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

Abstract

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.

Fig. 1. Scoping review flow diagram.

PRISMA-ScR flow diagram of source selection process (from Tricco et al., 2018).

Fig. 2. Summary figure showing timeline of included sources (n = 80) by year of publication, with key stages and publications in full-field stimulus test (FST) development and voretigene neparvovec (VN) clinical trial progression and approval.

CADTH Canadian Agency for Drugs and Technologies in Health, EMA European Medicines Agency, FDA Food and Drug Administration, TGA Therapeutic Goods Administration.

Fig. 3. Geographic infographic of institutional affiliations of all included sources (n = 85) by country and city (or USA state).

Area of circle is proportional to the total frequency count of mentions for the institution as listed within the Author Affiliations across all sources.

Fig. 4. Patient population of included studies (n = 79) categorised by pattern of retinal dysfunction, clinical phenotype and genotype.

The area of each segment is proportional to the number of FST studies with this clinical population. One study omitted from figure due to being a narrative review. BBS Bardet-Biedl syndrome, BCM blue-cone monochromacy, CORD cone-rod dystrophy, cCSNB complete congenital stationary night blindness, eAMD exudative age-related macular degeneration, LCA Leber congenital amaurosis, RP retinitis pigmentosa, XLRS X-linked retinoschisis.

Fig. 5. Ages of individual paediatric patients reported to have achieved results from FST testing (n = 148 children pooled from 31 studies where individual ages were reported).

Median age of these children is 11 (Interquartile range 9–14).

Fig. 6. Summary graph of FST studies (n = 71)* ordered by total population age range, showing also individual ages of patients with FST results where available.

The blue dashed line and grey area demarcates paediatric and adult patients. The green dashed line demarcates age 5 (pre-schoolage). *Nine studies were omitted from graph due to no available data on age.

Fig. 7. Variations in ‘FST’ full nomenclature used by sources (N = 80).

Some sources use more than one form of nomenclature within the same text.

Fig. 8. Colour and wavelength of flash stimuli used for full-field stimulus threshold testing (n = 80 studies).

*Assumed to be typographical error (should be 6500 K). †Assumed to be typographical error (should be 638 nm). ‡‘dim’ LED < 0.01 cd∙s/m², ‘bright’ LED > 0.01 cd∙s/m².

Fig. 9. Summary figure showing control reference data for full-field stimulus testing where available.

Studies are grouped according to units and 0 dB reference scaling. Note that data are plotted in their original reported values of each study, and so may not be directly comparable between studies that use different 0 dB scales. DA dark adaptation, FST full-field stimulus threshold, LA light adaptation.