New Strategies for the Management of Ocular Surface Disease in Glaucoma Patients

Laura Voicu; Sarwat Salim


Curr Opin Ophthalmol. 2021;32(2):134-140. 

In This Article

Advances in the Medical Management of Ocular Surface Disease in Glaucoma Patients

Management approaches for OSD in glaucoma patients are often multifaceted and should be targeted to the underlying causes of disease. In many glaucoma patients, preservative-containing glaucoma drops contribute to inflammation of the ocular surface. As discussed above, this can cause or exacerbate underlying MGD with decreased lipid layer thickness and hyperosmolarity. A reduction in the density of conjunctival goblet cells, responsible for maintaining the mucin layer and stabilizing the tear film, has also been reported.[23] Recently, a corneal confocal study demonstrated neuroinflammatory effects of preservative-containing glaucoma drops, visible structurally as increased nerve tortuosity and dendritic cell density.[24] Prior studies have linked trabeculectomy failure to reduced goblet cell density, and a recent report on the development of OSD after trabeculectomy pointed to preoperative chronic glaucoma drop use as a risk factor for postoperative development of dry eye and limbal stem cell deficiency.[25,26] Another study demonstrated improved OSD in eyes where glaucoma drops were stopped after successful trabeculectomy.[27] This evidence highlights the need to reduce drop burden, especially those with preservatives, as an important strategy for managing OSD.

Multiple strategies have emerged for reducing preservatives exposure in glaucoma patients, including consolidating medications to fixed-dose combination products or switching to preservative-free formulations.[28] A recent systematic literature analysis found that prostaglandin analogs, especially preservative-free formulations, had a less detrimental effect on conjunctival goblet cells than other antiglaucoma medications.[23] Another study demonstrated significant improvement in Ocular Surface Disease Index (OSDI) scores after 6 weeks of switching from a BAK-preserved prostaglandin to preservative free tafluprost.[29] Xelpros (Sun Pharmaceutical Industries, Cranbury, NJ, USA) is a commercially available formulation of preservative free latanoprost 0.005% in a multidose bottle that has been recently introduced to the market, joining other available preservative-free formulations of prostaglandin, timolol, and dorzolamide-timolol. Compounding pharmacies are also releasing fixed-dose combination formulations of preservative free glaucoma drops which are often affordable and conveniently available via mail-order. The expansion and availability of such formulations would help to reduce the excessive preservative burden and should be strongly considered.

Reducing bacterial load on the ocular surface and eyelid margins is also an important consideration in the management of blepharitis that contributes to OSD. As mentioned earlier, high ocular surface bacterial loads and MGD increase the risk of postoperative infection after glaucoma surgery.[8] Hypochlorous acid spray 0.1% is available from multiple manufacturers without prescription, and twice daily application to the eyelid margin has been shown to reduce the load of Staphylococcus aureus, Staphylococcus Epidermidis and other bacteria with efficacy similar to that of betadine application.[30] Further studies on the effects of chronic administration of hypochlorous acid on the ocular surface microbiome would be valuable to elucidate the optimal treatment period peri-operatively.

Topical anti-inflammatory medications for the treatment of OSD have advanced recently. Topical steroids are often implemented in the treatment of OSD. In glaucoma patients, steroid use should be closely monitored due to the potential risk of intraocular pressure elevation. Loteprednol etabonate is associated with lower rates of intraocular pressure elevation compared to prednisolone acetate or dexamethasone, and it may be particularly useful when steroids are required in these patients.[31] Cequa (Sun Pharmaceutical Industries, Cranbury, NJ, USA) is an aqueous, nanomicellar ophthalmic solution of cyclosporine 0.09% that has been approved to increase tear production in patients with dry eye.[32,33] Cequa is a lipophilic molecule within a hydrophobic core and outer hydrophilic shell, which has been shown to improve its bioavailability. Cyclosporine has been shown to increase the density of conjunctival goblet cells, which are reduced with the chronic use of topical glaucoma medications, and may be of particular benefit to glaucoma patients with OSD.[34] Xiidra (Lifitegrast 5.0%, Novartis, Cambridge, MA, USA) is a lymphocyte function-associated antigen (LFA)-1 antagonist that has been recently approved as twice daily application to treat signs and symptoms of dry eye.[35–37] Trials have demonstrated improvement in inferior corneal staining and eye dryness score with use of Xiidra versus placebo, and symptomatic improvement may begin as early as two weeks of use.[37]

The role of Omega-3 fatty acids in managing OSD remains somewhat unclear. Recently, the Dry Eye Assessment and Management (DREAM) study did not find a significant benefit to the use of Omega-3 supplements over the course of 12 months compared to placebo.[38] Interestingly, however, the benefit of Omega-3 fatty acids was demonstrated in a study of glaucoma patients with OSD.[39] This prospective, multicenter study of 1,255 patients on topical antiglaucoma drops found that supplementation of 1500 mg of Omega-3 fatty acids per day over a period of 12 weeks reduced symptoms of scratching, stinging, grittiness, tired eyes and blurry vision, as well as improvement in Schirmer's test and tear break up time scores.