huq provided an example of such a non-classical case. “So, when a young patient presents with myopic astigmatism and a history of frequent changes in glass power in recent years, and whose vision cannot be refracted to 20/20, there should always be consideration for keratoconus screening for that patient.”
We asked Dr. Huq how he manages a keratoconus patient in his practice.“When keratoconus is diagnosed, treatment will depend on the progression and severity. So, the first part of management is determining whether it is progressive or non-progressive,” he explained.
Due to the progressive nature of the disease, once the diagnosis has been confirmed, it is essential to encourage keratoconus patients to establish a long-term relationship with their cornea specialist. This is not always easy, as Dr. Huq emphasized, “The patient should receive empathic counseling about the disease and should be persuaded to commit to long-term follow-up.”
Dr. Huq also explained the factors that may influence keratoconus progression. “Patient age, ocular allergies, eye rubbing, corneal steepening, its location, and bestcorrected vision play a role in understanding the progression,” he said.
Strategies for high- and low-risk cases
If the patient is deemed to be at a high risk of progression, Dr. Huq recommends a specific initial course of action. “Go for collagen crosslinking (CXL) first. Study shows CXL stops the progression in 90% of cases,” he said. “However, CXL has limitations in advanced cases and also won’t work when hydrops or any scar is present in the cornea,” he cautioned.
CXL involves topical treatment plus ultraviolet light that adds bonds to the collagen fibers, improving the strength of the cornea.
How about our lower-risk patients? “In cases of low-risk progression, when the patient has good vision with glasses or contact lenses, we typically observe the patient and recommend regular follow-up. Scleral contact lenses are always often the preferred choice for visual rehabilitation in keratoconus patients,” Dr. Huq shared.
“CXL only stops the progression,” he added. “Scleral contact lenses are the first choice for visual rehabilitation in post-CXL or lowrisk progression patients.” However, patients also play a crucial role in their treatment. “Patient education on the proper use and storage of scleral contact lenses is another important aspect to consider,” noted Dr. Huq.
Modern approaches to keratoconus management
Dr. Huq also discussed additional management options for keratoconus patients. “Topography-guided PRK with CXL can be considered in patients who exhibit no documented progression and have significant higher-order aberrations that are not corrected with contact lenses. Another option for visual rehabilitation in non-progressive cases is the toric implantable contact lens. This involves precise measurement of corneal toricity and best-corrected vision,” he shared.
How about those with early to moderate keratoconus? “Intra corneal ring segment is one treatment option to consider when the corneal thickness is 450 microns in the central 6 mm zone,” Dr. Huq explained. “In cases of very thin corneas, hydrops, or post-hydrops scarring, planning for cornea transplantation is the recommended treatment. Deep anterior lamellar keratoplasty (DALK) is the preferred choice for managing keratoconus, although penetrating keratoplasty remains an option depending on the condition of the host cornea. Many times, keratoplasty induces unpredictable toricity, which may need adjustments with scleral contact lenses.”
In the past, treatment options for keratoconus were limited and often resulted in poor outcomes. However, as Dr. Huq explained, this is no longer the case. “Early diagnosis and management are the key to preserving vision and enhancing the quality of life for individuals living with keratoconus.”
Eyes on the future
Ongoing research is dedicated to making significant advancements in the management of corneal disease, with a primary focus on reducing the reliance on donated corneal tissue and finding ways to maximize its impact. Recent work exploring the delivery of cultured endothelial cells as an alternative to using corneal tissue has shown promising results. Additionally, a recent program is investigating non-surgical magnetic corneal endothelial cell delivery as a potential approach to treat corneal edema.
Despite significant advancements in the understanding and management of corneal diseases and trauma, the cornea remains both delicate and resilient. However, there’s still a shortage of available corneas for those in need of corneal transplants.
Hence, encourage your patients to consider cornea donation in your region, sign their donor card, and make their wishes known to their families. Spread the word about one of the most important donations we could ever make—the gift of sight.
References
- Gain P, Jullienne R, He Z, et al. Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol. 2016;134(2):167-173.
- Airaldi M, Zheng Y, Aiello F, et al. Preoperative surgeon evaluation of corneal endothelial status: the Viability Control of Human Endothelial Cells before Keratoplasty (V-CHECK) study protocol. BMJ Open Ophthalmol. 2023;8(1):e001361.
- Parekh M, Ruzza A, Rovati M, et al. DMEK surgical training: An instructional guide on various wetlab methods. Surv Ophthalmol. 2023;68(6):1129-1152.
Editor’s Note: A version of this article was first published in CAKE Magazine Issue 20.
