Treatment of Diabetic Macular Edema

Kim, Eric J.; Lin, Weijie; Rodriguez, Sean Michael; Chen, Ariel; Loya, Asad; Weng, Christina Y.

doi:10.1007/s11892-019-1188-4

Cited by 106 publications

(97 citation statements)

References 77 publications

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“…The characteristics of DR treatment highlighted other problem as well. Local/grid laser photocoagulation of the retina, which is now reserved mostly for non-center-involving DR according to the current treatment guidelines, remains the gold standard in DR treatment in Poland [28]. While anti-vascular endothelial growth factor (anti-VEGF) and intraocular corticosteroid therapies have become the first-line treatment [26], they have been used in only 6% of the DR patients treated in Poland.…”

Section: Discussionmentioning

confidence: 99%

First nation-wide study of diabetic retinopathy in Poland in the years 2013–2017

Kozioł

Nowak²,

Udziela

et al. 2020

Acta Diabetol

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Aims To assess the prevalence and time trends of diabetic retinopathy (DR) in the overall population of Poland from 2013 to 2017 and diagnose the risk factors of occurring DR among patients with diabetes mellitus (DM). Methods Data from all levels of healthcare services at public and private institutions recorded in the National Health Fund (NHF) database were evaluated. International Classification of Diseases codes (ICD-9 and ICD-10) and unique NHF codes were used to identify DM type 1 and type 2 patients, DR and treatment procedures including laser photocoagulation, pars plana vitrectomy (PPV), anti-VEGF and steroid intravitreal injections. Results The overall registered prevalence of DR in the entire population of Poland was 0.81%. The mean prevalence of DR was 20.01% in the population with type 1 DM and 9.70% in the population with type 2 DM. In the study period, women represented 56.36% of all individuals registered with DR and 55.09% of all DM patients. In Poland, only 6.34% of all DM patients with DR received specific treatment with laser photocoagulation of the retina (82.32%), PPV (11.56%), anti-VEGF or steroid injections (5.15% and 0.97%, respectively). Cox regression hazard analysis showed that the risk of DR was associated with DM treatment only by GPs, female sex, coexisting systemic diseases and urban residence in both type 1 and type 2 DM. Conclusions A 5-year retrospective analysis reveals the mean prevalence of DR in the population with type 1 and type 2 DM in Poland was rather low.

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Section: Discussionmentioning

confidence: 99%

First nation-wide study of diabetic retinopathy in Poland in the years 2013–2017

Kozioł

Nowak²,

Udziela

et al. 2020

Acta Diabetol

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“…Laser photocoagulation is the standard treatment for PDR, whereas intravitreal injections of anti-VEGF medications are the first-line therapy in patients whose vision is threatened by DME. 5,6 However, suboptimal and temporal responses, adverse effects, and high socioeconomic costs have stimulated the search for additional treatment options. Our ongoing clinical trial in patients with PDR and DME is investigating the therapeutic value of elevating the circulating levels of PRL by the oral administration of levosulpiride, the prokinetic dopamine D2 receptor blocker.…”

Section: Discussionmentioning

confidence: 99%

“…4 Current treatments-laser photocoagulation, intravitreal injections, and vitrectomy-are invasive, not always effective, temporary, and costly, thus emphasizing the need for additional therapeutic options. 5,6 An ongoing clinical trial is investigating a new therapy for DR and DME based on elevating the circulating levels of the hormone prolactin (PRL) with the prokinetic dopamine D2 receptor blocker, levosulpiride (ClinicalTrials.gov ID: NCT03161652).…”

Section: Introductionmentioning

confidence: 99%

Levosulpiride Increases the Levels of Prolactin and Antiangiogenic Vasoinhibin in the Vitreous of Patients with Proliferative Diabetic Retinopathy

Nuñez‐Amaro

Moreno-Vega

Adán‐Castro

et al. 2020

Trans. Vis. Sci. Tech.

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High circulating levels of the hormone prolactin (PRL) protect against experimental diabetic retinopathy (DR) due to the retinal accumulation of vasoinhibin, a PRL fragment that inhibits blood vessel permeability and growth. A phase 2 clinical trial is investigating a new therapy for DR based on elevating serum PRL levels with levosulpiride, a prokinetic dopamine D2 receptor blocker. Here, we tested whether levosulpiride-induced hyperprolactinemia elevates PRL and vasoinhibin in the vitreous of volunteer patients with proliferative DR (PDR) undergoing elective pars plana vitrectomy. Methods: Patients were randomized to receive placebo (lactose pill, orally TID; n = 19) or levosulpiride (25 mg orally TID; n = 18) for the 7 days before vitrectomy. Vitreous samples from untreated non-diabetic (n = 10) and PDR (n = 17) patients were also studied. Results: Levosulpiride elevated the systemic (101 ± 13 [SEM] vs. 9.2 ± 1.3 ng/mL, P < 0.0001) and vitreous (3.2 ± 0.4 vs. 1.5 ± 0.2 ng/mL, P < 0.0001) levels of PRL, and both levels were directly correlated (r = 0.58, P < 0.0002). The vitreous from nondiabetic patients or from PDR patients treated with levosulpiride, but not from placebotreated PDR patients, inhibited the basic fibroblast growth factor (bFGF)-and vascular endothelial growth factor (VEGF)-induced proliferation of endothelial cells in culture. Vasoinhibin-neutralizing antibodies reduced the vitreous antiangiogenic effect. Matrix metalloproteases (MMPs) in the vitreous cleaved PRL to vasoinhibin, and their activity was higher in non-diabetic than in PDR patients. Conclusions: Levosulpiride increases the levels of PRL in the vitreous of PDR patients and promotes its MMP-mediated conversion to vasoinhibin, which can inhibit angiogenesis in DR. Translational Relevance: These findings support the potential therapeutic benefit of levosulpiride against vision loss in diabetes.

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“…A metanalysis of 521 DME eyes also demonstrated that dexamethasone implant improved visual acuity similar to anti-VEGFs with a significant improvement in anatomical outcomes [16]. Nevertheless, the dexamethasone implant is often used as a second line therapy in anti-VEGF nonresponding eyes or pseudophakic eyes, given the risk of corticosteroid-associated cataract and ocular hypertension [17,18].…”

Section: Pathogenesis Of Dmementioning

confidence: 99%

Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment

Bhatwadekar

Kansara

Ciulla

2020

Expert Opinion on Investigational Drugs

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Introduction: Plasma kallikrein is a mediator of vascular leakage and inflammation. Activation of plasma kallikrein can induce features of diabetic macular edema (DME) in preclinical models. Human vitreous shows elevated plasma kallikrein levels in patients with DME. Because of the incomplete response of some patients to anti-VEGF agents, and the treatment burden associated with frequent dosing, there is still considerable need for VEGF-independent targeted pathways. Areas covered: This review covers the role of plasma kallikrein in the pathogenesis of DME and the therapeutic potential of plasma kallikrein inhibitors. It discusses early clinical studies of plasma kallikrein pathway modulation for DME, which have been associated with some improvement in visual acuity but with limited improvement in macular edema. This review also highlights KVD001, which is furthest along the development pathway, THR-149, which has recently completed a phase 1 study, and oral agents under development. Expert opinion: Plasma kallikrein inhibitors have a potential role in the treatment of DME, with mixed functional/anatomic results in early clinical trials. Given the large unmet need in DME treatment, further studies are warranted.

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Treatment of Diabetic Macular Edema

Cited by 106 publications

References 77 publications

First nation-wide study of diabetic retinopathy in Poland in the years 2013–2017

First nation-wide study of diabetic retinopathy in Poland in the years 2013–2017

Levosulpiride Increases the Levels of Prolactin and Antiangiogenic Vasoinhibin in the Vitreous of Patients with Proliferative Diabetic Retinopathy

Investigational plasma kallikrein inhibitors for the treatment of diabetic macular edema: an expert assessment

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