Do SGLT2 inhibitors prevent preclinical diabetic retinopathy? A Prospective Pilot Optical Coherence Tomography Angiography Study

Sabaner, Mehmet Cem; Duman, Rahmi; Doğan, Mustafa; Akdogan, Muberra; Vurmaz, Ayhan; Bozkurt, Erhan; Beysel, Selvihan

doi:10.1016/j.jfo.2021.01.005

Cited by 17 publications

(6 citation statements)

References 27 publications

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“…In addition, DME-related symptoms were improved in a T2DM patient with steroid-resistant DME after treatment with ipragliflozin, which is speculated to be related to SGLT-2i’s protection of pericytes from high glucose-induced damage and its direct attenuation of DME by inhibiting VEGF production ( 67 ). SGLT-2i is considered to be an alternative for retinal protection in metformin intolerant patients with T2DM ( 68 ). A retrospective study showed that treatment with SGLT-2i slowed the progression of DR in patients with T2DM compared with sulfonylurea, independent of its effect on glycemic control ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Zeng

Shi

et al. 2022

Front. Endocrinol.

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BackgroundThis meta-analysis was conducted to explore the association between sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and ocular diseases in type 2 diabetes mellitus (T2DM) patients.MethodsPubMed, Cochrane Central Registry of Controlled Trials, Web of Science and Springer were searched for articles on randomized controlled trials (RCTs) involving T2DM patients treated with SGLT-2i versus placebo or other hypoglycemic agents published prior to August 2021. The primary outcome of this meta-analysis was incidence of ocular diseases, which was assessed using risk ratios (RR) and 95% confidence intervals (CI). We reviewed 47 papers and compared the effect of SGLT-2i with the effect of the control groups (placebo and other hypoglycemic drugs) on the incidence of ocular diseases.ResultsCompared with controls, overall SGLT-2i use in T2DM patients was not associated with incidences of cataract, glaucoma, retinal disease and vitreous disease. Ertugliflozin (RR=0.47, P=0.01) reduced the risk for retinal disease, while empagliflozin (RR=0.44, P=0.05) reduced the risk for diabetic retinopathy (DR) compared with controls. SGLT-2i (RR=0.50, P=0.02), perhaps empagliflozin (RR=0.47, P=0.06), reduced the risk of retinal disease compared with active hypoglycemic agents. Canagliflozin (RR=4.50, P=0.03) increased the risk for vitreous disease compared with placebo.ConclusionsThere was no significant correlation between overall SGLT-2i and ocular diseases (cataract, glaucoma, retinal disease, vitreous disease, corneal disease, conjunctival disease, uveal disease, eye haemorrhage and vision problems) in T2DM patients. Ertugliflozin and empagliflozin may protect against ocular diseases, but canagliflozin may promote ocular diseases.

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Section: Discussionmentioning

confidence: 99%

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Zeng

Shi

et al. 2022

Front. Endocrinol.

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“…26 In addition, an SGLT2 inhibitor, tofogliflozin, has previously been shown to be effective in reducing glial fibrillar acidic protein and VEGF activation in db/db mice. Empagliflozin reduced preclinical DR, highlighting the potential benefit of SGLT2 inhibition in DR. [27][28][29] Our studies further add to the evolving role of SGLT2 inhibitors by showing the protective effect of dapagliflozin on retinal Pathophysiology/complications vascular and dysfunction. The protective effect was mainly mediated by improvement in systemic glycemic control, decrease in inflammation, decrease in wound healing response and glucose uptake, and improvement in hematocrit levels, which together helped to induce a protective effect on the neural and vascular retina.…”

Section: Discussionmentioning

confidence: 63%

Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes

Luo

Leley

Bello

et al. 2022

BMJ Open Diab Res Care

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IntroductionDapagliflozin, a sodium-glucose transporter inhibitor, effectively reduces blood glucose and is indicated for individuals with kidney diseases and cardiovascular disorders. In this study, we further expand the therapeutic benefit of dapagliflozin in the neural and vascular retina, with the potential to effectively manage diabetic retinopathy (DR), the most common complication of diabetes.Research design and methodsDb/db mice, an animal model of type 2 diabetes, were treated with dapagliflozin orally, and the electroretinogram (ERG) response and acellular capillary numbers were assessed. Messenger RNA levels of inflammatory cytokines were studied using real-time quantitative (q)PCR. We assessed endothelial cell migration in a scratch wound assay and retinal glucose uptake using human retinal endothelial cells.ResultsThe dapagliflozin treatment improved the ERG b-wave amplitude and decreased acellular capillary numbers. The scratch wound assay demonstrated a reduction in wound closure after dapagliflozin treatment. Retinal glucose uptake reduced after dapagliflozin treatment compared with the respective controls.ConclusionsOur studies suggest that dapagliflozin treatment effectively corrects neural and vascular dysfunction of the retina in diabetes. This effect is mediated by a decrease in inflammation and improved glycemic control. In addition, dapagliflozin exhibits decreased wound healing and glucose uptake, which could benefit the retina. Thus, dapagliflozin could be helpful in the management of DR, with multimodal therapeutic effects.

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“…The current theory holds that retinal capillaries are mainly divided into super cial capillary plexus (SCP), located in the ganglion cell layer, and deep capillary plexus (DCP), located in the inner nuclear layer. [12] . Sheikh et al [13] reported that the VD of the SCP of the eye during the NPDR period was lower than that of the control group, and they posited that the non-perfusion area of the SCP in the early stage of DR patients was larger as compared to the DCP.…”

Section: Discussionmentioning

confidence: 99%

OCTA detects and analyzes retinal vascular density changes from diabetes to diabetic retinopathy

Chen

Xiao

et al. 2022

Preprint

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Background To detect various indicators of retinal vascular plexus through optical coherence tomography angiography (OCTA) in non-diabetics and diabetics at various stages, and to analyze the characteristics of retinal microcirculation during each stage of diabetes. Methods OCTA was used to detect the four groups, namely non-diabetic, non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Furthermore, it was also used to measure the retinal vascular density (VD) of the fovea, parafovea, and perifovea areas of the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results The logarithm of the minimum angle of resolution (LogMAR) visual acuity of the four groups of patients revealed a gradual upward trend, and a significant statistical difference (P < 0.001). The VD of Whole, Parafovea and Perifovea of SCP and DCP were compared between the control group, NDR group, NPDR group and PDR group, respectively, and the differences were statistically significant (P < 0.001). There was no significant difference in VD between the SCP and DCP of the fovea in the four groups (P > 0.001). The whole blood vessel density of the superficial retina and deep retina was significantly negatively correlated with LogMAR visual acuity (P < 0.001); There was no significant correlation observed between the superficial and deep fovea VD and LogMAR vision (P > 0.001). The superficial and deep parafovea VD exhibited a significant negative correlation with LogMAR vision (P < 0.001). The superficial and deep perifovea VD was significantly negatively correlated with LogMAR visual acuity (P < 0.001). Conclusion OCTA is a potential non-invasive imaging tool that can assist in monitoring the development of diabetic retinopathy, and the longer the disease period, the more obvious the decrease of retinal VD in patients.

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Do SGLT2 inhibitors prevent preclinical diabetic retinopathy? A Prospective Pilot Optical Coherence Tomography Angiography Study

Cited by 17 publications

References 27 publications

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Relationship Between SGLT-2i and Ocular Diseases in Patients With Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials

Dapagliflozin protects neural and vascular dysfunction of the retina in diabetes

OCTA detects and analyzes retinal vascular density changes from diabetes to diabetic retinopathy

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