Current Challenges and Long-Term Outcomes in Corneal Transplantation in Infectious Keratitis—A Systematic Review

<b>Background/Objectives:</b> Infectious keratitis remains a major cause of blindness worldwide, and many cases progress to therapeutic keratoplasty despite advances in antimicrobial therapy. This systematic review aims to evaluate the outcomes of therapeutic keratoplasty in microbial keratitis and examine factors influencing anatomical success, graft survival, and visual rehabilitation. <b>Methods:</b> A systematic review was conducted following PRISMA guidelines, including English-language studies, published between 2000 and 2025. Studies with ≥10 eyes and ≥6 months follow-up were included. Data on infection control, graft clarity, anatomical success, visual acuity, and complications were extracted. <b>Results:</b> Fourteen studies encompassing 1527 eyes were analyzed. TPK accounted for 89% of procedures; DALK was used selectively for anterior or mid-stromal infections. Overall infection control ranged from 69 to 100%, with globe preservation in 85-100% of cases. Bacterial keratitis had higher cure rates and graft clarity than fungal or Acanthamoeba keratitis. Larger grafts (>8 mm) and deep stromal involvement were associated with increased graft rejection and postoperative complications. DALK offered higher graft survival and lower immunologic risk when the endothelium was spared. Visual outcomes were generally limited, reflecting preoperative disease severity, timing of surgery, and postoperative immunomodulation constraints. Early surgical intervention improved anatomical outcomes in severe fungal keratitis. <b>Conclusions:</b> Therapeutic keratoplasty is an effective globe-preserving intervention in advanced microbial keratitis, but with limited functional outcomes. Further prospective studies are needed to refine surgical indications, postoperative management, and long-term functional results.