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

Developments in the Diagnosis of Ocular Surface Disease

One of the most significant challenges in managing OSD in glaucoma patients, especially in a busy clinical practice, is to identify those patients who require treatment. OSD is known for signs and symptoms which may not necessarily correlate. For example, a patient may have minimal surface staining but significant symptoms or may present with severe surface staining and MGD while being asymptomatic.[13] Patient surveys, such as the standardized patient evaluation of eye dryness questionnaire, are simple to implement and can identify patients with OSD who may otherwise go unnoticed.[14] Patients who are asymptomatic but demonstrate signs of OSD may benefit from treatment prior to initiating glaucoma therapy or undergoing surgery to minimize symptoms later. Recently, an ocular surface frailty index for predicting OSD symptom onset after cataract surgery has been described.[15] Combining measurements of tear break up time, osmolarity, surface staining and Schirmer's test, the index successfully predicted postoperative dry eye symptoms in patients who were previously asymptomatic. It would be valuable to apply a similar index to patients undergoing glaucoma intervention to assist in identifying those requiring proactive treatment.

With multiple mechanisms contributing to OSD in glaucoma patients, identifying each underlying cause and appropriate treatment are both important and challenging. Overall, inflammation is a common disruptive force in the development of OSD among glaucoma patients. Recent research has demonstrated increased levels of IL-6, TNF-α, and VEGF in tear samples of glaucoma patients on chronic topical prostaglandins when compared with patients with dry eye not receiving any glaucoma therapy. Of note, patients on preservative-free prostaglandins had lower expression of IL-1β.[16] These findings indicate potential opportunities to develop additional biomarkers for patients with OSD and specifically for those with glaucoma. Point of care testing for the inflammatory marker extracellular matrix metalloproteinase-9 (MMP-9) is readily performed in clinic by collecting a small sample of tears into a test cassette and can alert the clinician to the need for managing inflammation, with results available in 10 min (InflammaDry, Quidel Corporation, San Diego, CA, USA).[17] A 2019 study demonstrated elevated MMP-9 levels in 46.7% of patients on preservative-containing glaucoma medications versus 16.7% on preservative-free medications or untreated patients. MMP-9 levels correlated with other markers of inflammation and OSD, including tear film break up time, Schirmer's test, and corneal staining. In MMP-9 positive eyes, one may consider reducing preservative burden or starting anti-inflammatory treatments, which are discussed below.

Chronic ocular surface inflammation in glaucoma patients may manifest as dysfunction of the meibomian glands, leading to an evaporative dry eye state with resultant hyperosmolarity. Osmolarity represents a balance between evaporation, drainage, and production of tears. Osmolarity testing can be easily performed in a busy clinic using a handheld osmometer to collect a tear sample which is analyzed in several seconds (TearLab Corporation, Escondido, CA, USA). Hyperosmolarity indicates more rapid tear evaporation and has been demonstrated in eyes treated with topical glaucoma medications.[18,19] In one study, patients who were treated with glaucoma drops in one eye had an average osmolarity of 313 mOsmol/L in the treated eye versus 305 mOsmol/L in the untreated eye (P = 0.04).[19]

MGD has been reported in up to 80% of patients on glaucoma drops.[20] Infrared meibography has become a valuable tool to assess gland structure and is performed in approximately 5 min using one of multiple available noninvasive imaging systems, such as LipiView (Johnson&Johnson, New Brunswick, NJ, USA). Significant gland truncation or loss may indicate the need to modify the glaucoma regimen, add anti-inflammatory agents, start rigorous eyelid hygiene, or utilize in-office treatments such as thermal pulsation and intense pulsed light, which are discussed below. Tear film lipid layer analysis can be performed with the LipiView ocular surface interferometer and has recently been conducted in glaucoma patients.[21] Lipid layer thickness (LLT) was found to be significantly thinner in patients on glaucoma medications than in normal eyes, and a longer duration of medication use and greater number of drops were associated with a thinner LLT. Tear film extensional viscosity, a measure of tear film integrity, has also been recently described as a promising new biomarker for dry eye disease, and its role in glaucoma patients with OSD remains to be determined.[22] These various tests can be performed at baseline and repeated at intervals to monitor treatment interventions. Further studies into the application of such tests to the glaucoma patients with OSD may help us fine-tune our approach to management.