Sathishkumar S, B.Optom

Research Fellow, Medical Research Foundation, Sankara Nethralaya, Chennai, India


In this rapidly evolving area of vision research, the investigation of histopathological biomarkers combined with improved imaging techniques will result in a new area of early diagnosis and treatment response in many ocular conditions. This blog explores the various techniques of imaging biomarkers beyond conventional measurements, revealing their ability to impact on early diagnosis and management. Excited by my recent investigation on Diabetic Macular Oedema (DME), we explored the wider field of imaging biomarkers and their potential use in treatment response. Though Macrophage Like Cells (MLCs) were the focus of our work, its wider implications fascinate me to investigate the many additional histopathological and imaging indicators. (1)

The range of imaging biomarkers:

Structural Biomarkers

Assessing structural changes in the retina and surrounding tissues is important to understand the progression of disease. As the DME study found out, parameters like retinal layer thickness and Central Foveal Thickness (CFT) are useful markers of structural changes. (2)

Functional Biomarkers

Structural findings are further clarified by functional assessments, such as visual acuity and visual field assessments. Functional biomarkers are useful in assessing how ocular diseases affect a patient’s quality of life and vision. (3)

Vascular Biomarkers

Many eye diseases have been significantly affected by angiogenesis and vascular changes. Imaging biomarkers that mark changes in blood vessel density, perfusion, and structure offer essential knowledge about conditions like age-related macular degeneration and diabetic retinopathy. (4)

Histopathological Biomarkers

Histopathological biomarkers provide a microscopic perspective on the cellular structure of ocular tissues in addition to MLCs which are seen in OCT. Changes in tissue structure, morphology of cells, and the presence of cellular components indication of disease processes are a few examples of these markers.

By using the latest technologies to eliminate distortions resulting from problems in the optics of the eye, adaptive optics provides retinal imaging with never-before-seen clarity. Adaptive Optics allows high-resolution imaging, which makes it possible to see micro cellular and subcellular features, including newly identified biomarkers. (Figure 1) (5)

Figure 1: OCT enface image with MLC
[Picture courtesy – Image capture by author]

The integration of Adaptive Optics and Histopathology explores its role in visualising emerging Biomarkers and its nature with histopathology for understanding of ocular diseases. Equipped with comprehensive imaging data and insights from histopathology, medical professionals can more accurately modify treatment options.

The combination of histology and adaptive optics is leading the way in introducing a new chapter in precision medicine in ophthalmology as technology develops.



  1. Ong, J. X., Nesper, P. L., Fawzi, A. A., Wang, J. M., & Lavine, J. A. (2021). Macrophage-Like Cell Density Is Increased in Proliferative Diabetic Retinopathy Characterised by Optical Coherence Tomography Angiography. Investigative ophthalmology & visual science, 62(10), 2.
  2. Borrelli, E., Barresi, C., Feo, A. et al. Imaging biomarkers and clinical factors associated with the rate of progressive inner and outer retinal thinning in patients with diabetic macular oedema. Sci Rep 13, 3224 (2023).
  3. Gao, S., Li, Y., Bissig, D. et al. Functional regulation of an outer retina hyporeflective band on optical coherence tomography images. Sci Rep 11, 10260 (2021).
  4. Lyu, X., Jajal, P., Tahir, M.Z. et al. Fractal dimension of retinal vasculature as an image quality metric for automated fundus image analysis systems. Sci Rep 12, 11868 (2022).
  5. Alexopoulos, P., Madu, C., Wollstein, G., & Schuman, J. S. (2022). The Development and Clinical Application of Innovative Optical Ophthalmic Imaging Techniques. Frontiers in medicine, 9, 891369.