Commentary: Evaluating ocular surface disease in glaucoma.

Ocular surface disease (OSD) includes dry eye disease (DED), anterior blepharitis, meibomian gland dysfunction (MGD), conjunctivitis, and keratitis. It is the leading cause for ophthalmic consultation, and its reported prevalence in medically treated glaucoma patients is 48–59% compared with the general elderly patients (15%).[1] Glaucoma patients who are either on anti-glaucoma medications (AGMs) or post-filtration surgery are at increased risk of developing OSD.

The diagnosis of OSD is essentially clinical and is often difficult owing to its multifactorial nature and discrepancies in symptoms and signs. Moreover, conventional diagnostics of DED such as Schirmer’s test and fluorescein tear film break up time (TBUT) have poor reliability and reproducibility, making the diagnosis and monitoring of OSD challenging.[2] Ex-vivo histological techniques and impression cytology tend to be invasive. Technological advances in ocular anterior segment imaging for objectively evaluating DED include non-invasive tear break-up time (NIBUT) measurements, anterior segment optical coherence tomography (AS-OCT), confocal microscopy, meibography, interferometry, aberrometry, thermography, and tear film imager.[2]

The NIBUT and AS-OCT are non-contact in nature and overcome the problem of reflex tearing. The NIBUT measures the thinning of the tear film and not the break-up of the full thickness tear film. A NIBUT cut-off value of ≤10 s was suggested as an indicator for DED diagnosis by the dry eye workshop II (DEWS II).[3] The AS-OCT parameters for evaluating DED are the tear meniscus height (TMH) and tear meniscus area (TMA). These parameters have been found to correlate well with Schirmer’s scores and aqueous deficient DED.[2] In glaucoma patients, AS-OCT is used mainly to visualize the anterior chamber anatomy aqueous humor outflow pathways and evaluate the bleb morphology to assess its functioning status. Available data on AS-OCT application to find detrimental effects of AGMs on the ocular surface are sparse. Agnifili et al.[4] reported significantly lower TMH and TMA in glaucoma patients on AGMs compared with normals, with worse scores in patients on multi-drug therapy.

The mechanisms by which topical AGMs predispose to OSD are multifactorial and include the number/dose of drugs, effect of active compounds and preservatives, and duration of therapy. At the cellular level, the presence of epithelial microcysts, decrease in the conjunctival goblet cell density, squamous metaplasia, infiltration of inflammatory cells (conjunctiva associated lymphoid tissue [CALT]), changes in corneal dendritic cells, and reduction in corneal sub-basal nerve plexus with increased nerve beading and tortuosity have been reported. These changes are particularly pronounced with preserved medications and multi-drug therapy.[56] The development of OSD can significantly affect the quality of life of these patients. More importantly, it can cause serious problems with medication compliance, compromising the target IOP and contributing to disease progression in these patients. The development of serious OSD on medical therapy for glaucoma is also an indication for discontinuing medications in favor of filtration surgery. In patients undergoing filtration surgery, the type of surgery, anti-mitotic agents, postoperative wound healing, and filtering bleb characteristics contribute to OSD development.[7] However, improvements in the ocular surface have been documented in glaucoma patients following surgery, particularly in minimally invasive glaucoma surgery (MIGS) and non-penetrating deep sclerectomy (NPDS), as demonstrated in this study.[58] This is most likely due to the cessation of toxic effects of AGMs and smoother bleb characteristics seen following these surgeries.[5] The ocular surface may be relatively spared from the effects of severe inflammation due to extensive conjunctival handling in conventional trabeculectomy and glaucoma drainage devices (GDDs). The choice of surgery is complex and dictated by several factors such as type and severity of glaucoma, baseline IOP, target IOP, any previous surgery, and the cost of the proposed procedure. However, in patients with co-existing OSD, NPDS and MIGS may be optimal choices for early intervention in the interest of the patient’s quality of life.

The comprehensive evaluation of the ocular surface, particularly in symptomatic patients, for appropriate decision-making, cannot be overemphasized. Effective treatment of OSD would also contribute to the success of any planned glaucoma filtration surgery. We recommend seeking a cornea expert’s consultation and collaborating to treat the patient. With advances in ocular surface imaging techniques, particularly in-vivo confocal microscopy (IVCM) and newer generation AS-OCT (swept-source OCT for tear film volume and en-face OCT for ocular surface)[2] that can provide accurate microstructural information of the ocular surface and adnexa, it may be possible to make better decisions for patient care and do more objective clinical studies of the ocular surface in patients with OSD.