Original Investigation

Intralesional Tetracycline Injection for Treatment of Lower Eyelid Festoons: A Preliminary Report Julian D. Perry, M.D.*, Viraj J. Mehta, M.D., M.B.A.†, and Bryan R. Costin, M.D.* *Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio; and †Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, U.S.A.

Purpose: To determine the safety and effectiveness of intralesional tetracycline 2% injection for the treatment of lower eyelid festoons. Methods: The authors retrospectively reviewed the charts of all patients undergoing tetracycline 2% injection of lower eyelid festoons at the Cole Eye Institute from August 2008 to August 2013. Charts were reviewed for patient demographic data, dose and number of tetracycline injections, follow-up interval, the presence of preinjection and postinjection photographs, and complications. Charts without preinjection and postinjection photographs were excluded from review. The preinjection and postinjection photographs were randomized, masked, and graded by 4 independent examiners. Photographs were graded on a scale of 0 (no festoon) to 4 (severe festoon). Student t test was used for statistical analysis. Results: Eleven patients met inclusion criteria. Each patient underwent bilateral injection. Average follow up was 121 days (range, 18–586 days). Patients received up to 0.75 ml (mean, 0.24 ml) of tetracycline 2% per side. Average preinjection grade was 2.1 (standard deviation, 0.89; range, 0–3), and average postinjection grade was 1.2 (standard deviation, 0.72; range, 0–2; p < 0.001). Three patients had follow up less than 60 days (mean, 34 days), with an average preinjection grade of 1.96 and postinjection grade of 1.23 (p < 0.001). Five patients had follow up between 60 and 100 days (mean, 82 days), with an average preinjection grade of 2.18 and postinjection grade of 1.38 (p < 0.001). Three patients had follow up longer than 100 days (mean, 275 days), with an average preinjection grade of 2.08 and postinjection grade of 0.78 (p < 0.001). Complications other than pain and bruising were not identified in any patient. Conclusions: Intralesional tetracycline 2% injection may offer a safe option to treat lower eyelid festoons. Complications such as cutaneous ischemia or necrosis were not identified in any patient. Further study may determine optimal treatment doses and intervals and detect infrequent but significant complications. (Ophthal Plast Reconstr Surg 2015;31:50–52)

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estoons, or malar bags, represent fluid accumulation at the lower eyelid–cheek junction and may be related to attenuations of the orbicularis oculi muscle caused by the laxity of Accepted for publication March 11, 2014. Presented at the ASOPRS Fall Symposium, New Orleans, LA on November 14, 2013. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Julian D. Perry, m.d., Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Mail Code i-20, Cleveland, OH 44195. E-mail: [email protected] DOI: 10.1097/IOP.0000000000000173

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dermal attachments (Fig. 1).1 Anatomically, the boundary of the lower eyelid festoon is defined by the malar septum. This relatively impermeable fascial structure originates from the orbital rim at the arcus marginalis and fuses with the fibrous septa of the superficial cheek fat and dermis.2 Various treatment options may improve the appearance of festoons, including surgical and nonsurgical options. Surgical options include blepharoplasty, midface lift, or excision.3 While blepharoplasty may theoretically restore some of the attenuations that cause the fluid buildup, it does not reliably improve festoons. Midface lift often elevates the festoon but may not completely eradicate it, and direct excision results in a visible scar. Less invasive options include botulinum toxin, chemical peels, and subcutaneous application of laser or cautery.4 However, in the authors’ opinion, none of these modalities predictably and reliably improve the appearance of festoons. The tetracycline family consists of an array of compounds that are well known for their antimicrobial actions. They also exhibit numerous nonantimicrobial properties. For example, tetracycline produces a growth factor–like activity that stimulates fibroblast proliferation. Tetracycline has also demonstrated the ability to inhibit matrix metalloproteinases from numerous cellular tissues to promote unopposed collagen and fibrin deposition.5–7 Tetracycline compounds have been used for decades to successfully achieve chemical pleurodesis.6 Doxycycline-induced sclerodesis has recently been found to improve subcutaneous fluid accumulation in Morel-Lavalee lesions, which represent post-traumatic shearing of the dermis from the underlying tissues.7 These compounds may improve ocular surface repair, and injection of these compounds has been used to treat a variety of ophthalmic conditions.8,9 Doxycycline sclerotherapy may effectively treat microcysts due to orbital venous lymphatic malformations10 and similar lesions in other body regions.11,12 Doxycycline injection of a recurrent intrascleral cyst after surgery has been described.13 Treatment of persistent bulbar chemosis in 3 patients with intralesional tetracycline 2% has also been reported.14 Based on this limited evidence supporting effective and safe sclerodesis using intralesional periocular tetracycline compound injection, the authors began using intralesional tetracycline 2% injection in an effort to improve lower eyelid festoons at the Cole Eye Institute since 2008. They sought to determine the safety and effectiveness of this treatment.

METHODS After institutional review board approval, the authors retrospectively reviewed the medical records of consecutive patients who had received 2% tetracycline injections to treat lower eyelid festoons at the Cole Eye Institute between August 2008 and August 2013. Charts were identified by reviewing order records for tetracycline 2% for intralesional injection from the compounding pharmacy. Only patients

Ophthal Plast Reconstr Surg, Vol. 31, No. 1, 2015

Ophthal Plast Reconstr Surg, Vol. 31, No. 1, 2015

with adequate preinjection and postinjection follow-up photos were included for study. Data collection included the following: age, gender, date of injection, date of preinjection photo, date of postinjection photo, volume of tetracycline injected, and complications. Photographs of patients taken before and after treatment were randomized, masked, and independently graded on a scale of 0 (no festoon) to 4 (severe festoon). Each photograph was taken using a Canon PowerShot Elph 110 HS 16.1 megapixel camera (Tokyo, Japan) in flash mode with additional lighting provided by 1 external halogen bulb (20 W, FL 36, Ushio, Inc., Tokyo, Japan) in front of the subject, 45° superior to the horizontal plane through the pupils. In each case, the tetracycline was prepared in an aseptic working environment using the following technique: 0.2 g tetracycline HCl USP powder (Fagron, St. Paul, MN, U.S.A.) was transferred to the barrel of a luer capped 20-ml syringe and the plunger was then carefully replaced. The luer cap was removed, and the powder was reconstituted by adding 10 ml preservative-free sterile water for injection (Hospira, Lake Forest, IL, U.S.A.) through the needle port. With the luer cap replaced, the solution was shaken well. A Millex GP 0.22-μm filter (EMD Millipore, Billerica, MA, U.S.A.) and a fluid dispensing connector (B. Braun, Melsungen, Germany) were then attached to the 20-ml syringe and prime filter. Finally, a 1-ml tuberculin syringe was attached and filled with 0.5 ml sterile reconstituted tetracycline 2% solution. The final solution had a pH of 2.1 to 2.3, and prior to its use, it was stored for at most 2 hours, protected from light. In each case, tetracycline was injected into several planes of the festoon using the 1-ml tuberculin syringe attached to a 30-gauge needle. Follow-up interval was defined as the time between injection and the date of first follow-up photograph.

RESULTS A total of 21 patients underwent tetracycline 2% injection for treatment of lower eyelid festoons during the study period, and 11 patients met inclusion criteria with pre- and postinjection photographs. There were 10 female patients and 1 male patient, with an average age of 63 years (range, 53–72 years). Mean follow up was 121 days (range, 18–586 days). All patients received bilateral injections. Four patients received tetracycline treatment in the operating room after undergoing bilateral upper and/or lower blepharoplasty. Four patients had a history of bilateral upper and/or lower blepharoplasty, 2 patients had a history of upper blepharoptosis repair, and 1 patient had a history of onabotulinum toxin A injections for lateral canthal rhytids prior to the tetracycline treatment. Mean injected volume of tetracycline in each festoon was 0.24 ml (range, 0.1–0.75 ml). The overall mean preinjection grade for all festoons was 2.1 (range, 0–3; standard deviation [SD], 0.89). There was no significant difference in preinjection grades between festoons of the right lower eyelid (mean, 2.2) and the left lower eyelid (mean, 2.0; p = 0.15). The overall mean postinjection grade for all festoons was 1.2 (range, 0–2; SD, 0.72). There was no significant difference in postinjection grades between festoons of the right lower eyelid (mean, 1.3) and the left lower eyelid (mean, 1.1; p = 0.21). The difference in mean festoon grade after intralesional tetracycline 2% injection was statistically significant (p 

Intralesional tetracycline injection for treatment of lower eyelid festoons: a preliminary report.

To determine the safety and effectiveness of intralesional tetracycline 2% injection for the treatment of lower eyelid festoons...
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