Corneal transplantation (keratoplasty)

Corneal transplantation, also called keratoplasty or corneal grafting, is a surgical procedure in which diseased or damaged corneal tissue is replaced with healthy corneal tissue obtained from a deceased donor.[1] The cornea is the clear, dome-shaped front surface of the eye and supplies roughly two-thirds of the eye's focusing (refractive) power; when it loses clarity or regular shape, vision is degraded.[1] Corneal transplantation is among the most common and most successful forms of human tissue transplantation, and unlike most solid-organ grafts it usually does not require systemic immunosuppression because the cornea is relatively immune-privileged.[1][2] In the United States, eye banks supplied tissue for 51,559 keratoplasty procedures performed domestically in 2024.[3]

The cornea is distinct from the organ transplantation system: it is recovered and distributed by eye banks rather than organ-procurement organizations, and is governed by tissue-banking rather than organ-allocation rules. See Eye banking and the EBAA and Tissue bank.

Corneal anatomy relevant to grafting

From front to back, the cornea has five principal layers: the epithelium, the acellular Bowman layer, the stroma (which provides most of the corneal thickness and mechanical strength), the Descemet membrane, and a single posterior layer of endothelial cells.[1] The endothelium maintains corneal clarity by pumping fluid out of the stroma; human corneal endothelial cells have very limited capacity to regenerate, which is why their loss or rejection is the most consequential threat to a graft.[1][4] The cornea is normally avascular (it has no blood vessels) and lacks lymphatic vessels, a property central both to its transparency and to its immune privilege.[2]

Indications

The relative frequency of indications differs between higher-income and lower-income settings. In developed countries the leading indications are endothelial diseases; in many developing countries, scarring from infection and injury predominates.[1]

Common indications include:

• Fuchs endothelial corneal dystrophy: a progressive loss of endothelial cells leading to corneal swelling (edema); the most frequent single indication for transplantation in developed countries.[1]
• Keratoconus: progressive thinning and conical bulging of the cornea that distorts vision; a leading indication in younger patients.[1]
• Bullous keratopathy: corneal edema and painful epithelial blisters caused by endothelial failure, classically after cataract surgery (pseudophakic or aphakic bullous keratopathy).[1]
• Corneal scarring: opacities from trauma, chemical burns, or prior infection.[1]
• Infection (microbial keratitis): bacterial, fungal, viral, or protozoal keratitis, which may require a graft acutely (for perforation) or for residual scarring; infectious scarring is the leading indication in many developing nations.[1]
• Failed previous graft (regraft): a prior corneal transplant that has decompensated or been rejected.[1]

Types of keratoplasty

Modern practice matches the procedure to the diseased layer. Full-thickness grafts have increasingly been replaced by selective ("lamellar") techniques that transplant only the affected layers, which generally offer faster visual recovery and lower rejection risk.[1][5] In the United States, endothelial keratoplasty has overtaken penetrating keratoplasty as the most common approach.[3]

| Type | Abbrev. | What is replaced | Typical indications | Notes | |------|---------|------------------|---------------------|-------| | Penetrating keratoplasty | PK / PKP | Full thickness of the cornea | Full-thickness disease, dense scarring, failed lamellar grafts | Historic "gold standard"; longest visual recovery (up to a year or more); slightly higher rejection risk than lamellar grafts.[1][6] | | Deep anterior lamellar keratoplasty | DALK | Anterior layers (epithelium and stroma), leaving host endothelium | Keratoconus, anterior scars/dystrophies with healthy endothelium | Spares the host endothelium, so endothelial rejection is largely avoided; shorter healing than PK.[1][6] | | Descemet stripping (automated) endothelial keratoplasty | DSEK / DSAEK | Endothelium plus a thin layer of posterior stroma | Fuchs dystrophy, bullous keratopathy, endothelial failure | Thicker donor lamella, technically easier to position than DMEK.[1][6] | | Descemet membrane endothelial keratoplasty | DMEK | Descemet membrane and endothelium only | Same endothelial indications as DSAEK | Thinnest graft; fastest visual recovery and lowest rejection risk, but technically more demanding; now the single most common keratoplasty type in the US.[1][3][6] | | Keratoprosthesis | KPro | Cornea replaced by an artificial device | Multiple failed grafts, severe ocular surface disease, limbal stem-cell deficiency | An artificial cornea (e.g., the Boston KPro Type I, made of PMMA and titanium) reserved for eyes that cannot succeed with donor tissue; requires lifelong antibiotic drops and close monitoring.[7] |

In 2024, US domestic keratoplasty was led by DMEK (18,256 procedures), followed by DSAEK (16,345) and PK (14,143), reflecting the shift toward endothelial techniques.[3]

How donor corneas are obtained and processed

Corneal tissue is recovered after death by eye banks, which evaluate, process, store, and distribute the tissue. In 2024, US eye banks reported 141,735 total tissue recoveries from 71,778 donors, and 65.1% of corneal donors were listed on a donor registry.[3] Recovery and banking in the United States are coordinated under the Eye Bank Association of America and regulated by the US Food and Drug Administration as human cell and tissue products; see also Tissue bank.

After recovery, tissue is screened against donor medical and social history and serologic testing, then evaluated. Eye banks assess the cornea by slit-lamp biomicroscopy and by specular microscopy to measure endothelial cell density, which is the principal determinant of suitability for endothelial grafts.[8]

Corneas for transplantation are typically stored by hypothermic (refrigerated, 2-8 °C) preservation in a specialized medium. As of 2026, four FDA-approved intermediate-term storage solutions are used in the US market (Optisol-GS, Life 4 °C, Eusol-C, and Kerasave), which preserve tissue for approximately 10-14 days.[8] The NIH-funded Cornea Preservation Time Study, a randomized trial in DSAEK, found that 94% of grafts remained clear at three years and that corneas preserved up to 11 days performed well, supporting longer usable storage windows than were previously standard.[9]

Immune privilege and why corneal grafts rarely need systemic immunosuppression

The cornea enjoys relative immune privilege: its normal lack of blood vessels and lymphatic vessels, its low expression of major histocompatibility complex (MHC) class II antigen-presenting cells, and several active immunoregulatory mechanisms together suppress the immune response to grafted tissue.[2] As a result, when a graft is placed into a normal avascular ("low-risk") recipient bed, two-year graft survival approaches 90% with topical corticosteroids alone, and routine donor-recipient tissue matching and systemic immunosuppression are generally unnecessary, in contrast to organ transplantation, where lifelong systemic immunosuppression is the norm.[2] For comparison with whole-organ grafts, see Transplant immunology.

Standard postoperative management relies chiefly on topical corticosteroid eye drops.[1][2] Immune privilege is not absolute: it is weakened in "high-risk" eyes, for example, those with corneal vascularization (in-growth of blood vessels), prior graft failure, or active inflammation, and such cases may warrant additional or systemic immunosuppression.[2]

Graft rejection

Rejection is an immune-mediated attack on the donor tissue and is a leading cause of graft failure, but most episodes can be reversed if treated promptly.[4] Patients are counseled to seek urgent care for the warning signs, sometimes summarized by the mnemonic RSVP: Redness, Sensitivity to light, Vision change, and Pain.[4]

Rejection is classified by the layer attacked: epithelial, stromal, or endothelial. Endothelial rejection is the most clinically important form, occurring in up to roughly half of rejection episodes, because the endothelium cannot regenerate.[4] A characteristic sign is the Khodadoust line: an advancing line of inflammatory white blood cells deposited on the endothelial (back) surface of the graft, marking the leading edge of an endothelial rejection.[4] Other signs include graft edema, keratic precipitates, anterior-chamber inflammation, and engorgement of limbal vessels.[4] Treatment is intensive topical corticosteroids (such as dexamethasone 0.1%), escalated for endothelial rejection; epithelial and stromal rejection respond more readily than endothelial rejection.[4]

Outcomes and graft survival

Corneal transplantation has high success rates, particularly in low-risk eyes. Reported overall graft survival is approximately 70% at five years and 50% at fifteen years, with outcomes varying substantially by indication, recipient risk, and graft type.[1] Selective lamellar procedures (DALK, DSAEK, DMEK) generally provide earlier visual recovery, less induced astigmatism, and lower endothelial-rejection rates than full-thickness PK.[1][5] In the Cornea Preservation Time Study, 94% of DSAEK grafts remained clear at three years.[9]

Volume and access: contrast with organ transplantation

Corneal grafts are performed at far higher volume than solid-organ transplants and, in countries with developed eye-banking systems, are generally not subject to the severe scarcity and waiting lists that characterize organs. In the United States, eye banks supplied tissue for 51,559 domestic keratoplasties in 2024 (up 1.2% from 50,925 in 2023), and US banks also exported tissue for 26,732 keratoplasties internationally.[3] US domestic supply consistently meets domestic demand, and the United States is one of only a small number of countries that export large quantities of donor corneas.[3][10] (Volume figures are point-in-time; see the footer note.)

Globally, however, access is highly unequal. A 2016 global survey reported that about 184,576 corneal transplants were performed worldwide in 2012, drawn from 283,530 donor corneas across 742 eye banks, but corneas were procured in only 82 of 148 countries surveyed.[10] The survey estimated that roughly 12.7 million people were awaiting corneal transplantation worldwide, that there was only about 1 cornea available for every 70 needed, and that about 53% of the world's population had no access to corneal transplantation.[10] The World Health Organization and the International Agency for the Prevention of Blindness identify corneal opacity as a leading cause of avoidable blindness, with the burden concentrated in low- and middle-income countries that often lack eye banks and trained corneal surgeons.[11]

History

Although the idea of replacing an opaque cornea was discussed for centuries, the first successful human corneal transplant was performed by the Austrian-Czech ophthalmologist Eduard Konrad Zirm on 7 December 1905 in Olomouc (in what is now the Czech Republic).[12] Zirm grafted full-thickness corneal tissue, taken from the enucleated eye of an injured 11-year-old boy, into a laborer blinded by lime burns; one graft remained clear and restored useful vision.[12] Because the cornea is avascular and immune-privileged, this preceded routinely successful whole-organ transplantation by decades.[1][12] Through the twentieth and early twenty-first centuries, advances in surgical technique, eye banking and tissue preservation, and the development of selective lamellar procedures progressively improved safety and outcomes.[1][5]

See also

• Eye banking and the EBAA
• Tissue bank
• Organ transplantation
• Transplant immunology

References

• Singh R, Gupta N, Vanathi M, et al. Cornea Transplantation. In: StatPearls. NCBI Bookshelf, National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK539690/
• Niederkorn JY, et al. Corneal Allograft Rejection: Immunopathogenesis to Therapeutics. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC3954811/
• Eye Bank Association of America. 2024 Eye Banking Statistical Report (and Executive Summary, Eye Banking and Corneal Transplantation, 2025). https://restoresight.org/wp-content/uploads/2025/04/2024_StatisticalReport_FINAL.pdf
• Sharma N, et al. Corneal Graft Rejection. In: StatPearls. NCBI Bookshelf, National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK519043/
• Corneal Endothelial Transplantation. In: StatPearls. NCBI Bookshelf, National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK562265/
• American Academy of Ophthalmology. Corneal Transplant Surgery Options. https://www.aao.org/eye-health/tips-prevention/corneal-transplant-surgery-options
• Boston Type 1 Keratoprosthesis. EyeWiki (American Academy of Ophthalmology). https://eyewiki.org/Boston_Type_1_Keratoprosthesis
• A Comprehensive Review of Donor Corneal Preservation Strategies. PubMed / National Library of Medicine. https://pubmed.ncbi.nlm.nih.gov/39102308/
• National Eye Institute (NIH). NIH study finds donor corneas can be safely preserved for longer period (Cornea Preservation Time Study). https://www.nei.nih.gov/research-and-training/research-news/nih-study-finds-donor-corneas-can-be-safely-preserved-longer-period
• Gain P, Jullienne R, He Z, et al. Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmology. 2016. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2474372
• International Agency for the Prevention of Blindness. Corneal Surgery, Transplant Tissue, and Eye Banking. https://www.iapb.org/blog/corneal-surgery-transplant-tissue-and-eye-banking/
• Armitage WJ, et al. The first successful full-thickness corneal transplant: a commentary on Eduard Zirm's landmark paper of 1906. PMC / National Library of Medicine. https://pmc.ncbi.nlm.nih.gov/articles/PMC1857444/