Diagnostic Role of Chromatic Full-Field Stimulus Test in Rod-Cone Versus Cone Dystrophies

Background: Inherited retinal dystrophies are a heterogeneous group of progressive disorders impacting photoreceptor function, often limiting the usefulness of standard electroretinography in advanced cases. Full-field stimulus test (FST) testing has become a sensitive psychophysical technique for detecting residual visual function when traditional electrophysiology is non-recordable. This study evaluated the ability of chromatic FST to differentiate rod-cone from cone photoreceptor dysfunction in patients with genetically confirmed inherited retinal dystrophies. Methods: Cross-sectional FST data were analyzed from 39 patients (mean age 45.7 ± 20.0 years) with genetically confirmed inherited retinal dystrophies at a tertiary academic center. All participants underwent standardized FST testing using white, red, and blue stimuli. Patients were classified into rod-cone dystrophy (n = 27) or cone dystrophy (n = 12) groups based on genetic and clinical criteria. Group comparisons focused on FST thresholds and especially blue-red threshold differences as markers of photoreceptor-mediated function. Bonferroni correction was applied to adjust for multiple comparisons across four primary FST parameters. Additional analyses by genotype were performed with nonparametric tests. Results: Eight different genetic mutations were represented, including Phosphodiesterase 6A (PDE6A) (n = 10), Rhodopsin (RHO) (n = 7), Phosphodiesterase 6B (PDE6B) (n = 6), Cyclic Nucleotide-Gated Channel Beta 1 (CNGB1) (n = 4), Cyclic Nucleotide-Gated Channel Alpha 3 (CNGA3) (n = 4), Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3) (n = 4), Guanylate Cyclase 2D (GUCY2D) (n = 2), and Cyclic Nucleotide-Gated Channel Beta 3 (CNGB3) (n = 2). Blue-red FST threshold differences exhibited moderate group discrimination in uncorrected analysis, with rod-cone dystrophies averaging -8.35 ± 10.37 dB and cone dystrophies -11.20 ± 14.60 dB. The area under the receiver operating characteristic curve for blue-red difference was 0.74 (95% CI: 0.59-0.90), with 75% sensitivity and 70.4% specificity at a -10 dB cutoff. However, no chromatic FST parameter maintained statistical significance between groups after Bonferroni correction. Inter-eye FST correlation was high (r = 0.758, p < 0.001), supporting test reliability. Conclusions: Chromatic FST testing provides a practical and sensitive means to assess photoreceptor function in advanced inherited retinal dystrophies, particularly when standard electrophysiologic methods are uninformative. Although the blue-red threshold difference offers moderate discrimination between rod-cone and cone dystrophies in uncorrected analysis, no chromatic parameter reached statistical significance after adjustment for multiple testing. Chromatic FST should be considered a supplementary approach for clinical monitoring and therapeutic studies in advanced retinal dystrophies, with further validation needed in larger cohorts.