Retinal ganglion cell (RGC) axons converge at the optic nerve head to convey visual information from the retina to the brain. Pathologies such as glaucoma, trauma, and ischemic optic neuropathies injure RGC axons, disrupt transmission of visual stimuli, and cause vision loss. Animal models simulating RGC axon injury include optic nerve crush and transection paradigms. Each of these models has inherent advantages and disadvantages. An optic nerve crush is generally less severe than a transection and can be used to assay axon regeneration across the lesion site. However, differences in crush force and duration can affect tissue responses, resulting in variable reproducibility and lesion completeness. With optic nerve transection, there is a severe and reproducible injury that completely lesions all axons. However, transecting the optic nerve dramatically alters the blood brain barrier by violating the optic nerve sheath, exposing the optic nerve to the peripheral environment. Moreover, regeneration beyond a transection site cannot be assessed without reapposing the cut nerve ends. Furthermore, distinct degenerative changes and cellular pathways are activated by either a crush or transection injury. The method described here incorporates the advantages of both optic nerve crush and transection models while mitigating the disadvantages. Hydrostatic pressure delivered into the optic nerve by microinjection completely transects the optic nerve while maintaining the integrity of the optic nerve sheath. The transected optic nerve ends are reapposed to allow for axon regeneration assays. A potential limitation of this method is the inability to visualize the complete transection, a potential source of variability. However, visual confirmation that the visible portion of the optic nerve has been transected is indicative of a complete optic nerve transection with 90-95% success. This method could be applied to assess axon regeneration promoting strategies in a transection model or investigate interventions that target the axonal compartments.

Purpose

To characterize the change of ganglion cell complex (GCC) thickness and macular vessel density in glaucoma suspect eyes with ocular hypertension (OHT) or glaucomatous optic neuropathy (GON).

Design

Prospective, longitudinal study.

Participants

Eight-three eyes (24 healthy, 30 OHT, and 29 GON) of 65 patients who underwent at least 3 visits were included from the Diagnostic Innovations in Glaucoma Study. The mean follow-up was at least 3 years.

Methods

OCT angiography (OCTA)-based vessel density and OCT-based structural thickness of the 3 × 3-mm¹ GCC scan slab were evaluated at each visit. The rates of vessel density and thickness change were compared across diagnostic groups using a linear mixed-effects model.

Main outcome measures

Change rates of macula GCC thickness and superficial vessel density.

Results

Significant mean rates of both GCC thinning and vessel density loss were detectable in OHT and GON groups. Of the individual suspect eyes, 49.1% showed significant loss (P < 0.05) with either vessel density or GCC thickness. Of the GON eyes, 31.0% showed both significant GCC loss and vessel density loss, 51.7% showed only significant GCC loss, whereas 17.2% showed only significant vessel density loss. Vessel density loss was faster than GCC thinning in half of the suspect eyes based on percent loss analysis. The age and scan quality-adjusted GCC thinning rates of the OHT group (-0.59 μm/year; P = 0.025) and GON group (-0.79 μm/year; P = 0.058) were faster than those of the healthy group (-0.11 μm/year), whereas the rate of vessel density loss was not significantly different among the diagnostic groups (all P > 0.2). Higher mean intraocular pressure during follow-up was associated with faster GCC thinning in the OHT group (P = 0.065) and GON groups (P = 0.015), but was not associated with the rate of vessel density decrease.

Conclusions

Whereas the rate of GCC thinning was faster on average in suspect eyes than in healthy eyes, some suspect eyes showed significant loss of vessel density and faster vessel density loss than GCC thinning. OCT and OCTA are complementary and useful for evaluating eyes with OHT or GON.