Mechanical Management of Medicamentosa

A 66-year-old White male presented on referral for an ocular surface disease (OSD) evaluation. He noted significant irritation OU, which was recently worsening. His ocular surface irritation had become so severe that it was limiting his ability to enjoy his hobbies.

HISTORY & EXAMINATION FINDINGS

His ocular history was significant for a central retinal vein occlusion with macular edema OD requiring anti-VEGF intravitreal injections every 6 to 8 weeks. He was on timolol 0.5% twice daily OU for ocular hypertension and had a history of cataract extraction OU with IOL implantation.

His medical history was pertinent for hypertension and sleep apnea. The patient reported using preserved artificial tears with a detergent-like preservative derived from benzalkonium chloride (BAK) roughly 40 to 50 times a day to manage his ocular surface irritation. At the initial presentation, his Standardized Patient Evaluation of Eye Dryness (SPEED) score was 15/28. Tear osmolarity was 383 mOsm/L OD and above the readable range OS. Point-of-care matrix metalloproteinase-9 (MMP-9) was positive OU.

His VA was 20/40 OD and 20/20 OS, and his IOP was 18 mm Hg OU. On external examination, lid rosacea with trace anterior blepharitis and lid margin telangiectasia were noted bilaterally. On slit-lamp examination, pertinent findings included 2+ injection of the bulbar conjunctiva and 2+ follicular reaction of the palpebral conjunctiva with a mildly increased tear lake and no corneal staining OU. Meibomian gland evaluation revealed clear secretions in both lids. Due to the overuse of preserved artificial tears, the patient had developed a follicular conjunctivitis, also known as ocular surface medicamentosa. Ocular surface medicamentosa is often caused by a chemical toxicity from a delayed, cell-mediated hypersensitivity response of the ocular surface due to eye drop preservatives (Figure).

TREATMENT STRATEGY

My therapeutic goals for this patient were to:

• Reset his ocular surface
• Improve his symptoms
• Reduce his dependency on preserved artificial tears
• Keep his IOP under control with the preserved timolol drops

We performed a probe and irrigation of the patient’s bilateral nasolacrimal system and a full ocular surface lavage using the an irrigating eyelid retractor. The patient was also switched to preservative-free artificial tears to be used no more than four times daily and was continued on the timolol. In addition, he was started on a topical steroid four times daily for 2 weeks and told to follow-up in 3 to 4 weeks.

FOLLOW-UP

When the patient returned 4 weeks later, he noted major improvement in all symptoms. His OSD vitals included a SPEED score of 2/28, an osmolarity of 310 mOsm/L OD and 298 mOsm/L OS, and a negative MMP-9 OU. His full examination revealed no follicular reaction and a return of normal tear meniscus. I instructed him to continue therapy with the preservative-free artificial tears and to return in 3 to 4 months.

DISCUSSION

The rationale behind performing ocular surface lavage with an irrigating lid retractor was influenced by the results of a recent clinical trial, which showed that preservatives often cause these follicular reactions and are embedded or trapped within the palpebral conjunctiva and fornices. By using high-pressure irrigation targeted specifically at the palpebral conjunctiva, the irrigating eyelid retractors can help to remove both the high inflammatory and irritant loads from the ocular surface.¹

Toxic keratoconjunctivitis is damaging to the ocular surface and typically follows contact with an offending agent, such as a preservative or chemical injury. In our case, the patient was using a preserved artificial tear more than 40 times daily. BAK is the most ubiquitously used ocular medication preservative, known to be used in approximately 70% of topical ophthalmic eye drops.² BAK is a quaternary ammonium compound that is hydrosoluble and acts as a detergent, disrupting the lipid component of microbial cell walls and making it an effective bactericidal agent. However, BAK is thought to have cytotoxic effects at extremely low concentrations, resulting in both corneal epithelial damage and conjunctival inflammatory changes. In our patient, this resulted in significant OSD, follicular reaction, and conjunctival redness.

Historically, the treatment of medicamentosa has been aimed at eliminating the offending agent, as we did in this case by having the patient use only preservative-free artificial tears. Supportive care with cold compresses and topical antiinflammatory medications can also help.

In this case, we performed a full ocular surface lavage using an irrigating eyelid retractor to help improve the patient’s symptoms. Our hypothesis was that the inflammatory reaction from the preservatives was happening at the palpebral-conjunctiva interface. By targeting high-pressure irrigation at the palpebral conjunctiva and fornix, where we believed these preservatives were trapped, we were able to successfully lavage and remove the preservatives from the tear film.

Clinical trial evidence of the irrigating eyelid retractor has illustrated that there was an improvement in the reduction in MMP-9 with the device-assisted rinse compared with a standard rinse. In fact, 72% reduction in MMP-9 was noted with the device rinse, which was significantly superior to a standard rinse.¹

ANOTHER USE FOR AN OSD TOOL

This is the first case, to my knowledge, to show an improvement in ocular surface medicamentosa with complete ocular surface lavage using an irrigating eyelid retractor. This procedure improved the signs and symptoms of follicular conjunctivitis secondary to preservatives in artificial tears. Thus, it can be a useful tool in the treatment of multiple OSDs, including superior limbic keratoconjunctivitis, dry eye disease, allergic keratoconjunctivitis, and, as this case demonstrates, ocular surface medicamentosa.