Topical Use of Cyclosporine in the Treatment of Vernal Keratoconjunctivitis

doi:10.1016/S0002-9394(14)77061-8

American Journal of Ophthalmology

Volume 110, Issue 6, December 1990, Pages 641-645

https://doi.org/10.1016/S0002-9394(14)77061-8 Get rights and content

We treated 11 patients with vernal keratoconjunctivitis for four to nine months with topical cyclosporine as a 2% dilution in castor oil. No significant side effects occurred, except for mild and transient burning upon administration. Within the first 15 days, both symptoms and signs of the condition improved significantly, and these results were maintained throughout the entire treatment. Relapses of the disease occurred two to four months after the end of the therapy. A double-masked clinical trial of nine patients (2% cyclosporine in castor oil vs castor oil alone) confirmed the results. Treated eyes improved significantly for both signs and symptoms as compared to control eyes. Topical cyclosporine may, therefore, be considered an effective substitute for corticosteroids, with an excellent anti-inflammatory activity in patients with both corticosteroid-dependent and corticosteroid-resistant vernal keratoconjunctivitis.

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2024, Survey of Ophthalmology
Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients’ quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.
NOVATIVE: A Phase II/III, Multicenter, Double-masked, Randomized Study of Cyclosporine A 0.05% and 0.1% Ophthalmic Cationic Emulsion Versus Vehicle in Patients with Vernal Keratoconjunctivitis
2023, Clinical Therapeutics
This study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC).
This Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale.
All groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable.
Although treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). ClinicalTrials.gov identifier: NCT00328653.
Executive summary: Japanese guidelines for allergic conjunctival diseases 2021
2022, Allergology International
Citation Excerpt :
Strength of recommendation: Weakly recommended for use. Level of evidence: C. Evaluation of evidence: The PubMed search yielded 33 articles.17,55,59,62,67,68,70–72,74–76,79–81,83,85,86,89–102 Two randomized controlled studies were included in the analysis.5559
Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD.
Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.
Efficacy of medical treatments for vernal keratoconjunctivitis: A systematic review and meta-analysis
2021, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Results of SIGN randomized controlled trials criteria ranged from 33.3%40 to 100%25,37,44,48,51 for yes responses, with a mean score of 80.2 ± 15.5 (Fig 2, and see Appendix E3 in this article’s Online Repository at www.jacionline.org). Inclusion criteria were VKC without precision,20-22,25,28,29,42,47,50,51 active VKC,18,24,27,30,36,37,39,40,44,46,55,56 active severe VKC or refractory to medical treatment15,16,18,19,23,25,31-35,41,43,45,48,49,52-54,57-59 (especially first-line drugs,48 resistance or dependency to corticoids,15,19,23,34,43,58,59 and resistance to cyclosporine16,49,54,57). Only 4 studies had age criteria with age required over 3,45 4,41,55 or 6 years old59 and under 16,45 17,55 or 18 years old.41,59
Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctivitis for which treatment strategies are still under debate.
This study sought to conduct a systematic review and meta-analysis to evaluate the efficacy of medical treatments for VKC.
The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched to assess the efficacy of treatments for VKC. Random-effect meta-analyses on changes in clinical scores of symptoms and signs between baseline and after treatment, stratified on treatment classes, were computed. Meta-regressions were searched for potential influencing parameters.
Included were 45 studies (27 randomized controlled trials and 18 prospective cohort studies), 1749 patients (78% were men; mean age, 11.2 years), and 12 different treatment classes. Mast cell stabilizers (MCSs; usually considered as first-line therapy), cyclosporine, and tacrolimus were the most studied drugs (in three-quarters of studies). Overall, all clinical scores improved. Total symptom and sign score decreased for MCSs (effect size, −3.19; 95% CI, –4.26 to −2.13), cyclosporine (effect size, −2.06; 95% CI, −2.72 to −1.40), and tacrolimus (effect size, −2.39; 95% CI, −3.36 to −1.43). No significant differences were shown depending on treatment classes, concentration, age, sex, baseline activity scores, and atopy. Sensitivity analyses demonstrated similar results.
This study confirms the efficacy of MCSs in the treatment of VKC. Efficacy of cyclosporine and tacrolimus did not differ, suggesting that tacrolimus is a good alternative to cyclosporine for severe cases of VKC. Further studies are needed to compare other drugs and their precise place in treatment strategy.
Management of corneal complications in vernal keratoconjunctivitis: A review
2021, Ocular Surface
Citation Excerpt :
They block Th2 lymphocyte proliferation and IL-2 production, inhibit histamine release from basophils and mast cells by blocking IL-5 production, and inhibit chemotaxis of eosinophils [8,50]. Several studies have demonstrated that topical cyclosporine A 0.05%–2% four times a day can reduce the signs and symptoms of VKC with no serious adverse reactions [51–54]. This treatment reduces steroid demand, resulting in the control of VKC with mast cell stabilizers alone.
Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, allergic conjunctivitis with episodes of acute exacerbations. Although VKC has a self-limiting course, chronic recurrent inflammation can cause long-term visual impairment due to corneal complications including shield ulcers, infectious keratitis, keratoconus, corneal opacities, and limbal stem cell deficiency. The initial step in the management of corneal involvement is medical treatment of the acute stage of VKC and prevention of recurrences. Giant papillae not responding to medical treatment can be removed surgically in the case of corneal involvement. Shield ulcer with no inflammatory plaque usually heals with appropriate medical therapy. For shield ulcer with inflammatory plaque, however, surgical debridement with or without amniotic membrane transplantation might be necessary. Keratoconus may develop in chronic and severe VKC. An annual evaluation of these patients with corneal topography and/or tomography is essential for early detection of keratoconus and its timely management that includes collagen cross-linking and intrastromal corneal ring segment implantation. Corneal transplantation may be required in the advanced stage of keratoconus. Both penetrating keratoplasty and deep anterior lamellar keratoplasty can result in excellent visual outcomes in keratoconic eyes with concomitant VKC. Appropriate management of inflammation in the perioperative period is crucial for achieving successful outcomes after corneal transplantation. Limbal stem cell deficiency, a rare complication of long-standing and severe VKC, might be treated with living-related conjunctival limbal allograft.
Giant papillary conjunctivitis: A review
2020, Ocular Surface
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The case described had not responded to antihistamines, mast cell stabilizers, topical corticosteroids, and surgical resection-cryopexy [114]. Moreover, there are many reports on the safety and efficacy of topical tacrolimus and cyclosporine A in treatment of the giant papillae associated with vernal keratoconjunctivitis [115–119]. Additional studies are needed to evaluate the role these immunomodulatory medications in treatment of GPC.
Giant papillary conjunctivitis (GPC), which is characterized by the development of “giant” papillae on the superior tarsal conjunctiva, is a common complication in contact lens wearers. This condition can be associated with excessive mucus production, itching, blurry vision, and diminished contact lens tolerance. Risk factors for GPC include non-disposable lenses, infrequent lens replacement, long wearing time, inadequate lens hygiene, and atopy. Although the exact pathophysiology of GPC remains incompletely understood, it likely develops from the combination of mechanical trauma to the superior tarsal conjunctiva and an immunologic response by the conjunctiva to deposits on the anterior surface of the contact lens. With proper management, GPC has an excellent prognosis. In mild cases, prompt contact lens cessation is sufficient for the resolution of signs and symptoms. For more severe cases, the use of topical anti-histaminic agents is indicated. Uncommonly, topical steroids, non-steroidal anti-inflammatory agents, immunomodulatory medications, or very rarely surgery may be needed. In this review article, we provide a comprehensive review of the available literature on GPC, with an emphasis on recent findings and treatment advances for this common condition.

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Topical Use of Cyclosporine in the Treatment of Vernal Keratoconjunctivitis

Lancet

Am. J. Ophthalmol.

Cyclosporin A and dexamethasone suppress T-cell responses by selectively acting at distinct sites of the triggering mechanism

J. Immunol.

Effects of Cs-A in T-cell subsets in experimental autoimmune uveitis

Invest. Ophthalmol. Vis. Sci.

Differential effect of cyclosporin A on the expression of T and B lymphocyte activation antigens

J. Immunol.

Cyclosporine-induced alterations of humoral response in experimental autoimmune uveitis

Invest. Ophthalmol. Vis. Sci.