Interobserver Agreement of Electrode to Retina Distance Measurements in a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis

Abstract

Purpose: The electrode to retina (ER) distance is an important contributory factor to the safety and efficacy of a suprachoroidal retinal prosthesis. Measuring ER distance may be performed by different observers during multisite studies. The aim of this study was to assess the interobserver agreement in measuring ER distance.

Methods: Three independent, trained observers measured ER distance from the center of each suprachoroidal electrode to the inner retinal pigment epithelium in spectral-domain optical coherence tomography (SD-OCT) B-scans. A total of 121 ER distance measurements from 77 B-scans collected over 5 months from one subject implanted with a second-generation 44-channel suprachoroidal retinal prosthesis (NCT03406416) were made by each observer.

Results: ER distance ranged from 208 to 509 µm. Pearson's correlation coefficient (ρ) showed agreement of 0.99 (95% confidence interval [CI] = 0.98-0.99) in measuring ER for each pairwise comparison. The mean difference in ER distance between observers ranged from 2.4 to 6.4 µm with pairwise limits of agreement (95% CI) of ±20 µm (5.5% of mean). Intraclass correlation coefficient (ICC) showed agreement of 0.98 (95% CI = 0.97-0.99) between observers.

Conclusions: There is high agreement in measuring ER distances for suprachoroidal retinal prostheses using our systematic approach between multiple, trained observers, supporting the use of a single observer for each image.

Translational relevance: High interobserver agreement outcomes indicate that multiple, trained observers can be used to take ER measurements across different images in suprachoroidal retinal prosthesis studies. This improves multisite study efficiency and gives confidence in interpreting results relating to the safety and efficacy of suprachoroidal retinal prostheses.

Figure 1.

The second-generation, 44-channel, suprachoroidal retinal prosthesis. (A) Photograph of the retinal array showing the 44 stimulating platinum electrodes (Ø 1 mm) and 2 return platinum electrodes (Ø 2 mm) within a silicone substrate (19 × 8 mm). (B) Color fundus photograph showing the position of the array (dotted lines) implanted under the macula in the right eye of a subject with retinitis pigmentosa. Fovea = F.

Figure 2.

Timeline that interobserver SD-OCT measures were taken (orange) within the overall second-generation retinal prosthesis clinical trial for this subject (not to scale). SD-OCT measures were part of the suite of clinical assessments performed 2 to 4 weekly in the first 6 months after surgery, then at approximately 12 weekly intervals after the device fitting and training was complete (§), until the trial end point at 2.8 years postsurgery. Yellow lightning sign = device switch on (day 62 postsurgery).

Figure 3.

Electrode to retina (ER) distance measurement method. (A) IR image with green arrow indicating B-scan position aligned with the rows of the suprachoroidal electrode array. The accompanying SD-OCT B-scan image shows the position of the electrode array relative to the retina. (B) Magnified view of the region in the blue box in A, showing the inner retina, retinal pigment epithelium/Bruch's membrane (RPE/BM complex), choroid and suprachoroidal electrode, and the ER distance measurement (red line), measured perpendicularly from the center of the electrode to the inner RPE/BM complex.

Figure 4.

Distribution of electrode to retina (ER) measurements for each observer. On average, observer 1 had the shortest measurements (mean = 368 µm, range = 216–509 µm) and observer 3 had the longest (mean = 374 µm, range = 225–508 µm), with observer 2 (the most experienced observer) in between (mean = 370 µm, range = 208–505 µm). Each circle represents a single ER measurement; the boxes indicate the median and interquartile range with whiskers to the 5th and 95th centile for each observer.

Figure 5.

Scatter plot matrix showing a high level of agreement between each pair of observers. Pearson's ρ ≥ 0.99 for each pairwise comparison.

Figure 6.

Bland-Altman plots for electrode to retina (ER) distance for (A) Observer 1 versus 2, (B) Observer 2 versus 3, and (C) Observer 1 versus 3. The mean difference in ER distance between observers ranged from 2.4 to 6.4 µm with limits of agreement (±1.96 SD) shown in grey, representing the range of normal measurement variation relevant clinically. Each circle represents a single measurement location.

Figure 7.

Example of ER distance measurement variation among observers related to pigment migration/clumping at the RPE. Infrared and accompanying SD-OCT B-scan images. The green arrow indicates the position of the B-scan in the infrared image. Measurement of the ER distance for 2 electrodes as marked by observer 1 (A) and observer 3 (B). Blue box regions show a magnified view of one ER measurement. The 32 µm difference in ER distance between observers in this example is due to a difference in identification of the center of the electrode and local variation in pigment clumping (white arrow) at the inner RPE boundary.

Figure 8.

Representative comparison of ER distance measures between observers for HR mode compared to HS mode. (A) Infrared and OCT B-scan in HR mode (ART 3, image quality 32) for electrode #B6. (B) Infrared and OCT B-scan in HS mode (ART 40, image quality 34) for electrode #B4. The green arrows indicate B-scan position on the infrared image, the green circles indicate the electrode position measured for each example. The difference in ART between HR and HS mode likely explains the difference in apparent image quality. The agreement was higher between observers in HR mode, which may be due to differences in positioning of the ER distance measurement bar along the X axis, and/or reduced image quality causing smoothing of the RPE boundary line.