Akova, Yonca A.

Gungor, Sire G.

Muftuoglu, Ilkay Kilic

International Journal of Ophthalmology

English

Baskent Universtiy

Effect of 0.05% topical cyclosporine for the treatment of
symptomatic subepithelial infiltrates due to adenoviral
keratoconjunctivitis
窑Letter to the Editor窑
1Department of Ophthalmology, Istanbul Training and
Research Hospital, Istanbul 34098, Turkey
2Department of Ophthalmology, Bayindir Kavaklidere
Hospital, Ankara 06490, Turkey
3Department of Ophthalmology, Ba鬤kent University, Ankara
06490, Turkey
Correspondence to: Yonca A. Akova. Department of
Ophthalmology, Bayindir Kavaklidere Hospital, Ataturk
Bulvari No: 201 06250 Kavaklidere, Ankara 06490, Turkey.
yoncaakova@yahoo.com
Received: 2014-07-29 Accepted: 2015-07-07
DOI:10.18240/ijo.2016.04.26
Muftuoglu IK, Akova YA, Gungor SG. Effect of 0.05% topical
cyclosporine for the treatment of symptomatic subepithelial
infiltrates due to adenoviral keratoconjunctivitis
2015;9(4):634-635
Dear Sir,
I am Yonca A. Akova, MD-from the Department ofOphthalmology, Bayindir Kavaklidere Hospital, Turkey. I
wrote this letter to evaluate the efficacy of 0.05% topical
cyclosporine A (CsA) eye drops (Restasis Allergan, Irvine,
USA) in symptomatic patients with recurrent subepithelial
infiltrates (SEIs) due to adenoviral keratoconjunctivitis
following steroid eye drops tapering or discontinuation.
During the natural course of epidemic keratoconjunctivitis,
some patients develop SEIs and those may persist for several
months to years and cause visual impairment, halos and glare
in a subset of patients [1]. Histopathologic studies suggest that
SEIs are composed of lymphocytes, histiocytes and
fibroblasts and are thought to occur as a result of delayed
immune response to viral antigens in the corneal stroma [2].
This hypothesis is supported by good response to topical
steroid therapy, however undesirable complications like
cataract, glaucoma and microbial superinfections may occur
with prolonged use of topical steroids and also relapse may
occur after tapering or discontinuation of steroids[1]. Recently,
few reports that have shown the efficacy of topical CsA in
various concentrations on SEIs have been published[3-7].
Eighteen eyes of 13 patients who used topical steroid eye
drops for SEIs after epidemic keratoconjunctivitis and
became symptomatic after steroid eye drops tapering or
discontinuation were included in this study. None of the
patients received topical steroids in the acute stage of
conjunctivitis; they were only given to patients with
symptomatic SEIs in the chronic phase the disease. We
administered topical 0.05% CsA eye drops 4 times a day in
addition to loteprednol etobonate (LE) 3 times a day (3wk)
and LE was tapered weekly and therapy was continued with
topical 0.05% CsA for 6mo. Restasis therapy was
discontinued if the patients were asymptomatic. If symptoms
were markedly increased after discontinuation, the therapy
was extended to 12mo. For subjective evaluation, patients'
symptoms were graded by using a symptom questionnaire
with a score varying between 0-3 (0: none; 1: mild, 2:
moderate; 3: severe). The images of SEIs before treatment
and after 3mo of therapy were analyzed with an image
analysis and processing software program called ImageJ
(1.44p, Wayne Rasband, National Institutes of Health,
Bethesda, MD, USA). The number of SEI was counted and
the area of SEI was measured in terms of pixels and its ratio
to the entire corneal area was determined as the percentage.
Figure 1A and 1B show the anterior segment photograph and
image of SEIs in a patient.
Wilcoxon signed-rank test was used to compare the pre- and
post-treatment data. value of <0.05 was considered
statistically significant.
There were 9 females (69.2%) and 4 males (30.8%) with a
mean age of 34.2依17.6y (range 17-57y). The mean duration
of follow up was 17.8依8.6mo (range 14-23mo). The degree
of symptoms after treatment was significantly reduced ( <
0.05 for all symptoms). The severity of discomfort was scored
as moderate in 1 of 13 patients and mild in 2 (15.38% )
following the treatment. Ten patients (76.9% ) reported
having no discomfort. One patient (7.7%) noticed mild halo/
glare sensation while none had photophobia at the end of
treatment period. The score of subjective evaluation of visual
improvement was statistically significant after treatment ( <
0.05). The mean BCVA was 0.17依0.20 (logMAR) at first
month and 0.12依0.29 (logMAR), at 6mo ( <0.05). Seventeen
of 18 eyes (94.4% ) gained two or more lines of Snellen
BCVA after treatment, in 1 eye (5.6%) BCVA increased only
one line. Three eyes (16.7%) had an attack presenting with
severe redness, discomfort, tearing and visual disturbance
while receiving topical 0.05% CsA, and all of the symptoms
disappeared with LE administration for 2wk. After cessation
Topical cyclosporine for subepithelial infiltrates
634
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of the topical 0.05% CsA treatment, 2 of 18 eyes (11.1%)
showed recurrence at seven and eight months, respectively.
Topical 0.05% CsA therapy was restarted and extended to 1y
in those eyes. The number of SEIs and percentage of SEIs
area were decreased from 13.45依3.28 to 3.25依2.14 ( <0.05)
and 17.76依12.45% to 5.36依2.35% ( <0.05) respectively.
In our study, symptoms in patients with SEIs including
discomfort, halo/glare and photophobia significantly
decreased with topical 0.05% CsA therapy. These symptoms
were scored as mild or none by 76.9%, 100%, and 100% of
patients following treatment, respectively. In addition to
symptomatic relief, the number of SEIs and percentage of
SEIs area decreased in the ratio of 76.9% and 69.7% ,
respectively. These results suggested that the commercially
available form of topical 0.05% CsA treatment was effective
and well tolerated in eyes with symptomatic and steroid
dependent.
SEIs may resolve spontaneously or with topical steroid
therapy without leaving permanent subepithelial scarring in
the cornea, but similar to our patients, subset of patients may
need to have topical steroids however, prolonged use of steroids
may cause serious complications such as steroid-induced
glaucoma, cataract formation and secondary infections[1,3].
Recently, the efficacy of topical CsA in different
concentrations for the treatment of SEIs has been reported in
a number of studies[3,5-7]. The largest series of patients received
topical CsA for the treatment of SEIs was reported by a
German group[6]. They treated 70 eyes of 48 patients with 2%
CsA four times a day at the beginning and reduced the
frequency of 2% CsA depending on resolution of the SEIs.
Forty eyes responded well, 16 eyes showed no change and
the therapy was stopped in 4 eyes because of severe
intolerance to 2% CsA therapy. Complete cure was achieved
without recurrence in 10 eyes. Levinger [7] treated 9
steroid resistant or steroid responder patients with 1% CsA
eye drops twice daily. Sixty-six percent of patients showed
clinical improvement, while thirty-four percent remained
stable [7]. To the best of our knowledge, there has been only
one report regarding the efficacy of commercially available
topical CsA 0.05%, which is a lower concentration than the
preparations previously used for this indication in the
literature[5]. This group used topical 0.05% CsA in 16 patients
(22 eyes) with SEIs who had been previously treated with
topical steroids without any improvement or had to stop
topical steroids secondary to intraocular pressure elevation.
0.05% CsA was administered four times for the first 15d, and
then 2 times a day for next 15d. Eighteen eyes (81.9% )
showed clinical improvement while SEIs did not completely
disappear in 4 eyes [5]. Although we found similar results
compare to those of eyes, we evaluated the number and the
percentage of SIEs using an image analysis program to have
objective results, whereas they made corneal subepithelial
scoring according to the number of SEI seen in
biomicroscopic examinations.
There were some limitations of our study. The evidence of
efficacy of topical 0.05% CsA was not based on a controlled
trial and the number of patients was small. Prospective,
double-masked, placebo controlled further studies are needed
to show the efficacy of topical CsA in different
concentrations. Also we could not clearly state that the initial
improvement in symptoms was only due to topical 0.05%
CsA treatment, it could be due to either LE or topical 0.05%
CsA. However we thought that the anti-inflammatory effect
of topical 0.05% CsA might reduce the need for topical
steroids and made contributions to the symptomatic relief of
patients during the follow-up without having the risk of
steroid treatment side effects.
In conclusion, our study found that topical 0.05% CsA
seemed to be safe and effective in patients with symptomatic
SEI who were resistant to steroid eye drops tapering or
discontinuation. It should be kept in mind that in some cases,
the duration of topical 0.05% CsA therapy may need to be
extended.
ACKNOWLEDGEMENTS
Conflicts of Interest: Muftuoglu IK, None; Akova YA,
None; Gungor SG, None.
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2 Lund OE, Stefani FH. Corneal histology after epidemic
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3 Hillenkamp J, Reinhard T, Ross RS, Bohringer D, Cartsburg O,
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controlled clinical pilot study. 2001;119 (10):1487-1491.
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5 Cetinkaya A, Akova YA, Dursun D, Pelit A. Topical cyclosporine in the
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6 Reinhart T, Godehardt E, Phahl HG, Sundmacher R. Local cyclosporin A
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2000;97(11):764-768.
7 Levinger E, Slomovic A, Sansanayudh W, Bahar I, Slomovic AR. Topical
treatment with 1% cyclosporine for subepithelial infiltrates secondary to
adenoviral keratoconjunctivitis. 2010;29(6):638-640.
Figure 1 Images of a patients with subepithelial infilatrates A:
Anterior segment photography of a patient showing subepithelial
infiltrates around the pupil border taken by a digital camera; B:
Analysis of the subepithelial infiltrates by a software in the same
eye.
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Effect of 0.05% topical cyclosporine for the treatment of symptomatic subepithelial infiltrates due to adenoviral keratoconjunctivitis

http://acikerisim.baskent.edu.tr/xmlui/bitstream/11727/3910/1/ijo-09-04-634.pdf

Effect of 0.05% topical cyclosporine for the treatment of symptomatic subepithelial infiltrates due to adenoviral keratoconjunctivitis

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