Perimetric Measurements With Flicker-Defined Form Stimulation in Comparison With Conventional Perimetry and Retinal Nerve Fiber Measurements

Background: In this study, optic coherence tomography (OCT) examination was performed to check whether there was any interaction between ophthalmic axonal structures in unilateral tinnitus patients, and the relationship between optic nerve thickness and cochlear nerve thickness was evaluated. Objective: The aim of the study was to evaluate the relatioship between hearing loss, tinnitus, and nerve thicknesses. Study Design: Prospective study. Setting: Tertiary referral university hospital. Patients: The study included 88 patients with unilateral tinnitus, for which no organic cause could be found in physical examination, psychiatric evaluation, or with imaging methods. Study groups were formed of the tinnitus side and control groups were formed of the healthy side as follows: Group 1 (Non-tinnitus side normal hearing values – n = 30), Group 2 (non-tinnitus side minimal hearing loss – n = 27), Group 3 (non-tinnitus side moderate hearing loss – n = 31), Group 4 (tinnitus side normal hearing values – n = 25), Group 5 (tinnitus side minimal hearing loss – n = 25), and Group 6 (tinnitus side moderate hearing loss – n = 38). Intervention: Retinal nerve fiber layer (RNFL) thickness was evaluated with OCT, and the cochlear nerve cross-sectional area was evaluated with MRI. Main Outcome Measures: RNFL measurements were taken with OCT from the subfoveal area (RNFL-SF) and 1.5 mm temporal to the fovea (RNFL-T µm) and nasal (RNFL-N µm) sectors. On MRI, 3 measurements were taken along the nerve from the cerebellopontine angle as far as the internal auditory canal, and the mean value of these 3 measurements was calculated. Results: When the groups were evaluated in respect of cochlear nerve thickness, a significant difference was seen between Group 1 and both the groups with hearing loss and the tinnitus groups. In the subgroup analysis, a statistically significant difference was determined between Group 1 and Groups 3, 4, 5, and 6 (p = 0.013, p = 0.003, p < 0.001, and p < 0.001, respectively). When the groups were evaluated in respect of the RNFL-SF (µm), RNFL-T (µm), and RNFL-N (µm) values, the differences were determined to be statistically significant (p < 0.001 for all). In the correlation analysis, a negative correlation was determined between hearing loss and cochlear nerve diameter (r: −0.184, p = 0.014), and RNFL-N (r: −0.272, p < 0.001) and between tinnitus and cochlear nerve diameter (r: −0.536, p < 0.001), and RNFL-T (r: −0.222, p < 0.009). Conclusion: The study results clearly showed a relationship between cochlear nerve fiber thickness and hearing loss and the severity of tinnitus in cases with unilateral tinnitus and that there could be neurodegenerative factors in the disease etiology. A similar relationship seen with the RNFL supports the study hypothesis.

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Retinal Optical Coherence Tomography Metrics Are Unchanged in Verubecestat Alzheimer’s Disease Clinical Trial but Correlate with Baseline Regional Brain Atrophy

Journal of Alzheimer s Disease ◽

10.3233/jad-200735 ◽

2021 ◽

Vol 79 (1) ◽

pp. 275-287

Author(s):

Robert C. Sergott ◽

Annaswamy Raji ◽

James Kost ◽

Cyrille Sur ◽

Saheeda Jackson ◽

...

Keyword(s):

Clinical Trial ◽

Optical Coherence Tomography ◽

Nerve Fiber ◽

Retinal Nerve Fiber Layer ◽

Brain Atrophy ◽

Retinal Thickness ◽

Optical Coherence ◽

Fiber Layer ◽

Nerve Fiber Layer ◽

Retinal Nerve Fiber

Background: We performed exploratory analyses of retinal thickness data from a clinical trial of the AβPP cleaving enzyme (BACE) inhibitor verubecestat in patients with Alzheimer’s disease (AD). Objective: To evaluate: 1) possible retinal thickness changes following BACE inhibition; and 2) possible association between retinal thickness and brain atrophy. Methods: Retinal thickness was measured using spectral-domain optical coherence tomography in a 78-week randomized placebo-controlled trial of verubecestat in 1,785 patients with mild-to-moderate AD. Changes from baseline in retinal pigment epithelium, macular grid retinal nerve fiber layer, central subfield retinal thickness, and macular grid volume were evaluated for verubecestat versus placebo. Correlation analyses were performed to investigate the potential association between macular grid retinal nerve fiber layer and central subfield retinal thickness with brain volumetric magnetic resonance imaging (vMRI) data at baseline, as well as correlations for changes from baseline at Week 78 in patients receiving placebo. Results: Verubecestat did not significantly alter retinal thickness during the trial compared with placebo. At baseline, mean macular grid retinal nerve fiber layer and central subfield retinal thickness were weakly but significantly correlated (Pearson’s r values≤0.23, p-values < 0.01) with vMRI of several brain regions including whole brain, hippocampus, and thalamus. At Week 78, correlations between retinal thickness and brain vMRI changes from baseline in the placebo group were small and mostly not statistically significant. Conclusion: BACE inhibition by verubecestat was not associated with adverse effects on retinal thickness in patients with mild-to-moderate AD. Correlations between retinal thickness and brain volume were observed at baseline. Trial registration: Clinicaltrials.gov NCT01739348 (registered December 3, 2012; https://clinicaltrials.gov/ct2/show/NCT01739348).

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