Reassessing the role of therapeutic keratoplasty: Perspectives for 2025 and beyond

Therapeutic keratoplasty (TPK) has long been recognized as a crucial surgical intervention, primarily intended to control infection and preserve the structural integrity of the eye in cases of severe microbial keratitis or corneal perforation. The field of corneal transplantation traces its origins to the pioneering work of Eduard Zirm in 1905, whose successful graft marked a milestone in the management of corneal blindness. However, the conceptual roots of this procedure extend much further, as far back as Galen’s time in ancient Rome. Over the decades, the success of TPK has been greatly enhanced through continual advancements in microsurgical methods, improved donor tissue preservation, and more effective postoperative management strategies.[1] In India, the burden of infectious keratitis is reported to be nearly tenfold higher than that observed in developed nations,[2,3] a disparity largely attributed to factors such as high population density, socioeconomic challenges, predominance of agrarian occupations in rural areas, and the country’s tropical climate. Several studies have indicated that therapeutic keratoplasty constitutes approximately 12–28% of all corneal transplants performed in India.[4,5] Reported outcomes demonstrate a graft survival rate ranging from 48% to 73%, with infection eradication achieved in up to 98.6% of cases.[4–6] Successful visual rehabilitation with good functional outcomes is achievable through repeat penetrating or endothelial keratoplasty after failed TPK, reinforcing that TPK serves not merely as a globe-preserving intervention but also as a pivotal step toward visual restoration.[7] In recent years, the therapeutic approach to infectious keratitis has undergone significant transformation. The advent of adjunctive treatment options—such as photoactivated chromophore for keratitis–collagen cross-linking (PACK-CXL), photodynamic therapy (PDT), and the development of newer antifungal and antibacterial agents—has broadened the management spectrum. Additionally, advances in diagnostic modalities, including polymerase chain reaction (PCR) and in vivo confocal microscopy, have facilitated earlier and more precise pathogen identification. Although these innovations have reduced the overall need for surgical intervention, the prevalence of severe, refractory infections—particularly those of fungal, pythium, or polymicrobial origin—continues to sustain the global demand for therapeutic keratoplasty.[8] The present editorial aims to underscore the continuing relevance of TPK in the modern era, while outlining key considerations and surgical principles essential to optimizing outcomes in these challenging cases. Determinants of Successful Outcomes Causative organism The microbial etiology of the corneal ulcer is one of the most critical determinants of outcome after TPK. Multiple retrospective series have shown that bacterial keratitis (especially when promptly treated) fares significantly better than fungal, protozoal (e.g., Acanthamoeba spp.), or emerging pathogens like Pythium insidiosum.[9,10] In a large Chinese series of 561 eyes undergoing therapeutic keratoplasty, anatomical success was 95.0% for bacterial ulcers compared with 84.2% for fungal ulcers (P = 0.012) and only 73.3% for mixed bacterial/fungal infection.[11] Fungal keratitis carries a higher risk of recurrence, deep stromal invasion, limbal or scleral involvement, and delayed healing. In a review of 198 eyes that underwent therapeutic penetrating keratoplasty for fungal keratitis, larger infiltrate size was identified as a significant predictor of recurrence.[5] Timing of surgery While surgical intervention is sometimes seen as the “last resort,” mounting evidence suggests that earlier TPK (with adequate preoperative control) may yield higher success rates. Delays allow the infection to spread and cause corneal melt, perforation, scleral/uveal extension, secondary glaucoma, or even endophthalmitis—each of which worsens prognosis.[12] In a study comparing early (<15 days) versus late (≥15 days) TPK for bacterial/fungal ulcers, graft clarity at follow-up was 100% in the early group versus 83.3% in the late group (though P = 0.125) and recurrence of infection was none versus 16.7%.[13] Therefore, both the causative organism and the timing of surgical intervention in relation to disease progression are critical determinants of therapeutic success. Infections caused by refractory pathogens such as Pythium often necessitate earlier surgical management, whereas early-diagnosed Acanthamoeba keratitis, despite its slow therapeutic response, typically responds well to medical therapy with a comparatively lower requirement for keratoplasty. Size of the graft Smaller grafts that cover the infected area with minimal healthy margin lower the risk of rejection, promote faster healing, reduce postoperative astigmatism, and conserve host tissue. Evidence indicates that grafts ≤9 mm achieve superior clarity and fewer complications. In a fungal keratitis cohort (198 eyes), grafts <8 mm showed significantly better survival than those >8 mm (P = 0.026).[5] Nevertheless, graft size must ensure complete excision of infected tissue, so most surgeons select a diameter approximately 0.5–1 mm larger than the infiltrate margin. Role of surgical adjuncts Beyond the core surgery, the use of adjunctive intraoperative measures and modifications can influence outcomes. Several recent reports highlight the role of cryotherapy (freeze–thaw at the graft–host junction or limbus), application of absolute ethanol (especially for limbal/scleral spread or in Pythium keratitis), intraoperative antimicrobial irrigation or intracameral antibiotics, and amniotic membrane grafting in promoting healing and reducing recurrence.[8,14] In a series of 46 eyes with Pythium keratitis, Agarwal et al. found that medical management alone offered limited benefits, with nearly half of therapeutic keratoplasties (TPKs) experiencing recurrence requiring repeat surgery. However, the use of adjunctive procedures during TPK significantly reduced recurrence by sterilizing the margins beyond visible infiltration, improving graft survival, and may be considered as part of routine surgical care in refractory organisms or infections involving limbus/sclera.[14] Lamellar versus full thickness keratoplasty Therapeutic deep anterior lamellar keratoplasty (TDALK) has emerged as an alternative for select cases of bacterial, fungal, and Acanthamoeba keratitis. While incomplete removal of infection remains a potential limitation, TDALK preserves host endothelium, reduces the risk of graft rejection, and minimizes intraocular contamination. In a series of 126 eyes with medically unresponsive keratitis, Anshu et al. reported comparable graft survival and no increased risk of recurrence with TDALK (n = 26) versus TPK (n = 100), supporting its role as a viable alternative to full-thickness keratoplasty.[15] Conclusion Therapeutic keratoplasty remains pivotal in managing severe corneal infections, evolving from a purely globe-salvaging procedure to one that also prioritizes visual rehabilitation. Success hinges on early intervention, pathogen-specific strategies, and judicious graft selection. With advances in surgical techniques, adjunctive therapies, and tissue preservation, TPK is poised to deliver improved anatomical and functional outcomes, cementing its role as a mainstay in contemporary corneal care.