Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema

AbstractThis study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

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Analysis of Cytokines in the Aqueous Humor During Intravitreal Treatment With Ranibizumab in Diabetic Macular Edema

10.21203/rs.3.rs-803720/v1 ◽

2021 ◽

Author(s):

Luiz Guilherme Azevedo Freitas ◽

David Leonardo Cruvinel Isaac ◽

Murilo Batista Abud ◽

Alexandre Dantas Soares Quintas Segundo ◽

Mariana Larissa Alvino Barros ◽

...

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Aqueous Humor ◽

Control Group ◽

Peripheral Ischemia ◽

End Of Treatment ◽

Intravitreal Treatment ◽

Group 3 ◽

Group 2 ◽

Group 1

Abstract Purpose: This study aimed to analyze the concentrations, in aqueous humor, of VEGF, b-FGF, TNF, and interleukins 1, 6, 8, 10, and 12 in patients with diabetic macular edema, with and without peripheral retinal ischemia, and to analyze the variation of the levels of these molecules, during the treatment with ranibizumab.Methods: A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied, divided into 3 groups. Group 1, (9 eyes), patients with EMD without peripheral ischemia. Group 2 (10 eyes), patients with EMD with peripheral ischemia. Group 3, (5 eyes), control group, formed by patients without systemic and/or eye diseases. Patients in groups 1 and 2 were treated with 3 intravitreal injections of 2 mg/0.05 ml of ranibizumab, with intervals of approximately 30 days. Before performing the injections, the aqueous humor was collected. In the control group, the material was collected before the facectomy procedure. Results: During treatment, the medians of IL-6 concentrations showed a statistically significant increase, in group 1 and group 2, there was a slight decrease, not statistically significant. Interleukin 8 showed statistically significant variations in groups 1 and 2, at the end of treatment. TNF, IL-1, IL-10, and IL-12 had their concentrations practically unchanged, in both groups. VEGF showed a statistically significant reduction in groups 1 and 2 at the end of the study. B-FGF was not detected in most of the studied patients, and in those that were found, they did not present statistically significant numbers. Conclusion: There were statistically significant variations in the increase of their median levels in interleukin 6, in the group without ischemia and a decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show statistically significant variations.

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Diabetic macular edema with pachychoroid features

BMC Ophthalmology ◽

10.1186/s12886-020-01663-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Kyungeun Kang ◽

Hyungwoo Lee ◽

Minsu Jang ◽

Hyung Chan Kim ◽

Hyewon Chung

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Clinical Manifestations ◽

Control Group ◽

Diabetic Patients ◽

Diffuse Type ◽

Imaging Parameters ◽

Significant Difference ◽

Group 2 ◽

Group 1

Abstract Background To investigate the clinical features of diabetic macular edema (DME) in eyes with pachychoroid phenotypes using multimodal retinal imaging. Methods We retrospectively reviewed 210 eyes from 210 DME patients and analyzed the clinical and imaging parameters, including visual acuity, central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and neural retina layer thickness (NRT). The DME eyes were divided into two groups: group 1 (80 eyes with submacular detachment [SMD]) and group 2 (130 eyes without SMD). The clinical and imaging parameters of 285 eyes from 285 diabetic patients without DME were collected as a control group. Results DME eyes with pachychoroid phenotypes were more frequent in group 1 than in group 2 (53 eyes [66.25%] and 53 eyes [40.77%], respectively, P < 0.001). Pachychoroid phenotypes were identified in 108 (37.90%) of the control eyes. CMT and NRT were greater in group 1 than in group 2. In group 1, 37 eyes had SMD combined with focal edema, and 43 eyes had SMD combined with diffuse-type edema. No significant difference in pachychoroid phenotypes was found between the focal and diffuse types (26 [70.27%] and 27 [62.79%], respectively, P = 0.481). In group 2, 70 eyes had focal-type edema, and 60 eyes had diffuse-type edema. No significant difference in the frequency of pachychoroid phenotypes was found (32 [45.71%] and 21 [35.00%], respectively, P = 0.215). Interestingly, among the 70 eyes with focal edema in group 2, 13 (40.6%) and 5 (13.2%) eyes with and without pachychoroid phenotypes showed no definite microaneurysms, respectively. Conclusion SMD and focal edema without definite microaneurysms may be clinical manifestations of DME with pachychoroid phenotypes and possibly related to choroidal circulation disturbance in DME.

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Efficacy of Intravitreal Dexamethasone Implant in Different Patterns of Diabetic Macular Edema

Journal of Ophthalmic and Vision Research ◽

10.18502/jovr.v15i4.7787 ◽

2020 ◽

Author(s):

Claudio Furino ◽

Alfredo Niro ◽

Michele Reibaldi ◽

Maria Oliva Grassi ◽

Francesco Boscia ◽

...

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Serous Retinal Detachment ◽

Intravitreal Dexamethasone Implant ◽

The Mean ◽

Group 2 ◽

Intravitreal Dexamethasone ◽

Pattern Group ◽

Group 1

Purpose: Different patterns of diabetic macular edema (DME) suggest different pathogenesis and drug response. We evaluated the outcomes after intravitreal dexamethasone (DEX) implant for DME with or without serous retinal detachment (SRD). Methods: In this retrospective study, 22 naïve patients (23 eyes) with DME who underwent a single DEX implant were evaluated. Based on the optical coherence tomographic pattern of DME, 12 eyes had a cystoid macular edema pattern (Group 1) and 11 eyes had an SRD pattern (Group 2). The best-corrected visual acuity (BCVA), central retinal thickness (СRТ), central retinal volume (CRV), SRD height (SRDh), and intraocular pressure (IOP) were recorded before and at two and four months after the treatment. Results: There were no significant differences between the groups regarding demographic, clinical data and outcomes at baseline. In Group 1, the CRT and CRV significantly decreased at two months (P = 0.002 and P = 0.01, respectively), while the BCVA significantly improved at four months (P = 0.03). In Group 2, the CRT and CRV significantly improved (P < 0.01 and P ≤ 0.01, respectively) during the follow-up period. At four months, both groups showed a recurrence of DME, Group 1 in particular (two-month CRT reduction, –149 ± 127 μm vs four-month CRT reduction, –72 ± 174 μm; P = 0.04). The mean reduction in CRV was significantly different at four months (Group 1, –0.49 ± 1.7 mm3 vs Group 2, –1.3 ± 1.3 mm3; P = 0.04). In Group 2, the SRDh significantly decreased at two (P = 0.01) and four months (P = 0.01). Four cases with elevated IOP were managed. Conclusion: DEX implants were found to be effective in different patterns of DME. The SRD pattern may predict a longer-lasting morphologic efficacy.

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Anatomical and functional outcomes of subthreshold micropulse laser versus intravitreal ranibizumab injection in treatment of diabetic macular edema

International Journal of Retina and Vitreous ◽

10.1186/s40942-020-00265-6 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Amr Abdelrahman ◽

Wagiha Massoud ◽

Ahmed Mohamed Kamal Elshafei ◽

Mahmoud Genidy ◽

Raafat Mohyeldeen Abdelrahman Abdallah

Keyword(s):

Macular Edema ◽

Intravitreal Injection ◽

Diabetic Macular Edema ◽

Functional Outcomes ◽

Implicit Time ◽

Therapeutic Effects ◽

Micropulse Laser ◽

Subthreshold Micropulse Laser ◽

Group 2 ◽

Group 1

Abstract Background To compare the therapeutic effects of subthreshold micropulse laser (SML) versus intravitreal injection of ranibizumab in treatment of diabetic macular edema (DME) both anatomically using optical coherence tomography (OCT) and functionally using best corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG). Methods his study was an interventional prospective randomized comparative study. The study included 120 eyes classified into 3 groups: Group 1 included 40 eyes of 28 patients treated by SML laser, group 2 included 40 eyes of 32 patients treated by intravitreal injection of ranibizumab, and group 3 (control group for mfERG) included 40 eyes of 20 patients with diabetes mellitus (DM) of more than 10 year duration with no signs of diabetic retinopathy (DR). BCVA measurements, OCT and mfERG were done for the cases before and after interference and were followed up for 6 months Results By the end of the follow up period, BCVA significantly improved by 31% in group 1 vs 93% in group 2 with a statistically highly significant difference between the two groups (p value < 0.001). There was also a significant decrease in central subfield thickness in both groups with more reduction in group 2 compared with group 1 (p value < 0.001). There was a significant improvement in P1 amplitude of mf-ERG in group 2 (p value < 0.002) with no significant improvement in group 1. There was a significant decrease in P1 implicit time in group 2 (p value < 0.001) while there was no significant decrease in group1. Conclusions Intravitreal injection of ranibizumab is a superior treatment modality for DME compared with SML regarding both anatomical and functional outcomes. Trial registration: This study has been approved by the local ethical committee of faculty of medicine of Minia University and retrospectively registered at the clinical trial gov. with Identifier: NCT04332133.

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Comparison of the Safety and Efficacy of Intravitreal Ranibizumab with or without Laser Photocoagulation Versus Dexamethasone Intravitreal Implant with or without Laser Photocoagulation for Macular Edema Secondary to Branch Retinal Vein Occlusion

Folia Medica ◽

10.2478/folmed-2018-0081 ◽

2019 ◽

Vol 61 (2) ◽

pp. 240-248

Author(s):

Prashant Kumar ◽

Yog Raj Sharma ◽

Parijat Chandra ◽

Rajvardhan Azad ◽

Girish Gulab Meshram

Keyword(s):

Macular Edema ◽

Retinal Vein Occlusion ◽

Branch Retinal Vein Occlusion ◽

Laser Photocoagulation ◽

Intravitreal Ranibizumab ◽

Dexamethasone Intravitreal Implant ◽

Vein Occlusion ◽

The Difference ◽

Group 2 ◽

Group 1

Abstract Background: There is an ambiguity regarding the therapy of choice for patients with macular edema following branch retinal vein occlusion (BRVO). Aim: The purpose of the study was to compare the efficacy and safety of ranibizumab (3 injections 0.5 mg) versus ranibizumab (1 injection 0.5 mg) with laser photocoagulation (LP) versus dexamethamethasone intravitreal (IVT) implant (0.7 mg) with or without LP in patients with macular edema following BRVO. Materials and methods: 60 eyes of 60 patients were divided into 4 groups. Group 1 received IVT ranibizumab (3 injections 0.5 mg), Group 2 received IVT ranibizumab (1 injection 0.5 mg) + LP, Group 3 received dexamethasone IVT implant (0.7 mg), and Group 4 received dexamethasone IVT implant (0.7 mg) + LP. The endpoints were the difference in mean changes in best corrected visual acuity (BCVA), central macular thickness (CMT), and inter-group differences in contrast sensitivity (CS), retinal sensitivity (RS), and intraocular pressure (IOP). Results: BCVA gains in Group 1 (18.00±8.51) patients were significantly (p < 0.05) higher than patients in Groups 2 (10.00±10.26), 3 (9.50±9.60), and 4 (10.50±10.97), after 6 months of therapy. No significant inter-group variation was found in the CMT, CS, and RS. Conclusions: Ranibizumab (3 injections 0.5 mg) showed significantly higher BCVA gains at 6 months post-therapy. Improvements in the BCVA, CMT, CS, and RS were comparable initially in all the therapies.

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Aqueous Humor Cytokine Levels in Diabetic Macular Edema Patients with Cotton-Wool Spots

Journal of Diabetes Research ◽

10.1155/2019/8137417 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Young-Gun Park ◽

Donghyun Jee ◽

Jin-woo Kwon

Keyword(s):

Growth Factor ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Aqueous Humor ◽

Multiple Logistic Regression Analysis ◽

Intercellular Adhesion Molecule ◽

Control Group ◽

Cotton Wool ◽

Cotton Wool Spots ◽

Significant Difference

Purpose. To determine the characteristics of diabetic macular edema (DME) patients with cotton-wool spots (CWS). Methods. We classified 80 treatment-naïve DME patients according to whether or not they had CWS involving macula and then compared the concentrations of interleukin- (IL-) 1β, IL-6, IL-8, IL-10, IL-17, placental growth factor, vascular endothelial growth factor (VEGF), and intercellular adhesion molecule (ICAM)-1 in the aqueous humor between the groups, as well as optical coherence tomography (OCT) findings, baseline characteristics, and intravitreal bevacizumab responsiveness. Results. Aqueous levels of ICAM-1 and VEGF in the group with CWS were significantly higher than those in the non-CWS (control) group (p<0.001 and p=0.006, respectively). In multiple logistic regression analysis to identify factors associated with CWS, the aqueous ICAM-1 (≥0.36 ng/mL) was significantly associated with CWS (odds ratio=13.26, p<0.001). Based on OCT, ellipsoid zone (EZ) disruption distribution was significantly different between the two groups (p=0.038). Regarding responsiveness to treatment, although there was no significant difference in central subfield thickness between the two groups after treatments, the best-corrected visual acuity was worse in the group with CWS. Conclusions. The presence of CWS was accompanied by higher levels of aqueous ICAM-1. Based on OCT, EZ disruption was greater in DME patients with CWS, and their short-term visual prognosis was poorer.

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Factors Influencing Intravitreal Bevacizumab and Triamcinolone Treatment in Patients with Diabetic Macular Edema

European Journal of Ophthalmology ◽

10.5301/ejo.5000974 ◽

2017 ◽

Vol 27 (6) ◽

pp. 746-750 ◽

Cited By ~ 6

Author(s):

Tai K. Kim ◽

Hye Y. Shin ◽

Su Y. Kim ◽

Young C. Lee ◽

Mee Y. Lee

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Intravitreal Bevacizumab ◽

Retrospective Chart Review ◽

Diabetic Control ◽

The Other ◽

Intravitreal Triamcinolone ◽

Group 3 ◽

Group 2 ◽

Group 1

Purpose To evaluate factors associated with response to intravitreal bevacizumab (IVB) and intravitreal triamcinolone acetonide (IVTA) in diabetic macular edema (DME). Methods Ninety-one eyes of 88 patients diagnosed with DME were enrolled in this retrospective chart review. Group 1 included eyes that showed good response to IVB. Group 2 included eyes that did not respond to IVB but responded to IVTA. Group 3 included eyes that responded to neither. Clinical factors, HbA1c, and optical coherence tomography (OCT) findings including patterns of macular edema were compared among the 3 groups. Results A total of 44, 27, and 20 eyes were included in groups 1, 2, and 3, respectively. HbA1c was higher in group 3 than in the other groups. Proportion of full (combination of all patterns) type edema was higher in group 3 than in the other 2 groups. In group 1, the proportion of sponge-like diffuse retinal thickening type was higher and cystoid macular edema type was lower than in the other groups. Conclusions The degree of diabetic control and morphologic subtypes with OCT should be considered to better predict the prognosis after treatment in DME.

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Early treatment with dexamethasone intravitreal implants in diabetic macular edema: Naïve versus refractory patients

European Journal of Ophthalmology ◽

10.1177/11206721211024804 ◽

2021 ◽

pp. 112067212110248

Author(s):

Anna V Bux ◽

Francesca Fortunato ◽

Antonio Barone ◽

Vincenzo Russo ◽

Nicola Delle Noci ◽

...

Keyword(s):

Visual Acuity ◽

Macular Edema ◽

Diabetic Macular Edema ◽

First Line ◽

Corrected Visual Acuity ◽

Real World Setting ◽

Treatment Naïve ◽

Group 2 ◽

Group 1

Purpose: To assess the efficacy and safety of dexamethasone 0.7 mg implants (DEX-I) in patients with diabetic macular edema (DME) either naïve to therapy or refractory to anti-VEGF treatment, in a single-center, real-world setting. Methods: Patients diagnosed with DME and treated with DEX-I were retrospectively enrolled in the study and split in two groups: naïve (Group 1, n = 64) and refractory (Group 2, n = 64) to treatment. Patients were evaluated at baseline, at 1 month, and every 3 months after each DEX-I implant. Main outcome measures were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to follow-up visits. Results: Significant improvements in BCVA were observed in treatment-naïve patients at 6 months following the first and second DEX-I injection ( p = 0.0023 and p = 0.0063, respectively), with significant reductions in mean CMT at 6 months after all DEX implants. In treatment-refractory patients, mean CMT was significantly reduced from baseline to 6 months ( p < 0.05) after all DEX-I injections, although no changes were observed in BCVA. Conclusions: DEX-I improved visual acuity and macular edema mostly in treatment-naïve patients, suggesting DEX-I may be a viable first-line treatment option in DME.

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Comparison of the Effect of Intravitreal Dexamethasone Implant in Vitrectomized and Nonvitrectomized Eyes for the Treatment of Diabetic Macular Edema

Journal of Ophthalmology ◽

10.1155/2018/1757494 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Sadık Görkem Çevik ◽

Sami Yılmaz ◽

Mediha Tok Çevik ◽

Fatma Düriye Akalp ◽

Remzi Avcı

Keyword(s):

Macular Edema ◽

Diabetic Macular Edema ◽

Reduction Rate ◽

Foveal Thickness ◽

Intravitreal Dexamethasone Implant ◽

Intravitreal Implant ◽

Pars Plana ◽

Group 2 ◽

Intravitreal Dexamethasone ◽

Group 1

Purpose. To compare the effectiveness of sustained-release dexamethasone (DEX) intravitreal implant in nonvitrectomized eyes and vitrectomized eyes with diabetic macular edema (DME). Methods. A retrospective review of the medical records of 40 eyes of 30 consecutive patients with diabetic macular edema who underwent intravitreal DEX implant injection. Patients were divided into 2 subgroups: 31 eyes that were nonvitrectomized (group 1) and 9 eyes that had previously undergone standard pars plana vitrectomy (group 2). The main outcome measures were BCVA and foveal thickness (FT). Results. A significant improvement was seen in BCVA in both group 1 and group 2 at the 1st, 2nd, and 6th months after treatment with DEX implant (p<0.05). In group 1, a significant reduction in FT was observed at the 1st, 2nd, and 6th months (p<0.05). In group 2, a significant reduction in FT was seen at the 1st and 2nd months (p<0.05), but the reduction rate at the 6th month after the injection was not statistically significant (p=0.06). Conclusion. DEX implant is effective for the treatment of diabetic macular edema, and the effectiveness of the drug is similar in vitrectomized and nonvitrectomized eyes.

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Inflammatory cytokines, oxidative and antioxidative stress levels in patients with diabetic macular edema and hyperreflective spots

European Journal of Ophthalmology ◽

10.1177/1120672120962054 ◽

2020 ◽

pp. 112067212096205

Author(s):

Mehmet Cem Sabaner ◽

Muberra Akdogan ◽

Mustafa Doğan ◽

Ayse Yesim Oral ◽

Resat Duman ◽

...

Keyword(s):

Growth Factor ◽

Macular Edema ◽

Diabetic Macular Edema ◽

Inflammatory Cytokines ◽

Cross Sectional ◽

Inflammatory Biomarker ◽

Macular Volume ◽

Group 3 ◽

Group 2 ◽

Group 1

Purpose: To determine the levels of serum oxidative, antioxidative markers and inflammatory cytokines in patients diagnosed with diabetic macular edema (DME) whose hyperreflective spots (HRS) were detected by optical coherence tomography (OCT). Methods: In this prospective cross-sectional clinical study included a total of 88 patients; 31 patients (group-1) with DME and HRS detected by OCT, 29 patients (group-2) with DME without HRS, and 28 patients (group-3) diagnosed with diabetes mellitus (DM) without any diabetic retinopathy findings. The main outcomes were best-corrected visual acuity (BCVA), CMT (central macular thickness), CMV (central macular volume), TMV (total macular volume), CT (choroidal thickness), serum TAS (total antioxidant status), TOS (total oxidant status), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and IL-1b levels. OCT parameters and biochemical measurements were compared statistically between the three groups. Results: A total of 88 patients (43 females (48.9%) and 45 males (51.1%)) were included in the study. The mean age was 56.29 ± 9.23 years. There was no difference between the three groups in age-and-sex. In group-1 and 2, BCVA(LogMAR) was statistically higher than group 3. CMT, CMV, TMV, TAS, TOS, VEGF and FGF were significantly higher in group-1 than in group-3. CMT, CMV, TMV, VEGF and FGF were significantly higher in group-2 than group 3. TOS and VEGF were significantly higher in group-1 than group-2. Conclusions: This study demonstrates that in patients with DME and HRS, TOS and VEGF levels were higher than those without HRS. Hence, hyperreflective spots may be an inflammatory biomarker.

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