Epidemic keratoconjunctivitis (EKC) can present with symptoms such as chemosis, eye pain, itching, hyperemia, photophobia and swelling of eyelids that can have a negative effect on everyday life. In approximately 80% of the patients, keratitis with subepithelial infiltrations (SEI) can ensue the conjunctivitis
[3, 4]. SEI can result in a decrease of visual acuity, halo, irregular astigmatism and photophobia. Some studies report that the decrease in visual acuity caused by SEI can resolve in a matter of weeks and that it can persist for years in some cases
[1, 10]. In ocular adenovirus infections, virus static agents; such as trifluridine, vidarabine and ganciclovir; were tried but none were found to be effective in treatment
[12–14]. It is reported that long term corticosteroid use in adenovirus infections are effective but can cause cataracts, glaucoma and super infections
Our study group consisted of patients who had no regression in SEI in spite of corticosteroid use of 3–14 months (average 6.7 ± 3.9 months) and those who had to stop the corticosteroids because of intraocular pressure due to 5 long term use. There was enough intraocular pressure to cause varying visual loss in twelve eyes with values of 0.40 – 0.10 logMAR and anti glaucomatous therapy to start in 8 eyes.
It is reported that topical CsA plays a role in the inhibition of T lymphocyte proliferation and activation and suppression of the inflammation of the ocular surface lacrimal gland
. It is reported in the literature that topical CsA is effective in various concentrations in ocular inflammation cases such as vernal keratoconjunctivitis, ulcerative keratitis due to rheumatoid artritis, Thygeson superficial punctate keratitis, anterior uveitis, corneal graft rejection, superior limbic keratoconjunctivitis, greft versus host disease, micotic keratitis, Cogan syndrome, Behçet’s disease, herpetic stromal keratitis, Mooren ulcer and atopic keratoconjunctivitis
[16–30]. Topical 0.05% CsA was used in the treatment of dry eye syndrome, in minimizing the risk of recurrence after pterygium surgery, in treatment of ocular graft-versus-host disease and in the treatment of meibomian gland dysfunction successfully without any systemic or ocular side effects
[31–35]. In our study, there were improvements in the signs and symptoms caused by SEIs, that developed after EKC infections, by using topical 0.05% CsA and there were no ocular or systemic side effects observed.
In studies conducted by using topical CsA in the treatment of acute and chronic adenovirus infections, it was reported that CsA was effective in concentrations of 1% and 2% and that the SEI’s were completely obliterated or majorly reduced after a 3 to 4 week therapy
[1, 3, 8–10, 16]. After a one month topical 0.05% CsA therapy, it was observed that in 8 (36.3%) eyes SEIs were completely cleared, and in 10 eyes (45.45%) this result was achieved in the last follow up visit. In remaining 4 eyes (18.2%) they were not completely cleared but decreased in number. The treatment was discontinued in the eyes with no SEI left, and it was continued in doses of once a day or once in every other day in eyes which still had SEIs.
Jeng and colleagues have reported that a single dose per day or every other day of 1% or 0.05% topical CsA treatment following an initial therapy of topical 1% CsA and steroids for a month was effective in SEI treatment
. The average topical 0.05% CsA use of the patients was 5.1 ± 3.5 months (1–13 months), and the follow up time was 9.2 ± 4.7 months (4–22 months). The increase in the visual acuity, decrease in CSIS score and the intraocular pressure in the last follow up visit was significant. There were no patients on antiglaucomatous therapy. In the last follow up visit, 18 eyes out of 22 (81.8%) had a CSIS score of 0, and 4 (18.2%) eyes had a decrease in SEI numbers. There were 2 recurrences out of 18 eyes (11%) after the therapy was discontinued.
Reinhart and colleagues have reported that there were amelioration and decrease in SEI number in the 48 eyes out of 70 which had SEIs after EKC infection after a therapy with 2% topical CsA, and there were no recurrences after therapy was discontinued
. In the literature, it has been reported that 1% topical CsA was tolerated well and did not cause any systemic side effects in long term follow ups
[8, 9]. Romanowski and colleagues reported that in their trials 0.5% and 2% topical CsA treatments were effective in decreasing the number of SEI formations, however it was claimed that this agent could facilitate the risk of endemics by increasing viral replication
When the studies in the literature were analyzed, it was observed that topical CsA of varying concentrations between 0.5-2% were used in the inhibition of T lymphocyte proliferation and activation and in eradicating the symptoms and minimizing the recurrences of SEI in acute adenoviral infections. In chronic phases, it is reported to be an effective and safe treatment of SEIs and minimizing the recurrence risk. However, there were no detailed studies concerning the corneal subepithelial infiltration therapy with lesser concentrations of topical 0.05% CsA.
In this study, we had two recurrent cases (11.12%) who were treated with topical CsA for 4 and 8 months. While the average treatment time for all eyes was 5.1 ± 3.5 months. After 9.2 ± 4.7 months (4 – 22 months) of treatment, only 2 eyes (recurrence in two eyes was seen in 3rd month) out of 18 were detected as recurrent. In 16 of the 18 eyes, which were free of subepithelial infiltrates, had no recurrences. As for our experience, treatment of SEI by using CsA should be continued until the CSIS is seen as 0. However, whether SEI will recur after treatment or when will it recur cannot be foreseen. Therefore, follow up visit duration should be as longer as possible. Further studies regarding the ideal follow up visit duration after treatment with CsA is warranted. The small number of the patients, the absence of control group, and the retrospective design of the study seems to be the limitations of this study. For treatment of SEI development after EKC, two different treatment methods are used which were proven to be efficient are topical korticosteroid and topical CsA. Because the patient group was consisted of patients who did not benefit from at least 3 months of treatment with topical corticosteroids or who develop steroid-related side effects; current treatment could not be continued. Because the clinical symptoms of patients affect their daily life, control group who will be treated with placebo could not be constructed. However, the difficulty of building control group for the cases with subepithelial infiltrates who do not exert improvement in symptoms and findings after 3-month treatment with corticosteroids should be taken into consideration. On the other hand, clinician must choose and apply the most reliable treatment strategy which resolve patient complaints and improves clinical findings for SEI. Since our data were acquired without a control group, we cannot resolve the possibility of spontaneous remission of SEI as the natural history of the disease in this study.
A masked controlled study of topical 0.05% CsA in human subjects with larger patient populations could better define the natural history and effect of treatment of this disorder. As an alternative approach, different concentrations of CsA can be compared using different treatment groups for prospective studies.