Safety and efficacy of topical tacrolimus 0.03% in the management of vernal keratoconjunctivitis: a non-randomized controlled clinical trial

Abstract

Background: Vernal keratoconjunctivitis (VKC) is a bilateral, recurrent, chronic conjunctival inflammatory disease with seasonal exacerbations. This study aimed to assess the efficacy and safety of tacrolimus 0.03% eye ointment in the management of chronic VKC.
 Methods: This was an open-label, prospective, non-randomized, comparative interventional study that enrolled 50 patients with chronic VKC, who were allocated to one of two groups. The first group was treated with tacrolimus 0.03% eye ointment twice daily for 2 months then once daily for 2 months, followed by once every other day for another 2 months. The control group was treated with standard anti-allergic drugs, topical fluorometholone 0.1% eye drops three times daily for 2 weeks and gradually tapered for another 2 weeks, with topical olopatadine 0.1% administered twice daily during the follow-up period. Disease severity was assessed using a four-point scale for symptoms and signs. Treatment efficacy was assessed by analyzing changes in symptoms and signs, and by clinical photography.
 Results: Fifty patients with bilateral chronic VKC completed the follow-up. The mean (standard deviation) ages of the tacrolimus and control groups were comparable (16.20 [5.10] years versus 16.48 [4.19] years, P > 0.05). The most commonly reported symptom was itching, and the most common signs were papillary hypertrophy and conjunctival hyperemia. All symptoms and signs were significantly reduced after treatment in both groups. The tacrolimus group showed a more significant improvement at 3 and 6 months in the mean composite symptom score (both P < 0.05) and in the mean composite sign score (both P < 0.05). Regarding complications, one case of increased intraocular pressure occurred in the control group (4%) after 2 weeks of steroid treatment, while there were no complications in the tacrolimus group, except for some reports of stinging sensation, which was well tolerated.
 Conclusions: Treatment of chronic bilateral VKC with tacrolimus 0.03% eye ointment is effective and safe. It could be considered an alternative treatment to reduce steroid-associated complications in patients with chronic VKC. Future double-blinded clinical trials with a longer follow-up period are necessary to confirm our findings and to determine the long-term safety of topical tacrolimus 0.03% ointment in VKC.

Vernal Keratoconjunctivitis: Immunopathological Insights and Therapeutic Applications of Immunomodulators

“…Resolution of the papillary component of VKC depends on the strength of treatment, where a higher strength (0.1%) provides increased efficacy in controlling papillary hyperplasia [ 137 ]. This effect was also observed in another study evaluating the efficacy of 0.03% tacrolimus in VKC [ 134 ], which reported a significant reduction in papillae in the tacrolimus-treated group compared to the control group (fluorometholone 0.1%). In another study evaluating the efficacy of 0.1% tacrolimus, patients previously treated with 2 months of 0.1% cyclosporine only experienced significant resolution of their papillae with administration of 0.1% tacrolimus for 1 month [ 140 ].…”

“…This interferes with the ability of calcineurin to dephosphorylate NFAT [ 120 ]. Thus, tacrolimus suppresses the production of cytokines such as IL-2, IL-4, and IL-5 [ 133 ] and also suppresses histamine release by mast cells [ 134 ]. This agent has a long history of being used as an immunosuppressant after organ transplantation [ 109 ] and is significantly more potent than cyclosporine [ 134 , 135 ].…”

“…Thus, tacrolimus suppresses the production of cytokines such as IL-2, IL-4, and IL-5 [ 133 ] and also suppresses histamine release by mast cells [ 134 ]. This agent has a long history of being used as an immunosuppressant after organ transplantation [ 109 ] and is significantly more potent than cyclosporine [ 134 , 135 ]. This increased potency of tacrolimus is beneficial in treating cases refractory to cyclosporine [ 136 ].…”

“…In another study evaluating the efficacy of 0.1% tacrolimus, patients previously treated with 2 months of 0.1% cyclosporine only experienced significant resolution of their papillae with administration of 0.1% tacrolimus for 1 month [ 140 ]. Patients treated with tacrolimus can exhibit improvements in their clinical signs and symptoms as early as three days [ 141 ], where the most common adverse events reported are transient burning [ 137 , 140 , 142 , 143 ] and ocular stinging [ 134 , 137 ]. Both cyclosporin and tacrolimus reduce the transcription of cytokine genes required for encoding T cell-derived cytokines [ 119 , 120 ] and are effective immunomodulators for controlling the inflammatory reaction seen in VKC.…”

Alleviation of allergic rhinoconjunctivitis symptoms in participants treated with a 0.005% tacrolimus eye drop solution

“…The high dose Tacrosolv failed to reduce TOSS on Day 1, presumably based on a short-term adverse reaction of a stinging or burning sensation that is well known for tacrolimus [13][14][15] and that obscures the beneficial, immune suppressive effect at the start of treatment. Such an instillation site discomfort is also frequently reported for other immunomodulatory ocular medications like cyclosporine or lifitegrast.…”