Viral conjunctivitis accounts for almost 700,000 yearly visits to the emergency department1 and 92% of those can be attributed to adenovirus, termed Adenoviral Conjunctivitis (Ad-Cs)2. Patients may experience ocular irritation, photophobia, blurred vision, eyelid swelling, and conjunctival edema. Although the condition is generally self-limited, it is highly infectious and occasionally leads to more serious sequelae such as pseudomembrane formation and chronic nummular keratitis.3 Given that Ad-Cs can last from 2 to 4 weeks and has no FDA-approved treatment as of yet, it would be great if there was some silver bullet treatment we could offer in the ED to reduce the severity and longevity of symptoms…
The ‘Silver Bullet’ Treatment for Ad-Cs
The treatment that has been gaining traction among ophthalmologists: diluted Betadine straight to the eyeball. We first learned about this from one of our ophthalmology residents and were skeptical (to say the least), especially with regards to the safety of the technique. However, Betadine wash-outs (heretofore referred to as the unbranded version- povidone-iodone or PVP-I) have long been used in ophthalmology in a variety of contexts- most frequently in the preoperative setting (in a 5% concentration) to establish a sterile field4,5, peri-operatively (in a 5% concentration) as prophylaxis against endophthalmitis5,6, and in neonates (in a 2.5% concentration) as prophylaxis against ophthalmia neonatorum5. It is especially popular in low resource settings where it is frequently substituted for erythromycin due to its anti-microbial properties.
Safety
In addition to the aforementioned historical precedents, a double-blinded randomized trial out of Washington University in St. Louis known as the RAPID (Reducing Adenoviral Patient-Infected Days) Study7 seems to support the safety of a one-time wash-out with Povidone-Iodine (PVP-I) 5%. Fifty-six patients with Ad-Cs confirmed by rapid immunoassay were assessed for safety (corneal fluorescein staining and visual acuity) and tolerability (patient comfort) at baseline, immediately following a 2-minute exposure to PVP-I 5% solution and at day 1.
The group randomized to the PVP-I wash-out had a statistically significant increase in corneal fluorescein staining (CFS), a marker for epithelial damage, directly following the wash-out as compared to the group receiving artificial tears (AT).7 However, there was no statistically significant difference between the groups on day 1. On later days, CFS increased in the AT group as well, likely reflecting the natural course of the Ad-Cs disease process. There was no statistically significant effect on visual acuity in either of the groups.
Patients receiving artificial tears had a statistically significant improvement in comfort immediately post-administration, but the group receiving PVP-I had no increase in discomfort from baseline immediately post-administration or at day 1.7 To mitigate the discomfort of the PVP-I wash-out, the authors suggest pre-treating the patients with a topical anesthetic and sending patients home with artificial tears.
Efficacy
PVP-I has been shown to have in vitro virucidal activity against most types of adenovirus, decreasing viral load and thus, viral shedding.8 In practice, a handful of studies have shown decreased time to cure with some form of PVP-I treatment.
The RAPID Study referenced above included 28 patients (with qPCR+ adenoviral test) and found that the patients randomized to receive the PVP-I 5% wash-out had decreased signs and symptoms (participant-reported tearing, eyelid swelling, and redness) at day 4 when compared to the group receiving artificial tears.8 Of note, the participants were only included if their symptoms had been present for 4 days or less prior to PVP-I administration; therefore, it’s unclear if a PVP-I wash-out administered further on in the disease course will yield similar benefits or not.9
Several other studies have found that varying concentrations of PVP-I/dexamethasone drops administered 3-4 times daily have reduced time to recovery in adenovirus-confirmed conjunctivitis when compared to either dexamethasone-only drops, PVP-I-only drops, or artificial tears.10–12
Interestingly, a high-powered, double-blinded, randomized trial out of Philippines (in partnership with UCLA-Harbor Medical Center) showed that a PVP-I 1.25% solution QID was non-inferior to neomycin-polymixin-B-gramicidin ophthalmic solution in treating all types of conjunctivitis (viral and bacterial) and was marginally more effective in treating Chlamydial conjunctivitis, although no statistically significant.13 Although not the point of this particular post, perhaps it lends more credibility to the feasibility of sending patients home with lower concentration PVP-I drops.
How to perform this procedure9,14:
• Instill one or two drops of tetracaine 0.5% in the affected eye for analgesia.
• Optional: instill one or two drops of an NSAID (diclofenac or ketorolac) to prevent mild corneal stippling and to provide longer-term pain relief.
• The PVP-I solution most common in the ED is a 10% solution. Use a 10 cc syringe to dilute the PVP-I 10% with saline in a 1:1 ratio to achieve a 5% solution.
• Instill four to five drops of the PVP-I 5% solution in the eye.
• Allow the patient to blink and look left to right to ensure that the entire surface of the eye is coated.
• Use a swab dipped in the PVP-I 5% solution to clean along the lid margins.
• After 30 to 60 seconds, use 2 to 3 saline flushes to flush out the PVP-I, taking special care to flush out beneath the eyelid.
• Consider giving one dose of steroid and one additional dose of NSAID following irrigation.
• Patch eye to decrease eye rubbing.
• Schedule ophthalmology follow up in 3 to 4 days.
Please note that the full 10 cc syringe of PVP-I 5% as demonstrated in the video was slightly excessive and 4 to 5 drops will suffice.
Read more at Review of Optometry’s blog post on how to Stop EKC with a ‘Silver Bullet.’
Pitfalls:
It’s important to note that all the research studies referenced here were carried out in outpatient ophthalmology clinics and have not yet been validated in the setting of the Emergency Department. As of yet, there is little to no literature exploring the uses of PVP-I for ocular pathologies in the ED.
Furthermore, all of the populations studied were confirmed to have adenoviral conjunctivitis by either PCR or immunoassay- a technology not yet available to us in the emergency department. The main risk of using a PVP-I 5% wash-out on a patient with a non-adenoviral conjunctivitis is that the patient would experience discomfort without necessarily experiencing benefit (although this is debatable). For some, this may be an acceptable risk when faced with the possibility of a shortened disease course.
However, PVP-I/dexamethasone drops should not, by any means, be prescribed to a patient with un-typed conjunctivitis in the event that a patient is suffering from herpes-simplex conjunctivitis. Steroids in the treatment of herpes-simplex conjunctivitis can potentiate the disease severity.15 Since most Emergency Departments have access to a slit lamp, it’s strongly advised that the practitioner conduct a slit lamp exam on all patients presenting with conjunctivitis prior to committing to a treatment course.
Take Home Points:
‣ A 2-minute exposure to PVP-I 5% is safe and reasonably tolerable.
‣ Early studies show promise regarding shortened disease course; however, we need more evidence in the setting of Emergency Medicine to validate a one-time wash-out with PVP-I 5% as a viable treatment for adenoviral conjunctivitis.
‣ Ensure close follow-up with ophthalmology!!
Special Thanks
SUNY Downstate Ophthalmology, Drs. Pia Daniels, Jessica Paulson, Kathy Chu, Andrew Aherne, and most importantly, Dr. Duo Xu who volunteered his eye for the purposes of our demonstration.
Related Reading
Review some common eye complaints with Eye Started Crying II: Conjunctivitis (pics included)!
Or maybe ocular ultrasound is more up your alley?
And if you just need a quick refresher of basic eye anatomy and ocular terminology, check out this post on anterior uveitis.
References
1Channa R, Zafar SN, Canner JK, Haring RS, Schneider EB, Friedman DS. Epidemiology of Eye-Related Emergency Department Visits. JAMA Ophthalmol. 2016;134(3):312-319. doi:10.1001/jamaophthalmol.2015.5778
2Aoki A, Isobe K, Ohno S. Nationwide surveillance program of epidemic conjunctivitis in Japan. In: Infectious Diseases of the Eye. Butterworth-Heinemann; 1984:309-316.
3 Bialasiewicz A. Adenoviral Keratoconjunctivitis. Sultan Qaboos Univ Med J. 2007;7(1):15-23.
4 Apt L, Isenberg SJ, Yoshimori R, Spierer A. Outpatient topical use of povidone-iodine in preparing the eye for surgery. Ophthalmology. 1989;96(3):289-292. doi:10.1016/s0161-6420(89)32897-1
5 Isenberg SJ. The Ocular Application of Povidone-Iodine. Community Eye Health. 2003;16(46):30-31.
6 Trinavarat A, Atchaneeyasakul L, Nopmaneejumruslers C, Inson K. Reduction of endophthalmitis rate after cataract surgery with preoperative 5% povidone-iodine. Dermatol Basel Switz. 2006;212 Suppl 1:35-40. doi:10.1159/000089197
7 Shorter E, Whiteside M, Harthan J, et al. Safety and tolerability of a one-time, in-office administration of 5% povidone-iodine in the treatment of adenoviral conjunctivitis: The Reducing Adenoviral Patient Infected Days (RAPID) study. Ocul Surf. 2019;17(4):828-832. doi:10.1016/j.jtos.2019.08.005
8 Yazar H, Yarbag A, Balci M, Teker B, Tanyeri P. The effects of povidone iodine (pH 4.2) on patients with adenoviral conjunctivitis. JPMA J Pak Med Assoc. 2016;66(8):968-970.
9 Hartwick A, Than T, Rodic-Polic B, et al. Reducing Adenoviral Patient-Infected Days (RAPID) Study: A Randomized Trial Assessing Efficacy of One Time, In-Office Application of 5% Povidone-Iodine in Treatment of Adenoviral Conjunctivitis. Invest Ophthalmol Vis Sci. 2019;60(9). Accessed July 18, 2020. https://iovs.arvojournals.org/article.aspx?articleid=2745291
10 Kovalyuk N, Kaiserman I, Mimouni M, et al. Treatment of adenoviral keratoconjunctivitis with a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study. Acta Ophthalmol (Copenh). 2017;95(8):e686-e692. doi:10.1111/aos.13416
11 Pelletier JS, Stewart K, Trattler W, et al. A combination povidone-iodine 0.4%/dexamethasone 0.1% ophthalmic suspension in the treatment of adenoviral conjunctivitis. Adv Ther. 2009;26(8):776-783. doi:10.1007/s12325-009-0062-1
12 Pepose JS, Ahuja A, Liu W, Narvekar A, Haque R. Randomized, Controlled, Phase 2 Trial of Povidone-Iodine/Dexamethasone Ophthalmic Suspension for Treatment of Adenoviral Conjunctivitis. Am J Ophthalmol. 2018;194:7-15. doi:10.1016/j.ajo.2018.05.012
13 Isenberg SJ, Apt L, Valenton M, et al. A controlled trial of povidone-iodine to treat infectious conjunctivitis in children. Am J Ophthalmol. 2002;134(5):681-688. doi:10.1016/s0002-9394(02)01701-4
14 O.D RM OD and Randall Thomas. Stop EKC with a “Silver Bullet.” Accessed July 18, 2020. https://www.reviewofoptometry.com/article/stop-ekc-with-a-silver-bullet
15 Holland EJ, Fingeret M, Mah FS. Use of Topical Steroids in Conjunctivitis: A Review of the Evidence. Cornea. 2019;38(8):1062–1067. doi:10.1097/ICO.0000000000001982
Edited by Robby Allen
nicanthony
Latest posts by nicanthony (see all)
- Abortion Care in the ED - May 23, 2023
- DNR Orders in the Suicidal Patient - September 22, 2022
- Sono of the Week: Neck Swelling - August 2, 2022
0 Comments