Topical treatment warning for orbital soft tissue

Dr. CusterSt. Louis-Oculoplastic surgeons need to be aware that orbitopathy arising from the use of topicalprostaglandin analogues is a real disorder, said Philip L. Custer, MD.

The treatment-induced orbital soft tissue changes develop in many patients on long-term topical prostaglandin analogue treatment, said Dr. Custer, professor of ophthalmology and visual sciences, Washington University School of Medicine, St Louis.

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In most, these changes are subtle. However, they can manifest as a variety of cosmetic and functional orbital and eyelid disorders that may be indications for surgery, or can complicate the execution and outcome of other oculoplastic procedures.

The deformities in some patients may be reversible after treatment is discontinued, and in the future, these unintended effects of prostaglandins may be harnessed for therapeutic purposes.

“If you encounter a patient with prostaglandin orbitopathy, work with the prescribing physician to determine if the medication can be withheld, and then, if possible allow a period of observation before proceeding with surgery,” Dr. Custer said. “In the future, we may see new delivery methods to protect the orbit from prostaglandin analogue exposure, and we may also see designer prostaglandin analogues developed to treat a variety of esthetic and functional eyelid disorders.”

The development of periorbital changes in patients using topical prostaglandin analogues was first reported in 2004, and then again 4 years later. Both studies involved small series of patients and did not appear in mainstream journals.

These initial reports may have been viewed with skepticism, owing to disbelief that a topical treatment could have such profound effects.

“Over the years, I am increasingly encountering patients with prostaglandin orbitopathy,” Dr. Custer said.

He discussed findings from a review he undertook of 35 patients with prostaglandin orbitopathy. The information was recently published online [Ophthal Plast Reconstr Surg. 2015 Feb 25. Epub ahead of print].

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Multiple prostaglandin analogues were represented in the series, and about one-third of patients were using the medication unilaterally, allowing for comparison with the contralateral eye.

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The most common findings in the series were marginal eyelid thinning with posterior migration of the lash line, hypertrichosis, periocular erythema, deepening of the superior sulci, and meibomian gland dysfunction. In addition, almost all patients had increased eyelid margin tension from horizontal eyelid shortening, often leading to lateral canthal deformity or displacement.

About 50% of the patients presented with lower eyelid retraction. The tight eyelids and canthal malposition may have been a factor contributing to ptosis, because of traction on the upper lid.

Other functional disorders included cicatricial entropion or ectropion, eyelid subluxation, and chalazia.

“It was also remarkable to me that 23% of the patients in my series were using various topical lubricants, antibiotics, and anti-inflammatory agents,” Dr. Custer said. "I wonder how many of these drops were being used to treat inflammation associated with their topical prostaglandin analogue.”

He also reviewed several cases illustrating how the prostaglandin-induced tissue changes can be self-limiting after treatment is discontinued or affect surgical intervention. One patient was operated on for lower lid retraction, trichiasis, and inferior corneal thinning.

“I addressed the lashes first with a marginal blepharotomy,” Dr. Custer said. “Never before, however, have I seen such fibrosis and contracture immediately after surgery.

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“The prostaglandin analogue was then stopped and the scarring resolved after 5 months,” he added. “In retrospect, however, I wonder what the outcome would have been if the patient simply stopped the medication and did not undergo surgery.”

In addition to the functional and cosmetic consequences Dr. Custer described, he noted that Pasquale and Berke have raised concerns that the treatment-induced lid changes can interfere with the evaluation and management of glaucoma patients by making applanation tonometry more difficult and limiting surgical access to the superior limbus.

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Turning a negative into a positive

The effects of prostaglandin analogues on orbital soft tissues are not always unwanted. For example, the possibility of using a topical prostaglandin to reduce orbital and submental fat is under investigation.

In addition, Dr. Custer raised the possibility that a prostaglandin analogue could be designed for the purpose of producing eyelid tightness in patients with facial palsy or floppy eyelid syndrome.

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Philip L. Custer, MD

E: custer@vision.wustl.edu

This article was adapted from Dr. Custer’s Wendell Hughes Lecture at the 2014 meeting of the American Academy of Ophthalmology. Dr. Custer holds stock in Johnson & Johnson and Pfizer.