Ocular surface disease: a known yet overlooked side effect of topical glaucoma therapy

Abstract

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

Keywords: alpha-adrenergic agonists; beta blockers; carbonic anhydrase inhibitors; dry eye disease; nitric oxide-donating prostaglandin analogs; ocular surface disease; prostaglandin analogs; rho-kinase inhibitors.

FIGURE 1

General mechanism of ocular surface toxicity due to pressure-lowering medications (PLMs). Within the ocular surface, PLMs cause overexpression of C-C chemokine receptors (CCR)-type 4 and 5, leading to an IgE-mediated allergic reaction on the ocular surface. Also, they cause to disrupt the degrading-remodeling balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the extracellular matrix (ECM). The latter results in decreased goblet cell density, squamous metaplasia, and ocular surface damage. Footnote: HLA-DR, human leukocyte antigen DR isotype; MMPs, matrix metalloproteinases; TIMPs, tissue inhibitors of metalloproteinases; ECM, extracellular matrix; CCR, C-C chemokine receptor.

FIGURE 2

Ocular surface adverse effects of pressure-lowering medications. Footnote: CAIs, carbonic anhydrase inhibitors; PGAs, prostaglandin analogs; CCT, central corneal thickness; PSK, pseudodendritic sterile keratitis; NO, nitric oxide; ROCK, rho-kinase. “Created with BioRender.com”.

FIGURE 3

A 91-year-old female patient with a history of chronic angle-closure glaucoma treated with benzalkonium chloride (BAK)-containing 0.03% bimatoprost qHs and a fixed combination of 0.5% timolol maleate/2% dorzolamide BID eyedrops for at least 10 years. (A) Significant erythema of the periorbital skin and lid margin are consistent with allergic contact dermatitis. (B) After 4 weeks of treatment with ocular lubricants and preservative-free (PF) IOP-lowering eyedrops, there was a significant reduction of the periorbital skin and lid margin erythema. However, residual skin pigmentation (white arrows) is observed. Footnote: Written informed consent was obtained from both patients to publish the clinical images.

FIGURE 4

A 61-year-old female patient with a 7-year history of primary open-angle glaucoma (POAG) was treated with BAK-containing 0.005% latanoprost qHs eyedrops. (A,B) Significant lid margin erythema, telangiectasias (white arrow), meibomian gland clogging (yellow arrow). Footnote: Written informed consent was obtained from the patient to publish the clinical images.

FIGURE 5

Keratograph analysis from a patient with a 12-year history of POAG treated with BAK-containing 0.005% latanoprost qHs eyedrops showing significant meibomian gland dropout (yellow arrow).

FIGURE 6

Clinical photographs of the patient from Figure 4 showing (A) conjunctival hyperemia with lissamine green staining and (B) central and inferior corneal staining (white arrow).