Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

Vision Screening and Self-Testing by Mobile-Based Automated Visual Acuity Assessments Apps: A Systematic Review with Meta-Analysis (Preprint)

BACKGROUND Vision impairments (VI) and blindness are one of the core global public health issues. Visual acuity (VA) is one of the most crucial standard psychophysical test of visual function, and used widely in a broad range of healthcare domain, especially in many clinical settings. OBJECTIVE To assess the accuracy and application of using Mobile devices-based visual acuity measurement apps. METHODS We searched Pubmed, Embase, Cochrane Library, and Google Scholar for relevant articles published between January 1, 2008 and July 1 2020. Two reviewers independently selected studies that assessed the mobile-based VA measurement apps. We included all studies that assessed a tablet and/or smartphone VA measurement apps. RESULTS Most of the enrolled 22 studies considered as high quality studies, evaluating by QUADAS-2. In meta-analysis, six studies involving 24284 participants were included. In 3~5 years old group, the pooled sensitivity was 0.87 (95% CI 0.79, 0.93); the pooled specificity was 0.78 (95% CI 0.70, 0.85); In 6~22 years old group, the pooled sensitivity was 0.86 (95% CI 0.84, 0.87); the pooled specificity was 0.91 (95% CI 0.90, 0.91). In ≥55 years old group, the pooled sensitivity was 0.85 (95% CI 0.55, 0.98); the pooled specificity was 0.98 (95% CI 0.95, 0.99). CONCLUSIONS In this study, we conducted a comprehensive review of the state-of-the-art research to investigate the diagnostic value and limitations of existing mobile-based VA test applications. Evidence from this study shows that mobile-based app VA measurements may be useful tools for VI detection.

The olfactory deficits of depressed patients are restored after remission with venlafaxine treatment

Background It is unclear whether olfactory deficits improve after remission in depressed patients. Therefore, we aimed to assess in drug-free patients the olfactory performance of patients with major depressive episodes (MDE) and its change after antidepressant treatment. Methods In the DEP-ARREST-CLIN study, 69 drug-free patients with a current MDE in the context of major depressive disorder (MDD) were assessed for their olfactory performances and depression severity, before and after 1 (M1) and 3 (M3) months of venlafaxine antidepressant treatment. They were compared to 32 age- and sex-matched healthy controls (HCs). Olfaction was assessed with a psychophysical test, the Sniffin’ Sticks test (Threshold: T score; Discrimination: D score; Identification: I score; total score: T + D + I = TDI score) and Pleasantness (pleasantness score: p score; neutral score: N score; unpleasantness score: U score). Results As compared to HCs, depressed patients had lower TDI olfactory scores [mean (s.d.) 30.0(4.5) v. 33.3(4.2), p < 0.001], T scores [5.6(2.6) v. 7.4(2.6), p < 0.01], p scores [7.5(3.0) v. 9.8(2.8), p < 0.001)] and higher N scores [3.5(2.6) v. 2.1(1.8), p < 0.01]. T, p and N scores at baseline were independent from depression and anhedonia severity. After venlafaxine treatment, significant increases of T scores [M1: 7.0(2.6) and M3: 6.8(3.1), p < 0.01] and p scores [M1: 8.1(3.0) and M3: 8.4(3.3), p < 0.05] were evidenced, in remitters only (T: p < 0.01; P: p < 0.01). Olfaction improvement was mediated by depression improvement. Conclusions The olfactory signature of MDE is restored after venlafaxine treatment. This olfaction improvement is mediated by depression improvement.

Validation of a novel functional test for assessing metamorphopsia using epiretinal membranes as a model

Current tests for assessing metamorphopsia do not account for confounders such as perceptual filling-in and spatial redundancy, which affect its sensitivity and repeatability. This proof-of-concept study aimed to assess the performance of a novel laboratory-based psychophysical test (Line Sag Test, LST) which addresses these issues for quantification of metamorphopsia in idiopathic epiretinal membranes. The LST quantifies perpendicular metamorphopsia at three eccentricities (3°, 6°, and 9°) along eight meridians (45° steps). Metamorphopsia was assessed using the LST and Amsler grid and the hit rates of both tests for detecting metamorphopsia were compared. Normal metamorphopsia scores using the LST did not differ significantly from 0 and fell within one step-size (p = 0.500). The LST detected significantly more cases of metamorphopsia than the Amsler grid (14/21 versus 3/21) (p = 0.003). Similarly, significantly more cases of visual distortions in asymptomatic iERMs were detected using the LST than the Amsler grid (11/18 versus 0/18) (p = 0.008). The LST has a higher hit rate compared to the Amsler grid (67% versus 14%). This work demonstrates a psychophysically-robust functional test addressing perceptual confounders is more sensitive for quantifying and localising metamorphopsia in macular disease, particularly in asymptomatic disease.

A Tactile Device Generating Repulsive Forces of Various Human Tissues Fabricated from Magnetic-Responsive Fluid in Porous Polyurethane

In this study, a controllable tactile device capable of realizing repulsive forces from soft human tissues was proposed, and its effectiveness was verified through experimental tests. The device was fabricated using both porous polyurethane foam (PPF) and smart magnetorheological fluid (MRF). As a first step, the microstructural behavior of MRF particle chains that depended on the magnetic field was examined via scanning electron microscopy (SEM). The test samples were then fabricated after analyzing the magnetic field distribution, which was crucial for the formation of the particle chains under the squeeze mode operation. In the fabrication of the samples, MRF was immersed into the porous polyurethane foam and encapsulated by adhesive tape to avoid leakage. To verify the effectiveness of the proposed tactile device for appropriate stiffness of soft human tissues such as liver, the repulsive force and relaxation stress were measured and discussed as a function of the magnetic field intensity. In addition, the effectiveness and practical applicability of the proposed tactile device have been validated through the psychophysical test.

The effect of free-field presentation and processing strategy on a measure of spectro-temporal processing by cochlear-implant listeners

The STRIPES (Spectro-Temporal Ripple for Investigating Processor EffectivenesS) test is a psychophysical test of spectro-temporal resolution developed for cochlear implant (CI) listeners. Previously, the test has been strictly controlled to minimize the introduction of extraneous, non-spectro-temporal cues. Here, the effect of relaxing many of those controls was investigated to ascertain the generalizability of the STRIPES test. Pre-emphasis compensation was not applied to the spectrum of the STRIPES stimuli, the test was presented over a loudspeaker at a level above the automatic gain control (AGC) threshold of the CI processor, and listeners were tested using the “everyday” setting of their clinical devices. There was no significant difference in STRIPES thresholds measured across conditions for the majority of the CI listeners tested. One listener obtained thresholds above the theoretical spectral limit of performance when listening with their clinical processor. An analysis of longitudinal results showed excellent test-retest reliability over multiple listening sessions. Overall the results show that the STRIPES test is robust to extraneous cues, and that thresholds are reliable over time. Above a threshold limit defined by the filter settings of the CI processor used, no guarantee of the validity can be made of measured thresholds, and thresholds may be more variable. The STRIPES test may be sufficiently robust for use across CI manufacturers and in non-research settings.

The effect of age on white light perception.

The way that persons from different age groups experience “white light” is investigated. Human eye lens transmission changes spectrally with age and this may influence the way that humans from different ages experiences light. Such a difference may be important in industrial and medical environments. Two different age groups, one group younger than 40 years of age and another group older than 50 years of age were subjected to the same “white” definition task. A conventional single-booth setup was used where observers were able to adjust the intensity of four coloured LED’s. Results of the psychophysical test procedure were used to generate specifications of two light sources, as selected by the two age groups. The two age groups selected two very different light sources when tasked to achieve a “perception” of white. Results show that the older group prefers a source with a colour rendering index number of 89 and the younger group prefers a source with a colour rendering index number of 74. The sources selected by the two age groups specifies correlated colour temperature values of 5150 K for the older age group and 6592 K for the younger group.

Headphone screening to facilitate web-based auditory experiments

Psychophysical experiments conducted remotely over the internet permit data collection from large numbers of participants, but sacrifice control over sound presentation, and therefore are not widely employed in hearing research. To help standardize online sound presentation, we introduce a brief psychophysical test for determining if online experiment participants are wearing headphones. Listeners judge which of three pure tones is quietest, with one of the tones presented 180° out of phase across the stereo channels. This task is intended to be easy over headphones but difficult over loudspeakers due to phase-cancellation. We validated the test in the lab by testing listeners known to be wearing headphones or listening over loudspeakers. The screening test was effective and efficient, discriminating between the two modes of listening with a small number of trials. When run online, a bimodal distribution of scores was obtained, suggesting that some participants performed the task over loudspeakers despite instructions to use headphones. The ability to detect and screen out these participants mitigates concerns over sound quality for online experiments, a first step toward opening auditory perceptual research to the possibilities afforded by crowdsourcing.