In this study, generalized decreased MRS was detected more frequently in eyes with cuticular drusen type 2 (73.7%, 14/19) and type 3 (85.7%, 18/21) than in normal eyes. As mentioned earlier, since types 2 and 3 have hyporeflective internal contents,4 relatively elevated drusen over the RPE-basal laminar band render outer segments non-reflective13 compared to type 1 cuticular drusen on SD-OCT. Histopathologically, drusen over retinal cells exhibit structural and molecular abnormalities suggestive of photoreceptor degeneration and Muller glial activation, implying that the photoreceptor cell function is compromised owing to drusen formation.16 Similarly, Curcio et al. reported that photoreceptor morphology was disturbed over subretinal drusenoid deposit formation, manifesting as outer segment shortening and loss with inner segment deflection and absence.17
Referring to these reports, our results suggest that when the drusen are elevated enough to deform the RPE shape, the overall retinal sensitivity is lowered.
This is further reinforced by the use of microperimetry as a subjective measurement of retinal sensitivity at the mesopic adaptation level, which may be arbitrated by both rod and cone photoreceptors.8 Retinal sensitivity measured by microperimetry strongly correlates with photoreceptor band integrity on high-resolution OCT imaging in AMD, which is consistent with the damage primarily to the outer retina.12,18,19
By applying these results to our study, it appears that as the type of cuticular drusen increases, the height of the drusen increases, which results in RPE deformation, leading to lower MRS in microperimetry.
Several reports have suggested that impaired scotopic and mesopic sensitivity are spatially correlated with the occurrence of large soft drusen or reticular pseudodrusen,20–24 whereas other studies have reported poor association between the distribution of lesions and loss of retinal sensitivity.25,26
In this report, we did not find a significant association between microperimetric sensitivity and the presence or extent of cuticular drusen. Acton et al. revealed that in locations with visual field defects compared to locations without defects, the outer segment layer was thinner in defect locations.13 Iwama et al. also reported that retinal sensitivities within an area with an irregular ellipsoid zone were significantly lower than those within intact retina in eyes with confluent soft drusen.26
From these results, our findings suggest that not all cuticular drusen lesions had an effect on exceeding the threshold enough to deform the outer segments; hence, these lesions do not possess decreased retinal sensitivity on microperimetry.
It is noteworthy that a significant correlation between MRS and the type of cuticular drusen was observed in patients with cuticular drusen (r = 0-0.310, p = 0.005). Hence, eyes with a lower MRS were correlated with an bigger type of cuticular drusen. The MD value was the only parameter significantly correlated with MRS, which seems to be influenced by age; however, our results demonstrate that it is not influenced by age in multivariate linear regression (Table 3). Therefore, regardless of age, lower MD values on microperimetry in eyes with cuticular drusen suggest an bigger type of cuticular drusen.
The strengths of our study include the first presentation of microperimetric analysis of cuticular drusen. There have been no reports on the differences in retinal sensitivity among cuticular drusen types. In this study, we evaluated the differences of retinal sensitivity for patients with each type of cuticular drusen. Since significant differences in MRS on microperimetry are presented for each cuticular drusen type, this study suggests that determining the type of cuticular drusen on SD-OCT is valuable (Table 1).
This study proves that MRS on microperimetry can be used as a sensitive tool to measure visual quality and is clinically useful. This is the first report to suggest that it can be a useful tool to measure the quality of vision in patients with cuticular drusen, even in those with good visual acuity.
Our study had several limitations. First, normative data from a previously published report15 were used for the normal control group. Second, inexperience with CMP resulted in a deviated age group (65.7 ± 7.2); however, the age group showed a normal distribution according to the Shapiro-Wilk test (p = 0.481). Third, since this was a cross-sectional study, we did not consider that cuticular drusen could remodel with time. Longitudinal studies that evaluate topographical associations could help draw more definitive conclusions on the changes in the outer segment thickness associated with drusen volume and visual function in eyes with cuticular drusen. Nevertheless, this study is the first to demonstrate the significance of microperimetric visual function in patients with cuticular drusen.
In conclusion, our study showed that MRS decreased based on the type of cuticular drusen on SD-OCT. Our findings suggest that these visual function tests might be useful measurements, especially in terms of cuticular drusen type.