|Year : 2015 | Volume
| Issue : 4 | Page : 233-236
Efficacy of topical cyclosporine 0.05% eye drops in the treatment of dry eyes
Haitham Y Al-Nashar
Department of Ophthalmology, Zagazig Faculty of Medicine, Zagazig, Egypt
|Date of Submission||29-May-2015|
|Date of Acceptance||10-Jul-2015|
|Date of Web Publication||22-Jan-2016|
Haitham Y Al-Nashar
Department of Ophthalmology, Zagazig Faculty of Medicine, Zagazig
Source of Support: None, Conflict of Interest: None
The aim of the present study was to evaluate the effectiveness of cyclosporine 0.05% in the treatment of dry-eye disease.
Patients and methods
A total of 35 eyes of 20 patients with dry-eye disease were included in the present study. Ten patients (20 eyes) had dry eyes associated with systemic rheumatologic disease (Sjögren's syndrome), five patients (10 eyes) had dry eyes after undergoing laser in-situ keratomileusis, and five patients (five eyes) had dry eyes after cataract surgery. Detailed history taking along with full ophthalmic examination was carried out for all patients. In addition, Schirmer's test and break-up time (BUT) test were conducted for all patients. The patients were examined for ocular symptoms of dry eyes (ocular pain, burning, and foreign body sensation). Cyclosporine 0.05% eye drops were prescribed twice daily for 3 months. The patients were followed up after 1, 2, and 3 months.
In total, 35 eyes of 20 patients diagnosed with dry-eye syndrome were included in this study. The mean age of the patients was 37.3 years (range: 26-65 years).The patients were evaluated for ocular symptoms (burning, pain, and foreign body sensation). Schirmer's paper test and BUT test were conducted for all patients. The score of ocular symptoms before the beginning of the treatment was 2.50 ± 0.46, and this score improved to 0.9 ± 0.52 after 3 months with a statistically significant difference (P = 0.01). Schirmer's paper test was performed before the beginning of the treatment, and showed a wetting of 1.15 ± 0.58 mm of the paper, and improved after 3 months to 5.86 ± 0.29 mm (P = 0.001). BUT improved from 5.57 ± 1.36 s before the treatment to 9.9 ± 0.92 s after 3 months of treatment (P = 0.001).
Topical cyclosporine 0.05% is effective in the treatment of dry-eye syndrome, which has an inflammatory cause.
Keywords: cyclosporine, dry eye, Sjögren′s syndrome
|How to cite this article:|
Al-Nashar HY. Efficacy of topical cyclosporine 0.05% eye drops in the treatment of dry eyes. J Egypt Ophthalmol Soc 2015;108:233-6
| Introduction|| |
Dry-eye disease or keratoconjunctivitis sicca (KCS) is a common, multifactorial, symptomatic disease that is associated with increased osmolarity of the tear film and ocular surface inflammation . It is associated with symptoms of ocular discomfort such as burning, sense of dryness, foreign body sensation, ocular pain, and is sometimes associated with photophobia, blurred vision, visual fatigue, and sight-threatening corneal complications in severe cases . Pathogenesis of KCS has not been completely clarified. Many clinical and pathological changes affecting tear film, lacrimal glands, and eyelids with resulting deficiency in the tear film whether caused by decreased lacrimation or excessive evaporation . A wide spectrum of ocular surface cells, including epithelial, inflammatory, immune, and goblet cells, may play a role in its pathogenesis . Many studies propose new concepts of its pathogenesis, including that KCS seems to be caused by inflammation mediated by T-cell lymphocytes . Decreased tear volume, increased osmolarity, disorder of cytokine balance, and increased matrix metalloproteinases can be seen in dry-eye disease. It has been demonstrated that inflammation and apoptosis might play a role in the development of dry eyes . Currently, artificial tears are the most common initial approach used to relieve symptoms in patients with mild dry eyes.
Anti-inflammatory therapies, namely topical cyclosporine and corticosteroids, were recommended for patients with moderate to severe symptoms, mild corneal staining, conjunctival staining, followed by options such as tetracyclines and punctal plugs for severe symptoms, marked or central corneal staining, and filamentary keratitis . Long-term use of topical corticosteroids may be associated with glaucoma, cataracts, and other steroid-related side effects. In contrast, topical cyclosporine, which specifically blocks T-cell activation, may be a more appropriate long-term therapy because it is not associated with either significant systemic adverse events or the common steroid-related ocular side effects .
Topical cyclosporine ophthalmic emulsion 0.05% is a topical anti-inflammatory drug that has been approved by the United States Food and Drug Administration for the treatment of moderate to severe dry eyes. It is indicated to increase tear production in patients with reduced tear production presumably due to ocular inflammation . Cyclosporine A (CsA) is a fungal-derived peptide that inhibits T-cell activation and consequently inhibits the inflammatory cytokine production (selective inhibition of interleukin-1). In addition, CsA inhibits apoptosis and increases the density of conjuctival goblet cells .
In two multicenter, randomized, prospective, phase III clinical trials, topical cyclosporine 0.05% was shown to improve categorized Schirmer values, reduce corneal staining, and improve subjective measures, including blurred vision and dependence on artificial tears relative to vehicle. Burning and stinging upon instillation were the most common treatment-related side effects .
The aim of this study was to assess the effectiveness and tolerability of cyclosporine eye drops 0.05% in the treatment of patients with dry eyes.
| Patients and methods|| |
In this study, 35 eyes of 20 patients with dry-eye disease were included. Ten patients (20 eyes) had dry eyes associated with systemic rheumatologic disease (Sjögren's syndrome), five patients (10 eyes) had dry eyes after undergoing laser in-situ keratomileusis (LASIK), and five patients (five eyes) had dry eyes after cataract surgery. The patients were treated with cyclosporine 0.05% eye drops.
Detailed history was taken from all patients, including age, sex, previous medical and ocular diseases, and duration of symptoms. For all patients, routine ophthalmic examination was carried out. Slit-lamp biomicroscopy, Schirmer's test, and break-up time (BUT) test were also conducted. Before the beginning of the treatment the patients were examined for ocular symptoms of dry eye (ocular pain, burning, and foreign body sensation). Each symptom was given a score from 0 to 1 so that the ocular symptoms were given a score from 0 to 3.
Schirmer's test was performed after the installation of local anesthetic agent (Schirmer-1). Then the filter paper was folded 5 mm from one end and inserted at the junction of middle and outer-third of the lower eyelid; the patient was asked to keep the eyes gently closed, and then after 5 min the filter paper was removed and the amount of wetting from the fold was measured in millimeters.
BUT test was conducted by instilling a fluorescein drop in the eye. The patient was asked to blink several times, after which the tear film was examined with a broad beam cobalt-blue filter in slit lamp. After an interval of time, black spots or lines appeared in the fluorescein-stained film indicating formation of dry areas. The BUT is the interval (s) between the last blink and the appearance of the first dry spot.
Cyclosporine 0.05% eye drops were prescribed after informed consent was obtained. It was prescribed twice daily for 3 months.
The patients were followed up for 3 months. They were followed up after 1, 2, and 3 months. They were examined and scored for ocular symptoms, amount of wetting on Schirmer paper, and for the BUT. In addition, they were examined for any ocular complication and side effects.
| Results|| |
A total of 35 eyes of 20 patients diagnosed with dry-eye syndrome were included in this study. The mean age of the patients was 37.3 years (range: 26-65 years). The study included 13 women and seven men. Ten patients (20 eyes) had dry eyes due to systemic rheumatologic disease (Sjögren's syndrome), five patients (10 eyes) had dry eyes after undergoing LASIK, and five patients (five eyes) had dry eyes after cataract surgery. The patients were treated with cyclosporine 0.05% eye drops twice daily. All patients were followed up for 3 months.
The patients were evaluated for ocular symptoms (burning, pain, and foreign body sensation), and the Schirmer's paper test and BUT test were conducted for all patients.
The score of ocular symptoms before the beginning of the treatment was 2.50 ± 0.46 and this score improved after 1 month to 1.12 ± 0.16, to 1.08 ± 0.24 after 2 months, and to 0.9 ± 0.52 after 3 months with a statistically significant difference (P = 0.01).
Schirmer's paper test was carried out before the beginning of the treatment and showed a wetting of 1.15 ± 0.58 mm of the paper, and improved after 1 month of treatment to 2.2 ± 0.12 mm, to 4.82 ± 0.51 mm after 2 months, and to 5.86 ± 0.29 after 3 months with a statistically significant difference (P = 0.001).
BUT test showed early break-up of the tear film before the beginning of the treatment (5.57 ± 1.36 s), and improved after 1 month of treatment to 8.02 ± 0.98 s, to 7.28 ± 0.15 s after 2 months, and to 9.9 ± 0.92 s after 3 months with a statistically significant difference (P = 0.001).
Only four eyes of two patients (11.4%) reported ocular side effects in the form of ocular irritation and pain.
These results are shown in [Table 1].
| Discussion|| |
Dry eyes is a multifactorial condition that results in a dysfunctional lacrimal. Evidence suggests that inflammation is involved in the pathogenesis of the disease. There are several anti-inflammatory therapies for dry eyes that target one or more of the identified inflammatory mediators/pathways .
CsA is an immune-modulatory agent that suppresses activation and proliferation of T-cells. It may be appropriate for treating Sjögren's syndrome, in which there occurs a major lymphocytic infiltration of the lacrimal and salivary glands .
Moon et al.  compared the short-term effects of topical 0.05% cyclosporine (CsA) and a mixture of 0.08% chondroitin sulfate and 0.06% sodium hyaluronate on dry-eye ocular surfaces. They treated 36 patients with moderate to severe dry eyes (5 mm/5 min or less with Schirmer's test or tear BUT less than 6 s) with a topical application of CS-HA on one eye and CsA on the other four times a day for 6-8 weeks. After treatment, BUT was significantly prolonged in each group. Topical CsA-treated eyes had greater increase in BUT (P = 0.026). This result is comparable to the present study, where BUT increased from 5.57 ± 1.36 s before treatment to 9.9 ± 0.92 s after 3 months of treatment (P = 0.001).
Perry et al.  evaluated the use of topical cyclosporine 0.05% (Restasis; Allergan Inc., Irvine, California, USA) for the treatment of mild, moderate, and severe dry-eye disease unresponsive to artificial tears therapy. A total of 158 patients with dry-eye disease were evaluated using the Ocular Surface Disease Index for symptomatic improvement, tear BUT, fluorescein staining, lissamine green staining, and Schirmer's testing. Patients were observed for 3 to 16 months. They concluded that topical cyclosporine shows beneficial effects in all categories of dry-eye disease. Symptomatic improvement was greatest in the mild group, and the best results in improvement of disease signs were seen in patients with severe dry-eye disease.
In a prospective, multicenter, open-label, surveillance study, Byun et al.  treated 362 patients with moderate to severe dry-eye disease with CsA 0.05% for 3 months. After the treatment, all ocular symptom scores were significantly reduced compared with the baseline values, while the Schirmer's scores were significantly increased relative to baseline (P<0.0001).
In this study, Ocular Symptoms Score reduced from 2.5 ± 0.46 before treatment to 0.9 ± 0.52 after 3 months of treatment (P = 0.01). In addition, the Schirmer's paper test scores improved from 1.15 ± 0.58 to 5.86 ± 0.29 mm, which is significantly different (P = 0.001).
Prabhasawat et al.  studied 30 cases of Steven Johnson Syndrome patients who developed dry eyes defined by symptoms and signs, including the Schirmer I test, the fluorescein clearance test, and corneal staining (fluorescein and rose Bengal staining). They were treated with CsA 0.05% eye drops twice daily for 6 months. They found that 17 patients (56.67%) completed the study. Eight patients (26.67%) withdrew from the study as a result of intolerable side effects of CsA, which included pain, redness, and eyelid swelling. Five cases were lost in follow-up. All 17 cases demonstrated significant improvement in dry-eye symptoms, conjunctival injection, corneal staining, Schirmer I test, and fluorescein clearance test (P<0.05).
In this study, ocular side effects were reported only in four (11.4%) eyes.
Salib et al. , in a randomized parallel double-masked prospective clinical trial, evaluated dry-eye signs and symptoms in 42 eyes of 21 myopic patients with dry-eye disease and who had undergone LASIK. They were treated with unpreserved artificial tears or cyclosporine 0.05% ophthalmic emulsion twice a day. They found statistically significant increases from baseline in Schirmer scores for artificial tears at 1 month (P = 0.036) and for cyclosporine 0.05% at 6 months after surgery (P < 0.018). There were no significant differences from baseline or between groups in response to the Ocular Surface Disease Index questionnaire.
Guzey et al.  treated 32 severe trachomatous dry-eye patients with CsA 0.05% ophthalmic emulsion twice daily. After 6 months of treatment, the differences between the pretreatment and post-treatment test results, including total symptoms scores, the rose Bengal and fluorescein staining scores, and the Schirmer testing measurements were found to be statistically significant. Impression cytology also showed improvement of squamous metaplasia in 26 patients (81.25%) and increase in goblet cell density in 23 patients (71.88%). They concluded that topical CsA was effective in the treatment of severe trachomatous dry eye, yielding improvements in both objective and subjective measurements with a safety profile.
| Conclusion|| |
Topical cyclosporine eye drops are effective in the treatment of dry-eye syndrome, which is caused by inflammatory disease. Cyclosporine eye drops improve the BUT with less ocular symptoms and improved Schirmer paper test.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol 2003; 136
Zoukhri D. Effect of inflammation on lacrimal gland function. Exp Eye Res 2006; 82
Gayton JL. Etiology, prevalence, and treatment of dry eye disease. Clin Ophthalmol 2009; 3
Johnson ME, Murphy PJ. Changes in the tear film and ocular surface from dry eye syndrome. Prog Retin Eye Res 2004; 23
Chen Q, Li X, He W, Zhang H, Gao A, Cheng Y, et al.
The epitope study of alpha-fodrin autoantibody in primary Sjögren's syndrome. Clin Exp Immunol 2007; 149
Pflugfelder SC. Anti-inflammatory therapy for dry eye. Am J Ophthalmol 2004; 137
Behrens A, Doyle JJ, Stern L. Dysfunctional tear syndrome: a Delphi approach to treatment recommendations. Cornea 2006; 25
Rajpal RK, Digby D, D'Aversa G, Mah F, Hollander DA, Conway T. Intraocular pressure elevations with loteprednol etabonate: a retrospective chart review. J Ocul Pharmacol Ther 2011; 27
Rao SN. Topical cyclosporine 0.05% for the prevention of dry eye disease progression. J Ocul Pharmacol Ther 2010; 26
Matsuda S, Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology 2000; 47
Sall K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology 2000; 107
De Paiva CS, Pflugfelder SC. Rationale for anti-inflammatory therapy in dry eye syndrome. Arq Bras Oftalmol 2008; 7
Gokce EH, Sandri G, Bonferoni MC, Rossi S, Ferrari F, Güneri T, Caramella C. Cyclosporine A loaded SLNs: evaluation of cellular uptake and corneal cytotoxicity. Int J Pharm 2008; 364
Moon JW, Lee HJ, Shin KC, Wee WR. Short term effects of topical cyclosporine and viscoelastic on the ocular surfaces in patients with dry eye. KJO 2007; 2
Perry HD, Solomon R, Donnenfeld ED, Perry AR, Wittpenn JR, Greenman HE, Savage HE. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthalmol 2008; 126
Byun YS, Rho CR, Cho K, Choi JA, Na KS, Joo CK. Cyclosporine 0.05% ophthalmic emulsion for dry eye in Korea: a prospective, multicenter, open-label, surveillance study. Korean J Ophthalmol 2011; 25
Prabhasawat P, Tesavibul N, Karnchanachetanee C, Kasemson S. Efficacy of cyclosporine 0.05% eye drops in Stevens Johnson syndrome with chronic dry eye. J Ocul Pharmacol Ther 2013; 29
Salib GM, McDonald MB, Smolek M. Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis. J Cataract Refract Surg 2006; 32
Guzey M, Karaman SK, Satici A, Ozardali I, Sezer S, Bozkurt O. Efficacy of topical cyclosporine A in the treatment of severe trachomatous dry eye. Clin Experiment Ophthalmol 2009; 37
|This article has been cited by|
||A study to assess the efficacy of topical cyclosporine A 0.05% in the management of dry eye with meibomiam gland dysfunction
| ||Prajwalli Reddy, Wajeeha Umam |
| ||Indian Journal of Clinical and Experimental Ophthalmology. 2022; 7(4): 667 |
|[Pubmed] | [DOI]|
||Effect of vitamin D on the efficacy of topical artificial tears in patients with dry-eye disease
| ||MarwaA Zaky, HatemM Marey, DinaG. H. Abd Elmonem, AM. S. Fayed |
| ||Menoufia Medical Journal. 2022; 35(2): 856 |
|[Pubmed] | [DOI]|
||Topical Cyclosporine A 0.05% for the Treatment of Dry Eye Disease
| ||Naeima M. Elzlitni,Samar A. Bukhatwa,Sabah S. Eldressi |
| ||AL-MUKHTAR JOURNAL OF SCIENCES. 2021; 36(1): 34 |
|[Pubmed] | [DOI]|
||A prospective study to assess the role of vitamin D individually and in combination with cyclosporine in the treatment of dry eye in patients with deficient serum 25(OH)D levels
| ||Palak Watts,Anshu Sahai,PRatan Kumar,Mohd.Abid Shamshad,GopalKrishan Trivedi,Lokendra Tyagi |
| ||Indian Journal of Ophthalmology. 2020; 68(6): 1020 |
|[Pubmed] | [DOI]|