The future of microbial keratitis treatment is bright

Microbial keratitis (MK) is a significant global ophthalmic challenge, leading to severe visual impairment or blindness if not promptly treated. An estimated two million new cases of human monocular blindness are diagnosed from corneal disease every year.¹ It is a leading cause of blindness worldwide, with a higher prevalence in developing nations due to limited access to healthcare. The condition is often associated with contact lens use, trauma, ocular surface disease or systemic immunosuppression.

Despite advances in antimicrobial therapy, MK remains a challenge to manage. The increasing prevalence of antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa, further complicates treatment and limits the efficacy of conventional antibiotics. Given these challenges, the need for alternative, effective and non-antibiotic therapeutic approaches has never been more pressing.

Current treatment strategies and their limitations

The standard treatment for MK primarily involves corneal sampling for laboratory analysis followed by the commencement of empirical treatment with topical broad-spectrum antibiotics administered hourly day and night for the first 48 to 72 hours, with therapy tailored based upon microbial culture results. In cases of fungal or protozoal infections, antifungal or anti-amoebic agents are used.

However, several limitations exist:

• Incorrect initial agent: The choice of initial agent depends upon the clinical presentation and risk factors. Therefore, the choice of initial agent may be incorrect, with further destruction to the eye whilst microbial reports are awaited.
• Delayed efficacy: Antibiotics and antifungals may take days to show a clinical response, leading to progressive corneal damage.
• Side effects and corneal toxicity: Long-term antimicrobial use can cause corneal toxicity, epithelial damage and secondary fungal infections.
• Antimicrobial resistance: The overuse and misuse of antibiotics have led to increased resistance among bacterial pathogens, reducing treatment effectiveness.
• Biofilm formation: Many MK pathogens, such as Pseudomonas and Staphylococcus, form biofilms that make them resistant to standard antibiotics.
• High patient burden: Hourly treatment day and night for patients is very intense, necessitating patients to wake up in the night, be helped by a family member or be admitted to a hospital to be treated by nursing staff.
• Surgical intervention requirement: Severe or unresponsive cases may necessitate surgical approaches such as amniotic membrane transplantation or even keratoplasty.
• Lack of access to treatment: As previously mentioned, lack of access to healthcare or antibiotics in developing countries means patients go untreated, leading to irreversible corneal scarring and blindness.

Given these challenges, non-pharmacologic strategies such as UV light have gained attention for their antimicrobial properties, with UVC emerging as a promising option–a novel, non-invasive and resistance-independent treatment.

FIGURE 1. Clinical Properties of UV Wavelengths.

Biophysics of UV light and its application in healthcare and medicine

UV light is a form of electromagnetic radiation with wavelengths shorter than visible light but longer than X-rays.

It is categorised into three main types (Figure 1):

• UVA (315-400 nm): Penetrates deep into tissues, playing a role in skin aging and DNA damage. It has been utilised in phototherapy for conditions like psoriasis.
• UVB (280-315 nm): Partially absorbed by the ozone layer, UVB is known for inducing vitamin D synthesis in the skin but also contributes to sunburn and carcinogenesis.
• UVC (100-280 nm): The shortest wavelength and highest energy form of UV radiation, UVC is highly effective at microbial inactivation. Naturally blocked by the atmosphere, it has been widely applied in sterilisation and disinfection technologies.

UV light, particularly UVC, is a powerful antimicrobial tool due to its ability to damage microbial DNA and RNA throughpyrimidine dimer formation.^2,3These dimers distort DNA structure, preventing replication and transcription and ultimately leading to cell death. As a result, UV light is highly effective for disinfection, offering a fast, chemical-free method to inactivate bacteria, viruses, fungi and spores. In healthcare, UVC is widely used for sterilising surfaces, water and air and treating infections.

• Surface and air disinfection: UVC is widely used in hospitals to sterilise surgical instruments, operating rooms and intensive care units.⁴
• Water purification: UVC-based systems effectively eliminate pathogens in drinking water without the use of chemicals.⁵
• Dermatological treatments: UVA and UVB are used in phototherapy for psoriasis, vitiligo and eczema, as well as in wound infections.^6-10
• Infectious disease control: Recent research has explored UV light for reducing microbial transmission, particularly in respiratory infections like COVID-19.^11,12

Given its broad antimicrobial spectrum and resistance-independent mechanism, UV therapy has gained interest in ophthalmology as a potential treatment for infectious diseases like MK. A recent comprehensive review of UV treatments for superficial skin and ocular infections concluded that UVC therapy is a promising adjunct or alternative to conventional antibiotics.¹³

Application of UV light in ophthalmology

In ophthalmology, UV light has been primarily used in corneal collagen cross-linking (CXL) with UVA and riboflavin to strengthen the corneal stroma in keratoconus and ectasia.¹⁴ However, UV light’s potential extends beyond structural reinforcement to antimicrobial applications.

• UVA-riboflavin photodynamic therapy (photoactivated chromophore for infectious keratitis CXL): Used in cases of bacterial and fungal keratitis, this approach relies on reactive oxygen species generation to kill microbes. Its efficacy is limited in deep stromal infections and treatment requires prolonged exposure times.^15-18
• Blue light therapy: Antimicrobial blue light has been explored for the treatment of infectious keratitis, with in vivo and ex vivo efficacy shown.¹⁹
• Photodynamic therapy for ocular infections: UV light combined with photosensitising agents has been explored for treating infectious keratitis^20-22 and endophthalmitis.²³
• UVC for direct antimicrobial treatment: Unlike UVA-based CXL, UVC can directly target microbial DNA without requiring a photosensitiser. Research has shown that controlled low-dose UVC can effectively reduce microbial loads in corneal infections with minimal toxicity to host cells.^24-27

These applications highlight the growing role of UV therapy in ophthalmology, particularly for infections resistant to standard antimicrobial treatments (Figures 2a and 2b).

Application of UVC for microbial keratitis

Recent studies highlight UVC’s therapeutic potential in ophthalmology, particularly for infectious keratitis. Dean et al conducted one of the first in vitro studies assessing UVC for microbial clearance on bacterial lawn agar plates and its safety for corneal cell cultures. They observed bacterial growth inhibition across all four tested strains at all time points (1, 2, 4, 5, 10 and 30 seconds), with no significant increase in corneal cell death. Notably, Pseudomonas species, a highly aggressive MK pathogen, showed the highest susceptibility, underscoring UVC’s promise in MK treatment.²⁴

Marasini et al evaluated potential UVC-induced DNA damage, confirming that controlled, low-dose exposure does not cause significant genetic mutations or cytotoxicity in corneal epithelial cells. Safety was assessed in vitro, in vivo and ex vivo using human corneal cells, mouse corneas and porcine corneas, respectively. Cyclobutane pyrimidine dimer formation, a marker of DNA damage, remained undetectable after once-daily 15-second UVC exposure for 3 days, with minimal corneal penetration limited to superficial layers.²⁵ Another recent study found that UVC exposures of 5 seconds or less inhibited a broader range of microbes, including fungi, mixed cultures and antibiotic-resistant strains.²⁶ UVC disrupts biofilm formation in bacterial keratitis pathogens, enhancing antibiotic efficacy.²⁷

Conclusion

The emergence of UVC as a therapeutic option in ophthalmology represents a paradigm shift in the management of MK. UVC is effective against a whole host of pathogens associated with ocular surface disease whilst maintaining a high-quality safety profile in vivo. By offering a non-invasive, antimicrobial-independent approach, UVC therapy holds promise for improving clinical outcomes in cases where conventional antibiotics are limited in their success.

UVC therapy has the potential to become a gold standard treatment for MK, improving patient outcomes and reducing the global burden of corneal blindness. Future research should focus on piloting the in vivo use of UVC in patients to assess its safety and efficacy, optimising dosing protocols and eventually undertaking large-scale clinical trials.

References

1. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79(3):214-221.

2. Goodsell DS. The molecular perspective: ultraviolet light and pyrimidine dimers. Oncologist. 2001;6(3):298-299. doi:10.1634/theoncologist.6-3-298

3. Welch D, Buonanno M, Grilj V, et al. Far-UVC light: a new tool to control the spread of airborne-mediated microbial diseases. Sci Rep. 2018;8(1):2752. doi:10.1038/s41598-018-21058-w

4. Ramos CCR, Roque JLA, Sarmiento DB, et al. Use of ultraviolet-C in environmental sterilization in hospitals: a systematic review on efficacy and safety. Int J Health Sci (Qassim). 2020;14(6):52-65.

5. Meckes MC. Effect of UV light disinfection on antibiotic-resistant coliforms in wastewater effluents. Appl Environ Microbiol. 1982;43(2):371-377. doi:10.1128/aem.43.2.371-377.1982

6. Zhang P, Wu MX. A clinical review of phototherapy for psoriasis. Lasers Med Sci. 2018;33(1):173-180. doi:10.1007/s10103-017-2360-1

7. Singh RK. Impact of ultraviolet light on vitiligo. Adv Exp Med Biol. 2017;996:55-60. doi:10.1007/978-3-319-56017-5_5

8. Musters AH, Mashayekhi S, Harvey J, et al. Phototherapy for atopic eczema. Cochrane Database Syst Rev. 2021;10(10):CD013870. doi:10.1002/14651858.CD013870.pub2

9. Dai T, Garcia B, Murray CK, Vrahas MS, Hamblin MR. UVC light prophylaxis for cutaneous wound infections in mice. Antimicrob Agents Chemother. 2012;56(7):3841-3848. doi:10.1128/AAC.00161-12

10. Marasini S, Zhang AC, Dean SJ, Swift S, Craig JP. Safety and efficacy of UV application for superficial infections in humans: a systematic review and meta-analysis. Ocul Surf. 2021;21:331-344. doi:10.1016/j.jtos.2021.03.002

11. Song BM, Lee GH, Han HJ, et al. Ultraviolet-C light at 222 nm has a high disinfecting spectrum in environments contaminated by infectious pathogens, including SARS-CoV-2. PLoS One. 2023;18(11):e0294427. doi:10.1371/journal.pone.0294427

12. Ragan I, Perez J, Davenport W, Hartson L, Doyle B. UV-C light intervention as a barrier against airborne transmission of SARS-CoV-2. Viruses. 2024;16(1):89. doi:10.3390/v16010089

13. Marasini S, Zhang AC, Dean SJ, Swift S, Craig JP. Safety and efficacy of UV application for superficial infections in humans: a systematic review and meta-analysis. Ocul Surf. 2021;21:331-344. doi:10.1016/j.jtos.2021.03.002

14. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620-627. doi:10.1016/s0002-9394(02)02220-1

15. Makdoumi K, Mortensen J, Crafoord S. Infectious keratitis treated with corneal crosslinking. Cornea. 2010;29(12):1353-1358. doi:10.1097/ICO.0b013e3181d2de91

16. Said DG, Elalfy MS, Gatzioufas Z, et al. Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of advanced infectious keratitis with corneal melting. Ophthalmology. 2014;121(7):1377-1382. doi:10.1016/j.ophtha.2014.01.011

17. Alio JL, Abbouda A, Valle DD, del Castillo JMB, Fernandez JAG. Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis of reported cases. J Ophthalmic Inflamm Infect. 2013;3(1):47. doi:10.1186/1869-5760-3-47

18. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea. 2008;27(5):590-594. doi:10.1097/ICO.0b013e318169d698

19. Zhu H, Kochevar IE, Behlau I, et al. Antimicrobial blue light therapy for infectious keratitis: ex vivo and in vivo studies. Invest Ophthalmol Vis Sci. 2017;58(1):586-593. doi:10.1167/iovs.16-20272

20. Martinez JD, Arrieta E, Naranjo A, et al. Rose Bengal photodynamic antimicrobial therapy: a pilot safety study. Cornea. 2021;40(8):1036-1043. doi:10.1097/ICO.0000000000002717

21. Naranjo A, Arboleda A, Martinez JD, et al. Rose Bengal photodynamic antimicrobial therapy for patients with progressive infectious keratitis: a pilot clinical study. Am J Ophthalmol. 2019;208:387-396. doi:10.1016/j.ajo.2019.08.027

22. Altamirano D, Martinez J, Leviste KD, Parel JM, Amescua G. Photodynamic therapy for infectious keratitis. Curr Ophthalmol Rep. 2020;8:245-251. doi:10.1007/s40135-020-00252-y

23. Jin Y, Wang Y, Yang J, et al. An integrated theranostic nanomaterial for targeted photodynamic therapy of infectious endophthalmitis. Cell Rep Phys Sci. 2020;1(8):100173. doi:10.1016/j.xcrp.2020.100173

24. Dean SJ, Petty A, Swift S, et al. Efficacy and safety assessment of a novel ultraviolet C device for treating corneal bacterial infections. Clin Exp Ophthalmol. 2011;39(2):156-163. doi:10.1111/j.1442-9071.2010.02471.x

25. Marasini S, Mugisho OO, Swift S, et al. Effect of therapeutic UVC on corneal DNA: safety assessment for potential keratitis treatment. Ocul Surf. 2021;20:130-138. doi:10.1016/j.jtos.2021.02.005

26. Marasini S, Dean SJ, Swift S, et al. Preclinical confirmation of UVC efficacy in treating infectious keratitis. Ocul Surf. 2022;25:76-86. doi:10.1016/j.jtos.2022.05.004

27. Marasini S, Dean SJ, Swift S, Hussan JR, Craig JP. In vitro anti-biofilm efficacy of therapeutic low dose 265 nm UVC. J Photochem Photobiol B. 2025;263:113091. doi:10.1016/j.jphotobiol.2024.113091

Priyanka Mandal, MBChB FRCOphth | E: priyankamandal911@gmail.com

Mandal is a senior ophthalmic surgery registrar with a specialist interest in corneal disease and cataract surgery. She has a keen interest in academic research and has published in leading journals, including the British Journal of Ophthalmology and Eye. Beyond her clinical and research work, Miss Mandal is dedicated to global eye health and has volunteered with the Khmer Sight Foundation in Cambodia, providing care to patients with sight-threatening conditions.

Sunil Shah, MBBS, FRCS(Ed), FRCOphth, FBCLA, FWCRS | E: sunilshah@doctors.org.uk

Shah is a consultant ophthalmic surgeon specialising in corneal disease, cataracts, and refractive surgery. He reviews for multiple esteemed journals including Eye, American Journal of Ophthalmology, and Ophthalmology. A professor at Aston University, England, and an honorary professor at UKM Specialist Centre, Malaysia, he is also deeply committed to global eye care. Professor Shah has led numerous teams of international ophthalmologists in Cambodia, providing essential eye care to underserved communities.