Tacrolimus ointment in atopic blepharoconjunctivitis does not seem to elevate intraocular pressure


Anita Remitz MD, PhD
Skin and Allergy Hospital, Helsinki University Central Hospital
Meilahdentie 2, 00250 Helsinki
Tel: + 358 9 47186482
Fax: + 358 9 47186561
Email: anita.remitz@hus.fi


Long-term use or repeated courses of corticosteroids for atopic blepharoconjunctivitis (ABC) can easily cause side-effects like elevation of the intraocular pressure (IOP), cataract, and atrophy of the eyelid skin (Jones & Rhee 2006). Tacrolimus ointment is a topical calcineurin inhibitor and has been successfully used for atopic dermatitis (AD) (Reitamo et al. 2002). The main advantage compared with corticosteroids is that it does not cause skin atrophy and seems to be safe when used for the eyelids (Freeman et al. 2004; Virtanen et al. 2006).

We analysed retrospectively the patient records of 33 patients with severe ABC collected at our institution during 3 years (2004–2007). A total of 28 patients (age 45.9, range 19–84, 13 men) were accepted for the study. All patients included had used almost continuously topical corticosteroids before the study for at least 6 months. The mean interval from the start of tacrolimus treatment to the first follow-up visit was 10 weeks (4–17 weeks). A full ophthalmologic examination was performed to all patients before starting tacrolimus treatment and at individually scheduled follow-up visits. The severity of the symptoms and signs; blepharitis and conjunctivitis were assessed on a scale of 0–3. IOP was measured from both eyes with Goldmann applanation tonometer (Haag-Steit Ag, Bern, Switzerland) on each visit by the same investigator. A value of >20 mmHg was considered as elevated. Tacrolimus 0.03% ointment was applied to the eyelids once daily for the first 4 weeks and then intermittently depending on individual symptoms from 6 months to 2 years.

The data of the clinical score and IOP were analysed using Wilcoxon signed rank test with StatView for Windows®.

A statistically significant decrease in IOP was seen in the mean IOP of both eyes (p = 0.03). A total of 10 patients showed elevated IOP before the start of tacrolimus treatment (steroid responders), all except one in both eyes. They showed a more significant decrease in IOP (mean/median 24.5/24.0, range 21–37 versus 19.1/20.0, range 12–23, p = 0.0004) (Fig. 1). Elevated IOP was seen at the follow-up visit in nine eyes in five of these patients (mean/median 21.7/21.0, range 21–23). The clinical score decreased significantly from the start of the treatment to the first follow-up visit (mean/median 3.8/4.0 versus 1.3/1.0, p = 0.0001) (Fig. 2). No increased lens opacities or changes in vision were observed. All patients experienced subjective relief of the symptoms including itch. The treatment was well tolerated, and no marked adverse events appeared. Only mild burning sensation was experienced by three patients (10%) in the beginning of the treatment. A total of 16 patients have been further followed up for 6–12 months. All of them have shown a continuous good clinical response and IOP within normal limits (mean/median 15.5/15.0) including four patients with originally elevated IOP (mean/median 17.8/18.0, range 15–20).

Figure 1.

 Intraocular pressure (mean, median, and median + SD) A) as a mean of both eyes of all patients, n = 28; and B) in all eyes with elevated intraocular pressure (IOP), n = 19, before (white bars) and after (dark bars) the start of 0.03% tacrolimus ointment in patients with atopic blepharoconjunctivitis.

Figure 2.

 Clinical score (mean, median, and median + SD) before (white bars) and after (dark bars) the start of 0.03% tacrolimus ointment in A) all patients with atopic blepharoconjunctivitis, n = 28, and B) patients with elevated intraocular pressure (IOP), n = 10.

A major problem in treating chronic ABC has been lack of alternatives for corticosteroid therapy. We have earlier shown that 0.03% tacrolimus ointment is a good treatment alternative in patients with ABC (Virtanen et al. 2006). In a previous openlabel study by Freeman et al. (Freeman et al. 2004), a promising effect of 0.1% tacrolimus ointment treatment on IOP and clinical signs were reported during an 8 -week treatment period. However, 60% of the patients reported burning. Nivenius et al. (2007) published a short-term double-masked crossover study where 0.1% tacrolimus ointment was compared with clobetasol butyrate 0.05% for a 3 -week treatment period of ABC. Both treatments were effective in the treatment of clinical symptoms with a slight superiority to tacrolimus ointment. No serious side-effects or elevation in IOP were observed.

The present study shows a good clinical efficacy in eyelid dermatitis with 0.03% tacrolimus treatment without any elevation of IOP. In addition, there might perhaps even be other mechanisms in tacrolimus itself, like calcineurin inhibition, which could actively decrease IOP.