Abstract
Purpose:
The purpose of this study was to investigate whether optical coherence tomography angiography (OCTA) metrics are related to retinal vessel geometry parameters in diabetic retinopathy (DR).
Methods:
In total, 119 eyes (119 patients) were included in this retrospective cross-sectional study. Retinal vessel geometry parameters were analyzed using semi-automated software. OCTA metrics were analyzed using automated manufacturer-provided algorithms. Associations between the severity of DR and retinal vessel geometry parameters and OCTA metrics were evaluated. Multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and OCTA metrics after adjusting for clinical characteristics and DR severity.
Results:
DR severity was negatively associated with the following: arteriole–venular ratio (P = 0.039), arteriolar network fractal dimension (FDa; P = 0.003), arteriolar junctional exponent deviation (P = 0.037), venular junctional exponent deviation (P = 0.036), vessel area density (VAD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP; P < 0.001, both), vessel length density (VLD) of the SCP and DCP (P < 0.001, both), and foveal avascular zone (FAZ) circularity (P < 0.001). DR severity was positively associated with the central retinal venular equivalent caliber (P = 0.005), arteriolar branching coefficient (BCa; P = 0.010), venular branching coefficient (P = 0.007), and FAZ size (P = 0.002). In multivariable regression analyses, the following retinal vessel geometry parameters and OCTA metrics were associated: FDa with VAD of the SCP (β = 0.40, P < 0.001), FDa with VLD of the SCP (β = 0.01, P < 0.001), and BCa with FAZ circularity (β = −1.02, P = 0.001).
Conclusions:
In DR, changes in retinal arteriolar geometry parameters were significantly associated with OCTA metrics, which reflect DR pathophysiology.
Diabetic retinopathy (DR) is the leading cause of visual impairment and blindness worldwide, especially among people of working age.
1 Chronic diabetes mellitus (DM)-related hyperglycemia levels lead to macrovascular and microvascular complications. Macrovascular complications are mainly due to atherosclerotic narrowing of large arteries and veins, leading to cardiovascular, cerebrovascular, and peripheral arterial diseases.
2 Microvascular complications occur in small vessels, such as arterioles, venules, and capillaries, leading to diabetic microangiopathy, diabetic nephropathy, diabetic neuropathy, and DR.
3 DR is characterized as increased vascular permeability, vascular occlusions, ischemia, and subsequent angiogenesis, which starts with retinal capillary damage.
4 Clinical evaluation of DR is mainly based on a fundus examination; however, the severity of DR is assessed using semiquantitative grading systems based on the presence or absence of retinal lesions, including microaneurysms, hemorrhages, intraretinal microvascular abnormalities, venous beading/loops/reduplications, and neovascularization. These signs only partially reflect the microvascular changes associated with DR, especially those of retinal capillaries.
Retinal vessel geometry parameters, such as retinal arteriolar or venular diameters, tortuosity, fractal dimensions, and branching angles, can be derived quantitatively from the semi-automated analysis of fundus photographs.
5 Several studies have reported that changes in retinal vessel geometry parameters were associated with both retinal and systemic DM-related complications, including diabetic nephropathy and cardiovascular diseases.
6–8 However, possible mechanisms underlying the retinal vessel geometric changes involved in DM-related complications are not fully understood. This may be because retinal vessel geometric changes only reflect changes to retinal arterioles and venules and not those to retinal capillaries in which microvascular complications associated with DR largely take place.
Optical coherence tomography angiography (OCTA) is a recently developed technology that enables noninvasive, rapid, and accurate visualization of the retinal microvasculature, including the capillaries.
9 In this study, we hypothesized that alterations of retinal arteriolar and venular geometry in DR would be associated with retinal capillary changes. We aimed to evaluate geometric changes to retinal arterioles and venules and those to retinal capillaries in DR using fundus photography and OCTA. Moreover, we aimed to investigate the associations between retinal vessel geometry parameters and OCTA metrics that reflect retinal capillary changes, which reflect DR pathophysiology.
This single-center retrospective cross-sectional study comprised all consecutive patients who had been referred for DR screening and who had undergone digital retinal photography and OCTA scans between March 2019 and March 2020 at Jeju National University Hospital in Jeju-si, Jeju-do, Republic of Korea. Inclusion criteria comprised referred patients ranging from those with no DR to nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR). Exclusion criteria comprised patients who had previously undergone laser photocoagulation, intravitreal injections, and intraocular surgeries, except for cataract surgery. We also excluded patients with concurrent retinal diseases other than DR, media opacity adversely affecting fundus photography or OCTA acquisition, and those with poor image quality.
Data are expressed as mean ± standard deviation or as numbers and percentages. Snellen best corrected visual acuity measurements were converted to logMAR units prior to statistical analysis. The Kruskal-Wallis test, followed by the Mann-Whitney U test with Bonferroni correction, was used to assess associations between DR severity and clinical characteristics. Intergrader reliability estimates of retinal vessel geometry parameters were assessed using the intraclass correlation coefficient (ICC). The mean of the retinal vessel geometry parameters evaluated by the two graders was used in the analysis.
Associations between DR severity and retinal vessel geometry parameters and OCTA metrics were assessed using Pearson's correlation analysis. Exploratory univariable linear regression analyses were performed to evaluate associations between retinal vessel geometry parameters and OCTA metrics that showed an association with DR severity. All variables with P values < 0.05 in the univariable analysis were included in the multivariable linear regression analyses with stepwise variable selection. Multivariable regression analyses were performed after adjusting for clinical characteristics and DR severity and corrected for multiple testing using a Benjamini–Hochberg correction.
A P value < 0.05 was considered statistically significant. Statistical analyses were performed using IBM SPSS version 22.0 Statistics for Windows (IBM Corp., Armonk, NY, USA) and MedCalc version 12.3.0.0 (MedCalc Software, Mariakerke, Belgium) software.
Associations Between DR Severity and Retinal Vessel Geometry Parameters and OCTA Metrics
Supported by the Division of Biostatistics, Hallym Institute for Clinical Medicine, Hallym University Medical Center.
Disclosure: J.M. Choi, None; S.M. Kim, None; Y.H. Bae, None; D.J. Ma, None