Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials

Simunovic, Matthew P.; Grigg, John; Mahroo, Omar A.

doi:10.1016/j.survophthal.2022.01.008

Cited by 7 publications

(9 citation statements)

References 127 publications

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“…The patient response interface for psychometric testing was mentioned only by 17 (21%) of the 80 studies, seven of which specified a ‘two button box’, ‘binary’ or ‘yes-no’ input [ 3 , 27 , 56 , 59 , 60 ], four studies reported ‘button box’, or ‘button-press’ [ 33 , 48 , 61 , 62 ], and four ‘patient response’ [ 23 , 31 , 63 ], The review by Simunovic’s group [ 64 ] reported ‘target detection’. The perimeter-based methods with the original modified Humphrey or the MCvONE perimeters are known to use a single-button input [ 1 – 3 , 58 ].…”

Section: Resultsmentioning

confidence: 99%

Full-field stimulus threshold testing: a scoping review of current practice

Shi

Hall

Thompson

2023

Eye

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The full-field stimulus threshold (FST) is a psychophysical measure of whole-field retinal light sensitivity. It can assess residual visual function in patients with severe retinal disease and is increasingly being adopted as an endpoint in clinical trials. FST applications in routine ophthalmology clinics are also growing, but as yet there is no formalised standard guidance for measuring FST. This scoping review explored current variability in FST conduct and reporting, with an aim to inform further evidence synthesis and consensus guidance. A comprehensive electronic search and review of the literature was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) checklist. Key source, participant, methodology and outcomes data from 85 included sources were qualitatively and quantitatively compared and summarised. Data from 85 sources highlight how the variability and insufficient reporting of FST methodology, including parameters such as units of flash luminance, colour, duration, test strategy and dark adaptation, can hinder comparison and interpretation of clinical significance across centres. The review also highlights an unmet need for paediatric-specific considerations for test optimisation. Further evidence synthesis, empirical research or structured panel consultation may be required to establish coherent standardised guidance on FST methodology and context or condition dependent modifications. Consistent reporting of core elements, most crucially the flash luminance equivalence to 0 dB reference level is a first step. The development of criteria for quality assurance, calibration and age-appropriate reference data generation may further strengthen rigour of measurement.

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Section: Resultsmentioning

confidence: 99%

Full-field stimulus threshold testing: a scoping review of current practice

Shi

Hall

Thompson

2023

Eye

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“…This point should be taken into account when assessing threshold sensitivity as a measure of progression, or as a treatment effect, in emerging treatment paradigms. Accordingly, we propose that new approaches should be considered that differentially adapt the rods while leaving the cones in their dark‐adapted state (e.g., through the use of a short‐wavelength, rather than a white adapting background) 22 …”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, we propose that new approaches should be considered that differentially adapt the rods while leaving the cones in their dark-adapted state (e.g., through the use of a short-wavelength, rather than a white adapting background). 22…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of cone sensitivity loss in retinitis pigmentosa

Simunovic,

Mammo

2024

Ophthalmic Physiologic Optic

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PurposeTo explore the mechanisms of cone sensitivity loss in retinitis pigmentosa by combining two‐colour perimetry with threshold versus intensity (tvi) testing.MethodsSeven subjects with autosomal recessive retinitis pigmentosa and 10 normal subjects were recruited and underwent perimetric testing of one eye using 480‐ and 640‐nm Goldman size V targets presented under scotopic conditions (no background illumination) and against a white background ranging in luminance from −1.5 to 2 log cd m−2 in 0.5 log cd m−2 steps. Data were fitted with tvi functions of the form logT = logT0 + log ((A + A0)/A0)n, where T is the threshold, T0 is the absolute threshold, A is the background intensity, A0 is the ‘dark–light’ constant and n is a gain constant.ResultsReliable tvi functions could not be obtained within the region of the visual field corresponding to loss of the ellipsoid zone on optical coherence tomography. At fixation, changes in both T0 and A0 were observed, consistent with a d1 mechanism loss, which resulted in an upwards and rightwards shift of the tvi function. Losses at [±3°, ±3°] demonstrated changes in T0, consistent with a d3 mechanism loss, resulting in an upwards translation of the tvi curve.ConclusionsAlthough the absolute cone threshold was elevated at each location, shifts in the tvi function (so‐called d1 mechanism loss) at fixation minimise threshold elevation in the presence of white adapting backgrounds, such as those typically employed in standard two‐colour perimetry. At more peripheral testing locations, changes in threshold occurred independent of background luminance (so‐called d3 mechanism loss). These findings suggest that backgrounds which selectively adapt rods while maintaining cones at, or near, absolute threshold may be preferable to conventional two‐colour perimetry for assessing loss of cone sensitivity, especially at the point of fixation.

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“…The recovery of photopigment in cones has been previously hypothesized to use an additional pathway through the Müller cells besides the canonical pathway through the RPE. 27,28 Therefore, the effect may arise from a stronger dependency of rods on transport through the BrM, resulting in a functional decline first in rod-mediated parameters before in cone-mediated parameters are affected. 29,30 However, our findings raise the important question, how much restoration of vitamin A is provided by the Müller cells and how much via the "classic" pathway (RPE-BrM-choriocapillaris).…”

Section: Discussionmentioning

confidence: 99%

Low-dose supplementation with retinol improves retinal function in eyes with age-related macular degeneration but without reticular pseudodrusen

Pfau

Jeffrey

Cukras

2023

Retina

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The aim of this study was to determine the functional impact of oral vitamin A supplementation in patients with intermediate age-related macular degeneration with and without reticular pseudodrusen (RPD) demonstrating dysfunction in dark adaptation.Methods: Five patients with intermediate age-related macular degeneration and without RPD (AMD group; mean 6 SD age 78.0 6 4.7 years) and seven with RPD (RPD group; age 74.1 6 11.2 years) were supplemented with 16,000 IU of vitamin A palmitate for 8 weeks. Assessment at baseline, 4, 8, and 12 weeks included scotopic thresholds, dark adaptation, best-corrected and low luminance visual acuities, and the low-luminance quality of life questionnaire.Results: In the linear mixed model, rod intercept time improved significantly in the AMD group (mean [95% CI] change 21.1 minutes [21.8; 20.5] after 4 weeks (P , 0.001) and 22.2 min [22.9 to 21.6] after 8 weeks of vitamin A supplementation (P , 0.001). The dark adaptation cone plateau also significantly improved (i.e., more sensitive cone threshold) at 4 and 8 weeks (P = 0.026 and P = 0.001). No other parameters improved in the AMD group, and there was no significant improvement in any parameter in the RPD group despite significantly elevated serum vitamin A levels measurable in both groups after supplementation (P = 0.024 and P = 0.013).Conclusion: Supplementation with 16,000 IU vitamin A, a lower dose than used in previous studies, partially overcomes the pathophysiologic functional changes in AMD eyes. The lack of improvement in the RPD group may indicate structural impediments to increasing vitamin A availability in these patients and/or may reflect the higher variability observed in the functional parameters for this group.

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Vision at the limits: Absolute threshold, visual function, and outcomes in clinical trials

Cited by 7 publications

References 127 publications

Full-field stimulus threshold testing: a scoping review of current practice

Full-field stimulus threshold testing: a scoping review of current practice

Mechanisms of cone sensitivity loss in retinitis pigmentosa

Low-dose supplementation with retinol improves retinal function in eyes with age-related macular degeneration but without reticular pseudodrusen

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