Bridging gaps in corneal ulcer management: Can photoactivated chromophore for infectious keratitis–corneal collagen cross-linking delay or replace therapeutic keratoplasty?

Table 1 Proposed standardized photoactivated chromophore for infectious keratitis–corneal collagen cross-linking protocols by pathogen type and ulcer depth

Pathogen type	UVA exposure (fluence, intensity)	Riboflavin concentration	Treatment duration	Rationale/references
Bacterial Keratitis	7.2–10.0 J/cm² at 30 mW/cm² (4–5.5 minutes)	0.1% iso-osmolar with HPMC, applied every 2 minutes for 15–20 minutes	20–25 minutes (soak + irradiation)	Higher fluences achieve 97.50%–99.90% bacterial killing ratios for Staphylococcus aureus and Pseudomonas aeruginosa. Accelerated delivery is oxygen-independent, effective for ulcers < 300 μm[37,38]
Fungal Keratitis	7.2–15.0 J/cm² at 30 mW/cm² (4–8.3 minutes)	0.1% iso-osmolar with HPMC, applied every 2 minutes for 15–20 minutes	25–30 minutes (soak + irradiation)	Deeper ulcers (33%–67% stroma) require higher fluences due to ultraviolet absorption in opaque corneas. 7.2 J/cm² eradicated resistant cases[40,41]
Mixed bacterial/fungal	10.0 J/cm² at 30 mW/cm² (5.5 minutes)	0.1% iso-osmolar with HPMC, applied every 2 minutes for 15–20 minutes	25 minutes (soak + irradiation)	Broad-spectrum efficacy with high fluence targets both pathogens, with proven safety[39]
AK	Sequential: Riboflavin/UVA (7.2 J/cm² at 30 mW/cm², 4 minutes) + Rose bengal/green light (0.1–0.2 J/cm² at 532 nm, 15–30 second)	0.1% riboflavin (15–20 minutes soak) + 0.1% rose bengal (10 minutes soak)	35–45 minutes (dual soak + irradiation)	Dual-chromophore approach targets resistant AK cysts, leveraging complementary absorption spectra[42]
Ulcer depth adjustment	< 100 μm: 7.2 J/cm²; 100–300 μm: 10.0–15.0 J/cm²	As above	As above	Adjust fluence based on AS-OCT-measured depth to ensure ROS penetration in opaque ulcers[35]

AK: Acanthamoeba keratitis; AS-OCT: Anterior segment optical coherence tomography; ROS: Reactive oxygen species; HPMC: Hydroxypropyl methylcellulose; UVA: Ultraviolet-A.