Towards in vivo molecular imaging of the retina: OCT-guided Raman spectroscopy

Abstract

Purpose : Optical coherence tomography (OCT) has been extensively used for visualizing the structure and vasculature of the human retina, however, it does not provide molecular information, which might be relevant for early diagnostic purposes. Here we investigated the potential diagnostic capability of in vivo Raman spectroscopy (RS) of the retina in a clinical setting.

Methods : 10 human subjects with age-related macular degeneration (AMD) and 10 healthy controls were imaged by using a custom-built multimodal ophthalmic imaging device, combining IR fundus imaging, swept source (SS)-OCT and RS, covering an area of 18 x 18 mm² across the retina. The IR fundus imaging is operated at 730 nm. The OCT system is operated at 1060 nm with 100 kHz A-scan rate. The generated OCT en face image was used as a guidance to select the position for performing the RS measurement (operating at 785 nm). Each RS measurement was set to 3x20s as a compromise between signal to noise ratio and subject comfort. 40 Raman spectra were collected, 20 spectra for each group (AMD or Healthy). The processed Raman spectra were then analyzed using multivariate analysis.

Results : The IR fundus images and the corresponding en face projection images of the OCT data from a healthy subject and an AMD patient are shown in Figure 1a and 1b and in Figure 1d and 1e, respectively. Figure 1c and 1f show the mean and standard deviation of the Raman spectra of the healthy group and the AMD group, respectively. The blue and red arrows in the figure indicate the location of the RS measurement (around the peripapillary area). The RS analysis based on principal component analysis (PCA) yields a sensitivity of 100% and a specificity of 95%.

Conclusions : With our multimodal ophthalmic imaging device, we can acquire interpretable Raman spectra from AMD subjects and healthy controls. Our results confirmed the potential of RS to differentiate healthy and diseased retina tissue in vivo. In future clinical studies, we will investigate that the molecular information obtained by RS could enable an earlier diagnosis of retina diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1. Measurement results, a) and d) IR fundus image, b) and e) OCT en face projection, c) and f) mean and standard deviation of the Raman spectra (10 subjects from each group). Top row: healthy control. Bottom row: AMD subject. Scale bar: 1 mm