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.

Role of Inflammation in Canine Primary Glaucoma

“…Ocular surface inflammation —The detrimental impact of antiglaucoma medications on the ocular surface has been extensively reported in the human literature, with evidence of inflammation and disrupted ocular surface homeostasis from the majority of antiglaucoma drug classes, including carbonic anhydrase inhibitors, prostaglandin analogs, β-blockers, α-adrenergic, cholinergic, and ROCK inhibitors [ 10 , 30 ]. In humans, inflammatory/pathological changes to the ocular surface are diverse and include meibomian gland dysfunction, tear film deficiency, blepharitis, keratopathies (e.g., superficial punctate keratitis, reduced corneal sensitivity), and various conjunctival pathologies (e.g., hyperemia, keratinization, fibrosis, squamous metaplasia, and goblet cell deficiency) [ 30 ]. In contrast, very little is known about this topic in veterinary patients.…”

“…Inflammation can also reduce drug bioavailability due to blood-tear barrier breakdown and subsequent protein binding in the tear film [ 39 , 40 , 41 , 42 ]. Further, irritation from chronic glaucoma medications and associated toxic preservatives (e.g., benzalkonium chloride) can diffuse from the surface to deeper structures, leading to degeneration and inflammation of the trabecular meshwork and higher resistance to aqueous humor outflow [ 30 , 43 ]. This vicious cycle might clinically appear as an apparent loss of medication efficacy, namely, the more drugs, the greater the toxic reaction, leading to a higher IOP despite the initial therapeutic response [ 43 ].…”

“…Growth of the fibrotic capsule forming around the gonioimplant (bleb fibrosis), ultimately responsible for implant failure and IOP elevation, is believed to be stimulated (at least in part) by the ‘toxic’ inflamed aqueous humor of glaucomatous dogs that is drained in the subconjunctival space around the gonioimplant [ 48 , 49 , 50 ]. Moreover, antiglaucoma medications contribute to the development of subconjunctival fibrosis [ 30 ], further reducing the drainage of aqueous humor via the filtering device. As such, limiting inflammation appears to be a major factor in the control of bleb fibrosis [ 48 , 49 , 50 ].…”

Immune-Mediated Ocular Surface Disease in Diabetes Mellitus—Clinical Perspectives and Treatment: A Narrative Review

“…OSD encompasses a spectrum of ocular surface disorders characterized by abnormalities in the tear film, cornea, conjunctiva, and meibomian glands, leading to symptoms of ocular discomfort, visual disturbances, and potential vision-threatening complications [ 3 ]. While OSD can occur in various clinical contexts, its association with DM has gained increasing recognition in recent years.…”

Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations

“…Side effects are mainly topical and include conjunctival hyperaemia, induced iris darkening, periocular skin pigmentation and eyelash changes [ 5 ]. Meibomian gland dysfunction, conjunctival goblet cell dropout, tear films alterations and pseudodendritic keratitis are overlooked conditions that may also result from prostaglandin analogues therapy but seem more frequent in benzalkonium chloride (BAK)-containing and multiple anti-glaucoma medications [ 6 ].…”