Multimodal adaptive optics imaging of ganglion cells in patients with primary open angle glaucoma

Abstract

Purpose : To determine if there are changes in ganglion cell (GC) size and density in subjects with hemifield defect associated with glaucoma.

Methods : Two eyes in two glaucoma subjects (P1: advanced glaucoma, 54 yrs and P2: moderate glaucoma, 57 yrs) with hemifield defect were imaged with the FDA multimodal adaptive optics (AO) imager. Three locations were imaged (Fig. 1a) with the AO focus at the ganglion cell layer (GCL): one above and one below the raphe in the approximate location of maximum and minimum retinal thickness and visual field deficit as determined from clinical OCT collected prior to AO imaging; and a third location at 12° temporal. At each location, 1.5×1.5° field of view AOOCT volumes were collected and registered. Morphological parameters, such as nerve fiber layer (NFL) and GCL thickness and GC size (100 randomly selected GCs) were quantified at all three locations and GC density was measured only at 12° where the GCL is a monolayer.

Results : There were clear differences in thickness and GC size that were correlated to the hemifield defect. In P1, the NFL is almost absent at the examined locations. The GCL is 4× thicker at superior area (26.0 µm) than the inferior area affected by glaucoma (6.9 µm). The GC size is largest at 12° (24.3±6.8 µm, 2× larger than the healthy controls) with a significantly reduced cell density of 1062 counts/mm². Relative smaller GCs are found at the other two locations (superior: 17.6±3.3 µm and inferior: 18.1± 2.5 µm). Interestingly, the GC size at both locations is larger than that measured previously for healthy subjects (11.4±1.8 µm) [PNAS, 114(8), 2017]. In P2, NFL and GCL was extremely thin, 6.2 and 4.8 µm and the GC diameter measured 17.5±3.3 µm in areas of functional deficit (Fig. 1b, inferior). By comparison, the NFL and GCL thickness were nearly normal, 16.4 and 41.8 µm, and the GC diameter measured 14.6±2.2 µm in areas not yet affected by glaucoma (Fig. 1b, superior). At the 12° temporal location, GC diameter and density were 17.1±3.7 µm and 2370 counts/mm² in comparison to 13.9±3.1 µm and 3,817±719 counts//mm² for the healthy controls (Fig. 1c).

Conclusions : GC density is reduced throughout the retina in glaucoma subjects correlated to NFL thickness deficits, while GC size is significantly larger. The ability to resolve GCs may lead to new biomarkers such as size and density that enable earlier detection and characterization of the disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.