Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale.

OBJECTIVES: To compare and contrast 2 methods of quantitating papilledema, namely, optical coherence tomography (OCT) and Modified Frisén Scale (MFS). METHODS: Digital optic disc photographs and OCT fast retinal nerve fiber layer (RNFL) thickness, fast RNFL map, total retinal thickness, and fast disc images were obtained in 36 patients with papilledema. Digital optic disc photographs were randomized and graded by 4 masked expert reviewers using the MFS. We performed Spearman rank correlations of OCT RNFL thickness, OCT total retinal thickness, and MFS grade from photographs. RESULTS: OCT RNFL thickness and MFS grade from photographs correlated well (R = 0.85). OCT total retinal thickness and MFS grade from photographs had a similar correlation of 0.87. Comparing OCT RNFL thickness with OCT total retinal thickness, a slope of 1.64 suggests a greater degree of papilledema thickness change when using the latter. CONCLUSIONS: For lower-grade abnormalities, OCT compares favorably with clinical staging of optic nerve photographs. With higher grades, OCT RNFL thickness processing algorithms often fail, with OCT total retinal thickness performing more favorably.

Cell-autonomous generation of mitochondrial superoxide is a signal for cell death in differentiated neuronal precursor cells.

The vast majority of optic neuropathies result from retinal ganglion cell (RGC) axonal injury. This induces cell death and is associated with a burst of mitochondria-generated superoxide within the soma. It is unclear whether there is a clear causal relationship between superoxide generation and cell death. To determine whether mitochondrial-generated superoxide can cause cell-autonomous death signaling, we knocked down SOD2 in a pure population of RGC-5 cells, a neuronal precursor cell line that can be differentiated to resemble retinal ganglion cells. RGC-5 cells were differentiated and transfected with siRNA for SOD2 or a scramble control. Viability, superoxide production, cytotoxic RNA transfection efficiency, and measurement of SOD2 protein levels by immunoblotting were assayed at varying times after transfection. SOD2 knockdown increased intracellular superoxide levels and cell death was presumed triggered from knockdown. This was amplified when extramitochondrial superoxide was elevated with the redox cycling agent menadione. Dysregulation of mitochondrial superoxide in differentiated RGC-5 cells is likely a potent signal for cell death, consistent with a role of this reactive oxygen species in apoptosis signaling after axonal injury.