CORRELATION OF STRUCTURAL AND FUNCTIONAL OUTCOME MEASURES IN A PHASE ONE TRIAL OF CILIARY NEUROTROPHIC FACTOR IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA

Abstract

Purpose: Macular telangiectasia Type 2 is a bilateral, progressive, potentially blinding retinal disease characterized by both vascular and neurodegenerative signs. Both the area of the break in the ellipsoid zone seen in "en face" optical coherence tomographic (OCT) images and microperimetric focal retinal sensitivity loss have been proposed as potential measures of progression in macular telangiectasia. The authors aimed to assess the characteristics and interrelationship of these structural and functional disease markers from the data collected in a phase one clinical trial of ciliary neurotrophic factor in macular telangiectasia.

Methods: Orthogonal topographic (en face) maps of the ellipsoid zone were generated from Heidelberg Spectralis OCT volume scans (15 × 10° area, 30-μm B-scan intervals) or Zeiss Cirrus HD-OCT 4000 512 × 128 cube scans. Mesopic microperimetry was performed on CenterVue MAIA perimeters, using a Goldmann III stimulus in a custom test grid. Structural and functional data were analyzed by two methods: by calculating aggregate loss and by simple thresholding. The alignment quality of structural and functional data was also evaluated.

Results: Overall, the break area showed a good correlation with aggregate sensitivity loss (ρ = 0.834, P < 0.0001, 95% confidence interval 0.716-0.906) but also with the number of test points below a threshold value (e.g., <20 dB: ρ = 0.843, P < 0.0001, 95% confidence interval 0.755-0.902). Significant misalignment of the MAIA test grid was apparent in 13/48 visits of 7/14 eyes.

Conclusion: The authors found a good correlation between ellipsoid zone break area and function loss. En face OCT mapping of the ellipsoid zone appears to demonstrate structural change before mesopic microperimetry can detect a focal loss of retinal sensitivity. Thresholding offers a quick alternative to calculating aggregate sensitivity loss.

Figure 1

MAIA microperimeter test grid used in this study. A sample retinal sensitivity report, the spacing of the grid centrally is one degree between test points. The stimulus used was white, size Goldmann III.

Figure 2

Correlation of the number of subthreshold test points with EZ break area. Correlation of the the number of test points (y axis) with values below the selected threshold (in this graph 20dB) with EZ (IS/OS) break area size (x-axis). For easier reference, area sizes are presented here in approximate mm² rather than pixels. It needs to be noted however, that since the refractive properties of the eyes tested were not recorded, metric conversions from measured pixels values are subject to variability in axial length and refractive power of respective eye.