Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy

Sacconi, Riccardo; Casaluci, Marco; Borrelli, Enrico; Mulinacci, Giacomo; Lamanna, Francesca; Gelormini, Francesco; Carnevali, Adriano; Querques, Lea; Zerbini, Gianpaolo; Bandello, Francesco; Querques, Giuseppe

doi:10.3390/jcm8091409

Cited by 37 publications

(29 citation statements)

References 34 publications

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“…Our results are supported by previous findings of preclinical structural and functional changes in patients with diabetes. [16][17][18][19]37,39 The altered retinal vascular response that we observed also corroborates previous evidence on the importance of neurovascular coupling dysfunction very early in DR development. These studies used the laser Doppler blood flowmeter, functional magnetic resonance imaging, flicker electroretinography and the dynamic vessel analyzer as devices to assess retinal vascular function.…”

Section: Discussionsupporting

confidence: 89%

“…By examining serial images over time, the generated final image clearly defines retinal vascular plexuses. [10][11][12][13][14] Recently, a few studies using OCTA have been reporting structural quantitative changes (i.e., reduced vessel density and increased foveal avascular zone area) in patients with diabetes before clinically evident DR. [15][16][17][18][19][20] However, little is known about the possibility of using OCTA to evaluate individual functional retinal vascular changes. Our group recently published a safe, reproducible and inexpensive protocol to assess retinal microvasculature reactivity in healthy subjects, detailing how OCTA technology is able to detect retinal vasodilation and vasoconstriction in response to two physiological conditions-mild hypoxia and isometric exercise, respectively.…”

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confidence: 99%

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Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography

Sousa

Leal

Moreira

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. METHODS. Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. RESULTS. In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F 1,23 = 15.69, P < 0.001 and F 1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F 1,23 = 27.37, P < 0.0001 and F 1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F 1,23 = 11.04, P < 0.01). CONCLUSIONS. Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography

Sousa

Leal

Moreira

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…Carnevali et al showed in a small series of 25 eyes that OCTA was able to detect early vascular alterations even without any biomicroscopic signs of DR. 24 More recently, Sacconi et al described a series of 34 eyes where the only OCTA parameter that was significantly different in patients with type 1 DM compared to controls was the PD of the DCP, without differences in the rest of the studied parameters and plexuses. 25 The largest series in type 1 DM have been described in children, and they interestingly have shown controversial results. 26 – 30 Golebiewska et al reported that no differences were seen in the VD or FAZ area in any of the studied plexuses between patients with type 1 DM and controls ( n = 188 vs. 60); however, Niestrata-Ortiz et al described that FAZ area was different between diabetic and healthy children ( n = 112 vs. 30).…”

Section: Discussionmentioning

confidence: 99%

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 1: Diabetic Retinopathy

Barraso

Alé-Chilet

Hernandez

et al. 2020

Trans. Vis. Sci. Tech.

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The purpose of this study was to evaluate specifically in type 1 diabetes mellitus (DM) individuals the relationship between perifoveal superficial capillary plexus (SCP) parameters assessed by optical coherence tomography angiography (OCTA) and diabetic retinopathy (DR) grade. Methods: Cross-sectional analysis of a large scale prospective OCTA trial cohort (Clini-calTrials.gov NCT03422965). A total of 1186 eyes (593 individuals), 956 type 1 DM eyes (478 patients), and 230 control eyes (115 healthy volunteers) were included in this study. DR stage was graded according to the International Classification. OCTA imaging was performed with a commercially available device (Cirrus HD-OCT). Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) area, perimeter and circularity measurements were quantified in the SCP and receiver operating characteristic (ROC) curves were constructed for each OCTA parameter. Results: VD and PD (in both 3 × 3 and 6 × 6 mm captures) were inversely associated with DR stage (P < 0.001 in all cases) in a multiple regression analysis after controlling by age, gender, signal strength index, axial length, and DM duration. Greater FAZ area and perimeter and conversely lower circularity measurements were observed as DR severity increased in both scanning protocols (P < 0.05 in all cases). Conclusions: In type 1 DM individuals, OCTA provides an objective, continuous, and reliable method for accurate quantification of VD, PD, and FAZ parameters in the SCP, which ultimately correlate with DR stages. Translational Relevance: Objective OCTA measurements of the retinal microvasculature could substitute the clinical DR classification in patients with type 1 DM, identify patients at risk of DR progression, and inform treatment decisions to modify the evolution of the disease.

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“…Microperimetry. Assessment of retinal sensitivity was performed using microperimetry following the same procedure used in a previously published paper 21 . In detail, before the examination, all patients underwent at least 5 mm pupil dilation with 1% tropicamide and 15-minute mesopic adaptation.…”

Section: Oct-a Image Acquisition and Analysismentioning

confidence: 99%

Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease

Sacconi

Lamanna

Borrelli

et al. 2020

Sci Rep

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There is a lack of studies evaluating the sub-clinical retinal changes in patients with long-term type 1 diabetes mellitus (T1DM) and without history of systemic/ocular complications. The aim of this crosssectional study was to investigate sub-clinical structural and/or vascular retinal changes in patients with long-term (≥30 years) T1DM and without systemic/ocular complications ("happy few" patients) using structural optical coherence tomography (OCT), OCT-angiography and microperimetry. Twelve eyes of 12 consecutive T1DM patients (mean age 52 ± 12 years, mean duration of disease 35 ± 3 years, mean HbA1c level 7.3 ± 2.8%), without micro/macrovascular complications associated with long-standing T1DM, and twelve healthy subjects were consecutively included. No statistically significant differences were disclosed comparing patients and controls for age, sex, best-corrected visual acuity, central macular thickness, and choroidal thickness. Using OCT-angiography, we did not find any significant difference in foveal avascular zone area, perfusion density, vessel length density, and tortuosity. Moreover, no significant differences were disclosed in retinal nerve fiber layer and ganglion cell complex thickness using structural OCT. No differences were disclosed in retinal sensitivity by microperimetry. New diagnostic tools are able to confirm the presence of a particular population of patients with type 1 diabetes who have been completely spared from diabetic retinal complications. The finding of these "happy few" patients could help us to better understand and target future treatments for diabetes.Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and it develops in the majority of patients with long-standing type 1 diabetes mellitus (T1DM) 1 . For this reason, the American Diabetes Association (ADA) recommended a comprehensive ocular examination within 5 years after T1DM diagnosis in order to detect early signs of DR and to manage it promptly 2 . Retinal microaneurysms may represent the first visible clinical sign of DR and are secondary to small outpouchings of the retinal capillaries.Recently, new imaging technologies have enabled early identification of retinal structural and functional changes, even before DR is clinically evident. Optical coherence tomography angiography (OCT-A), a non-invasive dye-free imaging modality, provides a highly detailed view of the retinal and choroidal vasculature. Nowadays, optimized OCT-A algorithms may be used to detect early retinal and choriocapillaris (CC) microvascular flow alterations, which may be evident even before the DR presentation and may potentially result in irreversible retinal damage. As an example, De Carlo et al. 3 revealed OCT-A ability to detect foveal avascular zone (FAZ) remodeling and retinal capillary nonperfusion in T1DM patients without DR. Furthermore, both our group 4 and Simonett et al. 5 reported a significantly decreased perfusion density (PD) in the deep retinal vascular complex (DVC) in T1DM patients without evidence...

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Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy

Cited by 37 publications

References 34 publications

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography

Retinal Vascular Reactivity in Type 1 Diabetes Patients Without Retinopathy Using Optical Coherence Tomography Angiography

Optical Coherence Tomography Angiography in Type 1 Diabetes Mellitus. Report 1: Diabetic Retinopathy

Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease

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