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

Abstract

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.

Small extracellular vesicle-loaded bevacizumab reduces the frequency of intravitreal injection required for diabetic retinopathy

“…A significant number of adherent leukocytes still seen in the EV - BZ group could be a possible reason for unaltered inflammation with this treatment. Also, the present study was not targeting hyperglycemia which could be contributing to inflammatory response as hyperglycemia is directly linked with increased levels of pro-inflammatory cytokines 58 Alternatively the dose of VEGF and duration of treatment also could be contributing to the effectiveness in suppressing the inflammation as both responsiveness and unresponsiveness were reported with anti - VEGF treatments 59 - 60 .…”

The impact of intravitreal therapy of diabetic macular edema on the local and systemic production of cytokines

“…[8] исходный уровень IL-7 у пациентов с ДМО значимо не отличался от контроля, а уровень IL-15 находился за пределами значений, подлежащих определению. В другой работе, где уровень ЦК измерялся у пациентов с пролиферативной диабетической ретинопатией с последующим развитием / без последующего развития макулярного отека после витрэктомии, содержание IL-7 и IL-15 в стекловидном теле не имело ни значимых различий исходно, ни влияло на риски развития ДМО [9]. При этом IL-7 описан как один из ЦК, уровень которых значимо снижается на фоне антиангиогенной терапии [10].…”

The change of diabetic macular edema post vitrectomy in patients with proliferative diabetic retinopathy

“…It has been reported that after preoperative intravitreal anti-VEGF injection, the VEGF level dramatically decreased, whereas the in uence on the vitreous in ammatory cytokines and chemokines in PDR was limited. 12 Moreover, the decreased halflives and increased clearance of anti-VEGF drugs in vitrectomized eyes probably also contribute. 27 Despite the preoperative intravitreal injection of anti-VEGF agent, a series of cytokines, including IL-1β, TNF-α, CXCL9, G-CSF, MCP-1, and RANTES, remained at a high level and may lead to PV-DME.…”

“…27 Despite the preoperative intravitreal injection of anti-VEGF agent, a series of cytokines, including IL-1β, TNF-α, CXCL9, G-CSF, MCP-1, and RANTES, remained at a high level and may lead to PV-DME. 12 Yoshida et al reported that elevated MCP-1 and IL-6 levels may indicate prolonged in ammation even after successful vitrectomy, which was signi cantly associated with PV-DME. 7 Rather than with an anti-VEGF agent, we found an intraoperative intravitreal TA injection effectively prevented PV-DME development in this study.…”

“…8 Sun et al conducted a study focused on the effect of preoperative injection on vitreous in ammatory cytokines and chemokines and showed that 20 eyes (33.90%) presented ME. 12 In contrast with previous studies, we excluded patients with an unreadable preoperative OCT image and postoperative silicone oil tamponade to focus on the incidence of PV-DME. Patients frequently required the removal of the silicone oil within the 3-month follow-up, and the silicone oil frequently led to decreased macular thickness and microstructural changes.…”