Choriocapillaris changes in the pre- and early diabetic spectrum: valuable feature for disease monitoring

A new study¹ conducted by researchers from China and Singapore found that the macular microvasculature is altered as early as the pre-diabetic stage of the disease. The findings suggest that the choriocapillaris can be used to monitor early metabolic disease, according to senior author Gavin SW Tan, MD, and colleagues. He is from the Singapore Eye Research Institute, Singapore National Eye Centre, and Duke-NUS Medical School, both in Singapore.

The investigators reported their results in Investigative Ophthalmology and Visual Science.

Prediabetes, defined as impaired glucose tolerance or impaired fasting glucose, carries a high-risk state for progression to type 2 diabetes. Tan and colleagues explained, “Evidence suggests that even in the prediabetic stage, before clinically detectable organ dysfunction, microvascular abnormalities are already present in peripheral microvascular beds, including those of the skin, skeletal muscle, kidney, and retina.^2-7 Among these tissues, the retina provides a uniquely optically accessible window to observe microvascular alterations at the level of the terminal capillary networks.”

Although several years are typical for the onset of diabetes to progress to detectable diabetic retinopathy (DR),^8-10 the damage to the microvasculature microvascular injury begins earlier and occurs silently before DR becomes apparent, according to Tan and colleagues. For example, reduced retinal capillary density has been found before the DR is detected.^11,12 They also pointed out, “Within the first year after diabetes diagnosis, macular perfusion in the superficial capillary plexus (SCP) can already be reduced, while prolonged disease duration contributes to impairment in the SCP and deep capillary plexus (DCP) in the retina.¹³ Multiple studies have reported reduced vessel density (VD) and perfusion density (PD) of the retinal capillaries even in individuals with prediabetes.^3-7 However, findings related to foveal avascular zone morphology have been inconsistent across studies.¹⁴ Importantly, choriocapillaris alterations, representing a critical terminal capillary bed that may be particularly vulnerable to metabolic stress, remain insufficiently investigated in prediabetes and early diabetes.”

Study rationale and methods

In this cross-sectional observational study, the researchers sought to characterize the retinal and choriocapillaris changes from normoglycemia to prediabetes to early type 2 diabetes, before the development of clinically detectable DR.

The study included participants with prediabetes, recent-onset type 2 diabetes, and age-matched healthy controls who were evaluated using swept-source optical coherence tomography angiography. The metrics that were assessed using that imaging modality were the VD, PD, foveal avascular zone acircularity, and choriocapillaris flow-deficit (FD) density and size. One eye of each participant was analyzed, the researchers recounted.

The patients were from the Pre-DICTED EYE study (The Pre-Diabetes Interventions and Continued Tracking to Ease Out Diabetes trial), and the age-matched healthy controls were from the SIENA (Singapore Imaging Eye Network) study.

What did the analysis uncover?

Tan and colleagues reported, “Microvascular impairment was evident from the prediabetic stage. Compared with controls, the participants with prediabetes had lower VD and PD in the SCP and DCP, together with higher choriocapillaris FD density (P < 0.05 for all comparisons).”

The retinal capillary metrics were similar in the participants with prediabetes and those with early type 2 diabetes (P > 0.05 for all comparisons). The impairment in the choriocapillaris progressed across the dysglycemia stages, with the FD density increasing from prediabetes to type 2 diabetes with a duration of under 3 years and type 2 diabetes for 3 to 7 years (9.3 ± 0.9 vs 9.7 ± 1.1 and 9.8 ± 1.0, respectively; P < 0.05). The choriocapillaris FD density showed the strongest discriminatory ability and was the most influential feature identified in the analysis.

The findings emphasize the importance of the status of the choriocapillaris in disease monitoring.

The investigators concluded, “Macular microvascular impairment involving both the retinal capillary plexuses and the choriocapillaris is detectable as early as the prediabetic stage. Feature-importance analysis effectively identified stage-specific patterns of macular microvascular involvement across different dysglycemic states and diabetes durations. Collectively, these findings suggest that early microvascular alterations may predominantly affect the choriocapillaris, particularly large-size FD, before progressive involvement of the retinal capillary plexuses becomes evident with longer diabetes duration.”

References
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