Retinal Venular Tortuosity Jointly with Retinal Amyloid Burden Correlates with Verbal Memory Loss: A Pilot Study.

INTRODUCTION: Retinal imaging is a non-invasive tool to study both retinal vasculature and neurodegeneration. In this exploratory retinal curcumin-fluorescence imaging (RFI) study, we sought to determine whether retinal vascular features combined with retinal amyloid burden correlate with the neurocognitive status. METHODS: We used quantitative RFI in a cohort of patients with cognitive impairment to automatically compute retinal amyloid burden. Retinal blood vessels were segmented, and the vessel tortuosity index (VTI), inflection index, and branching angle were quantified. We assessed the correlations between retinal vascular and amyloid parameters, and cognitive domain Z-scores using linear regression models. RESULTS: Thirty-four subjects were enrolled and twenty-nine (55% female, mean age 64 ± 6 years) were included in the combined retinal amyloid and vascular analysis. Eleven subjects had normal cognition and 18 had impaired cognition. Retinal VTI was discriminated among cognitive scores. The combined proximal mid-periphery amyloid count and venous VTI index exhibited significant differences between cognitively impaired and cognitively normal subjects (0.49 ± 1.1 vs. 0.91 ± 1.4, p = 0.006), and correlated with both the Wechsler Memory Scale-IV and SF-36 mental component score Z-scores (p < 0.05). CONCLUSION: This pilot study showed that retinal venular VTI combined with the proximal mid-periphery amyloid count could predict verbal memory loss. Future research is needed to finesse the clinical application of this retinal imaging-based technology.

Sectoral segmentation of retinal amyloid imaging in subjects with cognitive decline.

INTRODUCTION: Despite advances in imaging retinal amyloidosis, a quantitative and topographical investigation of retinal amyloid beta burden in patients with cognitive decline has never been reported. METHODS: We used the specific amyloid-binding fluorophore curcumin and laser ophthalmoscopy to assess retinal amyloid imaging (RAI) in 34 patients with cognitive decline. We automatically quantified retinal amyloid count (RAC) and area in the superotemporal retinal sub-regions and performed correlation analyses with cognitive and brain volumetric parameters. RESULTS: RAC significantly and inversely correlated with hippocampal volume (HV; r = -0.39, P = .04). The proximal mid-periphery (PMP) RAC and RA areas were significantly greater in patients with Montreal Cognitive Assessment (MOCA) score < 26 (P = .01; Cohen d = 0.83 and 0.81, respectively). PMP showed significantly more RAC and area in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to cognitively normal (P = .04; Cohen d = 0.83). CONCLUSION: Quantitative RAI is a feasible technique and PMP RAC may predict HV. Future larger studies should determine RAI's potential as a biomarker of early AD.

Reduction of Amyloid in the Brain and Retina After Treatment With IVIG for Mild Cognitive Impairment.

OBJECTIVE: To assess whether intravenous immunoglobulin (IVIG) in subjects with mild cognitive impairment (MCI) results in a reduction in amyloid in the central nervous system (CNS). METHODS: Five subjects with MCI underwent baseline Florbetapir positron emission tomography and retinal autofluorescent imaging. All were administered IVIG (Octagam 10%) at 0.4 g/kg every 14 days for a total of 5 infusions. After 3 months, standard uptake value ratio (SUVR) and amyloid retinal deposits were reassessed. RESULTS: Three subjects had a reduction in amyloid SUVR and all 5 subjects had a reduction in amyloid retinal deposits in at least 1 eye. CONCLUSIONS: A short course of IVIG over 2 months removes a measurable amount of amyloid from the CNS in persons with MCI.

Microvascular abnormalities secondary to radiation therapy in neovascular age-related macular degeneration: findings from the INTREPID clinical trial.

PURPOSE: To report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites. METHODS: Two hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. INTERVENTIONS: 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment. RESULTS: The frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3. CONCLUSION: Treatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.