Evaluation of photoreceptor function in inherited retinal diseases using rod‐ and cone‐enhanced flicker stimuli

Abstract

Purpose: Clinical assessment of rod and cone photoreceptor sensitivity often involves the use of extended dark adaptation times to minimise cone involvement or the use of bright adapting backgrounds to saturate rods. In this study we examine a new rod/cone sensitivity test, which requires minimal dark adaptation. The aim was to establish whether rod/cone sensitivity losses could be measured reliably in patients with retinal diseases that selectively affect rods or cones when compared to age-matched subjects with normal vision. Methods: Flicker modulation thresholds (FMTs) were measured psychophysically, using cone-and rod-enhanced stimuli located centrally, and in four quadrants, at 5°retinal eccentricity in 20 patients (age range: 10-41 years) with conedominated (Stargardt's disease or macular dystrophy; n = 13) and rod-dominated (retinitis pigmentosa; n = 7) disease. These data were compared against age-matched normals tested with identical stimuli. Results: Across all retinal locations, cone FMTs in cone-dominated diseases (Median AE IQR: 32.32 AE 28.15% for central location) were greater than a majority (83%; 49/59) of corresponding rod FMTs (18.7 AE 3.29%; p = 0.05) and cone FMTs of controls (4.24 AE 2.00%). Similarly, rod FMTs in rod-dominant disease (14.99 AE 22.58%) were greater than a majority (88%; 29/39) of the corresponding cone FMTs (9.09 AE 10.33%) (p = 0.13) and rod FMT of controls (6.80 AE 2.60 %). Conclusions: Cone-specific deficits were larger than rod-specific deficits in conedominated diseases, and vice versa in rod-dominated disease. These results suggest that the new method of assessing photoreceptor sensitivity has potential application in detecting specific rod/cone losses without the need for dark adaptation.

Effect of monocular sensitivity on binocular summation of luminance-modulated flicker

“…This hypothesis was tested by experimentally varying the monocular FMTs changing the angular subtense, luminance, chromaticity and temporal frequency properties of the flicker stimulus ( Table 1 ). The monocular FMTs varied by a 4- to 16-fold range between the smallest and the largest target size and higher for mesopic than photopic viewing conditions, in accordance with previous literature ( Table 2 , Figs 3 – 5 ) [ 13 , 16 ]. These trends were also repeatable across experimental runs ( Fig 8 ), altogether indicating that the present experimental approaches were appropriate to test the study hypothesis.…”

“…The staircases employed a five-alternative, one-up, two-down response procedure to arrive at the threshold. Each staircase employed nine reversals and the subject’s threshold was computed by averaging the last six reversals [ 13 , 16 ]. The use of double guides and a dynamic fixation target at the beginning of each presentation with short stimulus presentation times made it easier for the subject to attend to the center of the screen and avoid eye-movements during the stimulus ( Fig 1 ).…”

Evaluation of Local Rod and Cone Function in Stargardt Disease

“…The higher susceptibility of cones to STGD1 are known. 28 – 31 The absence of a functional rod defect in these patients could be driven by their genotypes 30 or by the fact that only subjects in early and middle stages of STGD1 have been enrolled in this trial. The sensitivity maps of rods even indicate some level of increased responses in comparison to the control group in the regions beyond 20°.…”

Tablet‐based ‘ON/OFF’ pathway test can distinguish between rod‐ and cone‐dominated diseases

“…However, it is important to note that even in the cone‐dominated cohort, most of the key outcome measures were subnormal (see dashed horizontal lines in Figure 2). This is not uncommon in psychophysical testing of photoreceptor‐related function in patients with inherited retinal diseases 36 …”

“…This is not uncommon in psychophysical testing of photoreceptor-related function in patients with inherited retinal diseases. 36 Full-field ERG responses are sometimes weak for both photoreceptor types, which makes the diagnosis of photoreceptor-specific inherited retinal disease more complex. Depending on the type of IRD, the severity of photoreceptor involvement can vary, and that knowledge is important for counselling patients regarding the disease course and prognosis.…”