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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 16
| Issue : 1 | Page : 69-74 |
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The effect of povidone-iodine 2% eye drops in the treatment of adenoviral keratoconjunctivitis
Mohammad Soleimani1, Seyed Ali Tabatabaei1, Arash Mirzaei1, Amirreza Esfandiari1, Mahdi Soleymanzadeh1, Reza Sadeghi1, Afagh Hassanzadeh Rad2
1 Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Pediatric Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| Date of Submission | 15-Jun-2022 |
| Date of Decision | 03-Sep-2022 |
| Date of Acceptance | 03-Dec-2022 |
| Date of Web Publication | 21-Feb-2023 |
Correspondence Address:
Arash Mirzaei
Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ojo.ojo_180_22
 Abstract | | |
BACKGROUND: Keratoconjunctivitis is one of the most common pathologies worldwide, caused by several infectious and noninfectious factors. This study aimed to determine the effect of povidone-iodine 2% eye drops in treating adenoviral keratoconjunctivitis.
METHODS: This analytic cross-sectional study was conducted on patients referred to Farabi Eye Hospital Records of patients with adenoviral keratoconjunctivitis, more than 12 years of age, and no allergy to iodine who were treated by povidone-iodine 2% eye drops four times a day were assessed. Data included demographic characteristics, family history of adenoviral keratoconjunctivitis, follicular conjunctivitis, petechial conjunctival hemorrhages, periauricular lymphadenopathy, and the presence of conjunctival pseudomembrane were collected from the records. Discharge decrease, injection decrease, swelling decrease, pseudomembrane formation, periauricular lymphadenopathy, and subepithelial infiltration on the 7th day of assessment by physical examination were reported.
RESULTS: Patients with a mean (±standard deviation) age of 33.77 (11.01) years were assessed. At the baseline, 95 (99.0%) follicular conjunctivitis, 94 (97.9%) petechial conjunctival hemorrhages, 29 (30.2%) periauricular lymphadenopathy, and 5 (5.2%) conjunctival pseudomembrane were recorded. On the 7th day of treatment, the discharge decreased in 92.7% of patients, and the injection decreased in 90.6%. The swelling decrease was also detected in 79.2% of patients. Subepithelial infiltration was only seen in 21.9% of the study population. Results showed that 2.1% of patients had periauricular lymphadenopathy, and only 13 out of 96 patients (13.5%) had pseudomembrane formation after 7 days.
CONCLUSIONS: Based on the safety, availability, and tolerability of povidone-iodine and its promising effects on patients with adenoviral keratoconjunctivitis, further clinical trials assessing the impact of this drug in a longer duration of follow-up can be recommended.
Keywords: Keratoconjunctivitis, lymphadenopathy, povidone-iodine
How to cite this article:
Soleimani M, Tabatabaei SA, Mirzaei A, Esfandiari A, Soleymanzadeh M, Sadeghi R, Rad AH. The effect of povidone-iodine 2% eye drops in the treatment of adenoviral keratoconjunctivitis. Oman J Ophthalmol 2023;16:69-74 |
How to cite this URL:
Soleimani M, Tabatabaei SA, Mirzaei A, Esfandiari A, Soleymanzadeh M, Sadeghi R, Rad AH. The effect of povidone-iodine 2% eye drops in the treatment of adenoviral keratoconjunctivitis. Oman J Ophthalmol [serial online] 2023 [cited 2023 Mar 31];16:69-74. Available from: https://www.ojoonline.org/text.asp?2023/16/1/69/370036 |
| Introduction | |  |
Keratoconjunctivitis is one of the most common eye pathologies worldwide that is caused by several infectious and noninfectious factors. Many microorganisms with different pathogenic mechanisms are involved in the development of the infection.[1],[2] Adenovirus is the most common etiologic agent, with various strains worldwide accounting for 65%–90% of all viral keratoconjunctivitis.[1],[3],[4] The prevalence of adenoviral keratoconjunctivitis in patients with general signs and symptoms of conjunctivitis was 11.4%.[5] Furthermore, it has been reported that 94.5% of patients with suspected viral conjunctivitis or keratoconjunctivitis were positive for adenovirus.[6]
Adenoviral keratoconjunctivitis is an infection of the eye's outer surface.[7] It presents symptoms such as redness, tearing, photosensitivity, and decreased vision.[8] Eyelids edema, follicular conjunctivitis, conjunctival hyperemia, epithelial keratitis, and sometimes preauricular lymphadenopathy are the common findings in the physical examination.[7] While the virus was present for about a week before the onset of symptoms with an incubation period of about 1 week, the onset of adenoviral keratoconjunctivitis appears to be rapid and immediate. The opposite eye is often involved in the coming days, albeit less severely. Although the acute phase of adenoviral keratoconjunctivitis is characterized by severe conjunctivitis that lasts for 2–4 weeks,[9] the symptoms of the disease worsen in the first 4–7 days.[10] After the onset of conjunctivitis, there is a period of virus transmission when the patients should reduce their contact with others.[7] As long as there is redness of the eyes and active discharge (usually in the first 10–12 days), the disease is highly contagious.[10] The virus also triggers an immune response that manifests itself as a pseudomembrane and even a transient symblepharon or obstruction of the punctum.[7] Corneal involvement with the formation of subepithelial multifocal infiltration is one of its essential complications. It may usually last for months or years, reducing visual acuity and inducing photophobia.[9] Preventing virus transmission is one of the vital components of appropriate treatment. The patient should be aware that the virus is highly contagious and avoid manipulating and rubbing the eyes and contacting different surfaces.[11] Frequent hand washing should be considered, and the patient should refrain from sharing personal items such as towels.[12]
Although adenoviral keratoconjunctivitis is a self-limiting disease, treatments are often considered to reduce its symptoms and severity. Treatment for adenoviral keratoconjunctivitis often includes supportive therapies such as cold compresses and artificial teardrops.[13] According to studies, nonsteroidal anti-inflammatory drugs have neither the ability to reduce symptoms nor eliminate the virus compared to artificial tears.[14] Cyclosporine is used to treat subepithelial secretions.[15] Cidofovir eye drops are also effective but have limited use due to their local toxicity.[16] Povidone-iodine is another effective treatment with a wide range of antimicrobials that reduce the virus titer and improve symptoms rapidly.[17] Other benefits of povidone-iodine include reducing the free adenovirus component and, to some extent, the intracellular component and its infectivity.[7] Povidone-iodine belongs to a group of antiseptics known as iodophors, which exert their antiseptic effect by slowly releasing iodine. It is effective against Gram-negative and positive bacteria, fungi, protozoa, and viruses (including adenovirus) in out-of-body conditions. Its bactericidal properties have led to its widespread use in preoperative preparation.[18] Due to the spectrum of the effectiveness of povidone-iodine, the diluted solution is also used in the treatment of some corneal infections.[19] Among many antiseptics that have been used against adenoviruses in laboratory studies, a lower concentration of povidone-iodine can limit adenoviral activity. It has been mentioned that povidone-iodine is the only antiseptic that can inactivate adenoviral activity after 1-min exposure.[18] Previous studies showed that povidone-iodine could reduce adenoviral load, but it is more efficient on free adenoviruses than intracellular ones.[20],[21] In a recent study using the combination of dexamethasone and povidone-iodine as a new treatment approach, ocular symptoms were reduced, and it killed adenoviruses successfully.[22] Due to the limited evidence on the use of povidone-iodine as a commercially available treatment and its potential effect, the authors aimed to evaluate the results of povidone-iodine therapy in patients with adenoviral keratoconjunctivitis.
| Methods | | |
Patients and settings
This analytic cross-sectional study was conducted on patients who were referred to Farabi eye hospital, the largest and the most productive eye care facility in Iran, from September 2019 to February 2020. Records of 100 patients with suspected conjunctivitis of adenoviral keratoconjunctivitis were selected by convenient sampling. The clinical decision of the ophthalmologist confirmed the diagnosis. Records of patients with adenoviral keratoconjunctivitis, more than 12 years of age, and no allergy to iodine who were treated with povidone-iodine 2% eye drops four times a day for 2 weeks were assessed. As povidone-iodine drop was not commercially available, it was prepared in sterile condition at Farabi Eye Hospital's local pharmacy. For injection, we added 4 ml of sterile water to 1 ml of PI 10%. Then, we packed them in 5 ml bottles and stored them at a cold temperature of about 4°C. All patients were instructed to consider hand hygiene, use methods to prevent transmission, and not share personal items with others. Possible side effects of taking betadine drops, including redness and burning sensation when taking the drug, were explained to patients. Furthermore, in case of any allergy, their treatment was stopped, and they were excluded from the study, and other routines and standard treatments were performed for them.
Data gathering
Data included age, sex, onset day, educational level, family history of adenoviral keratoconjunctivitis, follicular conjunctivitis, petechial conjunctival hemorrhages, periauricular lymphadenopathy, the presence of conjunctival pseudomembrane, and upper respiratory tract infection were collected from the records. The examination for subepithelial opacity considered by the physician has been performed accurately for all patients, and the examination results were recorded. Discharge decrease, injection decrease, swelling decrease, pseudomembrane formation, periauricular lymphadenopathy, and subepithelial infiltration on the 7th day of assessment by physical examination were reported.
Ethical considerations
This study was ethically approved by the Ethics Committee of Farabi Eye Hospital-Tehran University of Medical Sciences (IR.TUMS.FARABIH.REC.1398.031).
Statistical analysis
Collected data were described in terms of number, percent, mean, standard deviation (SD), range, and median. For statistical analysis, SPSS for Windows, Version 16.0. (Chicago, SPSS Inc) was used. The baseline and 7th-day follow-up of pseudomembrane formation and periauricular lymphadenopathy were compared with the McNemar's test. The comparison was considered statistically significant when the P value was lower than 0.05. In this study, a 95% confidence interval was indicated.
| Results | | |
In this study, 100 records were checked, and based on the four incomplete records, 96 records were reported. Patients with a mean (± SD) age of 33.77 (11.01) with minimum and maximum ages of 12 and 62 years old were assessed. Results showed that 71.9% were male and 28.1% were female. Most of the patients (62.5%) had a high school level of education. Only 20 (20.8%) patients had a family history of adenoviral keratoconjunctivitis.
At the baseline, 95 (99.0%) follicular conjunctivitis, 94 (97.9%) petechial conjunctival hemorrhages, 29 (30.2%) periauricular lymphadenopathy, 5 (5.2%) conjunctival pseudomembrane, and 14 (14.6%) upper respiratory tract infection (a nonocular manifestation) were recorded. [Table 1] shows the demographic and baseline characteristics of the patients.
[Table 2] shows findings on the 7th day of treatment. The discharge decreased in 92.7% of patients, and injection decreased in 90.6% of them. The swelling decrease was also detected in 79.2% of patients. Subepithelial infiltration was only seen in 21.9% of the study population. Results showed that 2.1% of patients had preauricular lymphadenopathy, and only 13 out of 96 patients (13.5%) had pseudomembrane formation after 7 days. No patient mentioned allergy to PI and none of them was excluded due to allergy.
Comparing baseline and 7th-day assessments
Comparing the frequency of periauricular lymphadenopathy in the baseline and the 7th day showed that 29 and two patients had periauricular lymphadenopathy, respectively. Results demonstrated that the occurrence of periauricular lymphadenopathy on the 7th day was significantly decreased compared to the baseline (P = 0.001). Furthermore, the presence of conjunctival pseudomembrane in the baseline and the 7th day indicated that despite no statistical difference (P = 0.096), administering povidone-iodine showed clinical significance. Although pseudomembrane commonly occurs in patients with adenoviral keratoconjunctivitis, only 13.5% developed it after 7 days and the regimen was changed for them to artificial tear and a topical steroid.
| Discussion | | |
In this study, the investigators examined the effects of povidone-iodine 2% eye drops in treating adenoviral keratoconjunctivitis. Results showed that povidone-iodine administration in adenoviral keratoconjunctivitis reduced the incidence of complications such as pseudomembranes. Furthermore, the effects of povidone-iodine as a single treatment method showed promising results regarding the discharge decrease, injection decrease, swelling decrease, subepithelial infiltration, and periauricular lymphadenopathy on the 7th day of follow-up.
Povidone-iodine is an antiseptic and disinfectant used for the preoperative preparation of the skin and mucous membranes and for treating infected wounds. Due to the wide range of antimicrobial activity, povidone-iodine is widely used in ophthalmology. Preparing eyelids, eyelashes, and conjunctiva before intraocular surgery reduces the risk of endophthalmitis.[23] In 1970, Hale first introduced it. Povidone used iodine 5% based on the need for an antimicrobial agent as a nonresistant solution without ocular allergic reactions.[24] It was later shown that small amounts of povidone-iodine solution penetrating the conjunctival sac during intraocular surgery do not affect the symmetrical endothelium.[25] The use of povidone-iodine in anterior segment surgery is limited. Animal studies in rabbits have shown that 0.25% povidone-iodine is toxic to endothelial cells, leading to documented morphological changes, corneal edema, and increased corneal thickness.[26] In a recent double-masked, randomized clinical trial (2019), Shorter et al. evaluated the safety and efficacy of a 5% povidone-iodine solution in the treatment of adenoviral keratoconjunctivitis among 56 participants. No adverse effects have been reported in this study after 21 days of follow-up. They indicated that although a temporary increase in corneal staining may be observed following povidone-iodine use, these changes are transient. By informing and reassuring patients about these transient complications, its beneficial effects in treating adenoviral keratoconjunctivitis can be used.[27]
In a similar previous study, 66% of patients treated with 2% povidone-iodine solution four times a day for 1 week showed bilateral adenoviral keratoconjunctivitis. At the end of the study, watery and mucous secretion decreased significantly (P < 0.001). All ocular symptoms, such as lid swelling, irritation, photophobia, and red eye, showed significant improvement (P < 0.001), but periauricular lymph node involvement did not significantly change. The results indicated that the ocular application of a 2% povidone-iodine solution could successfully treat adenoviral keratoconjunctivitis, which was well tolerated by patients.[28] Moreover, Pelletier et al. used the combination of povidone-iodine 0.4%/dexamethasone 0.1% ophthalmic suspension to treat adenoviral conjunctivitis. Assessing the clinical resolution 3 days after treatment showed that eight of nine eyes had decreased secretion and reduced injection, and only one case did not show improvement due to the follow-up loss.[22]
Kovalyuk et al. assessed the effect of a combination of povidone-iodine 1.0% and dexamethasone 0.1% drops in a prospective, randomized, controlled, and double-blinded clinical trial. Eyelid swelling (P < 0.001), conjunctival injection, and conjunctival discharge demonstrated a superior reduction (P < 0.001). No pseudomembranes on the tarsal conjunctiva and corneal subepithelial infiltrates were found among patients.[29] Yates et al. evaluated povidone-iodine against multiple ocular adenoviral types (3, 4, 5, 7a, 8, and 19/64), which were collected from patients presenting with adenoviral conjunctivitis. The results indicated that 5%, 2%, and 0.4% concentrations of povidone-iodine had a successful virucidal effect on all adenoviral types.[30]
Povidone-iodine, in contrast with artificial teardrops, is the better option for managing adenoviral keratoconjunctivitis. Previous studies showed that patients in the artificial teardrops group had longer conjunctivitis and positive polymerase chain reaction (PCR) durations than dexamethasone 0.1% plus povidone-iodine 0.4% group, which was statistically significant. Furthermore, it is important to mention that the incidence of subepithelial corneal infiltration and intraocular pressure did not have any difference between the artificial teardrops group and dexamethasone 0.1% plus povidone-iodine 0.4% group. In the artificial teardrops group, the incidence of adverse effects, including stinging, was significantly higher than dexamethasone 0.1% plus povidone-iodine 0.4% group (22.4 vs. 1.1.9%, P = 0.001).[31] In another study (2021), the efficacy and tolerability of polyvinylpyrrolidone-iodine (PVP-I) 0.6% treatment in adenoviral keratoconjunctivitis was significantly higher than in the hyaluronate-based tear substitutes group. The incidence of adverse effects such as subepithelial corneal infiltration was significantly lower, and resolution time was shorter in the PVP-I 0.6% eye drop group versus the hyaluronate-based tear substitutes group (P = 0.005). The incidence of corneal haze also showed a significant reduction in PVP-I 0.6% eye drop group (0/34 vs. 3/25; P = 0.038).[32]
Strengths and limitations
While in this study, a larger sample size was indicated to measure the effect of only povidone-iodine 2% eye drop in patients with adenoviral keratoconjunctivitis, this study had some limitations. Investigators could not assess the PCR results for their patients, and this study had a short duration of follow-up.
| Conclusions | | |
Based on the safety, availability, and tolerability of povidone-iodine and its promising effects on patients with adenoviral keratoconjunctivitis, it seems that further clinical trials assessing the impact of this drug in a longer duration of follow-up can be recommended.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]
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