Diabetes is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies [
Nailfold videocapillaroscopy (NVC) is an easy, noninvasive, safe, and useful diagnostic tool to evaluate the microvascular structure of nailfold. NVC is used to assess disturbances in the skin capillaries of patients with autoimmune connective tissue disorders, especially in systemic sclerosis. NVC enables more accurate measurement and it is possible to store and analyze capillary data [
On the basis of this knowledge, the aim of the current study was to assess the nailfold capillaries to evaluate diabetic microvascular involvement, to determine any correlation between nailfold capillaroscopic findings and retinopathy and to search whether these changes have a relationship with duration of diabetes or not in patients with T2DM.
The study included 216 patients with T2DM and 101 healthy controls in the Internal Medicine Outpatient Clinic of University of Health Sciences Antalya Training and Research Hospital. Exclusion criteria were a history of ocular and retinal disease, Raynaud phenomenon, collagen tissue disease, drug usage affecting fibrinolysis metabolism (such as glucocorticoids and oral contraceptives), smoking, and occupation with a risk of microtrauma (e.g., farmer and gardener). All the patients were examined by an ophthalmologist for DR and by a rheumatologist for capillary assessment with the NVC device. Approval for the study was granted by the Local Ethics Committee and informed consent was obtained from all patients.
All subjects underwent a complete ophthalmic examination including best-corrected visual acuity, slip-lamp biomicroscopy, and dilated fundus examination. DR was confirmed by fundus photography (FFA Visucam NM/FA, Carl Zeiss, Germany) and optical coherence tomography imaging (Cirrus HD-OCT Model 5000, Carl Zeiss Meditec Inc., Dublin, CA, USA) and classified according to the ETDRS (Early Treatment of Diabetic Retinopathy Study, September 1, 2006) guidelines.
After 20 minutes resting at a room temperature of 20–24°C, immersion oil was applied on the nailfold of all participants for better visualization. Capillaroscopy was applied to 8 fingers (excluding the thumbs) of all participants at ×200 magnification with a capillaroscopy device (Videocap, DS MediGroup, Milan, Italy) by a rheumatologist blinded to patient’s condition and 4 images (1 × 1 mm in size) from the middle of the nailfold in each finger were evaluated [
The nailfold capillary system was assessed for capillary distribution, density, and morphology according to the Maricq criteria modified by Bergman et al. [
Abnormal capillaroscopic findings were defined as follows: (1) tortuosity: 2 or more cross capillaries, each over 1 mm in length; (2) neoangiogenesis: tortuous, bush-like capillaries with marked heterogeneity in size, (a) as the presence of extremely tortuous, bushy, branching, ramified and coiled capillaries, (b) ≥4 capillaries within a single dermal papilla, and (c) thin and branching interconnected capillaries originating from a single loop; (3) microhemorrhage: 2 or more punctate bleeds around a single capillary in at least 2 fingers (separate or confluent microhemorrhage areas); (4) extravasation: leakage of capillary content; (5) avascular area: loss of at least 2 consecutive capillaries or ≤6 capillaries over each 1 mm length; (6) bizarre capillary: capillaries with abnormal appearance but not resembling other defined abnormal capillaries (clover leaf, musical note G, etc.); (7) ectatic capillaries: capillary wall diameter between 0.02 and 0.05 micrometers (regular or irregular); (8) megacapillary: capillary wall diameter >0.05 micrometers (Figure
Normal and pathological videocapillaroscopy findings.
Descriptive statistics are presented as frequency (
The age was comparable between patients with DR group (
Demographical characteristics and frequencies of capillaroscopic findings of patients with DR, patients without DR, and healthy controls.
Diabetic patients ( | Controls ( | | ||
---|---|---|---|---|
DR (+) ( | DR (−) ( | |||
Mean age (SD) | 60.89 (8.21) | 58.92 (8.506) | 59.41 (11.867) | 0.316 |
Male gender, | 45 (36.6%) | 45 (48.4%) | 54 (53.5) | |
Hypertension, | 64 (68.8%) | 70 (56.9%) | 0 | 0.074 |
Hyperlipidemia, | 21 (22.6%) | 44 (35.8%) | 0 | |
HbA1c, % (min–max) | 8.7 (5.4–14.6) | 7.2 (5.0–12.3) | 0 | |
Diabetes years, median (min–max) | 14 (0–40) | 4 (0–25) | 0 | |
Tortuosity, | 75 (80.6%) | 71 (57.7%) | 6 (5.9%) | |
Bushy capillary, | 31 (33.3%) | 15 (12.2%) | 0 (0%) | |
Neoformation, | 29 (31.2%) | 15 (12.2%) | 0 (0%) | |
Bizarre capillary, | 36 (38.7%) | 37 (30.1%) | 7 (6.9%) | |
Microhemorrhage, | 11 (11.8%) | 5 (4.1%) | 0 (0%) | |
Capillary ectasia, | 11 (11.8%) | 7 (5.7%) | 0 (0%) | |
Aneurysm, | 10 (10.8%) | 7 (5.7%) | 0 (0%) | |
Extravasation, | 6 (6.5%) | 1 (0.8%) | 0 (0%) | NA |
Megacapillary, | 1 (1.1%) | 0 (0%) | 0 (0%) | NA |
Meander capillary, | 4 (4.3%) | 3 (2.4%) | 0 (0%) | NA |
Avascular area, | 3 (3.2%) | 0 (0%) | 0 (0%) | NA |
Interstitial edema, | 1 (1.1%) | 1 (0.8%) | 0 (0%) | NA |
NA: not applied; DR: diabetic retinopathy.
The frequencies of tortuosity [75 (80.6%) versus 71 (57.7%) versus 6 (5.9%);
Tortuosity [50 (80.6%) versus 25 (80.6%) versus 71 (57.7%);
Correlation of capillaroscopic findings with severity of DR.
Proliferative DR ( | Nonproliferative DR ( | Patients without DR ( | | |
---|---|---|---|---|
Tortuosity, | 50 (80.6%) | 25 (80.6%) | 71 (57.7%) | |
Bushy capillary, | 25 (40.3%) | 6 (19.4%) | 15 (12.2%) | |
Neoformation, | 22 (35.5%) | 7 (22.6%) | 15 (12.2%) | |
Capillary ectasia, | 10 (16.1%) | 1 (3.2%) | 7 (5.7%) | |
Bizarre capillary, | 25 (40.3%) | 11 (35.5%) | 37 (30.1%) | 0.372 |
Microhemorrhage, | 9 (14.5%) | 2 (6.5%) | 5 (4.1%) | NA |
Aneurysm, | 9 (14.5%) | 1 (3.2%) | 7 (5.7%) | NA |
Extravasation, | 6 (9.7%) | 0 (0%) | 1 (0.8%) | NA |
Megacapillary, | 1 (1.6%) | 0 (0%) | 0 (0%) | NA |
Meander capillary, | 4 (6.5%) | 0 (0%) | 3 (2.4%) | NA |
Avascular area, | 3 (4.8%) | 0 (0%) | 0 (0%) | NA |
Interstitial edema, | 0 (0%) | 1 (3.2%) | 1 (0.8%) | NA |
NA: not applied; DR: diabetic retinopathy.
Median (min–max) diabetes years of tortuosity [10 (0–40) versus 3 (0–23) years;
Comparison of median diabetes years of patients with and without significant capillaroscopic findings and comparison of median diabetes years of significant capillaroscopic findings patients with DR and without DR.
Median (min–max) diabetes years | | | ||||
---|---|---|---|---|---|---|
Patients with DR | Patients without DR | |||||
Tortuosity | + | 10 (0–40) | 14 (0–40) | 5.5 (0–25) | | |
− | 3 (0–23) | |||||
Bushy capillary | + | 12.50 (0–40) | 14 (0–40) | 8 (0–25) | | 0.169 |
− | 5 (0–40) | |||||
Aneurysm | + | 14 (2–33) | 18 (10–33) | 9 (2–14) | | |
− | 6 (0–40) | |||||
Neoformation | + | 12 (0–40) | 14 (0–40) | 8 (0–25) | | 0.143 |
− | 5.50 (0–40) | |||||
Bizarre capillary | + | 10 (0–40) | 14.5 (0–40) | 6.5 (0–25) | | |
− | 5.50 (0–33) | |||||
Microhemorrhage | + | 12.50 (0–33) | 16 (8–33) | 5 (0–9) | 0.050 | |
− | 7 (0–40) | |||||
Capillary ectasia | + | 10 (2–27) | 10 (2–27) | 8 (4–12) | 0.203 | 0.273 |
− | 7 (0–40) |
(+): capillaroscopic finding is present; (−): capillaroscopic finding is absent. DR: diabetic retinopathy;
Tortuosity [14 (0–40) versus 5.5 (0–25) years;
Tortuosity was significantly associated with DR [odds ratio 2.106, confidence interval 1.051 to 4.219;
Multivariate logistic regression analysis of significant capillaroscopic findings.
| OR (95% CI) | |
---|---|---|
Tortuosity | | 2.106 (1.051–4.219) |
Bushy capillary | 0.270 | 2.754 (0.455–16.648) |
Neoformation | 0.919 | 1.098 (0.182–6.635) |
Microhemorrhage | 0.119 | 2.505 (0.790–7.941) |
Bizarre capillary | 0.803 | 1.086 (0.568–2.077) |
Capillary ectasia | 0.778 | 1.172 (0.388–3.545) |
Aneurysm | 0.592 | 1.359 (0.443–4.173) |
The AUC (area under curve) values of tortuosity (0.615), bushy capillary (0.606), and neoformation (0.595) were lower than 80% with ROC (receiver operating characteristic) analysis (Table
Estimates of diagnostic test for significant capillaroscopic findings for DR detection.
AUC | 95% CI | |
---|---|---|
Tortuosity | 0.615 | 0.540 to 0.689 |
Bushy capillary | 0.606 | 0.528 to 0.683 |
Neoformation | 0.595 | 0.517 to 0.673 |
Microhemorrhage | 0.539 | 0.460 to 0.617 |
Bizarre capillary | 0.543 | 0.465 to 0.621 |
Capillary ectasia | 0.531 | 0.452 to 0.609 |
Aneurysm | 0.525 | 0.447 to 0.604 |
AUC: area under curve; CI: confidence interval.
ROC curve of tortuosity, bushy capillary, and neoformation.
DR is the leading cause of blindness and the goal is to detect clinically significant retinopathy before vision is threatened [
In the present study, we demonstrated that tortuosity, bushy capillary, neoformation, bizarre capillary, microhemorrhage, capillary ectasia, and aneurysm were significantly higher in patients with T2DM than healthy controls. Capillaroscopic findings including tortuosity, bushy capillary, neoformation, and capillary ectasia were also significantly higher in patients with proliferative DR than patients with nonproliferative DR and without DR. These findings show that there is a microvascular involvement in T2DM and a strong correlation with DR, and NVC can detect changes in the nailfold capillaries precisely. In 1997, Chang et al. evaluated 35 patients with diabetes (10 without DR, 10 with background DR, and 15 with proliferative DR) and 20 healthy controls. Tortuosity was the highest findings in group of proliferative DR (68%). It was found %20 in control group and %23 in group of without DR [
Diabetes years of patients with tortuosity, bushy capillary, aneurysm, neoformation, and bizarre capillary were longer than diabetic patients lacking these findings regardless of retinopathy in our study. When we compared the median diabetes years of significantly present capillaroscopic findings by the presence of DR, diabetes years of patients having tortuosity, aneurysm, bizarre capillary, and microhemorrhage were significantly longer in patients with DR than patients without DR. Positive correlation of capillaroscopic findings and diabetes duration was also stated in Chang et al. and Meyer et al. studies, whereas Barchetta et al. found that NVC findings were independent from duration of diabetes [
Although tortuosity was the most valuable capillaroscopic finding in logistic regression analysis, it cannot be used as a diagnostic tool since the AUC value was less than 80% in ROC curve (Figure
Compared to previous studies, this cross-sectional study has more T2DM patients and more capillaroscopic findings were evaluated. Our study population was homogeneous in terms of age and hypertension history between groups. HbA1c level was higher in patients with DR as expected and more patients were using antilipid drug in DR negative group. Relationship of other diabetic complications, such as nephropathy and neuropathy, and other comorbidities of patients with NVC findings were not evaluated in this study as a limitation. Also, quantitative evaluation of NVC findings and NVC score were not performed.
Our data have showed that there is a significant correlation with capillaroscopic findings and DR, and NVC can detect microvascular changes in T2DM patients without clinically apparent retinopathy. These findings may guide the detection of T2DM associated retinopathy and microvascular complications earlier. Capillaroscopic findings including tortuosity, bushy capillary, aneurysm, neoformation, and bizarre capillary were significantly linked with a longer DM duration and DR positive patients in our study. We suppose that tortuosity may be the leading finding for diagnosis of early DR according to our data. The evaluation of nailfold capillaroscopic findings may be a new modality for vascular assessment of diabetic patients to diagnose and follow up microvascular complications. Further NVC studies are needed to determine the timing and relationship of other comorbidities of DM.
The authors declare that there are no competing interests.