Diluted povidone in adenoviral keratocojunctivitis

·Clinical Research·

Effect of diluted povidone iodine in adenoviral

keratoconjunctivitis on the rate of subepithelial corneal
infiltrates
Rana Altan-Yaycioglu, Nedime Sahinoglu-Keskek, Handan Canan, Muge Coban-Karatas, Burak Ulas

Department of Ophthalmology, Baskent University School of ● KEYWORDS: conjunctivitis; corneal opacity; infectious
Medicine, Adana 01130, Turkey keratoconjunctivitis; keratoconjunctivitis; povidone-iodine;
Correspondence to: Rana Altan-Yaycioglu. Acibadem Adana viral conjunctivitis
Hospital, Cumhuriyet Cad, No.66, Seyhan, Adana 01130, DOI:10.18240/ijo.2019.09.08
Turkey. [email protected]; [email protected]
Received: 2018-11-30 Accepted: 2019-03-12 Citation: Altan-Yaycioglu R, Sahinoglu-Keskek N, Canan H, Coban-
Karatas M, Ulas B. Effect of diluted povidone iodine in adenoviral
Abstract keratoconjunctivitis on the rate of subepithelial corneal infiltrates. Int
● AIM: To evaluate the clinical characteristics of adenoviral J Ophthalmol 2019;12(9):1420-1425
keratoconjunctivitis, the management modalities, as well
as the incidence of subepithelial corneal infiltrates (SEI). INTRODUCTION
● METHODS: Patients with characteristic clinical symptoms
and signs, who presented to our clinic within the first week
of symptoms and received the diagnosis of adenoviral
A denoviral keratoconjunctivitis (AKC) is a highly
contagious infectious disease, which mainly involves
the ocular surface and cornea[1]. It can result in community
keratoconjunctivitis between January 2013 and April epidemic infections, and lead to waste in labor productivity.
2016, were included in the study. A total of 211 patients The virus is highly resistant to environmental conditions. The
were included in the study. Patients were evaluated for incubation time is between 4 and 24d. Infection usually starts
the incidence of clinical signs, late complications, in one eye and in 70% of the cases other eye becomes infected[1].
management preferences, and the effect of diluted AKC is a biphasic disease, beginning with the infectious
povidone-iodine (d-PVP-I) 2%. phase, which is followed by the inflammatory phase[2]. During
● RESULTS: Patients’ mean age was 33.03±14.76y. We the infectious phase, patients usually complain of foreign body
observed an increase in the number of cases according sensation, photophobia, and excessive tearing in one or both
to the years. At presentation and/or early follow-up, eyes. The clinical findings are swelling of the lids, conjunctival
the clinical signs were conjunctival hyperemia (100%), hyperemia, follicular conjunctivitis, chemosis, subconjunctival
conjunctival follicules (79.1%), edema of the eyelids hemorrhage, and pseudomembranes[1]. The infectious phase
(39.3%), chemosis (16.1%), pseudomembrane formation continues for about two weeks. Then, during the inflammatory
(16.6%), and corneal epitheliopathy (29.9%). During phase, approximately 40%-50% of the patients develop
late follow-up 13.3% patients developed conjunctival subepithelial corneal infiltrates (SEI). When these occur,
subepithelial fibrosis, and 39.8% developed SEI. A patients may complain of irritation, photophobia as well as
significant decrease in the incidence of SEI development decrease in vision, if the infiltrates obscure the optical axis[3].
was observed in patients who used d-PVP-I 2% (P=0.032; The SEI may last from a few months to few years.
33.3% vs 45.9%, respectively in patients who received There is currently no commercially available casually
d-PVP-I 2% and who did not). directed treatment for adenovirus. Considering the morbidity
● CONCLUSION: Adenoviral keratoconjunctivitis has and economic impact of the disease, a therapeutic agent
a tremendous effect on patient’s comfort and abilities that reduces the clinical symptoms and signs of AKC and
in short-term. Additionally, almost half of the patients minimizing the virus shedding would be desirable. Currently,
develop visual problems related to SEI. According to our the treatment usually targets the symptoms and auxiliary effects
clinical experience, using d-PVP-I 2% in the first days of the virus. Cold compresses, artificial tears, sometimes anti-
of adenoviral keratoconjunctivitis might be helpful in inflammatory agents are being added. The use of steroids is
reducing the risk of SEI as a complication. controversial[4].
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Tel: 8629-82245172 8629-82210956 Email: [email protected]

Table 1 The numbers of patients with and without the clinical signs
Patients not on d-PVP-I Patients on d-PVP-I
Total (n=211)
Clinical signs (n=109) (n=102) χ P
With sign No sign % With sign No sign With sign No sign
Eyelid edema 84 127 40 39 70 45 57 1.53 0.216
Chemosis 35 176 17 16 93 19 83 0.59 0.441
Folicular conjunctivitis 169 42 80 90 19 79 23 0.87 0.352
Pseudomembranes 15 176 7 19 90 16 86 0.12 0.733
Epithelial keratopathy 62 149 29 32 77 30 72 0.00 0.993
Subepithelial infiltrates 84 127 40 51 58 33 69 4.58 0.032a
Conjunctival fibrosis 31 180 15 18 91 13 89 0.60 0.440
Symblepharon formation 6 205 3 3 106 3 99 0.01 0.934
The column with title “total” represents the total number of patients with or without clinical signs. The following columns show the numbers
of patients who were not on (were not given) diluted povidone iodine (d-PVP-I), and who were given (patients on) diluted povidone iodine
(d-PVP-I). Patients who showed the clinical signs were shown as with sign, whereas who lack the particular sign were shown as no sign. The
numbers were compared using the Chi-square test, and results were shown with χ (Chi). aP<0.05 was accepted statistically significant.

Povidone-iodine is a broad-spectrum antiseptic agent. It is modalities were recorded. Patients were prescribed either
being used in ocular surgeries preoperatively, and in neonatal one or several of the following: antibiotics, artificial tears,
conjunctivitis. Several studies reported the use of povidone antivirals, steroids, non-steroidal anti-inflammatory drugs
iodine in AKC[5-6]. Recently, some of our authors (Altan- (NSAID), d-PVP-I, and cyclosporine A. For preparation of
Yaycioglu R and Ulas B) also added diluted povidone iodine d-PVP-I 2%, povidone iodine 10% was mixed with sterile
(d-PVP-I) in the treatment of AKC cases. physiologic serum in 1 to 4 ratios, in order to obtain 2%
Herein, we aimed to evaluate the clinical features of AKC povidone iodine. Patients were recommended to apply d-PVP-I
cases as well as the effect of d-PVP-I 2% on the clinical course 2% twice a day for 5d.
and late complications such as SEI. The average time frame for SEI formation was 14 to 20d.
SUBJECTS AND METHODS Topical steroids and cyclosporine A were started if the patient
Ethical Approval The study was conducted in accordance had any SEI resulting in visual disturbances.
with the Declaration of Helsinki. Local ethics committee We analyzed the incidences of clinical signs, and evaluated
approval was obtained. Informed consent was waived due to their relationship with d-PVP-I 2% use. Also, we compared the
the retrospective nature of the study. incidences of SEI development regarding the use of d-PVP-I
In this retrospectively designed study, the charts of patients 2%, corticosteroid and antiviral during the first week of clinical
who presented to our clinic between January 2013 and April symptoms. The incidences were compared using the Chi-
2016, and received the diagnosis of AKC according to the square test. A probability value less than 0.05 was accepted as
clinical signs were evaluated. Patients, with the complaints statistically significant.
of red eye and pain, and had the clinical signs of conjunctival RESULTS
hyperemia, chemosis, intense serous secretion, and/or eyelid Mean age (±standard deviation, SD) of the patients was
edema and pseudomembrane formation received the diagnosis 33.03±14.76y. The distribution of patients according to the
of AKC. Only patients, who had the symptoms and signs years was 22 cases in 2013, 41 cases in 2014, 115 cases in
for less than 1wk and had no previous treatment and were 2015, and 41 cases in the first 4mo of 2016. So, we observed
followed more than 1mo, were included. Patients with longer an increase in AKC cases during the study period. Although
history were excluded. the clinical severity of the disease was similar, a decrease in the
The charts of 285 patients were retrospectively evaluated. Of SEI formation was observed, as the incidence of SEI formation
those, 74 had incomplete follow-up, so they were excluded was 45% (10/22) in 2013, 68.3% (28/41) in 2014, 32.3%
from further evaluation. A total of 211 patients were included (37/115) in 2015, and 22% (9/41) in the first four months of
in the assessment. We recorded the age, sex, the incidence 2016.
of clinical signs at presentation, and late complications. As The incidences of clinical signs are shown on Table 1.
late complications we noted the data on SEI, conjunctival Early clinical signs were conjunctival hyperemia (100%),
subepithelial fibrosis, and symblepharon formation, which conjunctival follicles (79.1%), edema of the eyelids (39.3%),
were observed two to three weeks after the initial symptoms. chemosis (16.1%), pseudomembrane formation (16.6%), and
Additionally, the management and preferred treatment corneal epitheliopathy (29.9%). In the late phase, we observed
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Diluted povidone in adenoviral keratocojunctivitis

Table 2 The distribution of patients who developed subepithelial infiltrates (SEI+) or not (SEI-)
Medication SEI+ SEI- Total P
d-PVP-I 0.032a
Patients on d-PVP-I 33c 69b 102
b c
Patients not on d-PVP-I 51 58 109
Total 84 127 211
Topical corticosteroids 0.314
Patients on topical corticosteroids 20 23 43
Patients not on topical corticosteroids 64 104 168
Total 84 127 211
Antivirals 0.029a
Patients on antivirals 14b 9c 23
c b
Patients not on antiviral 70 118 188
Total 84 127 211
The number of patients and who used diluted povidone iodine (d-PVP-I), topical corticosteroids, and antivirals
are given in corresponding cells. Chi-square test was used for statistical comparison. aP<0.05 was accepted
statistically significant; bValues higher than expected cases; cValues lower than expected cases.

SEI in 39.3%, conjunctival subepithelial fibrosis in 13.3% and artificial tears only, because the opacities did not cause visual
mild symblepharon formation in 1.4% of cases. disturbances.
We included patients who were followed by 5 different When we evaluated the incidence of SEI development
ophthalmologists. So there were some differences in the according to the used medications during the first-week, we
management of patients. All patients were given only topical observed a statistically significant difference in d-PVP-I 2%
medication. The prescribed medication were antibiotics used patients (P=0.032; Table 2). The incidence was 46.8% in
in 93.4%, artificial tears in 88.2%, d-PVP-I 2% in 48.3%, patients who did not use d-PVP-I, and 32.3% in patients who
corticosteroids in 20.3%, antivirals (ganciclovir) in 10.9%, and were given d-PVP-I 2%. The topical corticosteroid use had no
NSAID in 5.2% of patients. significant effect on SEI development (P=0.314). On the other
A total of 102 patients received 2% d-PVP-I. All patients hand, a significant difference was observed in patients who
reported burning and stinging, particularly in the first days. used antivirals (P=0.029). The incidence of SEI development
However, all of the managed to use it for the recommended was 60.1% in patients, who used antivirals and 37.2% in
5d. We observed corneal epithelial defects in two cases, who patients who did not.
applied d-PVP-I 2% more than two times a day. Furthermore, when we further compared the use of d-PVP-I
In 35 patients (16.6%) pseudomembrane formation was and antivirals together or alone in different combinations as
observed. Of these 22 patients (62.9%) underwent membrane shown on Table 3. We observed that d-PVP-I 2% decreased
peeling. Of 35 patients with pseudomembrane formation, 21 the incidence of SEI development (Comparison VI, P=0.023).
developed SEI (60%), whereas 14 (40%) had none. In the Additionally, antiviral use did not have any inhibitory effect
reverse look of these results, of patients who developed SEI on SEI development (Combination V, P=0.238). Thus, we
(84 patients), 21 had pseudomembrane (25%), whereas 63 have shown that the use of povidone iodine does decrease the
(75%) had none. The occurrence of pseudomembrane formation incidence of SEI.
and SEI development was significantly related (P=0.008). DISCUSSION
During the late phase, 60.2% of patients (n=127) received Adenoviral keratoconjunctivitis is a highly contagious disease,
no treatment. The remaining 31.3% were treated for visual with uncomfortable clinical symptoms, limiting patients’ daily
disturbances related to SEI. Of patients with SEI (n=84), activity. Almost 40%-50% of patients with AKC develop SEI,
topical treatment was prescribed in 78.6% (n=66) if the which results in visual disturbances, such as decrease in vision,
infiltrates resulted in visual disturbances. Of these 40 patients photophobia, and glare. There is no definite treatment of AKC,
(47.6%) received only steroids, 23 patients (27.4%) used so we aimed to investigate the practice patterns in our clinic. In
steroids in combination with cyclosporine A, and 3 patients present study on 211 cases with AKC, we observed that almost
(3.6%) were given only cyclosporine A. On the other hand, half of the patients (48.7%) received d-PVP-I 2%, and these
21.4% of patients with SEI (n=18) were followed with patients showed significantly lower incidence of SEI.
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Table 3 The distribution of patients who developed subepithelial infiltrates (SEI+) or not (SEI-)
Medication SEI+ SEI- Total P
Comparison I 0.378
Patients who used both antivirals and d-PVP-I 7 5 12
Patients who used neither antivirals nor d-PVP-I 44 54 98
Total 51 59 110
Comparison II 0.020a
Patients who used antivirals, but not d-PVP-I 7b 4c 11
c
Patients who used d-PVP-I but not antivirals 26 64b 90
Total 33 68 101
Comparison III 0.794
Patients who used both antivirals and d-PVP-I 7 5 12
Patients who used antivirals, but not d-PVP-I 7 4 11
Total 14 9 23
Comparison IV 0.041
Patients who used both antivirals and d-PVP-I 7b 5c 12
Patients who used d-PVP-I but not antivirals 26c 64b 90
Total 33 68 101
Comparison V 0.238
Patients who used antivirals, but not d-PVP-I 7 4 11
Patients who used neither antivirals nor d-PVP-I 44 54 98
Total 51 58 109
Comparison VI 0.023a
Patients who used d-PVP-I but not antivirals 26c 64b 90
b
Patients who used neither antivirals nor d-PVP-I 44 54c 98
Total 70 118 178
The number of patients and who used diluted povidone iodine (d-PVP-I), topical corticosteroids, and antivirals are given in
corresponding cells. Chi-square test was used for statistical comparison. aP<0.05 was accepted statistically significant; bValues higher
than expected cases; cValues lower than expected cases.

The diagnosis of adenoviral conjunctivitis is usually made suggested in the first week, although there is a lack in definite
on the basis of clinical symptoms and signs. Recently, rapid dose and comparative studies [2,8]. Cidofovir was reported
detection testing kits have become available, which provide to have a therapeutic effect in the treatment of AKC in 1%
results in 10min and are highly sensitive and specific [7]. dosage[9]. It was reported to lower the frequency of severe
However, they are not easily available in our country. Thus, corneal opacities, but 4 to 10 times daily at a 1% concentration
our current diagnosis still depends on clinical findings. The resulted local toxicity, such as local toxic effect on the
weakness of this study is that it was entirely dependent on conjunctiva and eyelids, development of pseudomembranes
clinical diagnosis only, and no laboratory confirmation of AKC and lacrimal duct stenosis[9]. Ganciclovir is available as a
was performed. topical antiviral, and 10.9% of our cases were given ganciclovir.
AKC usually tends to resolve in three weeks. There is still no Yet, its effect against adenovirus is not definite. Considering
accepted treatment, and current management is targeted to the SEI as a late complication, topical ganciclovir resulted
relieve patient’s discomfort and help with the complications in an increase in SEI formation (P=0.029) in our cases. This
related troubles. In present study, most of our patients were result might be ambiguous, since relatively small number of
given antibiotics (93.4%) and non-preserved artificial tears patients who used ganciclovir. Still, according to our results,
(88.2%). In AKC, artificial tears are being used to relieve it definitely did not decrease the number of cases with SEI
patient discomfort, and antibiotics are being used to prevent (Table 2). Contrary to our results, one small clinical study
bacterial superinfection, however antibiotic use in AKC is showed that ganciclovir shortened the clinical course of AKC
debatable[2]. and reduced subepithelial infiltrates[10]. Nevertheless, the
Currently, no specific antiviral therapy is available to shorten results of this study should also be confirmed in studies on
the course of the infection, or stop the viral replication. larger patient numbers.
Several virustatic agents such as cidofovir and ganciclovir are Particularly in the early phase of AKC, corticosteroids should
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Diluted povidone in adenoviral keratocojunctivitis

be withheld at the time of initiating treatment, since they microscopic evaluation of infiltrations revealed hyperreflective
might increase the replication rate, prolong viral shedding, inflammatory cells in the basal epithelium and the anterior
and increase disabling subepithelial opacities [4,11]. Thus, stroma together with subepithelial infiltrations of dendritic
many clinicians believe that steroid treatment should be cells[16]. Histopathologic evaluation of SEI have shown that
spared for complicated cases[11]. Though, in cases with severe they are composed of lymphocytes, histiocytes and fibroblasts
inflammation or vision-threatening complications, steroids accompanied by a disruption of the collagen Ia, and are thought
might be useful to relieve patient discomfort. In present study, to be the result of delayed immune response to viral antigens in
20.3% of patients received topical corticosteroids in the early the corneal stroma[17]. SEI may resolve spontaneously or with
phase, and no significant effect on SEI was observed (P=0.314). topical steroid treatment, without leaving permanent scarring.
In 2015, there was an obvious increase in the numbers of AKC In the treatment of existing corneal opacities only topical
cases. During these epidemic two out of five authors started steroids and cyclosporine A have been shown to be effective[18].
to use d-PVP-I. If started in the first 3d of symptoms, we They probably suppress the immunologic response directed
observed a more rapid recovery (personal experience). Even against viral antigens that persists in the cornea[18].
if started later than 3d, we believed that it still might have an Topical steroids are being used to decrease the corneal
effect. So, we used d-PVP-I 2% two times a day for 5d. Care opacities, as 75% of our patients with SEI. Although they may
should be taken to use only one or maximum two drops at each help in short-term, they do not have any effect on long-term
time. If more is given, the epithelial cells on the ocular surface outcome[19]. The opacities may recur following cessation, thus
might be damaged, as we observed epithelial defects in two
a subset of patients may need prolonged use of topical steroids.
cases.
It was reported that in cases who were resistant to steroid
Povidone iodine is a potent disinfectant that kills extracellular
tapering or discontinuation, cyclosporine A 0.05% seemed to
organisms. In a study comparing the effectiveness of multiple
be effective[20]. Also, Levinger et al[21] reported on 12 eyes of
antiseptics, only povidone iodine with a concentration higher
9 patients with SEI related to AKC, who were unresponsive to
than 0.5% was shown to inactivate the adenoviruses within
topical corticosteroids or developed complications to their use.
1-minute of exposure[6]. In adenoviral conjunctivitis, it has
Switching to topical 1% cyclosporine A in aqueous vehicle
been shown to reduce the viral load[12]. It is highly effective
and carboxymethyl cellulose gel drops provided improvement
against free adenovirus, but less effective against intracellular
in symptom score and visual acuity of those patients.
adenoviral particles. And, if started in the first week, it might
Topical cyclosporine was reported to reduce the formation
decrease the severity of clinical signs, and result in decrease
of subepithelial infiltrates[22-23]. In our cases with SEI, we
in complications. A study reported that conjunctival irrigation
prescribed cyclosporine A in 31% of cases. Cyclosporine eye-
with 2.5% d-PVP-I was effective in the treatment of adenoviral
drops are recommended as steroid sparing agents, but they
conjunctivitis in infants[13]. Also, in a study including 150
are not effective in acute disease symptoms, and they have no
epidemic keratoconjunctivitis cases, Hutter[5] reported better
proven effect on the course of the disease[9].
clinical results in patients treated with povidone iodine. In
In conclusion, AKC has a very contagious potential, and is
present study, 48% of our patients were given d-PVP-I 2%.
The incidence of SEI was 32% in patients, who used d-PVP-I difficult to treat. It is a very distressing disease that limits the
2%, and 46% in patients who did not. The difference was patient’s comfort and daily activities for almost two weeks.
statistically significant (P=0.032). And, almost half of these patients develop decrease in vision
A new treatment of dexamethasone and povidone iodine related to SEI. According to our results, using d-PVP-I 2%
has been proposed. Topical PI 0.4% and dexamethasone 1% in the first few days of clinically significant AKC might help
combination was shown to decrease the secretion of virus and to reduce the risk of SEI as a complication. Diluted povidone
reduce disease progression[14]. The authors believed that topical iodine should be started as soon as possible when we suspect
dexamethasone relieves the symptoms, and povidone iodine AKC. Although we couldn’t show this in present study, our
kills the virus in tears reducing risk of spread and disease personal observation is that the disease does not show the
progression. severe clinical sings if we start it in the first few days. After 3d,
These SEI lesions are believed to represent a cellular immune it does not have much effect on clinical signs, however it does
reaction against viral antigens, deposited in the corneal stroma decrease the incidence of SEI, possibly by decreasing the virus
under the Bowman’s membrane[15]. Patients may complain load. It’s possible mechanism of action is probably decreasing
of irritation, photophobia as well as decrease in vision, the virus load in the first week. Thus, we believe that it might
if the infiltrates obscure the optical axis[3]. The infiltrates be a very useful, inexpensive, and easy to access aid in the
may last from a few months to few years. In vivo confocal management of AKC.
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 Int J Ophthalmol, Vol. 12, No. 9, Sep.18, 2019 www.ijo.cn
Tel: 8629-82245172 8629-82210956 Email: [email protected]

ACKNOWLEDGEMENTS The effects of corticosteroids of adenoviral replication. Arch Ophthalmol

This paper was presented at the ASCRS 2017 Meeting in Los 1996;114(5):581-585.
Angeles, CA. The authors are responsible for this paper. All 12 Monnerat N, Bossart W, Thiel MA. Povidone-iodine for treatment
authors have read, approved the manuscript. The requirements of adenoviral conjunctivitis: an in vitro study. Klin Monbl Augenheilkd
for authorship have been met. The authors believe that the 2006;223(5):349-352.
report represents a valid work. 13 Özen Tunay Z, Ozdemir O, Petricli IS. Povidone iodine in the
Conflicts of Interest: Altan-Yaycioglu R, None; Sahinoglu- treatment of adenoviral conjunctivitis in infants. Cutan Ocul Toxicol
Keskek N, None; Canan H, None; Coban-Karatas M, None; 2015;34(1):12-15.
Ulas B, None.. 14 Pelletier JS, Stewart K, Trattler W, Ritterband DC, Braverman S,
REFERENCES Samson CM, Liang B, Capriotti JA. A combination povidone-iodine
1 Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB. Adenoviral 0.4%/dexamethasone 0.1% ophthalmic suspension in the treatment of
keratoconjunctivitis. Surv Ophthalmol 2015;60(5):435-443. adenoviral conjunctivitis. Adv Ther 2009;26(8):776-783.
2 Kaufman HE. Adenovirus advances: new diagnostic and therapeutic 15 Dosso AA, Rungger-Brändle E. Clinical course of epidemic
options. Curr Opin Ophthalmol 2011;22(4):290-293. keratoconjunctivitis: evaluation by in vivo confocal microscopy. Cornea
3 Chodosh J, Miller D, Stroop WG, Pflugfelder SC. Adenovirus epithelial 2008;27(3):263-268.
keratitis. Cornea 1995;14(2):167-174. 16 Kocabeyoğlu S, Mocan MC, İrkeç M. In vivo confocal microscopic
4 Laibson PR. Ocular adenoviral infections. Int Ophthalmol Clin findings of subepithelial infiltrates associated with epidemic
1984;24(2):49-64. keratoconjunctivitis. Tjo 2015;45(3):119-121.
5 Hutter H. Epidemic keratoconjunctivitis: treatment results during an 17 Lund OE, Stefani FH. Corneal histology after epidemic
epidemic. Klin Monbl Augenheilkd 1990;197(3):214-217. keratoconjunctivitis. Arch Ophthalmol 1978;96(11):2085-2088.
6 Kawana R, Kitamura T, Nakagomi O, Matsumoto I, Arita M, Yoshihara 18 Reinhard T, Godehardt E, Pfahl HG, Sundmacher R. Lokales
N, Yanagi K, Yamada A, Morita O, Yoshida Y, Furuya Y, Chiba S. cyclosporin A bei nummuli nach keratoconjunctivitis epidemica. Der
Inactivation of human viruses by povidone-iodine in comparison with Ophthalmol 2000;97(11):764-768.
other antiseptics. Dermatology (Basel) 1997;195(Suppl 2):29-35. 19 Laibson PR, Dhiri S, Oconer J, Ortolan G. Corneal infiltrates in
7 Sambursky R, Tauber S, Schirra F, Kozich K, Davidson R, Cohen epidemic keratoconjunctivitis. Response to double-blind corticosteroid
EJ. The RPS adeno detector for diagnosing adenoviral conjunctivitis. therapy. Arch Ophthalmol 1970;84(1):36-40.
Ophthalmology 2006;113(10):1758-1764. 20 Muftuoglu IK, Akova YA, Gungor SG. Effect of 0.05% topical
8 Kaufman HE, Haw WH. Ganciclovir ophthalmic gel 0.15%: safety and cyclosporine for the treatment of symptomatic subepithelial infiltrates due
efficacy of a new treatment for herpes simplex keratitis. Curr Eye Res to adenoviral keratoconjunctivitis. Int J Ophthalmol 2015;9(4):634-635.
2012;37(7):654-660. 21 Levinger E, Slomovic A, Sansanayudh W, Bahar I, Slomovic AR.
9 Hillenkamp J, Reinhard T, Ross RS, Böhringer D, Cartsburg O, Topical treatment with 1% cyclosporine for subepithelial infiltrates
Roggendorf M, De Clercq E, Godehardt E, Sundmacher R. The effects secondary to adenoviral keratoconjunctivitis. Cornea 2010;29(6):
of cidofovir 1% with and without cyclosporin a 1% as a topical treatment 638-640.
of acute adenoviral keratoconjunctivitis: a controlled clinical pilot study. 22 Jeng BH, Holsclaw DS. Cyclosporine A 1% eye drops for the treatment
Ophthalmology 2002;109(5):845-850. of subepithelial infiltrates after adenoviral keratoconjunctivitis. Cornea
10 Tabbara KF, Jarade EF. Ganciclovir effects in adenoviral 2011;30(9):958-961.
keratoconjunctivitis. Invest Ophthalmol Vis Sci 2001;42(4, Suppl): 23 Asena L, Şıngar Özdemir E, Burcu A, Ercan E, Çolak M, Altınörs
S579-S579. DD. Comparison of clinical outcome with different treatment regimens in
11 Romanowski EG, Roba LA, Wiley L, Araullo-Cruz T, Gordon YJ. acute adenoviral keratoconjunctivitis. Eye (Lond) 2017;31(5):781-787.

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