A Novel Approach to Quantitative Evaluation of Outer Retinal Lesions Via a New Parameter "Integral" in Spectral Domain Optical Coherence Tomography

Abstract

Purpose: The purpose of this study was to design a new parameter "integral" to quantitatively evaluate the spatial cumulative reflectivity of the outer retinal layers in optical coherence tomography (OCT), and to investigate its role in the detection of outer retinal diseases.

Methods: This was a cross-sectional study. Fovea-centered line OCT scans were performed on 60 eyes of 60 healthy volunteers and 44 eyes of 44 patients diagnosed with outer retinal diseases. The integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured by respectively accumulating the grayscale values of all the pixels within the EZ and IZ at specified locations on the scanning lines, and were then adjusted by calculating their percentages on the outer retina. The integrals of the EZ and IZ were compared between the two groups.

Results: The integrals of the EZ and IZ were stably and normally distributed in the healthy eyes, and were significantly lower in eyes with outer retinal lesions than in healthy ones (P < 0.05). Moreover, the integrals of the EZ and IZ were correlated with best corrected visual acuity (BCVA; adjusted R² = 0.620) and the presence of outer retinal lesions (Nagelkerke R² = 0.767). The area under the receiver operating characteristic (ROC) curve was 0.954 (95% confidence interval [CI] = 0.918-0.990) when the integral was selected as a diagnostic variable.

Conclusions: Obtained from this novel quantification method, the new parameter integral was comparable between different individuals and had the potential to detect outer retinal abnormalities in reflectivity through OCT.

Translational relevance: Our work verified the feasibility of the new image analysis technique in the detection of the diseases affecting the outer retina.

Keywords: ellipsoid zone; interdigitation zone; outer retinal lesion; spectral domain optical coherence tomography.

Figure 1.

Positions of the sampling areas and their relations with the anatomic regions and ETDRS grid. Left: The infrared reflectance imaging of a radial scan; a horizontal scan and a vertical scan were selected for analysis in each eye. Right: The B-scan image of the horizontal scan. The white circles and scales showed the boundaries of the foveola, fovea, parafovea, and perifovea, respectively. On the 2 selected scanning lines, sampling areas 200 µm in width (yellow line segments) were set at different radiuses including 0, 500, 1000, and 2000 µm representing the corresponding regions. The ETDRS grid (red) was also marked as reference.

Figure 2.

Integral measurement of the four outer retinal layers. (A) At each sampling area, the grayscale value of each pixel was read as its reflectivity. The reflectivities of each row of pixels were averaged and converted into a matrix along with its corresponding depth. (B) The reflectivity curve (blue curve) was plotted according to the matrix and the boundaries (red lines) were set at the troughs between the ONL, ELM, EZ, IZ, and RPE. The lower boundary of RPE was set at the inflection point on the descending slope according to the second derivative curve (orange curve). The original integral of each numbered layer was calculated as the AUC of the corresponding peak through definite integral, and was then divided by the sum of the four layers in order to get the adjusted integral for further analysis. Abbreviation: R, the reflectivity value of the pixel; $\overline{\mathrm{R}}$, the average reflectivity value of this row of pixels; int, integral; ONL, outer nuclear layer; ELM, external limiting membrane; EZ, ellipsoid zone; IZ, interdigitation zone; RPE, retinal pigment epithelium.

Figure 3.

Example of the segmentation in the eyes with fusion or absence of specific layers. The OCT images of a patient with RP1L1 mutation at the first visit (A) and a follow-up visit 1 year later (B) were analyzed. A A fused waveform of the IZ and RPE was observed at the parafoveal sampling area. On the reflectivity curve (blue curve), a process (arrow) appearing between the EZ peak and the RPE peak generated two additional inflection points according to the second derivative curve (orange curve); the latter inflection point was recognized as the boundary between the IZ and the RPE (dashed line). B There was no additional inflection point between the EZ peak and the RPE peak. In this circumstance, the IZ peak was considered missing. Abbreviations: ELM, external limiting membrane; EZ, ellipsoid zone; IZ, interdigitation zone; RPE, retinal pigment epithelium.

Figure 4.

The ROC curve when the integrals of the EZ and IZ were used to detect outer retinal lesions. The predicted probability was calculated from the binary logistic regression as a comprehensive index of the EZ and IZ. The AUC of the ROC curve was 0.954 (95% CI = 0.918–0.990) when the predicted probability was used to detect outer retinal lesions. Abbreviations: ROC curve, receiver operating characteristic curve; AUC, area under curve; 95% CI, 95% confidence interval.

Figure 5.

Comparison between integral and an existing parameter as diagnostic tests in the detection of outer retinal lesions. We compared integral (black curve) with another existing parameter measuring the relative reflectivity to the RPE (gray curve). The sensitivity, specificity, Youden index, and AUC of ROC curve were 84.1%, 95.0%, 0.791, and 0.954 for integral, and 80.0%, 88.6%, 0.686, and 0.921 for relative reflectivity. Abbreviations: ROC curve, Receiver operating characteristic curve; AUC, area under curve.