Subretinal Pigment Epithelium Illumination Combined With Focal Electroretinogram and Visual Acuity for Early Diagnosis and Prognosis of Non-Exudative Age-Related Macular Degeneration: New Insights for Personalized Medicine

Maria Cristina Savastano, Benedetto Falsini, Silvia Ferrara, Alessandra Scampoli, Marco Piccardi, Alfonso Savastano, Stanislao Rizzo, Maria Cristina Savastano, Benedetto Falsini, Silvia Ferrara, Alessandra Scampoli, Marco Piccardi, Alfonso Savastano, Stanislao Rizzo

Abstract

Purpose: To evaluate the correlation between functional visual acuity and focal electroretinograms (fERGs) and morphological abnormalities in the retinal pigment epithelium and outer retinal atrophy (RORA) assessed by subretinal illumination (SRI) parameter at optical coherence tomography (OCT) examinations as signs of early disease in early and intermediate non-exudative age-related macular degeneration (ne-AMD).

Methods: One hundred forty-one eyes of 74 patients were retrospectively evaluated. A subgroup of patients (34/74) had a follow-up of at least 1 year. The study included both cross-sectional and longitudinal analyses. All eyes were assessed by OCT to measure the macular outer nuclear layer thickness, extent of ellipsoid zone interruption, absence or presence of drusen/reticular pseudodrusen in the foveal and perifoveal fields, and the SRI area closest to the fovea. Additionally, fERGs were performed.

Results: In the cross-sectional analysis, visual acuity and fERG amplitude were correlated (P < 0.01) with the SRI area. The fERG amplitude was correlated (P < 0.01) with the extent of ellipsoid zone interruption and tended to be lower in reticular pseudodrusen compared with drusen. In the longitudinal analysis, fERG amplitudes and outer retinal thickness tended to decrease on average by 15% and 18%, respectively, after 1 year of follow-up. The baseline RORA area, but not fERG amplitude or visual acuity, significantly predicted with 77% accuracy (P < 0.01) morphological deterioration, which was determined by an increase in the RORA area after 1 year.

Conclusions: Functional visual acuity and its morphological correlations can be assessed in early and intermediate ne-AMD eyes. SRI, as a result of RORA, is a potential predictor of ne-AMD progression in a short-term follow-up.

Translational relevance: SRI assessment, an objective method to measure RORA, is a potential biomarker for non-exudative AMD progression.

Conflict of interest statement

Disclosure: M.C. Savastano, None; B. Falsini, None; S. Ferrara, None; A. Scampoli, None; M. Piccardi, None; A. Savastano, None; S. Rizzo, None

Figures

Figure 1.
Figure 1.
Example of B-scan analysis. The ONL thickness (yellow arrow) was assessed in the foveal region; EZ interruption (green arrows) was assessed in to the 5 mm around the foveal region as the presence of drusen (blue asterisks) or pseudodrusen. Subretinal pigment epithelium transmission (red asterisks) was automatically measured by the advanced RPE analysis software embedded in the OCT device.
Figure 2.
Figure 2.
The values of BCVA plotted as a function of morphological parameters are shown. BCVA was positively correlated with ONL thickness (P < 0.001) and fERG amplitude (P < 0.001), and BCVA was negatively correlated with EZ interruption (P < 0.001) and SRI (RORA) area (P = 0.002).
Figure 3.
Figure 3.
The values of fERG amplitude plotted as a function of the SRI (RORA) area are shown. The negative correlations between fERG amplitude and SRI parameter (P = 0.006) and EZ interruption (P = 0.01) suggest a deterioration of the fERG response with an increase in the severity of damage to the photoreceptor–RPE complex (SRI).
Figure 4.
Figure 4.
The box plots show the fERG amplitude values as a function of presence or absence of drusen as well as drusen type (drusen or reticular pseudodrusen). fERG amplitude tended to be lower in eyes with reticular pseudodrusen compared with the drusen or no drusen group. The difference was not statistically significant (P = 0.13; F = 2.19) because the groups overlapped largely.
Figure 5.
Figure 5.
Morphological changes of one representative subject and presenting the findings at baseline and after 1 year. At baseline, the B-scan shows the pseudodrusen (pyramidal-shaped foci that extend radially through the photoreceptor layer) that result in greater irregularity after 1 year. Additionally, the RPE elevation map shows the growth of irregularity, and the sub-RPE illumination analysis indicates the progression of RORA.
Figure 6.
Figure 6.
ROC curve showing a sensitivity of 81.8%, a specificity of 36.4%, and a total accuracy of 77% (area under the curve = 0.77) to predict ne-AMD progression in the studied eyes.

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Source: PubMed

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