Povidone-iodine (PVI) is a disinfectant and antiseptic agent used for preoperative preparation of the skin and mucous membranes due to its broad spectrum of microbicidal activity. Preparation of the eyelids, eyelashes, and conjunctiva prior to intraocular surgery, decrease the risk of endophthalmitis [1].
PVI is composed of diatomic iodine and polyvinylpyrrolidone (povidone). Povidone is a water-soluble polymer that serves as a carrier for iodine. A 10% PVI solution contains 1% available iodine. Whic in aqueous solution releases ions that directly act on bacterial or viral membrane proteins providing a microbicidal effect [5]. Since iodine also acts on membrane proteins of normal human cells, a balance between an effective and nontoxic concentration needs to be achieved with appropriate exposure time [6].
The use of PVI in ophthalmic procedures
Bacterial cultures isolated from the vitreous of patients with postsurgical endophthalmitis are the same species comensal on the eyelids and conjunctiva. One of the aims of prophylaxis against postsurgical endophthalmitis is the reduction of the quantity of bacteria on the eyelids and conjunctiva. PVI for surgical antisepsis is a well established measure shown to reduce the risk of endophthalmitis [1]. Several issues including dosage, timing, different PVI solution concentrations used for conjunctival lavage and periorbital skin scrubbing wehave been studied.
The literature supports PVI use in preparation for cataract surgery and has become standard of care. It is a mandatory step to reduce bacteria on the ocular surface and PVI antisepsis is the only technique to reach category II evidence in reducing endophthalmitis rates [19]. According to the guidelines of the major world societies, PVI solution should be applied to the cornea, conjunctival sac and periocular skin for a minimum of three minutes prior to surgery, although the exct recommended regimen varies.
The use of PVI seems to be sufficient for reducing conjunctival sac colonisation before cataract surgery and use of an additional preoperative antibiotic does not influence the level of colonisation [10]. Antibiotic use is known to increase bacterial resistance, suggesting using only antiseptic solutions preoperatively [21,22]. An iterative technique of PVI application might be beneficial, and not only the concentration of the additional PVI, possibly because it increases the contact time and replenishes free iodine [23].
Initially antibiotic was used for prevention of endophthalmitis after intravitreal injections (IVI). The current evidence suggests that routine use of topical antibiotics in this context is not necessary and may in fact be harmful [25]. The use of PVI is a mandatory step in IVI antisepsis and eliminating this step of the surgical procedure may lead to serious consequences. In a recent report by Modjtahedi et al.[26] patients undergoing IVI with self-reported allergy to iodine did not receive PVI, nor any other antiseptic agent. In this group the incidence of postinjection endophthalmitis was 9.4% (5 cases per 53 injections). Cheung et al. [27] in large study on 15 895 procedures revealed that the overall rate of IVI-related endophthalmitis is greater with the use of topical antibiotics, given immediately or for 5 days after the injection, compared with no antibiotics. The recommendation of PVI alone by major organisations worldwide has eliminated antibiotics as a part of the IVI protocol antisepsis. It should be noted that the draping and the lack of a supine position for IVI is generally inferior to that of cataract surgery. Shimada et al.[28] compared the effects of intraoperative conjunctival irrigation with 1.25% PVI compared to pure balanced salt solution (BSS) for 25-Gauge vitrectomy. No endophthalmitis occurred in either group, but positive bacterial cultures were more frequently in the BSS group.
Effective concentration and exposure time.
In the United States and in Europe the recommended concentration of PVI is 5-10%, but there is no clear consensus on this issue [20]. The use of lower concentrations of PVI is common, particularly in China and Japan. Shimada et al.[28] recommend applying a 1.25% solution for preoperative preparation. In a study covering 59,392 cataract procedures performed in small- and medium-scale Chinese ophthalmic departments repeated irrigation with 0.5% PVI was effective in reducing the risk of development of postoperative endophthalmitis [35]. Berkelman et al. showed that low concentrations of PVI solutions manifest higher bactericidal activity, as a result of increased levels of free iodine.[36] Silas et al.[38] reported that PVI concentration of 2.5% and higher effectively eliminates Streptococcus epidermidis with a single application, while the use of 0.7% and higher PVI manifest the same efficacy after three 30-second applications. The authors suggest repeated use of a 1% solution for preoperative antisepsis, remarking less irritation is associated with the use of a more dilute solution as an additional benefit
The concentration of free iodine is 5 ppm in a 10% PVI solution, 13 ppm in a 1% solution, 24 ppm in a 0.1% solution, and 13 ppm in a 0.01% solution [39]. For this reason the time required for killing bacteria is shorter for 0.1 to 1% PVI (15 seconds) than for 2.5 to 10% PVI (30-120 seconds) [36]. Upon reaction with bacteria and organic matters, free iodine is inactivated and needs to be replenished. At the 2.5-10% concentration, the presence of abundant free iodine reserves in the surrounding matrix readily provides a source of replenishment. At 0.1-1.0% the bactericidal effect cannot be sustained, thus repeated applications are necessary. While 2.5-10% PVI requires a longer contact time, the duration of residual activity is also longer. Higher concentrations are recommended for situations of a single application- as for eyelid or skin disinfection, as well as for early conjunctival lavage, when PVI is not used for intraoperative irrigation. This also may help reduce the presence of biofilms that contain oils, mucus and foreign matter by flushing out biofilms that can trap and elute bacteria.
There is a lack of a uniformly accepted recommendation regarding the exposure time of 5% PVI in intraocular procedures. One reason for this is that it is not possible to establish how long does a drop or a flush last on the eye surface. Frequency may be more important than duration, as it is controllable by the surgeon, whereas contact time is not.
Toxicity and side-effects
The use of PVI in anterior segment surgery is limited by its toxicity to the corneal endothelium. The effects of PVI 0.25% injection into the anterior chamber were transient. In comparison, flushing the rabbit’s anterior chamber with 2 ml of 1% PVI led to endothelial cell death. In contrast the same volume of 0.1% PVI, which completely replaced the aqueous humor, did not disturb the anterior chamber. Surgeons should be aware of the potential toxicity of PVI, particularly in older people having fewer and less health endothelial cells. Another issue limiting the concentration of PVI for conjunctival lavage is its’ toxicity to the corneal epithelium which is directly correlated with the PVI concentration with damage higher in the 5% PVI group, compared to 2.5%, 1% and 0.5% [44].
Self-reported allergies to PVI, povidone, excipients such as surfactants, or iodine are a more important conundrum than the side effects of PVI application from a practical point of view. True allergies are rare, but in these situations 0.05% aqueous chlorhexidine may be used [20]. No reports of resistance to PVI have been published nor of anaphylaxis in topical ophthalmic use. Postprocedure pain is a commonly recognized adverse event of IVI and has typically been attributed to chemical sensitivity (not allergy) to povidone–iodine on the ocular surface (especially with PVI concentrations of 5–10%) [48].
Bacterial resistance
Coagulase-negative staphylococci strains from the same eye might harbour different antibiotic susceptibility profiles.[49] While some conjunctival cultures might be more resistant to antibiotics than their counterparts, there have been no reports of resistance to PVI. After repeated exposure to PVI, as in IVI, there was no evidence of significant alteration from baseline conjunctival flora or emergence of bacterial resistance to antibiotics [52].
Other applications of PVI
In a small pilot study conducted by Nakashizuka et al. the bactericidal effect of 0,025% PVI in BSS Plus for postoperative endophthalmitis has been evaluated. For 4 consecutive eyes undergoing vitrectomy a 0,025% PVI-BSS Plus solution was used as the irrigation solution. In all four eyes endophthalmitis was resolved with no adverse effects. No ocular toxicity was observed [65].
Conclusions
Despite introducing new antiseptics in surgery, PVI is still the standard antiseptic measure in ophthalmology. Its use is economically reasonable. There have been no reports on resistance to PVI nor anaphylaxis in topical ophthalmic use. Furthermore it does not induce resistance or cross-resistance to antibiotics. With these advantages of PVI, the range of indications for topical use of antibiotics might decrease. With these advantages the range of indications for topical use of antibiotics might decrease, precipitating their replacement with PVI.
Acknowledgements
This article is based on a publication on which I was a coauthor.
The use of povidone-iodine in ophthalmology. Grzybowski A, Kanclerz P, Myers WG.
Curr Opin Ophthalmol. 2018 Jan;29(1):19-32. doi: 10.1097/ICU.0000000000000437. PMID: 28984794 Review.
Dr. Myers reports consulting fees from Leiters and Carl Zeiss Meditech AG, outside the scope of the submitted work.
Conflicts of interest: None
By,
Dr William G. Myers, M.D.
Chicago, IL
wmyers2020@gmail.com