ARTICLE

Topical Cyclosporine A 1% for the Treatment of Chronic Ocular Surface Inflammation Ashwinee Ragam,

M.D.,

Anton M. Kolomeyer, M.D., Ph.D., Jason S. Kim, Natasha V. Nayak, Christina Fang, B.S., Eliott Kim, and David S. Chu, M.D.

Objective: To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI). Methods: We conducted a retrospective chart review of patients with various forms of OSI treated with topical CsA 1% from 2001 to 2012. Results: Twenty-nine patients (52 eyes) with various forms of OSI, including epidemic keratoconjunctivitis (n=14), chronic follicular conjunctivitis (n=12), Thygeson superficial punctate keratopathy (n=2), and vernal keratoconjunctivitis (n=1), were included. Twenty-seven patients had inflammation refractory to prior therapies. Twenty-four patients received concurrent medications with CsA 1%. Twenty-three of 24 patients on concurrent corticosteroids (CS) were able to taper their use while receiving CsA 1%. Thirteen patients experienced ocular discomfort with CsA 1%; one patient discontinued therapy all together as a result of these side effects; another switched to CsA 0.5% with improvement of adverse symptoms. Inflammation was controlled in 22 (92%) of the 24 patients who received CsA 1% for at least 2 months in duration. Conclusion: Topical CsA 1% helps to control inflammation and spares CS use in patients with chronic OSI. Key Words: Topical cyclosporine A—Chronic inflammation— Keratoconjunctivitis—CsA 1%. (Eye & Contact Lens 2014;40: 283–288)

C

ommon causes of chronic ocular surface inflammation (OSI) include dry eye and meibomian gland dysfunction, atopy, and infection. Clinically, the resulting conditions present with redness, tearing, itching, burning, photophobia, and foreign body sensation. Examination under slitlamp may reveal conjunctivitis (papillary or follicular), keratitis, lid edema, chemosis, ocular discharge, and on rare occasion, conjunctival membrane or pseudomembrane.1 Complications of chronic inflammation of the ocular surface are numerous and may include scarring, ulcers, and temporary or permanent vision loss. The first-line treatment of many types of OSI, such as atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), From the Institute of Ophthalmology and Visual Science (A.R., A.M.K., J.S.K., N.V.N., C.F., E.K., D.S.C.), Rutgers New Jersey Medical School, Newark, NJ; and Metropolitan Eye Research and Surgery Institute (D.S.C.), Palisades Park, NJ. Supported by the Lions Eye Research Association New Jersey, Clark, NJ. The authors have no funding or conflicts of interest to disclose. Address correspondence to David S. Chu, M.D., Metropolitan Eye Research and Surgery Institute, 540 Bergen Boulevard, Suite D, Palisades Park, NJ 07650; e-mail: [email protected] Accepted May 21, 2014. DOI: 10.1097/ICL.0000000000000055

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M.D.,

and epidemic keratoconjunctivitis (EKC), is topical corticosteroids (CS). Nonsteroidal anti-inflammatory drugs, mast cell stabilizers, and antihistamines may also be used as supplemental therapy. However, many cases remain refractory and may develop CS-associated side effects, such as cataract formation and ocular hypertension or glaucoma, as a result of chronic dependence.2,3 In such instances, alternative forms of topical anti-inflammatory agents may be required. Cyclosporine A (CsA) is a cyclic peptide metabolite produced by several aerobic fungi, first extracted from Tolypocladium inflatum in submerged fermentations. It was originally shown to function as a weak antifungal antibiotic.4 More notably, however, it has been used over the years as an immunomodulator, mainly in the prevention of transplanted solid organ rejection. It functions by inhibiting calcineurin, which in turn is responsible for activating the transcription of interleukin-2 in CD4+ helper T cells (Th1 cells). Consequently, CsA effectively reduces antigen sensitization and lymphocyte proliferation involved in chronic inflammation of many tissues, including the ocular surface.5–8 Systemic CsA has been beneficial in treating various autoimmune diseases, including those with ocular manifestations.9–11 Topical CsA has been shown to safely and effectively treat many forms of ocular inflammation, such as AKC, VKC, dry eye syndrome (DES), Thygeson superficial punctate keratopathy (TSPK), posterior blepharitis, ocular rosacea, acute corneal graft rejection, and conjunctival graft-versus-host disease.2,12 Ophthalmic emulsions of CsA are prepared in several different vehicles with concentrations ranging from 0.05% to 2.0%. Prior investigators have typically focused on the use of CsA 0.05%13–17 and CsA 2%18,19 for chronic OSI. The few studies evaluating CsA 1% showed that it is safe and effective in treating EKC,20,21 VKC,22 and DES23; however, while the study on VKC was very large (128 subjects), the other studies only included 7 to 9 subjects each. The purpose of this retrospective study was to describe the use of topical CsA 1% in a diverse sample of patients with a variety of chronic ocular surface inflammatory diseases that have failed prior treatment and/or became CS dependent. We set out to determine whether topical CsA 1% can be used in a broad approach to control refractory cases of OSI and spare concurrent CS use.

MATERIALS AND METHODS Institutional Review Board of the Rutgers Biomedical and Health Sciences (formerly, the University of Medicine and Dentistry of New Jersey) approved this study. We obtained a list from Leiter’s Pharmacy (San Jose, CA) containing the names of all 283

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A. Ragam et al. TABLE 1.

Patient Data and Clinical Outcomes of Topical CsA 1% Use in Chronic Ocular Surface Inflammationa

Age/Gender/Ethnicity

Type(s) of OSI

Other Ocular Condition(s)

Autoimmune Condition(s)

Prior Treatment of OSI

63/F/C 53/F/C 56/F/C 54/F/C 52/M/AA 13/M/C 52/F/C 56/F/AA 32/F/H 45/M/C 40/F/H 11/M/A 45/M/C 61/M/C 50/M/H 43/F/C 47/F/C 49/M/C 70/M/C 71/F/C 13/M/C 47/M/C 58/M/H 43/F/C 70/M/C 64/M/C 30/F/H 66/F/H 45/M/C

CFC CFC, AKC CFC, AKC EKC EKC TSPK CFC EKC EKC EKC CFC, VKC VKC EKC EKC EKC EKC CFC, AKC CFC CFC CFC CFC EKC EKC CFC EKC EKC TSPK EKC CFC, AKC

— — — — Uveitis — — — — — — — — — — — OCP Episcleritis, iritis, OCP — — — — — — — — — Iritis —

Sarcoidosis — — — — — — — — — — — — Graves disease — — Hashimoto thyroiditis, Sjo¨gren syndrome JRA Celiac disease — — — — — — — — — —

Tobradex, Zylet Tobradex, PF FML, Lotemax, Tobradex Restasis, PF, Voltaren Durezol, Nevanac PF Lotemax, Zylet, Tobradex FML, Restasis, PF Durezol Prednisone, Lotemax, Besivance Tobradex, cromolyn, Bepreve, Alrex Zylet FML PF Prednisone PF, Restasis PF, Tobradex Bromday, Lotemax

Case

Eye(s)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

OD OU OU OU OD OU OU OU OS OS OU OU OU OU OU OU OU OU OU OU OD OU OU OU OU OU OU OU OS

Case

Duration of CsA 1% Use, mo

Duration of Inflammation Control, mo

Concurrent Therapies

CS Sparing, %

Comments

1 2 3

7.0 4.4 10.8

6.3 Never 7.7

Tobradex Tobradex, PF, prednisone FML, Acular

100 100 100

4 5 6 7 8 9 10

9.0 0 16.5 0 13.8 3.2 2.0 7.0 Never 0 7.6 2.0 2.4 6.1 12.5 4.7 7.3 2.2 2.0 6.8 13.8 5.2 4.5 18.1 10.7 21.0 2.1 Never Never

PF None PF Tobradex FML Durezol None

25 N/A 100 100 100 100 N/A

Tobradex, cromolyn Zylet None PF

100 100 N/A 100

Did not achieve inflammation control and was lost to follow-up Had inflammation quiescence with CsA 1% at the final visit — —

PF None PF, FML Lotemax, Tobradex Tobradex Tobradex Pataday, Tobradex None Lotemax, PF, Durezol PF PF PF, Durezol

100 N/A 100 100 100 100 100 N/A 100 100 100 100

27 28

14.6 1.2 19.6 1.4 15 5.6 5.0 9.1 5.8 1.6 8.3 10.9 5.9 7.2 19.7 6.2 8.2 2.3 2.9 7.8 16.6 6.6 5.1 19.1 12.1 25.2 3.6 1.5 1.0

— Did not achieve inflammation control and switched to oral CsA 100 mg twice per day Had an inflammation flare at the final visit despite continued CsA 1% use, then was lost to follow-up — Had inflammation quiescence with CsA 1% at the final visit — Had inflammation quiescence with CsA 1% at the final visit — Switched to CsA 2% because of worsening clinical findings —

FML Alrex

50 0

29

7.9

6.8

Tobradex

100

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

Tobradex Pataday, Restasis, Tobradex Doxycycline, Lotemax, Restasis, PF Restasis PF, FML, Durezol Lotemax, PF PF, FML, Durezol Durezol Alrex, PF, Lotemax Tobradex, Pataday, Zylet

— — — — — — — — — — — —

Discontinued CsA 1% because of burning sensation, then was lost to follow-up Switched to CsA 0.5% because of burning sensation with CsA 1% use; she then achieved inflammation control for 8.0 mo —

OD, right eye; OS, left eye; OU, both eyes; F, female; M, male; C, Caucasian; AA, African American; H, Hispanic; A, Asian; OSI, ocular surface inflammation; CFC, chronic follicular conjunctivitis; AKC, atopic keratoconjunctivitis; EKC, epidemic keratoconjunctivitis; VKC, vernal keratoconjunctivitis; TSPK, Thygeson superficial punctate keratopathy; OCP, ocular cicatricial pemphigoid; JRA, juvenile rheumatoid arthritis; CsA, topical cyclosporine A; CS, corticosteroid; PF, Pred Forte; FML, fluoromethalone. a Tobradex, tobramycin 0.3% and dexamethasone 0.1% ophthalmic suspension (Alcon, Fort Worth, TX). Zylet, loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension (Bausch & Lomb, Inc, Rochester, NY). Fluoromethalone ophthalmic suspension 0.1% (Allergan, Inc). Lotemax, loteprednol etabonate ophthalmic suspension 0.5% (Bausch & Lomb, Inc). Restasis, cyclosporine ophthalmic emulsion 0.05% (Allergan, Inc). Pred Forte, prednisolone acetate ophthalmic suspension 1.0% (Allergan, Inc). Voltaren, diclofenac sodium (Novartis, Basel, Switzerland). Durezol, difluprednate ophthalmic emulsion 0.05% (Alcon). Nevanac, nepafenac ophthalmic suspension 0.1% (Alcon). Besivance, besifloxacin ophthalmic suspension 0.6% (Bausch & Lomb, Inc). Bepreve, bepotastine besilate ophthalmic solution 1.5% (Bausch + Lomb Inc). Bromday, bromfenac ophthalmic solution 0.09% (Bausch + Lomb Inc). Alrex, loteprednol etabonate ophthalmic suspension 0.2% (Bausch + Lomb Inc). Pataday, olopatadine hydrochloride ophthalmic solution 2.0% (Alcon). Acular, ketorolac tromethamine ophthalmic solution 0.4% (Allergan Inc).

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Topical Cyclosporine A 1%

FIG. 1. Patient outcomes of CsA 1% use for chronic OSI. OSI, ocular surface inflammation; CsA, topical cyclosporine A ophthalmic emulsion; OU, both eyes.

patients referred from our attending physician (D.S.C.) between August 2001 and November 2012. Using this list, we then identified patients receiving topical CsA 1% (which is compounded in a carboxymethylcellulose vehicle); their charts were subsequently located at our institutions. All available charts were reviewed between July 2012 and June 2013, and only patients who used topical compounded CsA 1% for at least 1 month were included. At the time of initiating CsA 1%, all patients had active OSI. Twenty-nine patients were included in our study. A database was created listing: gender; age at the initiation of CsA 1%; affected eye (s); cause, age at diagnosis, and prior treatments for chronic OSI; and associated autoimmune conditions. Inflammation grade and visual acuity at the initiation of therapy and at the final examination were documented. Additional measures included dosing of other medications (topical and/or systemic) used concurrently with topical CsA 1% for the treatment of chronic OSI. Because of the possibility of slow CsA onset of action and based on the clinical judgment, select patients were concurrently started on faster-acting therapies (i.e., CS) with the goal of gradually tapering them once CsA took effect. Adverse effects, concomitant ocular conditions, and changes in CsA concentration, if applicable, were also recorded. Minimum and maximum number of drops of CsA 1% per eye, per day, was © 2014 Contact Lens Association of Ophthalmologists

recorded for each patient over their duration of treatment; if drops were taken every other day, a value of 0.5 drops per day was given. The cause of chronic OSI was assigned based on clinical characteristics, findings on examination, serologic assessment, and biopsy (where applicable). Several patients included in this study had additional diagnoses of noninfectious ocular inflammation, including uveitis, iritis, episcleritis, and ocular cicatricial pemphigoid. Inflammation grading based on the degree of bulbar conjunctival injection ranged from 0 to 4, and it was determined by a single physician (D.S.C.) at every visit. Trace inflammation was given a grade of 0.5. This grading scheme is similar to the one proposed by Sen et al.24 for scleritis. Control of inflammation was defined as either trace or lack of OSI on slitlamp examination for at least 2 months of duration. Patients were considered to have failed topical CsA 1% if they never attained trace or less inflammation at any point during the treatment period or had side effects warranting discontinuation of CsA 1%. Snellen visual acuity was converted into values of logarithm of the minimum angle of resolution (logMAR) and is reported as such in the article. Several patients had more than one course of CsA 1% therapy. This occurred when patients clinically improved while on CsA 1%, 285

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Eye & Contact Lens  Volume 40, Number 5, September 2014

A. Ragam et al. which was subsequently tapered and discontinued, but had recurrence of inflammation warranting CsA reinitiation. These subsequent courses of CsA 1% were considered separate when evaluating changes in inflammation grading and visual acuity but were combined when discussing total duration of CsA 1% therapy. Paired t tests were performed using JMP version 9 statistical software (SAS, Cary, NC). Statistical significance was accepted at P,0.05.

RESULTS Twenty-nine patients (52 eyes) were included in the study. There were 15 men (52%) and 14 women (49%). Twenty patients (69%) were Caucasian, 6 (21%) Hispanic, 2 (7%) African American, and 1 (3%) Asian. The mean6standard deviation (SD) age at the start of treatment with topical CsA 1% was 48.2616.1 years (range, 11– 71 years). The mean6SD duration of follow-up at our institutions before starting CsA 1% was 16.4616.3 months (range, 1.6–72.7 months). The mean6SD duration of CsA 1% therapy was 8.566.2 months (range, 1.0–25.2 months). Over this duration, the mean6SD minimum number of drops of CsA 1% per eye per day in our patients was 2.261.4 (range, 0.5–4), whereas the mean6SD maximum number of drops was 3.361.0 (range, 1–4). The diagnoses of chronic OSI included in this study are listed in Table 1. Twelve patients (41%) had chronic follicular conjunctivitis (CFC), 4 with associated AKC, and 1 with associated VKC. Fourteen patients (48%) had EKC; 2 (7%) patients had TSPK, and 1 (3%) patient had VKC alone. Five patients (17%) had systemic autoimmune diseases (Table 1). Twenty-seven (93%) of our patients had been treated with an average of more than 2 forms of therapy before starting CsA 1%. Six (23%) of these patients failed to achieve inflammation control with CsA 0.05% (Restasis; Allergan, Inc, Irvine, CA) (Table 1). All 52 eyes in this study had active OSI at the initiation of topical CsA 1% therapy. Outcomes of all of the patients are outlined in Figure 1. The mean6SD initial inflammation grade of 1.7460.85 (range, 0.5–4) was significantly (P,0.001) reduced to a mean6SD final inflammation grade of 0.2860.63 (range, 0–3) with CsA 1% use. The mean6SD initial visual acuity in logMAR of 0.1360.12 (range, 0–0.54) was significantly (P=0.006) reduced to a mean6SD final logMAR of 0.0860.12 (range, 20.1 to 20.4). Inflammation control, which was defined as trace or less inflammation for at least 2 months of duration without adverse effects warranting CsA 1% discontinuation, was achieved in 22 (92%) of 24 patients after a mean6SD duration of 2.462.1 months (range, 0.2–8.9 months). Of note, all 6 patients who failed prior therapy with topical CsA 0.05% gained control of inflammation with CsA 1% after a mean6SD duration of 1.861.8 months (range, 0.6–5.6 months). Five patients (nine eyes) were not treated with CsA 1% for at least 2 months, and thus they were excluded from the above calculation of inflammation control. Three of these patients (patients 5, 7, and 12), however, had inflammation quiescence with continued CsA 1% use at the final examination. The remaining two patients (patients 27 and 28) had adverse effects warranting discontinuation of CsA 1%, as will be discussed below. Three patients with EKC (patients 10, 14, and 26) discontinued CsA 1% after achieving inflammation control but subsequently 286

experienced flare-ups, warranting restarting treatment. All three patients achieved inflammation control with every course of CsA 1%. For 1 patient with EKC (patient 9), CsA concentration was increased to 2% after 3.2 months of inflammation control with CsA 1% because of worsening clinical findings on examination. The quantity of subepithelial infiltrates decreased 0.9 months after switching to CsA 2%. No side effects were reported by the patient while on the higher concentration regimen. Eight eyes of four patients never achieved trace or less inflammation with CsA 1% use. As previously mentioned, patients 27 and 28 discontinued CsA 1% before inflammation control could be achieved as a result of burning sensations. Patient 2 had CFC associated with AKC and was treated with CsA 1% for 4.4 months with no resolution of inflammation from 3+ bilaterally. She was eventually switched to oral CsA 100 mg twice daily and achieved control of inflammation in 1.4 months. Patient 11, who had CFC associated with VKC, was only able to reduce inflammation from 3+ to 1+ bilaterally after 5.8 months of treatment and was lost to follow-up after that point. Thirteen patients (45%) experienced ocular discomfort (including burning, irritation, itching, redness, tearing, and pain) while receiving topical CsA 1%. As these data were collected retrospectively, however, it is difficult to ascertain whether these symptoms were directly related to CsA use, underlying OSI, or a combination of both. For 2 patients (7%) (patients 27 and 28), such symptoms were severe enough to warrant discontinuation of CsA 1% (Table 1). Twenty-four patients (83%) received additional therapies along with topical CsA 1% for the initial management of their chronic OSI (Table 1). Twenty-two (92%) of these patients were only on concurrent topical treatment, whereas two patients (8%) were on topical and systemic treatment. Twenty-three (96%) of 24 patients receiving concurrent CS (whether topical and/or systemic) were able to lower their dose, in milligrams per day or per week, by an average of 94.8% after a mean6SD duration of 2.261.9 months (range, 0.3–7.3 months). Twenty-one patients (88%) were able to discontinue the use of steroids altogether while receiving topical CsA 1% (Table 1). Twenty-five (86%) of the 29 patients were still receiving topical CsA 1% at the final follow-up. As previously mentioned, 1 patient switched to CsA 2%, 1 switched to CsA 0.5%, and 1 switched to oral CsA. Patient 27 discontinued CsA 1% and did not switch to an alternative therapy before being lost to follow-up. At the final examination, 23 (92%) of the 25 patients receiving CsA 1% had trace or less inflammation.

DISCUSSION In cases of OSI that fail to attain good inflammatory control with CS therapy, additional immunosuppression may be considered. Cyclosporine A is an immunomodulator that can be administered topically at various concentrations. There are a few studies published on the use of CsA 1% for chronic OSI. Levinger et al.20 examined the effect of CsA 1% on 9 patients (12 eyes) with EKC in a retrospective study. Six patients showed clinical improvement after initiating CsA 1%, and three remained stable. Only 2 patients (25%) reported mild side effects (as graded on a questionnaire), which included stinging on instillation and blurry vision. Jeng and Holsclaw21 retrospectively reviewed the use of CsA 1% in 7 patients (12 eyes) with steroiddependent EKC. All of their patients tolerated CsA 1% well and Eye & Contact Lens  Volume 40, Number 5, September 2014

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Eye & Contact Lens  Volume 40, Number 5, September 2014 were able to taper concurrent steroid use while receiving CsA 1%. Laibovitz et al.23 conducted a randomized, double-masked crossover study of CsA 1% use versus placebo in patients with chronic DES; although only eight patients continued the study, the agent seemed to benefit patients and only minimal, self-limited adverse reactions were reported. Pucci et al.22 published a large prospective study of CsA 1% and 2% in the treatment of VKC in children, showing that those 128 patients who received CsA 1% achieved safe and effective inflammation control. Our study retrospectively examined a relatively large sample size (52 eyes of 29 patients) treated with CsA 1% for various causes of chronic OSI. Overall, our results demonstrated a 92% success rate of inflammation control in patients receiving CsA 1% for at least 2 months of duration. Ninety-six percent of our patients on concurrent CS (topical or systemic) were able to taper their dose while on CsA 1%, with 88% being able to discontinue CS all together. There was a statistically significant improvement in the mean visual acuity after treatment with CsA 1%. Our study shows similarly favorable results of using topical CsA 1% in treating chronic OSI as the aforementioned studies. Although some patients in our study remained on treatment despite long durations of inflammation quiescence, other patients stopped CsA 1% use. We found three patients with EKC who, after stopping CsA 1%, experienced flare-ups in inflammation requiring reinitiation of CsA therapy; they all subsequently regained inflammation control. Therefore, CsA 1% may not be the optimal agent or concentration for long-term control of EKC. Further studies with larger sample sizes on CsA 1% for the management of chronic EKC may be warranted. Although CsA 0.05% ophthalmic emulsion, which is compounded in a lipid-based vehicle, is commercially available as Restasis, this concentration may not prove beneficial in treating more severe and/or steroid-dependent forms of OSI.25 In our study, 6 patients (23%) failed inflammation control with CsA 0.05%; all of these patients subsequently, and quickly (within 1.8 months), gained control of inflammation while on CsA 1%, which is compounded in carboxymethylcellulose, an aqueous vehicle. Therefore, resilient cases of OSI may benefit from topical CsA 1%, a 20-fold higher concentration of immunosuppression compared with Restasis. Studies have demonstrated that plasma levels of CsA eyedrops are minimal,26,27 and so the side effects associated with systemic CsA (bone marrow suppression, hepatotoxicity, nephrotoxicity, and increased susceptibility to infection11) are not anticipated. Clinical trials on topical CsA solutions ranging from 0.05% to 2.0% have shown them to be safe and free of serious adverse effects28; known mild reactions include burning, stinging, discharge, redness, pain, and visual blurring.29 In our study, 13 patients (45%) experienced some form of ocular discomfort with the use of topical CsA 1%, consisting of burning, irritation, itching, redness, tearing, and pain. However, these side effects were mostly self-limited; in only 2 patients (7%), were they severe enough to warrant reduction in the dose or treatment discontinuation. It appears that the side effect profile in our study mirrors that of prior studies and further underlines the successful clinical applicability of this therapy. No patients in our study developed or experienced worsening of cataracts or glaucoma during the follow-up period while on CsA 1%. These findings are consistent with those previously published, which did not find that topical CsA use resulted in cataractous © 2014 Contact Lens Association of Ophthalmologists

Topical Cyclosporine A 1% changes or development/worsening of glaucoma, making this therapy a potentially safer alternative to topical CS. The results of this study must be interpreted with caution. Because of its retrospective nature, all information obtained during the analysis was not applied to the patients as they were being treated. Our sample size is still considered small, making statistical analysis less effective. Most patients were receiving more than one form of therapy, making it difficult to parse out the true ability of CsA 1% in reducing and stabilizing OSI. It is also important to recognize that our 92% success rate only includes patients treated with CsA 1% for at least 2 months; 5 patients (9 eyes) had to be excluded from this calculation because they had less than 2 months of CsA 1% use. Further follow-up for these patients would be necessary to determine potential success with CsA 1%. Finally, our study may have been affected by selection bias because our institution is a tertiary referral center, and some of these patients may have already been worked up, diagnosed, and treated by other ophthalmologists using more conventional means. In our opinion, future studies directed at eliminating many of the above-mentioned limitations and seeking to answer some of the above-raised questions are warranted. In summary, topical CsA 1% provided significant relief of ocular symptoms in the majority of our patients with chronic OSI, many of who had failed prior forms of therapy, including CS. Our patient population was heterogenous in the cause of ocular surface disease, presence or absence of systemic autoimmune conditions, and severity of inflammation before starting CsA 1%. Their high rate of success with CsA 1%, however, may indicate that this therapy can be used broadly in managing OSI. Although some patients experienced mild side effects, most were selflimited, echoing the notion from other studies that topical CsA 1% has a commendable safety profile. Topical CsA use does not share the sight-threatening complications of topical CS use, such as cataract formation, glaucoma, or increased risk of infection. The CS-sparing properties of CsA also make it desirable in cases of CS-dependent OSI. REFERENCES 1. Ford E, Nelson KE, Warren D. Epidemiology of epidemic keratoconjunctivitis. Epidemiol Rev 1987;9:244–261. 2. Utine CA, Stern M, Akpek EK. Clinical review: Topical ophthalmic use of cyclosporin A. Ocul Immunol Inflamm 2010;18:352–361. 3. Meyer-Rüsenberg B, Loderstädt U, Richard G, et al. Epidemic keratoconjunctivitis: The current situation and recommendations for prevention and treatment. Dtsch Arztebl Int 2011;108:475–480. 4. Agathos SN, Marshall JW, Moraiti C, et al. Physiologic and genetic factors for process development of cyclosporine fermentations. J Ind Microbiol 1986;1:39–48. 5. Matsuda S, Koyasu S. Mechanism of action of cyclosporine. Immunopharmacology 2000;47:119–125. 6. de Smet MD, Nussenblatt RB. Clinical use of cyclosporine in ocular disease. Int Ophthalmol Clin 1993;33:31–45. 7. Liu J. FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunol Today 1993;14:290–295. 8. McDermott AM, Perez V, Huang AJ, et al. Pathways of corneal and ocular surface inflammation: A perspective from the cullen symposium. Ocul Surf 2005;3:S135–S138. 9. Nussenblatt RB, Palestine AG. Cyclosporine: Immunology, pharmacology and therapeutic uses. Surv Ophthalmol 1986;31:159–169. 10. Kaçmaz RO, Kempen JH, Newcomb C, et al. Cyclosporine for ocular inflammatory disease. Ophthalmology 2010;117:576–584. 11. Kashani S, Mearza AA. Uses and safety profile of ciclosporin in ophthalmology. Expert Opin Drug Saf 2008;7:79–89.

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Eye & Contact Lens  Volume 40, Number 5, September 2014

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Topical cyclosporine a 1% for the treatment of chronic ocular surface inflammation.

To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI)...
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