Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema

Figueras‐Roca, Marc; Matas, Jessica; Llorens, Víctor; Sala‐Puigdollers, Anna; Navarro, Manuel Jiménez; Zarranz‐Ventura, Javier; Adán, Alfredo; Molins, Blanca

doi:10.1007/s00417-021-05149-5

“…Disease development is widely accepted as resulting from the combined effects of angiogenesis and inflammation. 20 Systemic inflammation may not be correlated with local retinal inflammation in DR, 40,41 despite the elevation of systemic inflammatory biomarkers in DR, 41 similar to DME [42][43][44] and other disorders associated with macular edema, such as uveitis, 44 retinal vascular occlusion, 45 and retinal dystrophy. 46 We hypothesize that systemic inflammation may play a more critical role in DME than DR.…”

Section: Discussionmentioning

confidence: 99%

Diabetic Patients With Rosacea Increase the Risks of Diabetic Macular Edema, Dry Eye Disease, Glaucoma, and Cataract

Wang

¹

,

Kang

²

,

Liu

³

et al. 2022

Asia-Pacific Journal of Ophthalmology

3

0

View full text Add to dashboard Cite

Purpose: Inflammation plays a role in diabetic eye diseases, but the association between rosacea and eye diseases in patients with diabetes remains unknown. Design: This retrospective cohort study used claims data from the National Health Insurance Research Database in Taiwan to investigate the association between rosacea and eye diseases in patients with diabetes. Materials and Methods: Taiwanese patients diagnosed as having diabetes mellitus between January 1, 1997, and December 31, 2013, and using any hypoglycemic agents were included and divided into rosacea and nonrosacea groups. After applying 1:20 sex and age matching and exclusion criteria, 1:4 propensity score matching (PSM) was conducted to balance the covariate distribution between the groups. The risk of time-to-event outcome between rosacea and nonrosacea groups in the PSM cohort was compared using the Fine and Gray subdistribution hazard model. Results: A total of 4096 patients with rosacea and 16,384 patients without rosacea were included in the analysis. During a mean follow-up period of 5 years, diabetic patients with rosacea had significantly higher risks of diabetic macular edema [subdistribution hazard ratio (SHR): 1.31, 95% confidence interval (CI): 1.05–1.63], glaucoma with medical treatment (SHR: 1.11, 95% CI: 1.01–1.21), dry eye disease (SHR: 1.55, 95% CI: 1.38–1.75), and cataract surgery (SHR: 1.13, 95% CI: 1.02–1.25) compared with diabetic patients without rosacea. A cumulative incidence analysis performed up to 14 years after the index date revealed that the risks of developing ocular diseases consistently increased over time. No significant differences in diabetic retinopathy, age-related macular degeneration, retinal vascular occlusion, ischemic optic neuropathy, optic neuritis, uveitis, or retinal detachment were identified according to rosacea diagnosis. However, we observed significant associations between rosacea and psoriasis, irritable bowel syndrome, anxiety, and major depressive disorder among patients with diabetes. Conclusions: Rosacea is associated with diabetic macular edema, glaucoma, dry eye disease, and cataract development in diabetic patients, as well as increased risks of psoriasis, irritable bowel syndrome, anxiety, and depression in diabetic patients.

show abstract

“…Bevacizumab, as a full-length (Fab and Fc) humanized murine IgG1 monoclonal antibody against VEGF-A, while Ranibizumab is a recombinant, humanized murine IgG1 monoclonal antibody fragment (Fab) targeting VEGF-A with higher affinity; Aflibercept is a recombinant fusion protein with VEGF receptors-1 and −2 fused to the Fc fragment of human IgG1; Similarly, conbercept is a recombinant fusion protein with high affinity for VEGF-A isoforms and PIGF; Brolucizumab is a single-chain antibody fragment targeting all forms of VEGF-A with higher solubility and lower molecular weight, allowing for administration of increased molar equivalents and in turn, may allow for longer intervals between doses. Though PDR and DME are two complications of diabetes mellitus and accumulating clinical and laboratory studies have evidenced the role of inflammation in the two complications, especially in DME ( Hillier et al, 2017 , 2018 ; Figueras-Roca et al, 2021 ; Hu et al, 2021 ; Mao et al, 2021 ; Minaker et al, 2021 ). However, studies assessing how the inflammatory cytokines and cytokines change after anti-VEGF therapy of DME have shown inconsistent findings.…”

Section: Discussionmentioning

confidence: 99%

Vitreous Inflammatory Cytokines and Chemokines, Not Altered After Preoperative Adjunctive Conbercept Injection, but Associated With Early Postoperative Macular Edema in Patients With Proliferative Diabetic Retinopathy

Sun

¹

,

Zhou

²

,

Zhang

³

et al. 2022

View full text Add to dashboard Cite

PurposeTo investigate the influence of preoperative adjunctive anti-VEGF drug (Conbercept) on vitreous inflammatory cytokines and chemokines profiles and whether those cytokines were associated with early macular edema (ME) after surgery for patients with proliferative diabetic retinopathy (PDR).MethodsIn this post hoc analysis of the CONCEPT clinical trial, subjects with PDR underwent vitrectomy were included and vitreous samples were collected at the start of vitrectomy. Levels of vitreous VEGF, 17 inflammatory cytokines, and 11 chemokines were measured using Luminex multiplex technology. Subjects were then divided into groups based on with (Pre-IV) or without (No-Pre-IV) preoperative intravitreous injection of Conbercept; with or without early ME after surgery.ResultsThere was no difference between Pre-IV (13/30) and No-Pre-IV (7/29) concerning the ratio of patients with early ME (p = 0.17). After preoperative intravitreous injection of Conbercept, VEGF level dramatically decreased (p = 0.001), TNF-α (p = 0.002), and IP-10 (p = 0.018) increased in Pre-IV group. In patients with early ME after surgery, however, a number of cytokines increased, including IL-1β (p = 0.008), IL-2 (p = 0.023), IL-4 (p = 0.030), IL-9 (p = 0.02), IL-10 (p = 0.002), IL-12 (p = 0.001), IL-13 (p = 0.031), IL-17A (p = 0.008), TNF-α (p = 0.012), CXCL9 (p = 0.023), G-CSF (p = 0.019), MCP-1 (p = 0.048), and RANTES (p = 0.016).ConclusionWe found the preoperative adjunctive Conbercept injection has limited influence on the levels of vitreous inflammatory cytokines and chemokines in PDR. The elevated levels of a series of cytokines might be associated with early inflammation after vitrectomy, which may lead to postoperative ME.

show abstract

“…Moreover, it has been shown that patients with DME have increased levels of proinflammatory mediators in aqueous humor com-pared to non-DME cases [8], while there is a controversy whether the pathophysiology of DME is mainly attributed to such systemic affection or to a local intraocular response. Of note, several studies have shown that elevated serum lipids, including cholesterol and low-density lipoprotein (LDL), demonstrated a significant association with retinal hard exudates and formation of DME [9][10][11][12], while elevated IL-6 has also been correlated with diffuse retinal thickness or severity of DME [13,14].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Imaging Morphological Findings and Laboratory Biomarkers in Patients with Diabetic Macular Edema

Dimitriou

¹

,

Sergentanis

²

,

Lambadiari

³

et al. 2021

Journal of Diabetes Research

View full text Add to dashboard Cite

Purpose. To investigate the potential association between peripheral blood biomarkers and morphological characteristics of retinal imaging in patients with diabetic macular edema (DME). Methods. Participants in this cross-sectional study were 36 consecutive patients (36 eyes) with treatment-naïve DME, who underwent spectral domain-optical coherence tomography (SD-OCT), fundus photography, and fundus fluorescein angiography (FFA). In addition, peripheral blood samples were taken to evaluate full blood count and biochemical parameters. Correlation between imaging characteristics and laboratory parameters was examined. Results. Eyes with central subfield thickness greater than 405 μm presented significantly higher neutrophils/lymphocytes ( p = 0.043 ) and higher lipoprotein (a) compared to eyes with CST < 405 μ m ( p = 0.003 ). Presence of hyperreflective foci on SD-OCT was associated with significantly higher white blood cell count ( p = 0.028 ). Ellipsoid zone disruption was associated with significantly lower hematocrit ( p = 0.012 ), hemoglobin ( p = 0.009 ), and red blood cell count ( p = 0.026 ), as well as with higher lipoprotein (a) ( p = 0.015 ). Macular ischemia on FFA was associated with significantly higher monocytes ( p = 0.027 ) and monocytes/HDL ( p = 0.019 ). No significant associations were found between laboratory parameters and subretinal fluid, intraretinal fluid, exudates, cysts, disorganization of inner retinal layers, epiretinal membrane, and external limiting membrane condition. Conclusion. Specific imaging morphological characteristics were found to be associated with laboratory parameters in patients with DME. These findings may shed light on the pathophysiology of DME and its correlation with the development of specific clinical signs.

show abstract

Systemic contribution of inflammatory mediators to the severity of diabetic and uveitic macular edema

Cited by 5 publications

References 40 publications

Diabetic Patients With Rosacea Increase the Risks of Diabetic Macular Edema, Dry Eye Disease, Glaucoma, and Cataract

Diabetic Patients With Rosacea Increase the Risks of Diabetic Macular Edema, Dry Eye Disease, Glaucoma, and Cataract

Vitreous Inflammatory Cytokines and Chemokines, Not Altered After Preoperative Adjunctive Conbercept Injection, but Associated With Early Postoperative Macular Edema in Patients With Proliferative Diabetic Retinopathy

Correlation between Imaging Morphological Findings and Laboratory Biomarkers in Patients with Diabetic Macular Edema

Contact Info

Product

Resources

About