Betadine (povidone-iodine 5%) has become the standard of care for cleansing the eye during anti-VEGF injection procedures. Though the incidence of sensitivity to povidone-iodine (PVPI) is infrequent, some patients are reporting severe and prolonged burning of the conjunctiva.1,2,3 Even though the complaints are relatively few, a solution needs to be found to this problem.
Keeping exposure time at a minimum of 15 seconds might help. Further dilution of the PVPI may also be tried. At first thought, dilution would seem to weaken the bactericidal activity. An early study, however, demonstrated that low concentrations (i.e. 0.1 to 1%) were actually more effective than a full strength solution.4,5
Another viewpoint, addressed by leading ophthalmologists in a recent roundtable discussion published on line ,6 is to not administer Betadine drops at all or to quickly dab the eye with a swab. According to at least one of the participating doctors, it may not be absolutely necessary to perform antisepsis as long as antibiotics are used.
If these tactics are not acceptable or fail to relieve the pain, a substitute antiseptic must be found. Concerned physicians have tried various options:
- Baby shampoo is good for cleansing, but it is ineffective as a pre-surgical disinfectant. Brand names: Castile, Phisoderm.
- Chlorhexidine gluconate is known to cause eye pain and corneal injury,7 but recent studies have found that, in concentrations of 0.1% to 4%, it may be a safe and effective alternate ocular antiseptic.8 Brand names: Hibiclens, Hibiscrub
- Chloroxylenol topical is a broad spectrum antimicrobial that is safe around the eye. Based upon a literature review in 2004, the American Society of Ophthalmic Registered Nurses reported that chloroxylenol 3% holds the most promise as a pre-op lid and lash cleanser9 . Brand name: Caricia Care.
Eye pain should not have to be endured by even a small percentage of patients undergoing anti-VEGF injections. These and other options need to be considered in order to alleviate this added complication to an already burdensome treatment and to ensure continued patient compliance.
Archived Comments from Professionals
Joe Fontenot, MD: [This article] should be seen by the AAO. Well referenced and written.
David Bene, MD, FACS: One thing I do for patient comfort is to use NSAID’s after the Betadine. The adnexal is well-irrigated and usually Bromday is used post-injection for 2 days. (1x/day). This has diminished the post-ocular irritation significantly in my practice.
Ron Cole, MD: You have raised an issue of great importance to patients requiring anti VEGF drugs to maintain central vision. This treatment modality is now the most common procedure done by ophthalmologists in the United States, more than cataract surgery, and numbers over one million injections per year.
Prophylaxis is paramount and undoubtedly, povidone iodine is the best known prevention. Unfortunately, a few patients have an unusual sensitivity to this preparation. There are no known allergies to iodine but there may be reason to avoid its use. A person with a known adverse response, especially undue pain or discomfort, to its use, should alert the physician or his staff so that an individualized alternative can be discussed. Unfortunately, antibiotics do not have a reliable role, but may need to be considered as well as other measures. The worldwide development of resistant organisms resulting from overutilization of antibiotics is a consideration, too.
Comfort to the patient is a very important aspect of any medically necessary procedure and alternatives are important to consider when there is such an occurence, especially when adherence to a recommended protocol of anti VEGF treatments is required and shown to be effective in preventing vision loss.
Stewart, Michael W., MD: Common problem and interesting analysis…I believe that Betadine MUST be used prior to injection. For patients who display significant sensitivity I think that decreasing the concentration and irrigating after the injection are worth trying.
Archived Comments from Patients
Carol: Thank you! At least I know someone out there cares about this agony. It causes severe abrasions to my cornea, and unending pain and tearing for about 4-5 days after the injections. I simply do not understand why it’s used other than the retinologists now ceasing the use of the over-used antibiotics, and to keep me on Hydrocodone is senseless…I can’t sit up with just one dose; imagine days of that narcotic to remedy something that could be avoided.
I’ve spoken to four retinology groups at 3 medical centers in the US now, and each said the same thing about using the antibiotics: they are not using them because of the high number of resistant organisms that cannot be controlled after long-term use of the antibiotic. But, one medical school told me they would have me on the drops the day prior to an injection, then only use 1 drop of Betadine and flush 5-6 times before the injection to get it all off the cornea, which means I’d have to stay in that city 3 days, plus airfare.
My RS just stopped using it, but now insists more than ever on Betadine; however, I well recall back in my nursing days discussing Betadine’s limited effect. In my opinion, frankly, it’s another litigious defense tactic — if an infection occurs the patients “knows” how hard the doctor worked to avoid one, which is fool-hardy at best.
Forgive me, I’m angry about these months of agony when, at the same time, my vision’s so much better after a 3/4 black out from the hemorrhage and “rapid onset AMD.” I have enough other eye conditions to deal with and I think I’m getting old and frustrated with pain and then the anticipation thereof.
Sandy: Thanks for the research. And I was pleased to read that at least one of the Doctors mentioned not using Betadine at all. I have refused Betadine for at least 2 years at my every-2-month injections in both eyes. I use antibiotic drops for 3 days beforehand, and then the RS uses antibiotic drops at the time of the injections. I also do 4 days of antibiotics following my injections. This works for me, thus far. My RS does not encourage my “no Betadine” approach; in fact, he consistently tells me about the benefits of using Betadine, i.e. risk of infection gone. But he listens to me, and I, therefore, have almost no pain consequences following my injections.
As you said, no one should have to put up with the pain from the Betadine solution. It took a while for me to become ultra sensitive to it, but there must have been a cumulative effect, because I was sure getting sick of the burning before I asked that Betadine be stopped.
I can’t believe that any doctor would refuse a patient’s wishes. I would sign a release of liability, if requested, just to NOT have Betadine used. But I have not had to do that. My RS tells me the warnings, and then does as I request….which is no Betadine; no gel numbing stuff (I prefer liquid numbing drops); no pre-injection anesthetic injection; and the least amount of dilation that they have in the RS Office. I also request both injections at the same time: one in each eye. In fact, my chart now reflects all of my wishes and the doctor reads them back to me.
Jenny: Thanks for the Betadine info. My RS has been diluting the Betadine for the last 6 or so injections, and it makes a huge difference. I also use the antibiotic drops for a few days before and after the injection. I am pleased to hear that this is considered acceptable.
Sylvie: Thank you so much for the information regarding Betadine and the possibility that it is the cause of the serious pain, lasting for hours, that follows the Lucentis injections after the anesthesia wears off. I thought it was a common natural follow up and that I just had to bear it. Now I will be able to discuss it with my ophtalmologists on both continents, knowing that my reaction is not unique and can be avoided.
Lesley: Thanks for that research. I’m more than happy with my new antiseptic wash, no pain, etc. No antibiotics before or after injection, works fine for me, as well.
Jo Anne: I also asked about Betadine, because my eye gets very irritated. The RS says there is no other drug that will assure no infection, and he will not use anything else. My first Eylea shot was terrible. Sore, hurt, burned and a film was over my eye for three days. The one today is not too bad. Just wanted to give this info.
Helen: I also am one who is refusing the Betadine. It took a couple of injection visits to convince my retina specialist, but he was convinced when he saw my eyes and my face after the Betadine application.
There is no reason to go through that reaction, and it seems to get worse the more injections you have. Wishing you good results without the Betadine!
Mary: Betadine stings, and it’s caustic to the cornea. You really don’t need a ton of Betadine, but enough to clean the surface of the eye where the injection will be given. While it is not fun, I have been told it is the best defence against endophthalmitis. It is not fun having Betadine in one’s eye. but if numbed properly, you will not feel the burn as much. If rinsed properly, the after effects can be diminished significantly.
Ask your RS what type of sterile saline rinse you can use for rinsing later (after the numbing agents wear off). This too can be helpful in producing more comfort to the eye. The use of other agents, I am told, should be used only for those who truly have an allergic reaction to the Betadine.
Tina: As a Geriatric Nurse Practitioner, I cleansed many wounds with Betadine in nursing homes. Approximately 10 years ago, we stopped using Betadine with wounds because the literature showed it was caustic to new tissue growth. We were killing the healthy new tissue in the name of cleansing the wound and inhibiting bacterial growth. This comment does not concern the use as a disinfectant in eye procedures, but it is relevant.
In patient care, we are guided by “Do No Harm”, so it is beyond me how a physician can dismiss a patient’s documented adverse reaction to Betadine and insist on continuing to use it. I would hope he would actively look for alternatives or instruct someone else to do a search for him. Dan Roberts has done it for him.
1 Y. K. Ghosh, H. Ahluwalia, J. Beamer. Povidone-iodine antisepsis before ophthalmic surgery (Published online: 16 OCT 2006 at
2 Rees A, Sherrod Q, Young L. J. Chemical burn from povidone-iodine: case and review (Division of Dermatology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA. Drugs Dermatol. 2011 Apr;10(4):414-7).
3 Papanikolaou T, Islam T, Hashim A, Mariatos G. Tolerability and Safety Profile of Povidone Iodine in Pre-Operative Skin and Eye Disinfection Prior to Intraocular Surgery. (J Clinic Experiment Ophthalmol 2:125, 2011. doi:10.4172/2155-9570.1000125.)
4 Ruth L. Berkelman, et al. Increased Bactericidal Activity of Dilute Preparations of Povidone-Iodine Solutions (Journal of Clinical Microbiology, Apr. 1982, p. 635-639 Vol. 15, No. 4)
5 Bu P, et al. A comparison of topical chlorhexidine, ciprofloxacin, and fortified tobramycin/cefazolin in rabbit models of Staphylococcus and Pseudomonas keratitis (Department of Ophthalmology, Loyola University Medical Center, Maywood, IL 60153, USA. J Ocul Pharmacol Ther. 2007 Jun;23(3):213-20)
6 Kirk H. Packo, MD, David S. Dyer, MD, Thomas R. Friberg, Baruch Kuppermann, MD, PhD, Michael Tolentino, MD. Comparing Intravitreal Injection Protocols and Practices (Retinal Physician, article dated 9/1/2010 at www.retinalphysician.com/articleviewer.aspx?articleid=104699)
7 Source: Drugs.com (online at www.drugs.com/sfx/chlorhexidine-side-effects.html)
8 M B Hamill, M S Osato, and K R Wilhelmus. Experimental evaluation of chlorhexidine gluconate for ocular antisepsis (Antimicrob Agents Chemother. 1984 December; 26(6): 793–796. PMCID: PMC180025)
9 Jean Hill, RN, MSN, CRNO, and Lisa (Mary) Hill, RN, BSN. Eye Preps: When You Can’t Use Povidone-Iodine. How to determine true iodine allergy and how to pick an alternative agent. (Published online at www.outpatientsurgery.net/issues/2007/03/eye-preps-when-you-cant-use-povidone-iodine)