Quantifying Subclinical and Longitudinal Microvascular Changes Following Episcleral Plaque Brachytherapy Using Spectral Domain-Optical Coherence Tomography Angiography

Abstract

Purpose: To assess longitudinal microvascular changes in eyes treated with I-125 episcleral plaque brachytherapy (EPB).

Methods: High resolution OCT angiograms of the central 3×3mm macula were obtained from I-125 episcleral plaque brachytherapy treated and untreated fellow eyes of 61 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics.

Results: At 6 months, treated eyes had significantly lower VSD (0.145 ± 0.003 vs 0.155 ± 0.002; p = 0.009) and higher FIR (2.01 ± 0.199 vs 1.46 ± 0.104; p = 0.010) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.92 ± 0.025 vs 2.84 ± 0.018; p < 0.001). When our cohort was categorized into low dose radiation (<15Gy) and high dose radiation (>45Gy) to the fovea, there were significant differences in VSD and FIR between groups.

Conclusions: OCTA can be used to quantify and monitor EPB induced retinopathy, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.

Keywords: Biomarker; Capillary; Choroidal Melanoma; Episcleral Plaque Brachytherapy; Optical Coherence Tomography Angiography; Radiation Retinopathy.

Figure 1.

Longitudinal clinical and quantitative optical coherence tomography angiogram (data). All panels reflect data from our overall cohort. (A) Over the course of our 2-year follow-up period, there was an increasing percentage of treated eyes with clinically identifiable RR at each interval. Compared with fellow eyes over this period, treated eyes showed (B) decreasing vessel skeleton density, (C) increasing vessel diameter index, and (D) increasing flow impairment region. Relative significance between treated and fellow eyes at each time point is marked by asterisks, and error bars reflect SEM.

Figure 2.

Processed optical coherence tomography angiograms (OCTAs) from treated and fellow eyes of a single patient. OCTAs from the treated (left eye) and fellow eye (right eye) of a 20-year-old woman demonstrate marked qualitative differences in parafoveal vessel density (column 1). The OCTA of each eye was obtained 263 days (8.6 months) following placement in the treated eye of a 46.0-Gy dose at the fovea. Visual acuity at the time of image acquisition was 20/350 in the treated eye and 20/20 in the fellow eye. Skeletonized OCTAs with accompanying skeleton density heat maps were generated (columns 2 and 3). Warmer colors reflect areas of greater vessel skeleton density, with relative differences defined on the accompanying color scale demonstrating decreased vessel skeleton density in the treated eyes. Pseudocolor flow impairment maps (column 4) demonstrate absent flow signal (white areas). The flow impairment region was markedly increased in the treated eye.

Figure 3.

Longitudinal skeleton density and flow impairment maps of a treated eye. (Case 1) A 65-year-old man received 212 Gy to the fovea (right eye), with a range of 85 Gy to 250 Gy across the standard 3 × 3-mm optical coherence tomography angiogram (OCTA). OCTAs were acquired at postoperative months (POMs) 14, 26, and 30. The visual acuity of the treated eye at these dates was 20/25, 20/25, and 20/80, respectively. The visual acuity of the fellow eye at the same time points (OCTA images not shown) was 20/25, 20/20, and 20/25, respectively. In the skeletonized image, impaired perfusion is visible inferiorly at POM 26 compared with POM 14, with worsening perfusion at POM 30 (column 1). The loss of skeleton density is more clearly visualized in the heat map (column 2). Warmer colors reflect areas of greater vessel skeleton density, with relative differences defined on the color scale. A parallel trend is seen in the flow impairment region images (column 3).

Figure 4.

Spatial correlation of parafoveal microvascular changes with radiation dose. (A) The pretreatment fundus image of an individual (case 1) showing the choroidal melanoma. (B) A computed dosimetry simulation projected onto the pretreatment fundus image. A 3 × 3-mm optical coherence tomography angiogram of the eye was registered with the image using vessel bifurcation landmarks. Dosimetry contour lines and dosimetry tints delineate areas of the eye that received specific doses of radiation from the plaque. (C) An enlarged skeletonized 3 × 3-mm optical coherence tomography angiogram of the eye at postoperative month 30 with the corresponding dosimetry contour lines. Note the inferior areas of decreased vascular density (impaired perfusion) in the 3 × 3-mm image, which corresponds with the higher doses delivered inferiorly.