Correlation Between Macular Integrity Assessment and Optical Coherence Tomography Imaging of Ellipsoid Zone in Macular Telangiectasia Type 2

Abstract

Purpose: To correlate ellipsoid zone (EZ) defects on spectral-domain optical coherence tomography (SD-OCT) with retinal sensitivity loss on macular integrity assessment (MAIA) microperimetry in macular telangiectasia type 2 (MacTel).

Methods: Macular SD-OCT volumes and microperimetry maps were obtained during the international, multicenter, randomized phase 2 trial of ciliary neurotrophic factor for type 2 MacTel on two visits within 5 days of one another. Software was developed to register SD-OCT to MAIA scanning laser ophthalmoscopy images and to overlay EZ defect areas on the microperimetry maps generated from microperimetry sensitivity values at specific points and from interpolated sensitivity values. A total of 134 eyes of 67 patients were investigated.

Results: The semiautomated registration algorithm was found to be accurate, both qualitatively by visual inspection of the nearly perfect overlap of the retinal vessels and quantitatively as assessed by interobserver reliability metrics performed in 98 eyes of 49 patients (intraclass correlation of aggregate retinal sensitivity loss >0.99). Aggregate retinal sensitivity loss within the EZ defect area was highly correlated with EZ defect area (Pearson correlation coefficient 0.93 and 0.92 at screening and baseline for noninterpolated maps; both were 0.94 for interpolated maps; P values <0.001).

Conclusions: With our software and image processing algorithms, there is nearly perfect correlation between retinal sensitivity on microperimetry and EZ defect area on SD-OCT. Our software allows determination of functional and structural changes with increasing disease severity and demonstrates that functional loss on microperimetry may be used as a surrogate marker of EZ loss on SD-OCT in type 2 MacTel.

Figure 1

OCT imaging of a subject with type 2 MacTel. (Left) Representative zoomed-in section of a B-scan, where the orange and light green lines correspond to the boundaries of the EZ band. For clarity of visualizing pathology, this B-scan is laterally and axially clipped in the central portion. (Right) En face OCT created by averaging pixel intensities in the EZ band of 97 equally distanced B-scans. The horizontal red line in the en face image corresponds to the location and extent of the zoomed-in B-scan on the left. Note that each B-scan (before clipping) laterally spans 5800 μm, which corresponds to the horizontal length of the en face image. The vertical dark green lines (in both images) show corresponding positions on en face and B-scan images. A “collapse” or break in EZ band on the B-scan image corresponds to the prominent dark area on en face OCT. Units for x- and y-axes in both images are microns.

Figure 2

Registration of en face OCT SVP and microperimetry images. Each column represents a different eye. Rows from top to bottom display (first row) OCT SVP, (second row) MAIA SLO fundus image with microperimetry map, (third row) registered overlay, and (fourth row) B-scan crossing through the center of the EZ break anchored on the OCT SVP. The overlay image in the third row shows the smaller field-of-view OCT SVP (in green) registered on the microperimetry images (in red). The overlap of vessels in the overlay image qualitatively attests to the accuracy of our registration. In the fourth row, pseudo-color stripes on the central B-scan represent the corresponding sensitivity profile as obtained from the registered interpolated microperimetry maps, visualizing the morphology/sensitivity correlations. x-, y-, and z-axis units in the fourth row are microns.

Figure 3

Geometric correspondence of EZ defects on OCT with retinal sensitivity loss on MAIA microperimetry. (Top left) Microperimetry data overlaid on a red-free fundus image. (Top middle) Interpolated microperimetry data (map). (Top right) Abnormal microperimetry mask M (green) after thresholding (<25 dB) data. (Bottom left) OCT SVP registered and overlaid on microperimetry image. (Bottom middle) EZ mask O (red) after thresholding the EZ thickness (<12 μm) data from OCT. (Bottom right) Overlay of masks O (red) and M (green) with overlap area shown in yellow. In all images, the outer octagonal boundary in yellow shows the convex hull field of view of microperimetry sensitivity, inside which the interpolation and overlap are computed.

Figure 4

Correlation between EZ break and microperimetry sensitivity data. (Left column) Data from first visit; (right column) data from second visit. Top row represents correlation between interpolated aggregate sensitivity loss and EZ break area (0.94 for both first and second visit). Bottom row represents correlation between EZ break areas of the left and right eyes (0.56 for both first and second visits).

Figure 5

Correlation between the EZ defect areas on OCT and the abnormal sensitivity areas on microperimetry. The horizontal axis represents the threshold of normal from abnormal sensitivity values on microperimetry. The measure of correlation is the sum of specificity and sensitivity values achieved by matching the EZ defect map on OCT and abnormal sensitivity map on microperimetry. (Blue line) First visit with optimum threshold 25.0 dB, sensitivity 0.766, specificity 0.693. (Red line) Second visit with optimum threshold 25.0 dB, sensitivity 0.787, specificity 0.701.