Confocal Microscopy and Anterior Segment Optical Coherence Tomography Imaging of the Ocular Surface and Bleb Morphology in Medically and Surgically Treated Glaucoma Patients: A Review

Abstract

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.

Keywords: anterior segment optical coherence tomography; glaucoma; in vivo confocal microscopy; medical treatment; ocular surface; surgical treatment.

Figure 1

In vivo confocal microscopy (IVCM) of the ocular surface tissues in multi-treated medically controlled glaucoma. (A–E) Confocal frames taken from a patient controlled with a preserved fixed combination of timolol and dorzolamide and a preservative-free prostaglandin analog (PGA) (three eyedrops per day). (A) Goblet cells (GCs). GCs appear as hyper-reflective elements (black arrowhead) dispersed within the epithelium, and often appear scattered with an evident reduction of their density. (B) Inflammatory infiltrates. Inflammatory infiltrates appear as clusters of small hyper-reflective and mono-nucleate elements (presumably lymphocytes) infiltrating the epithelium of the tarsal or bulbar conjunctiva. (C) Epithelial microcysts. These structures (white asterisk) represent hallmarks of aqueous humor outflow stimulation through the uveo-scleral route, rather than detrimental effects induced by medications. (D) Meibomian glands. These glands appear markedly reduced in their dimension, with hyper-reflectivity of acinar wall and interstice; the black arrow indicates a glandular acinus. (E) CALT. Roundish immune follicles (black asterisk) appear infiltrated by numerous small hyper-reflective mono-nucleate cells (presumably lymphocytes). (F–L) Confocal frames taken from a patient controlled with a preserved fixed combination of timolol and dorzolamide, PGA, and brimonidine (five preserved eyedrops per day). (F,L) Limbal transition epithelium. The transition epithelium of the limbus appears irregular with scattered and highly hyper-reflective inflammatory elements (L), and with evident features of cellular polymegathism (undulated white arrow). (G–I) Cornea. The sub-epithelial layer and the Bowman’s membrane (G,H) present infiltration and activation of numerous dendritic cells (white arrowhead), with alterations of sub-basal nerve plexus morphology (white arrow). The corneal epithelium (I) appears markedly irregular with a higher degree of cellular polymorphism and polymegatysm. Bar represents 50 µm.

Figure 2

Anterior segment-optical coherence tomography (AS-OCT) of tear meniscus in medically controlled glaucoma. Fluorescein appearance of the tear meniscus and tear film in patients controlled with a preservative-free or preserved PGA mono-therapy (A,B), or with two or more drugs per day (C,D). AS-OCT shows the progressive reduction of the tear meniscus height (arrowhead) with increasing the number of medications, and the cumulative daily dose of preservative, required to control the disease (E–H).

Figure 3

AS-OCT and IVCM conjunctival bleb features after glaucoma filtration surgery. (A–D) Filtration bleb imaged by AS-OCT. Diffuse (A) or cystic (B) filtration bleb after completely successful trabeculectomy, showing numerous, differently sized hypo-reflective spaces filled with aqueous humor; incapsulated (C) and flat (D) filtration bleb after a failed trabeculectomy without evidence of hypo-reflective intra-bleb wall spaces. (E–N) Bleb-wall imaged by IVCM. In diffuse (E,F) or cystic (G,H) functioning filtration blebs, the bleb-wall epithelium (E,G) shows several microcysts with a loosely arranged stroma (F,H), indicating a good aqueous humor percolation and a minimal hydraulic resistivity through the bleb-wall layers. Opposite features are present in incapsulated (I,L) or flat (M,N) non-functioning filtration blebs: the bleb-wall epithelium (I,M) shows rare microcysts, whereas the stroma (L,N) appears densely arranged. These features indicate an inefficient aqueous humor percolation through the bleb-wall layers. Bar represents 50 µm.