Dermatology: Practical and Conceptual Letter to Editor | Dermatol Pract Concept. 2023;13(1):e2023042 1 Eyelid Lentigo Maligna Treated With Imiquimod 5%: Should We Fear of Ocular Side Effects? Claudio Conforti1, Carmen Dell’Aquila2, Daniele Tognetto2, Iris Zalaudek1, Nicola Di Meo1 1 Dermatology Clinic, Maggiore Hospital of Trieste, Trieste, Italy 2 Eye Clinic, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy Citation: Conforti C, Dell’Aquila C, Tognetto D, Zalaudek I, Di Meo N. Eyelid lentigo maligna treated with imiquimod 5%: should we fear of ocular side effects? Dermatol Pract Concept. 2023;13(1):e2023042. DOI: https://doi.org/10.5826/dpc.1301a42 Accepted: July 25, 2022; Published: January 2023 Copyright: ©2023 Conforti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: CC and CD wrote the article; DT and IZ reviewed the literature; NDM provided images of the patients. Corresponding Author: Claudio Conforti, MD, Dermatology clinic, Maggiore Hospital of Trieste, Trieste, Italy. Phone +390403992056 E-mail: claudioconforti@yahoo.com To the Editor, Lentigo maligna (LM) represents the most common subtype of melanoma in the elderly, affecting predominantly the head and neck region in photodamaged patients. Surgery with 5 mm margins is the treatment of choice but patient comor- bidities, impact of surgery intervention and the reduction of quality of life resulting from surgery can limit its application. In situations for which surgery would have a major impact on the functionality of the anatomic region or would results in cosmetically devasting outcome, radiotherapy or imiqui- mod (IMQ) represent valid alternatives. IMQ could cause significant skin reactions and little is currently known on its impact of the eye if applied in the periorbital region. Herein, we report the case of a 74-year-old woman, referred to our skin cancer department for a brownish macule located on left lower eyelid. Previous history revealed the excision with 5 mm margins of a LM 4-years before. A first recurrence appeared two years later and was surgically treated. At current visit, a brownish macule of about 6-mm located on the lower eyelid was observed (Figure 1A). Dermoscopic evaluation showed a brown pseudo-network with intense pigmentation and obliterations of follicles (Figure 1B). A 4mm punch biopsy was performed, confirming the dermo- scopic diagnosis of lentigo melanoma. The patient was dis- cussed in our multidisciplinary tumor board because surgery would have an impact on the functionality of the eye and also because the patient refused further surgery. Based on the data suggesting a good response of LM to topical treatment with IMQ 5%, it was started five days per week. Consider- ing the tumor closeness to conjunctiva and cornea and the risk of occasional applications of the drug in the eye during the treatment, a close dermatological and ophthalmological evaluations were performed every two weeks. After 4 weeks a partial response was observed ( Figure 1, C  and D) and after 6 weeks a complete response was achieved (Figure 1, E and F). At the ophthalmologic evaluation after 2  weeks of treatment, redness, burning and foreign body sensation of the conjunctivae was noted, without any decreased vi- sual acuity. However, to limit discomfort, a combination of topical steroid and hyaluronic acid eyedrops were pre- scribed every day for ten days with a rapid improvement of the symptoms. Then, to prevent redness and burning sensa- tion, hyaluronic acid eyedrops were prescribed for the entire 2 Letter to Editor | Dermatol Pract Concept. 2023;13(1):e2023042 treatment period. At 6 months follow up visit, no clinical and dermoscopic signs of recurrence were observed and the conjunctiva did not show inflammation or impairment. The optimal response of LM to IMQ and its dermoscopic eval- uation has been already proved (1,2); moreover, clinicians may be reluctant to prescribe IMQ on the eyelid because of risk of ocular adverse effects. However, O’Neill et al (3) de- scribed the case of a 52-year-old woman affected by LM, successfully treated with IMQ and, despite the patient giving a history of having applied treatment into the eye on occa- sion (in error) there were no adverse effects. Other reports show that the most common side effects during treatment of LM of the eyelids with IMQ are redness and burning, improved without permanent ocular damages after its dis- continuation (4,5). To prevent ocular redness and burning, the first advice to be given to patients is undoubtedly to use daily hyaluronic acid tears associated with good eyelid hygiene. In more se- vere scenarios, non-steroid tears should be prescribed to reduce discomfort and to increase therapeutic compliance. Therefore, considering the benefits of IMQ and the absence of permanent ocular side effects, the use of IMQ in the perio- cular area should not be avoided for fear of conjunctival inflammation which, if it occurs, can be treated, and pre- vented with topical therapy. References 1. Lallas A, Moscarella E, Kittler H, et al. Real-world experience of off-label use of imiquimod 5% as an adjuvant therapy after surgery or as a monotherapy for lentigo maligna. Br J Derma- tol. 2021;185(3):675-677. DOI: 10.1111/bjd.20407. PMID: 33894006. 2. Hamilko de Barros M, Conforti C, Giuffrida R, Seabra Resende FS, Di Meo N, Zalaudek I. Clinical usefulness of dermoscopy in the management of lentigo maligna melanoma treated with topi- cal imiquimod: A case report. Dermatol Ther. 2019;32(5):e13048. DOI: 10.1111/dth.13048. PMID: 31365164. 3. O’Neill J, Ayers D, Kenealy J. Periocular lentigo maligna treated with imiquimod. J Dermatolog Treat. 2011;22(2):109-112. DOI: 10.3109/09546630903559798. PMID: 20666668. 4. Elia MD, Lally SE, Hanlon AM, et al. Periocular Melanoma In Situ Treated With Imiquimod. Ophthalmic Plast Re- constr Surg. 2016 Sep-Oct;32(5):371-373. DOI: 10.1097/ IOP.0000000000000554. PMID: 26325381. 5. Murchison AP, Washington CV, Soloman AR, Bernardino CR. Ocular effects of imiquimod with treatment of eyelid mel- anoma in situ. Dermatol Surg. 2007;33:1136–1138. DOI: 10.1111/j.1524-4725.2007.33232.x. PMID: 17760609. Figure 1. A brownish macule of about 6-mm located on the lower eyelid was observed. [Fig.1A] Dermoscopic evaluation showed a brown pseudo-network with intense pigmentation and obliterations of follicles. [Fig1B]. After 4 weeks of treatment with imiquimod 5%, a partial response was observed [Fig1C, Fig1D] and after 6 weeks a complete response was achieved. [Fig1E, Fig1F]