Changes in retinal capillary density in female with type 2 diabetes and gestational diabetes-an analysis based on OCTA technology

Abstract

Aim: To evaluate alterations in conjunctival vascular density (CVD) and macular capillary density (MCD) in female patients with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) using optical coherence tomography angiography (OCTA).

Methods: A total of 60 female participants were recruited, comprising 20 patients with T2DM, 20 patients with GDM, and 20 healthy age-matched controls (HCs). OCTA was used to assess superficial and deep retinal and conjunctival capillary plexuses. Subsequently, changes in MCD were analyzed using a circular segmentation method (C1-C6), a hemispheric quadrant segmentation method [superior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and the early treatment diabetic retinopathy study (ETDRS) segmentation method (S, I, R, L).

Results: OCTA unequivocally demonstrated that the variations in CVD among HCs, T2DM, and GDM groups were statistically significant (P<0.001). In the superficial retinal capillary plexus (sRCP), significant differences were observed in the densities of total microvascular (TMI), microvasculature (MIR), and macrovascular (MAR) between patients with T2DM and HCs (P<0.05). Furthermore, the GDM group exhibited a more substantial reduction in MIR density compared to the T2DM group (P<0.01). In the deep retinal capillary plexus (dRCP), significant differences in the densities of TMI and MIR were identified between the T2DM group and HCs (P<0.05), with a notable difference in TMI density also observed between the GDM and T2DM groups (P<0.01). In the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUC) for TMI in sRCP between the T2DM group and HCs was 0.975, with a 95% confidence interval (CI) of 0.941-1. The AUC for MIR was highest in dRCP, with an AUC value of 0.914 and a 95%CI ranging from 0.847 to 0.981. In comparing the GDM and T2DM groups, the AUC for I region was maximized in sRCP, achieving a value of 0.978 with a 95%CI of 0.953-1. Additionally, the AUC for R region was maximized in dRCP, reaching a value of 0.99 with a 95%CI of 0.975 to 1.

Conclusion: The sRCP and dRCP densities show higher diagnostic sensitivity for T2DM and GDM. OCTA holds potential as a significant instrument for the early diagnosis and differentiation of T2DM and GDM.

Keywords: deep retinal capillary plexus; diabetes; optical coherence tomography angiography; retinal region segmentation method; superficial retinal capillary plexus.

Figure 1. Participant recruitment flowchart.

Figure 2. OCTA images 3×3 mm² of the macular retina in the right eye and schematic diagrams of the three segmentation methods

A: OCTA images 3×3 mm² of the macular retina in the right eye; B: Schematic diagrams of the three segmentation methods. sRCP: Superficial retinal capillary plexus; dRCP: Deep retinal capillary plexus; RE: Right eye; TMI: Total microvascular; MAR: Macrovascular; MIR: Microvasculature; ETDRS: Early treatment diabetic retinopathy study; S: Superior; I: Inferior; L: Left; R: Right; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right.

Figure 3. OCTA images 3×3 mm² of the macular retina in the left eye and schematic diagrams of the three segmentation methods

A: OCTA images 3×3 mm² of the macular retina in the left eye; B: Schematic diagrams of the three segmentation methods. sRCP: Superficial retinal capillary plexus; dRCP: Deep retinal capillary plexus; LE: Left eye; TMI: Total microvascular; MAR: Macrovascular; MIR: Microvasculature; ETDRS: Early treatment diabetic retinopathy study; S: Superior; I: Inferior; L: Left; R: Right; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right.

Figure 4. Heat maps of the parameters with statistically significant differences among the three groups in Table 2

A: Heat map for multiple comparisons of SBP among the three groups; B: Heat map for multiple comparisons of HADS scores among the three groups; C: Heat map for multiple comparisons of VA among the three groups; D: Heat map for multiple comparisons of IOP among the three groups; E: Heat map for multiple comparisons of tBUT among the three groups; F: Heat map for multiple comparisons of TMH among the three groups; G: Heat map for multiple comparisons of SIT among the three groups. HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; SBP: Systolic blood pressure; HADS: Hospital anxiety and depression scale; VA: Visual acuity; IOP: Intraocular pressure; tBUT: Tear break-up time; TMH: Tear meniscus height; SIT: Schirmer's test; ns: Not significant. ^aP<0.05; ^bP<0.01; ^cP<0.001.

Figure 5. OCTA images 3×3 mm² of the macular superficial retina and schematic diagrams of the three segmentation methods for the three groups of subjects

A: OCTA images of the macular retinal sRCP, STMI, SMAR, and SMIR in the HCs, T2DM, and GDM groups; B: Schematic diagrams representing the shallow retinal capillary density using the three segmentation methods for the HCs, T2DM, and GDM groups. The colored areas in the T2DM group represent statistically significant differences compared to the HCs; the colored areas in the GDM group represent statistically significant differences compared to the T2DM; and the colored areas in the merged figure represent overlapping regions with statistically significant differences identified by the three segmentation methods. sRCP: Superficial retinal capillary plexus; STMI: Superficial total microvascular; SMAR: Superficial macrovascular; SMIR: Superficial microvasculature; HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; ETDRS: Early treatment diabetic retinopathy study; S: Superior; I: Inferior; L: Left; R: Right; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right.

Figure 6. Bar charts of macular superficial retinal capillary density with statistically significant differences among the three groups of subjects

A: Bar charts of STMI, SMIR, and SMAR densities for the three groups of subjects; B: Bar charts of superficial retinal vascular density using the hemispheric quadrant segmentation method for the three groups of subjects; C: Bar charts of superficial retinal vascular density using the ETDRS segmentation method for the three groups of subjects; D: Bar charts of superficial retinal vascular density using the central circular segmentation method for the three groups of subjects. STMI: Superficial total microvascular; SMAR: Superficial macrovascular; SMIR: Superficial microvasculature; HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; ETDRS: Early treatment diabetic retinopathy study; S: Superior; I: Inferior; L: Left; R: Right; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right; ns: Not significant. ^aP<0.05; ^bP<0.01; ^cP<0.001.

Figure 7. Three-group subject macular deep retinal 3×3 mm² OCTA images and schematic diagrams of the three segmentation methods

A: OCTA images of the macular retinal dRCP, DTMI, DMAR, and DMIR for the HCs, T2DM, and GDM groups; B: Schematic diagrams representing deep retinal capillary density using the three segmentation methods for the HCs, T2DM, and GDM groups. The colored areas in the T2DM group represent statistically significant differences compared to the HCs; the colored areas in the GDM group represent statistically significant differences compared to the T2DM; and the colored areas in the merged figure represent overlapping regions with statistically significant differences identified by the three segmentation methods. dRCP: Deep retinal capillary plexus; DTMI: Deep total microvascular; DMAR: Deep macrovascular; DMIR: Deep microvasculature; HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; ETDRS: Early treatment diabetic retinopathy study; S: Superior; I: Inferior; L: Left; R: Right; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right.

Figure 8. Bar charts of macular deep retinal capillary density with statistically significant differences among the three groups of subjects

A: Bar charts of DTMI and DMIR densities for the three groups of subjects; B: Bar charts of deep retinal vascular density using the hemispheric quadrant segmentation method for the three groups of subjects; C: Bar charts of deep retinal vascular density using the ETDRS segmentation method for the three groups of subjects; D: Bar charts of deep retinal vascular density using the central circular segmentation method for the three groups of subjects. HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; DTMI: Deep total microvascular; DMIR: Deep microvasculature; I: Inferior; R: Right; SR: Superior right; IL: Inferior left; IR: Inferior right; ns: Not significant. ^aP<0.05; ^bP<0.01; ^cP<0.001.

Figure 9. Heat maps and ROC curves of temporal CVD among the three groups of subjects

A: Heat maps of temporal CVD among the three groups of subjects; B: ROC curves of temporal CVD among the three groups of subjects. CVD: Conjunctival vascular density; HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; GDM: Gestational diabetes mellitus; ROC: Receiver operating characteristic; AUC: Area under the ROC curve. ^aP<0.05; ^bP<0.01; ^cP<0.001.

Figure 10. ROC curves of macular capillary density in the superficial and deep layers for the T2DM versus HCs groups

A: ROC curves for STMI, SMIR, and SMAR densities in the macular retina of the T2DM versus HCs groups; B: ROC curves for superficial retinal capillary density in the regions formed by the three segmentation methods for the T2DM versus HCs groups; C: ROC curves for DTMI, DMIR, and DMAR densities in the macular retina of the T2DM versus HCs groups; D: ROC curves for deep retinal capillary density in the regions formed by the three segmentation methods for the T2DM versus HCs groups. HCs: Healthy controls; T2DM: Type 2 diabetes mellitus; ROC: Receiver operating characteristic; AUC: Area under the ROC curve; STMI: Superficial total microvascular; SMAR: Superficial macrovascular; SMIR: Superficial microvasculature; DTMI: Deep total microvascular; DMIR: Deep microvasculature; SR: Superior right; IL: Inferior left; IR: Inferior right; S: Superior; I: Inferior; R: Right; L: Left.

Figure 11. ROC curves of macular capillary density in the superficial and deep layers for the GDM versus T2DM groups

A: ROC curves for STMI, SMIR, and SMAR densities in the macular retina of the GDM versus T2DM groups; B: ROC curves for superficial retinal capillary density in the regions formed by the three segmentation methods for the GDM versus T2DM groups; C: ROC curves for DTMI, DMIR densities in the macular retina of the GDM versus T2DM groups; D: ROC curves for deep retinal capillary density in the regions formed by the three segmentation methods for the GDM versus T2DM groups. GDM: Gestational diabetes mellitus; T2DM: Type 2 diabetes mellitus; ROC: Receiver operating characteristic; AUC: Area under the ROC curve; STMI: Superficial total microvascular; SMAR: Superficial macrovascular; SMIR: Superficial microvasculature; DTMI: Deep total microvascular; DMIR: Deep microvasculature; SR: Superior right; SL: Superior left; IL: Inferior left; IR: Inferior right; S: Superior; I: Inferior; R: Right; L: Left.