Abstract
Purpose::
To introduce a 3D histomorphometric strategy for characterizing laminar and prelaminar components of ONH cupping and use it to describe early cupping following moderate IOP elevation in the young adult monkey eye.
Methods::
Trephinated ONH and peripapillary sclera from both eyes of three early glaucoma monkeys (one eye normal, one eye given laser-induced EG) were 3D reconstructed (2.5 x 2.5 x 3.0 µm voxel) as previously described (Burgoyne, et al, IOVS, 2004; 45:4378). Both eyes of a bilaterally normal monkey were later reconstructed using a high-resolution version (1.5 x 1.5 x 1.5µm voxel) of the same technique. Within each ONH reconstruction, the internal limiting membrane, Bruch’s membrane opening, neural canal wall and anterior lamina position were delineated within 40 serial, radial, digital, sagittal section images (every 4.5°). A least-squares ellipse was fit to the 80 BMO points to establish a BMO-centroid and a BMO-zero reference plane. Three volumetric parameters: Prelaminar Neural Tissue Volume; post-BMO cup (the clinical cup) and Total Post-BMO Prelaminar Volume (a global measure of ONH connective tissue (CT) deformation) were calculated between 10 degree radials for each eye; and a fourth parameter - Prelaminar Neural Tissue Thickness was continuously mapped to the anterior laminar surface. For each monkey, a between-eye difference map for each parameter was generated by converting all OS data to OD configuration, overlaying BMO-centroids and subtracting (EG - N) or (OD - OS) data at each laminar location.
Results::
Overall expansion of post-BMO cup volume (247-880%) and total post-BMO prelaminar volume (87-127%) was present in the setting of Prelaminar neural tissue volume expansion (11-56%), and thickening (30-50%) in all 3 EG eyes. For each parameter, the EG eye changes far exceed the between-eye differences present in the bilaterally normal monkey (50%,14%,6% and 2%, respectively).
Conclusions::
Early cupping in young adult monkeys following chronic, moderate IOP elevation is mostly the result of fixed CT deformation of the neural canal and laminar cribrosa, rather than prelaminar neural tissue thinning due to compression or loss. Interestingly, the location of low CT volume fraction in the N eye (abstract by J.Grimm, et al) predicts the location of greatest CT deformation and prelaminar neural tissue thickening in the EG eye in all 3 monkeys.
Keywords: lamina cribrosa • optic nerve