Diabetic retinopathy (DR) lesions are often found in the peripheral retina, so generally these regions are carefully watched to assess disease stage. An added tool for the clinician’s diagnostic kit is emerging; white blood cell ratios. This systemic evidence of inflammation could enhance understanding of how vasculature damage progresses. A study published in BMC Ophthalmology uses ultra-widefield fluorescein angiography (UWFA) to identify peripheral changes in eyes with DR, and demonstrates how these features are associated with specific leukocyte indexes.

Investigators retrospectively reviewed records for 119 eyes of 115 individuals with type 2 diabetes (T2D) and DR (mean age 56.7±8.9 years) who were hospitalized at an academic center in Nantong, China from January 2016 to March 2019. The research examined peripheral features, such as microvascular leakage; as well as patient bloodwork that measured HbA1c and proportions of circulating leukocytes. In the sample, 118 eyes presented nonproliferative DR (NPDR), and 81 displayed proliferative DR (PDR).

The study also gathered clinical charts from this time period for 80 individuals who had diabetes but no DR. Intergroup comparisons revealed significant differences in leukocyte indexes, including white blood cell count (P =.004), monocyte ratio (P =.002), and eosinophil ratio (P =.042).


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In eyes with retinopathy, relationships of UWFA image features and white blood cell ratios were well-defined. Microvascular leakage was significantly correlated with neutrophil-to-lymphocyte ratio (r=0.186, P =.027). Regions of capillary nonperfusion also correlated with monocyte ratio (r=0.144, P =.042), and eosinophil ratio (r=0.123, P =.044). Similarly, neovascularization related to monocyte ratio (r=0.324, P =.018), as did fibrous proliferative membrane (r=0.418, P =.002). 

Regarding variables affecting PDR, univariable analyses uncovered impacts of patient sex, monocyte ratio, and eosinophil ratio. However, in multivariable analysis PDR was significantly associated with only 1 index, the eosinophil ratio (P =.018). Eosinophil-specific chemokines may be an important factor involved in DR inflammation, the investigators speculate.

Examining microvasculature lesions and systemic markers allows a deeper understanding of DR’s progression, the analysis explains. Thus, it may be possible to more precisely gauge the degree of disease by using angiography and bloodwork. Prior research has demonstrated monocytes and granulocytes can get caught in small retinal vessels, and white blood cells of diabetic individuals discharge more reactive oxygen species — creating oxidative stress that prompts retinopathy. Neutrophils have also been implicated in weakening the RPE barrier. “In this study, microvascular dye leakage in UWFA images suggested BRB destruction and vascular endothelial function damage,” according to the investigators.

Their data revealed a correlation between the amount of capillary occlusion and levels of monocytes and eosinophils in blood samples. This may signal the endothelial cells of retinal vessels are first damaged, with disease subsequently advancing to capillary occlusion.

The investigation was conducted at a single center, representing a limitation, as well as analyzing leukocyte ratios only, not including other kinds of inflammatory markers. Also, aqueous humor may be a better medium to look for signs of inflammation. Notably, this is the first study using UWFA in comparing DR features and systemic white blood cell ratios. 

Reference

Huang L, Li L, Wang M, Zhang D, Song Y. Correlation between ultrawide-field fluorescence contrast results and white blood cell indexes in diabetic retinopathyBMC Ophthalmol. Published online May 21, 2022. doi:10.1186/s12886-022-02442-7