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Effects of Povidone-Iodine Toxicity and Aqueous Chlorhexidine on Ocular Surface Disease: A Brief Review

Despite retina specialists' efforts, PI and chlorhexidine remain the main culprit for injection-related OSD, especially in elderly and diabetic patients

By: Yingna Snowy Liu, MD, Cynthia Matossian MD, FACS
Ophthalmology Management December 13, 2024

This article was originally published in a sponsored newsletter.

While intravitreal injection (IVI) preparation protocols vary considerably among retinal specialists, the use of topical anesthetics and antimicrobials such as povidone-iodine (PI) or chlorhexidine, with or without topical antibiotics, remains universal despite the ocular discomfort and exacerbated dry eye symptoms that can result from their use.1,2 To minimize these effects, many retinal specialists avoid topical antibiotics, recommend preservative-free artificial tears after injections or both. Despite these mitigating measures, the main culprit for IVI-related ocular surface disease is the universal use of antimicrobial agents such as PI and chlorhexidine, especially among elderly and diabetic patients3 who are already predisposed to ocular surface issues.

PI toxicity to the cornea is well-documented in human and animal models.4–6 Not surprisingly, studies found increased epitheliopathy, ocular discomfort and lower tear breakup times (TBUT) in eyes shortly after IVIs compared to fellow untreated eyes (see Table 1).7,8 Longer-term effects of IVIs on the ocular surface are mixed, as are study methods (e.g., timing of evaluations and injection protocols; see Table 1).8–12 Some studies reported higher Ocular Surface Disease Index (OSDI) scores,11,13 more corneal staining9,13 and lower meiboscore10 2 to 6 weeks after injections. In contrast, one study found less meibomian gland loss, less bulbar redness and higher tear meniscus height more than a month after injections.12 Another study noted a paradoxical decrease in tear osmolality as the number of injections increased.7 The authors postulated that repeated PI application could limit the bacterial flora and protect against ocular surface damage associated with eyelid margin diseases and reduced goblet cell density.7,12,14,15 The jury is still out regarding the sustained overall effects of PI on the ocular surface.

 

 

Aqueous chlorhexidine (AC) has become a popular alternative to PI in many retina practices, with several large studies showing equivalent post-injection endophthalmitis rates.16,17 In my (Dr. Liu’s) clinical experience, patient complaints in the hours post-injection have decreased significantly with the switch from PI to AC. This observation is supported by a study that found significantly less patient-reported ocular discomfort and corneal epitheliopathy with AC compared to PI immediately after injections.18 However, more research is needed with larger patient populations and longer follow-ups to confirm these findings and better understand the long-term effects of AC on ocular surface health.

References

  1. Li X-M, Hu L, Hu J, Wang W. Investigation of dry eye disease and analysis of the pathogenic factors in patients after cataract surgery. Cornea. 2007 Oct;26(9 Suppl 1):S16-20. doi:10.1097/ICO.0b013e31812f67ca
  2. Souki S, Cochener B, Labetoulle M, Güell JL. Phase IV clinical study to evaluate the effects of an intracameral combined mydriatic and anesthetic agent and standard topical mydriatics and anesthetics on the ocular surface after cataract surgery. J Cataract Refract Surg. 2021 May;47(5):570-578. doi:10.1097/j.jcrs.0000000000000491
  3. Bu Y, Shih KC, Tong L. The ocular surface and diabetes, the other 21st Century epidemic. Exp Eye Res. 2022 Jul;220:109099. doi:10.1016/j.exer.2022.109099
  4. Mac Rae SM, Brown B, Edelhauser HF. The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol. 1984 Feb;97(2):221-232.
  5. Jiang J, Wu M, Shen T. The toxic effect of different concentrations of povidone iodine on the rabbit’s cornea. Cutan Ocul Toxicol. 2009;28(3):119-124. doi:10.1080/15569520903080511
  6. Kim S, Ahn Y, Lee Y, Kim H. Toxicity of povidone-iodine to the ocular surface of rabbits. BMC Ophthalmol. 2020 Sep;20(1):359. doi:10.1186/s12886-020-01615-6
  7. Dohlman TH, Lertsuwanroj B, D’Amico DJ, Ciralsky JB, Kiss S. Evaluation of signs and symptoms of ocular surface disease after intravitreal injection. Acta Ophthalmol. 2019 Dec;97(8):e1154-e1156. doi:10.1111/aos.14146
  8. Verrecchia S, Chiambaretta F, Kodjikian L, et al. A prospective multicentre study of intravitreal injections and ocular surface in 219 patients: IVIS study. Acta Ophthalmol. 2021 Dec;99(8):877-884. doi:10.1111/aos.14797.
  9. Saedon H, Nosek J, Phillips J, Narendran N, Yang YC. Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections. Cutan Ocul Toxicol. 2017 Dec;36(4):343-346. doi:10.1080/15569527.2017.1291665
  10. Kıyat P, Palamar M, Nalçacı S, Akkın C. Dry eye and meibomian gland dysfunction in neovascular age-related macular degeneration patients treated with intravitreal injections. Turk J Ophthalmol. 2022 Jun;52(3):157-161. doi:10.4274/tjo.galenos.2021.66168
  11. Ulutas HG, Yener NP. Effects of intravitreal injection on ocular surface and anterior segment parameters. Beyoglu Eye J. 2021 Jun;6(2):84-89. doi:10.14744/bej.2021.65487
  12. Malmin A, Thomseth VM, Førland PT, et al. Associations between serial intravitreal injections and dry eye. Ophthalmology. 2023 May;130(5):509-515. doi:10.1016/j.ophtha.2023.01.009
  13. Srinagesh V, Ellenberg D, Scharper PH, Etter J. Intravitreal dry eye study. Invest Ophthalmol Vis Sci. 2014;55(13):3696.
  14. Terzulli M, Contreras-Ruiz L, Kugadas A, Masli S, Gadjeva M. TSP-1 deficiency alters ocular microbiota: implications for Sjögren’s syndrome pathogenesis. J Ocul Pharmacol Ther. 2015 Sep;31(7):413-418. doi:10.1089/jop.2015.0017
  15. Graham JE, Moore JE, Jiru X, et al. Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes. Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5616-5623. doi:10.1167/iovs.07-0588
  16. Merani R, McPherson ZE, Luckie AP, et al. Aqueous chlorhexidine for intravitreal injection antisepsis: a case series and review of the literature. Ophthalmology. 2016 Dec;123(12):2588-2594. doi:10.1016/j.ophtha.2016.08.022
  17. Stephenson KA, Merkur A, Kirker A, Albiani D, Pakzad-Vaezi K. Rates of endophthalmitis before and after transition from povidone-iodine to aqueous chlorhexidine asepsis for intravitreal injection. Can J Ophthalmol. 2024 Dec;59(6):424-429. doi:10.1016/j.jcjo.2024.01.012
  18. Ali FS, Jenkins TL, Boparai RS, et al. Aqueous chlorhexidine compared with povidone-iodine as ocular antisepsis before intravitreal injection: a randomized clinical trial. Ophthalmol Retina. 2021 Aug;5(8):788-796. doi:10.1016/j.oret.2020.11.008

 

Yingna Snowy Liu, MD

Yingna Snowy Liu, MD is a vitreoretinal surgeon at Bay Area Retina Associates in California.

Cynthia Matossian MD, FACS

Cynthia Matossian MD, FACS is the founder of Matossian Eye Associates. She specializes in refractive cataract surgery and dry eye disease. She was named one of Ocular Surgery News' Premier Surgeon 300—an elite group of 300 premium refractive cataract surgeons in the United States. She was the 2017 winner of the Ophthalmic World Leaders Visionary Award. She has been named one of the Top 25 Leading Women Entrepreneurs in New Jersey and one of New Jersey and Pennsylvania’s Best 50 Women in Business. She is a clinical assistant professor of ophthalmology (adjunct) at Temple University School of Medicine. She has published numerous articles and participated in national and international meetings in leadership roles.

 

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