shows the AO images of a normal retina (control subject 1) at six retinal locations. The scale bar represents 10 μ
m on the retina. The photoreceptor mosaic were regularly spaced in a hexagonal array across the retina. The cone diameter and the gaps between the cones increased with increasing eccentricity, as expected.52
AO images of normal retina at six retinal locations from control subject 1. N, nasal; S, superior; I, inferior; VF, visual field. Scale bar, 10 μm.
show the AO retinal images obtained from the three subjects with rod– cone dystrophy (RCD1, RCD2, and RCD3) at different retinal locations. The retinal locations tested were selected based on the visual field results so that areas with varying severity of functional loss could be imaged by the AO fundus camera. The consistent finding in all subjects with rod– cone dystrophy was that the cone mosaic is not regular (unlike that of normal eyes) at the retinal locations where sensitivity is reduced (i.e., there were areas of dark spaces between groups of cones, where no cones were visible). show the AO images from patients with cone–rod dystrophy (CRD) and juvenile macular dystrophy (JMD), respectively, at different retinal eccentricities. These subjects also showed photoreceptor irregularity at the locations where retinal sensitivity was reduced.
Figure 5 AO-corrected retinal images for each subject with a retinal dystrophy at different locations of the retina shown with the corresponding visual field maps. HVF 24-2 SITA Standard was used on all subjects except for the subject CRD, for whom HVF 10-2 FP (more ...)
Cone density was calculated for each retinal image and is compared in with the extrapolated cone densities from Curcio’s histologic data at corresponding locations.52
The relative percentage values provided an indication of relative cone loss at each retinal location. The variation in cone density from the least to the most affected areas was 96% to 49% for RCD1, 59% to 32% for RCD2, 33% to 22% for RCD3 (the three rod–cone dystrophy cases), 41% to 26% for CRD (cone–rod dystrophy), and 81% to 9% for JMD (juvenile macular dystrophy). These numbers provide a quantitative index of cone loss in various forms of retinal dystrophy.
Cone Density from AO Retinal Images for all Subjects
The relation between cone density as measured by AO fundus photography and retinal sensitivity as measured by the Humphrey visual field (HVF) analyzer is shown in . These data represent HFV sensitivity data for all regions in the five dystrophy subjects where AO fundus photography yielded cone density measurements. The HVF analyzer reports sensitivity data on a decibel scale. Visual inspection of the data relating these sensitivity measures and cone density clearly indicated that the linear
sensitivity values would capture more of the variance in the cone density measurements in these dystrophic retinas. For the purposes of this analysis, HVF sensitivity is expressed as the linearized values
This operation simply inverts the decibel equation. When represented in this way, the linear relation between sensitivity and cone density becomes apparent. In fact, most of the variability in the HVF sensitivity measurements is explainable by the cone density measurements (R2
= 0.75; P
Figure 6 Linear HVF sensitivity (Equation 2) plotted as a function of cone density from all subjects with retinal dystrophy.
The mfERG results are summarized in for the rod– cone dystrophy subjects (RCD1, RCD2, and RCD3). The left figure in each panel shows the recordings from all 103 locations in the central 45° of the retina. The overall pattern of cone responses in the mfERG closely matched the visual field results, that is, the areas in the visual field that showed depression in retinal sensitivity were registered with flatter traces and longer latencies. The right figure shows the average cone responses from hexagons that correspond to the retinal locations used for AO imaging. The resolution of the mfERG is not fine enough to make a 1:1 correspondence with the AO imaging location. The size of each hexagon was calculated to be 4.4° on the retina. Therefore in some cases, a single hexagon represents the combined responses from more than one imaging location (e.g., in RCD1, trace 1 represents averaged response from the area that includes both 2° nasal visual field and 2° temporal visual field, whereas trace 3 includes 7° and 8° temporal visual fields). All three subjects with rod– cone dystrophy showed that as retinal sensitivity decreased, the mfERG trace became gradually flatter with longer latencies between peaks. Right images in demonstrate this trend. The top trace represents averaged response from the retinal location that corresponds to healthier part(s) of the retina used for AO imaging. The bottom trace represents that of the most affected part of the retina imaged, and the middle trace(s) represent intermediate locations. At the retinal locations that were significantly affected by the disease, the amplitudes of mfERG evoked responses were reduced to near the noise level. show the mfERG recordings from subjects with cone–rod dystrophy (subject CRD) and juvenile macular dystrophy (subject JMD), respectively. Both subjects had no visible responses across all retinal locations tested (refer to second figure in ). For subject CRD, trace 1 represents averaged response from the area that includes the 3° and 4° nasal visual fields, whereas trace 2 represents averaged responses that include the 1° and 2° nasal visual fields. To relate cone density to mfERG responses quantitatively, we chose the locations where responses above the noise level were obtained from the mfERG. When an mfERG response captured more than one of the cone regions imaged in AO, the cone densities from those areas were averaged. shows the relation between mfERG response density and cone density for the six regions where sufficiently adequate mfERG data were available from the subjects with dystrophy. Although this correlation is represented by a small data set (six locations), the correlation is statistically significant (R2 = 0.80, P < 0.05). There is a suggestion of a negative relation between cone density and response latency; however, the correlation with cone density fails to reach significance for both N1 and P1.
Figure 7 Multifocal ERG recordings showing the traces from all 103 hexagons as well as the ones that closely match the retinal locations used for AO imaging. (a) Subject RCD1; left eye with rod– cone dystrophy. The line plots (from top to bottom) correspond (more ...)
Response density of mfERG recordings plotted as a function of cone density from all subjects with retinal dystrophy. Measurable mfERG responses were obtained from six retinal locations across subjects.
show the luminance CSF from the three subjects with rod–cone dystrophy (RCD1, RCD2, and RCD3) at each retinal location, and corresponding CSFs from control subjects. Contrast sensitivity decreases were similar to the other functional tests and AO images, and disease-related reductions in contrast sensitivity were seen across all spatial frequencies tested. show the results from the subject with cone–rod dystrophy (CRD) and the one with juvenile macular dystrophy (JMD), respectively. The subject with cone–rod dystrophy had significantly reduced CSFs at all retinal locations compared with the control subject. These CSFs decreased in parallel with reduction in retinal sensitivity, as measured from other functional tests in the study. The subject with juvenile macular dystrophy did not have measurable contrast sensitivity at any of the retinal locations tested and therefore showed flat CSFs. To relate cone density to contrast sensitivity, we collapsed the CSF curves into a single value by averaging sensitivity across frequencies. shows the relation between mean contrast sensitivity and cone density for the retinal locations where AO images are available from the subjects with dystrophy. The linear relation was significant (R2 = 0.71, P < 0.01). This relation is similar to that between linear HVF sensitivity and cone density, due to the strong correlation between mean contrast sensitivity and linear HVF sensitivity (R2 = 0.88, P < 0.01).
Contrast sensitivity functions for retinal dystrophy and control subjects at the retinal locations corresponding to those imaged with AO. Separate graphs denote the different subjects: (a) RCD1, (b) RCD2, (c) RCD3, (d) CRD, and (e) JMD.
Mean contrast sensitivity is plotted as a function of cone density from all subjects with retinal dystrophy.