Managing Ocular Surface Disease in Glaucoma Treatment: A Systematic Review

Abstract

Ocular surface disease (OSD) is a frequent disabling challenge among patients with glaucoma who use benzalkonium chloride (BAK)-containing topical glaucoma medications for prolonged periods. In this comprehensive review, we evaluated the prevalence of OSD and its management, focusing on both current and future alternatives. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria were used to assess a) the impact of active ingredients and preservatives on the ocular surface and b) the efficacy of preservative-free (PF) alternatives and adjunctive therapies. BAK-containing glaucoma medications were found to significantly contribute to OSD by increasing corneal staining, reducing tear film stability, and elevating ocular surface disease index (OSDI) scores. Transitioning to PF formulations or those with less cytotoxic preservatives, such as Polyquad^® and SofZia^®, demonstrated a marked improvement in OSD symptoms. In particular, the use of adjunct cyclosporine A, through its anti-inflammatory and enhanced tear film stability actions, was shown to be very beneficial to the ocular surface. Therefore, the most effective management of OSD is multi-factorial, consisting of switching to PF or less cytotoxic medications, adjunct use of cyclosporine A, and early incorporation of glaucoma surgical treatments such as laser trabeculoplasty, trabeculectomy, glaucoma drainage devices, or minimally invasive glaucoma surgery (MIGS).

Keywords: benzalkonium chloride; glaucoma; ocular surface disease; preservatives; topical medications.

Figure 1

Representation of the ocular surface and tear film composition (corneal epithelium, mucous layer, aqueous layer, and lipid layer). (Figure made using BioRender^® software, version 201 and adapted from [9]).

Figure 2

A brief overview of the immune-inflammatory mechanisms in the pathogenesis of ocular surface disease (Figure made using BioRender^® software, version 201).

Figure 3

External photograph of an eye with OSD showing MGD, blepharitis, and conjunctival hyperemia. Image courtesy of Karanjit S. Kooner, MD, PhD (University of Texas Southwestern Medical Center, Dallas, TX, USA).

Figure 4

Clinical photographs of ocular surface disease. (A) External photograph of a patient with chronic hyperemia and MGD. (B) Slit lamp photograph of an eye with superficial punctate keratitis (red curly bracket). Images courtesy of Özlem Evren Kemer, MD (Ankara Bilkent City Hospital, Ankara, Turkey) and Margaret Wang French, MD (University of Texas Southwestern Medical Center, Dallas, TX, USA).

Figure 5

Keratograph of an eye with OSD. (A) Keratograph of an eye with areas of dryness (arrow) disrupting the placido disk reflections on the cornea. (B) Red-orange areas correspond to faster NITBUT. (OCULUS Keratograph^®, OCULUS, Wetzlar, Germany). Images courtesy of Karanjit S. Kooner, MD, PhD (University of Texas Southwestern Medical Center, Dallas, TX, USA).

Figure 6

Clinical examples of meibography. (A) Meibography in a patient with healthy meibomian glands (asterisk). (B) MGD with significant atrophy of meibomian glands with ghosting (pale glands with abnormal meibomian gland architecture, asterisk). Images courtesy of Karanjit S. Kooner, MD, PhD (University of Texas Southwestern Medical Center, Dallas, TX, USA).

Figure 7

PRISMA flow chart.

Figure 8

Two patients with ocular cicatricial pemphigoid ((A–C) patient 1) and ((D–F) patient 2). (A) symblepharon (arrow); (B) supratarsal conjunctival scarring (arrow); (C) corneal scarring, neovascularization (arrow), and healed descemetocele (arrowhead); (D) symblepharon (arrow) and subconjunctival fibrosis (arrowhead); (E) symblepharon (arrow), subepithelial fibrosis (arrowhead), inferior forniceal shortening; (F) meibomian gland dropout with subepithelial fibrosis (asterisk). Images courtesy of Karanjit S. Kooner, MD, PhD (University of Texas Southwestern Medical Center, Dallas, TX, USA) and Özlem Evren Kemer, MD (Ankara Bilkent City Hospital, Ankara, Turkey).