Inner limiting Membrane Peel Extends In vivo Calcium Imaging of Retinal Ganglion Cell Activity Beyond the Fovea in Non-Human Primate.

High resolution retinal imaging paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of activity dependent calcium changes in retinal ganglion cells (RGCs) at single cell resolution in the living eye. The inner limiting membrane (ILM) is a barrier for viral vectors, restricting transduction to a ring of RGCs serving the fovea in both humans and non-human primates (NHP). We evaluate peeling the ILM prior to intravitreal injection as a strategy to expand calcium imaging beyond the fovea in the NHP eye in vivo. Five Macaca fascicularis eyes (age 3-10y; n=3 individuals; 2M, 1F) underwent vitrectomy and 5 to 6-disc diameter ILM peel centered on the fovea prior to intravitreal delivery of 7m8:SNCG:GCaMP8s. Calcium responses from RGCs were recorded using a fluorescence adaptive optics scanning laser ophthalmoscope. In all eyes GCaMP was expressed throughout the peeled area, representing a mean 8-fold enlargement in area of expression relative to a control eye. Calcium recordings were obtained up to 11 degrees from the foveal center. RGC responses were comparable to the fellow control eye and showed no significant decrease over the 6 months post ILM peel, suggesting that RGC function was not compromised by the surgical procedure. In addition, we demonstrate that activity can be recorded directly from the retinal nerve fiber layer. This approach will be valuable for a range of applications in visual neuroscience including pre-clinical evaluation of retinal function, detecting vision loss, and assessing the impact of therapeutic interventions.

Retinal vessel diameter changes after 6 months of treatment in the Idiopathic Intracranial Hypertension Treatment Trial.

BACKGROUND/AIMS: Prior studies support an association between increased retinal venule diameter and elevated intracranial pressure (ICP). The purpose of this study was to test the hypothesis that retinal venule diameters decrease in association with long-term therapy for high ICP in subjects with idiopathic intracranial hypertension (IIH). METHODS: This is a retrospective analysis of multicentre randomised controlled trial data. Standardised procedures were used to measure area of optic nerve head elevation (ONHA) and diameters of 4 arterioles and 4 venules 2.7 mm from the optic disc centre on fundus photos collected at baseline and after 6 months of randomised treatment with placebo+diet or acetazolamide+diet in subjects participating in the IIH Treatment Trial (IIHTT) (n=115). Change in arteriole (Da) and venule (Dv) diameters from baseline to 6 months was studied as a function of IIH, haemodynamic and demographic variables. RESULTS: Dv decreased following 6 months of therapy (8.1 µm, 5.9%, p<0.0005) but Da did not change. Dv change was associated with ONHA change (p<0.0005, r=0.47) and this association persisted in multiple variable models. CONCLUSIONS: Retinal venule diameter decreased, and arteriole diameter did not change in association with treatment for elevated ICP with a weight loss intervention and placebo or acetazolamide in IIHTT participants. Further study is needed to determine how retinal vessel measurements can be combined with other clinical observations to inform disease management.

The Relationship Between Optic Disc Volume, Area, and Frisén Score in Patients With Idiopathic Intracranial Hypertension.

PURPOSE: To compare measurements of papilledema using fundus photography, optical coherence tomography (OCT), and Frisén score in patients with idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, noncomparative analysis of randomized controlled trial data. METHODS: The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) evaluated weight management and treatment with acetazolamide compared with placebo in patients with IIH and mild visual loss. Among the 126 subjects in the IIHTT OCT substudy, fundus photographs and OCT scans of the optic disc were taken at baseline and at 6 and 12 months after enrollment. Trained readers scored each eye using a modified Frisén scale and measured the area of disc elevation. OCT scans assessed optic nerve head (ONH) volume. Correlations between volume and area were computed for both study and nonstudy eyes. RESULTS: Disc area and ONH volume were positively correlated at baseline (R2 = 0.77 in study eyes, P < .001). Correlations between area and volume were similar in the treatment groups at baseline, but were weaker in the acetazolamide group compared with the placebo group at 6 months (R2 = 0.25 vs R2 = 0.76 in study eyes) and 12 months (R2 = 0.19 vs R2 = 0.65 in study eyes). At 6 and 12 months after enrollment, there was no consistent relationship between Frisén score, disc area, and ONH volumes in the acetazolamide group. CONCLUSION: Frisén score fails to reflect the photographic area and OCT volume of papilledema after treatment with acetazolamide. Clinicians should use caution when using the Frisén scale to monitor the effect of treatment on papilledema over time.