Choroidal Hyperreflective Foci Acts as Biomarker in Leukemic Choroidopathy

The reversible increase in stromal choroidal area seen was postulated by the researchers to represent subclinical neoplastic infiltration.

Subclinical choroidal involvement manifesting mainly as a stromal thickening, occurs in the acute phase of patients with acute leukemia (AL), according to a study published in Acta Ophthalmologica. Previous studies show diffuse choroidal thickening on spectral-domain optical coherence tomography (SD-OCT) of patients with leukemia; however, none of them included a quantitative analysis of the choroid and the choriocapillaris, the researchers explain.

This prospective, longitudinal study included 26 eyes of 14 patients (mean age, 59±12 years; 9 men) diagnosed with myeloid or lymphoblastic AL between March 2021 to December 2021 at the Haematology and Bone Marrow Transplant Unit of San Raffaele Scientific Institute in Milano, Italy. Additional 26 eyes of 13 volunteers were included as control eyes. 

All the eyes were imaged during initial evaluation using a single line horizontal SD-OCT with enhanced depth intensity, ultrawide field pseudocolor fundus photography, and optical coherence tomography angiography (OCT-A). Ten eyes of 5 patients were imaged again during AL remission. Demographic and systemic parameters of the patients were collected.

The study authors normalized the signal intensity of the images using the mean intensity of the vitreous and the retinal pigment epithelium. They manually segmented the choroid and assessed the central 1500 µm quantitatively. Their measurements included subfoveal choroidal thickness (CT), total choroidal area (TCA), luminal choroidal area (LCA), and stromal choroidal area (SCA). The ratio between LCA and TCA was termed choroidal vascularity index (CVI). The number of hyperreflective foci (HRF) in the choroid was also found. The 20 µm thick choriocapillaris slab automatically generated by the OCT-A software was processed and evaluated for areas of flow deficit (FD).

In our study, we separately investigated the different choroidal components, and we found patients with active AL had supranormal values of SCA, LCA and TCA.

The team found significantly higher measurements of TCA (1.65±0.43 vs 1.38±0.41 mm2, P =.028), LCA (1.06±0.27 vs 0.91±0.26 mm2, P =.044) and SCA (0.59±0.19 vs 0.48±0.17 mm2, P =.024) among AL eyes compared with those in the control group. Areas of flow deficits did not significantly differ between the groups. After AL remission, TCA (1.86 ±0.31 vs 1.65±0.35 mm2, P =.047) and SCA (0.70±0.15 vs 0.58±0.14 mm2, P =.007) were significantly reduced. 

The number of Choroidal HRF, which the researchers speculated to be either leukemic or inflammatory cells, was significantly higher in the leukemic patients than in the controls (88±24 vs. 67±15 cells, P =.001). They were mainly traced superficially in the stroma, around the small vessel. HRF number was correlated among the leukemic patients with TCA (P =.001) and the (P =.01). A significant reduction in the number of HRF was found after AL remission (75±23 vs 47±11 cells, P =.002). 

“In our study, we separately investigated the different choroidal components, and we found patients with active AL had supranormal values of SCA, LCA and TCA. While the LCA remained unchanged, the SCA significantly reduced after disease remission, suggesting the largest changes in active AL occurred in the choroidal stroma,” according to the researchers

The reversible increase in the SCA values could be related to neoplastic infiltration, the researchers hypothesize. This is in accordance with previous histopathology studies, which demonstrated mottled thickening of the choroid and sheets of neoplastic cells in the innermost stromal interstices, the researchers explain. Increased fluid inflow and general thickening due to inflammation could be other alternative explanations.

The limitations of the study include a small sample size and a lack of longitudinal analysis for all AL eyes.


Menean M, Apuzzo A, Mastaglio S, et al. Imaging biomarkers of leukaemic choroidopathy. Acta Ophthalmol. Published online January 26, 2023. doi:10.1111/aos.15637