Bimatoprost-Induced Iris Hyperpigmentation: Beauty in the Darkened Eye of the Beholder
Practice Points
- Bimatoprost ophthalmic solution 0.03% was approved by the US Food and Drug Administration in 2008 as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis.
- Iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for treatment of ocular hypertension and glaucoma, but reports associated with bimatoprost eyelash solution are rare.
- It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information to avoid potential adverse events. The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye.
Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.10
In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension3 as well as a formulation for topical application on the eyelids/eyelashes.5 A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.14
,The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%4 to 50%9 of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.18 The rest of the solution remains on the applicator.
It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.5 Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.
Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.19 Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.5 It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.
Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.20
Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.21 Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.22 In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.
