Topical Bimatoprost for Chemical Blepharoplasty

• ClinicalTrials.gov Identifier: NCT02830776
• Recruitment Status: Unknown
• First Posted: July 13, 2016
• Last Update Posted: May 2, 2017
• Sponsor: Tulane University
• Collaborator: Allergan
• Information provided by (Responsible Party): Megan Couvillion, Tulane University

Study Description

Brief Summary:

Topical bimatoprost has been shown to cause periorbital changes of soft tissue which are most pronounced when used directly onto the cornea for the treatment of glaucoma. Changes are primarily felt to be the result of prostaglandin-mediated adipocyte loss, resulting in deepening of the upper eyelid sulcus and recession of infraorbital pseudoherniation. Use of topical bimatoprost to the upper eyelid margin, now FDA approved for eyelash enhancement, may provide a metered effect on the periocular tissues and allow for a topical approach to periocular rejuvenation.

This is a proof of concept study which aims to enroll a series of patients with mild to severe dermatochalasis, treat with topical bimatoprost 0.03% solution to the upper lid margin, and evaluate for cosmetic improvement of the periocular area.

Condition or disease	Intervention/treatment	Phase
Dermatochalasis	Drug: bimatoprost 0.03% ophthalmic solution	Early Phase 1

Detailed Description:

Perception of beauty in the periocular region is influenced by several factors, including symmetry, population norms, and skin texture and tone. Soft tissue and skin changes over time create an aged appearance with the development of dermatochalasis, blepharoptosis, lacrimal gland prolapse, and fat prolapse. Techniques for periocular rejuvenation are well established and include soft tissue augmentation, resurfacing, and surgical correction. In May 2015, Sarnoff and Gotkin reported a case of "chemical blepharoplasty" achieved with topical bimatoprost ophthalmic 0.03% solution applied to the upper eyelid margin. After three months of use, the author noted a more youthful appearance of the periocular region, with deepening of the upper eyelid sulcus, reduction in dermatochalasis, and diminution of the inferior eyelid fat pad. These changes were attributed to the prostaglandin associated periorbitopathy (PAP), a well described phenomenon observed with the use of topical prostaglandin analogues use for glaucoma.

Periorbital changes observed with topical prostaglandin analogues are primarily due to effects on aponeurotic and deep orbital adipocytes. Prostaglandins activate the adipocyte mitogen-activated protein kinase (MAPK) pathway, leading to inactivation of peroxisome proliferator-activated receptor (PPAR)-gamma, inhibition of adipocyte differentiation, and decreased fat accumulation within adipocytes. Bimatoprost concentration-dependent contractions of ciliary muscles and activation of matrix metalloproteinases may also contribute to periocular changes. Patients using topical ophthalmic prostaglandin analogues commonly develop periorbital fat loss, which has been well characterized in the ophthalmology literature.

Bimatoprost applied to the upper eyelid margin for eyelash enhancement attempts to capitalize on the desirable effects of darker, longer, thicker eyelashes, while limiting more significant and undesirable effects through limited exposure of the drug to ocular tissues. This same concept may apply for dermatochalasis: at a metered dose, topical bimatoprost to the lid margin could lead to subtle periorbital fat loss resulting in improved dermatochalasis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 14 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Topical Bimatoprost for Chemical Blepharoplasty
• Actual Study Start Date: November 2016
• Actual Primary Completion Date: April 30, 2017
• Estimated Study Completion Date: June 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment group; This is a single-arm open label proof of concept pilot study evaluating use of Latisse (bimatoprost 0.03% ophthalmic solution) applied to the eyelid margin for dermatochalasis (upper eyelid drooping).	Drug: bimatoprost 0.03% ophthalmic solution; Latisse (bimatoprost 0.03% ophthalmic solution) applied to the eyelid margin for dermatochalasis (upper eyelid drooping); Other Name: Latisse

Outcome Measures

Primary Outcome Measures :

1. Graded improvement in dermatochalasis [ Time Frame: Weeks 0, 4, 8, 12 ]
   Patients will be followed Q 4 weeks in clinic with followup photodocumentation at each visit for a total of 4 visits, 3 months of treatment. At completion of the study period, each patient's photographs at weeks 0, 4, 8, and 12, will be graded by 2 blinded evaluators for level of dermatochalasis: -1 (deep upper eyelid sulcus), 0 (no dermatochalasis), 1 (mild, slightly noticeable), 2 (moderate, noticeable), or 3 (severe, distinctive).

Secondary Outcome Measures :

1. Improved patient satisfaction [ Time Frame: Weeks 0, 12 ]
   Entry and exit surveys will be completed about self perception of the periocular area

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 18+,
• mild to severe dermatochalasis, desire for enhanced eyelashes.

Exclusion Criteria:

• Patients with current use of ophthalmic prostaglandin analogues,
• history of blepharoplasty,
• history of neuromodulators or fillers to the periocular region or frontalis in the last 6 months,
• existing deep upper eyelid sulcus,
• opposition to eyelash enhancement,
• pregnancy.

Contacts and Locations

Locations

United States, Louisiana

Tulane Department of Dermatology

New Orleans, Louisiana, United States, 70112

Sponsors and Collaborators

Tulane University

Allergan

Investigators

• Principal Investigator: Megan P Couvillion, MD, MS; Tulane University School of Medicine, Department of Dermatology

More Information

Publications:

Sarnoff DS, Gotkin RH. Bimatoprost-induced chemical blepharoplasty. J Drugs Dermatol. 2015 May;14(5):472-7.

Filippopoulos T, Paula JS, Torun N, Hatton MP, Pasquale LR, Grosskreutz CL. Periorbital changes associated with topical bimatoprost. Ophthalmic Plast Reconstr Surg. 2008 Jul-Aug;24(4):302-7. doi: 10.1097/IOP.0b013e31817d81df.

Reginato MJ, Krakow SL, Bailey ST, Lazar MA. Prostaglandins promote and block adipogenesis through opposing effects on peroxisome proliferator-activated receptor gamma. J Biol Chem. 1998 Jan 23;273(4):1855-8.

Kucukevcilioglu M, Bayer A, Uysal Y, Altinsoy HI. Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost. Clin Exp Ophthalmol. 2014 Mar;42(2):126-31. doi: 10.1111/ceo.12163. Epub 2013 Aug 4.

Cohen JL. Enhancing the growth of natural eyelashes: the mechanism of bimatoprost-induced eyelash growth. Dermatol Surg. 2010 Sep;36(9):1361-71. doi: 10.1111/j.1524-4725.2010.01522.x. Review.

Shah M, Lee G, Lefebvre DR, Kronberg B, Loomis S, Brauner SC, Turalba A, Rhee DJ, Freitag SK, Pasquale LR. A cross-sectional survey of the association between bilateral topical prostaglandin analogue use and ocular adnexal features. PLoS One. 2013 May 1;8(5):e61638. doi: 10.1371/journal.pone.0061638. Print 2013.

• Responsible Party: Megan Couvillion, Dermatology Resident, Tulane University
• ClinicalTrials.gov Identifier: NCT02830776
• Other Study ID Numbers: 833277-1
• First Posted: July 13, 2016
• Last Update Posted: May 2, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Megan Couvillion, Tulane University:

dermatochalasis; bimatoprost; blepharoplasty

Additional relevant MeSH terms:

Cutis Laxa; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin Diseases; Bimatoprost; Ophthalmic Solutions; Pharmaceutical Solutions; Antihypertensive Agents