BMC Ophthalmology · 8 authors, 4 centres
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Collagen cross-linking (CXL) as monotherapy effectively eradicated Fusarium solani keratitis in rabbits, with no fungal growth by week 4, but failed to eliminate Pseudomonas aeruginosa infection despite an initial reduction in colony-forming units. The study suggests CXL is a promising alternative treatment for fungal keratitis but less effective as monotherapy for bacterial keratitis caused by Pseudomonas aeruginosa.
**Background:** Corneal abscess is a sight-threatening condition often managed with topical antibiotics or keratoplasty. Collagen cross-linking (CXL) uses riboflavin and UVA light to induce collagen crosslinks, providing antimicrobial effects and increasing corneal resistance to enzymatic digestion. This study evaluates CXL as monotherapy for infectious keratitis caused by Fusarium solani and Pseudomonas aeruginosa in an animal model.
**Methods:** Forty-eight white New Zealand rabbits (1.5–2 kg) were divided into three groups. Group A (control, n=16) was subdivided into A1 (Fusarium solani, n=8) and A2 (Pseudomonas aeruginosa, n=8). Group B (n=16) received Fusarium solani inoculation, and Group C (n=16) received Pseudomonas aeruginosa inoculation. One week after inoculation, when corneal abscess was confirmed, Groups B and C received CXL treatment: corneal epithelium was scraped, isotonic riboflavin (0.1% riboflavin-5-phosphate in dextran 20%) was applied every 5 min for 30 min pre-irradiation, then every 3 min during 15 min of UVA irradiation (365 nm, 3.0 mW/cm² at 45 mm distance). Control animals were untreated. Corneal scrapings were performed at weeks 1, 2, 3, and 4 post-CXL for CFU counting. Rabbits were sacrificed at week 4, and corneas were examined histopathologically with hematoxylin/eosin, Mallory’s trichrome, and immunohistochemistry for CD20+ B cells.
**Key Results:** For Fusarium solani (Group B), there was a statistically significant reduction in CFU compared to control (p<0.001). Mean CFU in treated group decreased from 34.50 (SD 4.11) at week 1 to 3.40 (SD 2.30) at week 4, with no growth in any sample by week 4. Histopathology showed well-formed corneal structure and complete healing in treated corneas, while controls showed severe destruction and inflammation. For Pseudomonas aeruginosa (Group C), there was a statistically significant reduction in CFU at week 2 (mean 54.25 vs 72.25, p<0.01), but regrowth occurred thereafter. By week 4, mean CFU was 79.75 (SD 8.73) in treated vs 84.50 (SD 3.34) in control, with no significant difference (p=0.17). All 16 treated samples showed extensive growth at subsequent follow-ups. Histopathology revealed less corneal thinning in treated corneas but active ulceration and stromal infiltrates. Immunohistochemistry showed similar CD20+ B cell infiltrates in both control and treated corneas.
**Clinical Implications:** CXL as monotherapy is effective for Fusarium solani keratitis, achieving complete microbial eradication and corneal healing. However, it is insufficient for Pseudomonas aeruginosa keratitis, providing only temporary reduction without eradication. The study suggests CXL may be a promising alternative for fungal keratitis but should be combined with antimicrobial therapy for bacterial infections. Limitations include the animal model and lack of comparison with antimicrobial therapy alone. Large clinical trials are needed to confirm these findings and evaluate CXL for other pathogens.