Flare levels after intravitreal injection of brolucizumab for diabetic macular edema.

PURPOSE: This study aimed to evaluate anterior flare intensity (AFI) after intravitreal injection of brolucizumab (IVBr) in patients with diabetic macular edema (DME), and to identify the factors associated with the change of AFI after IVBr. METHODS: This prospective multicenter study was conducted at five sites in Japan for patients with DME who underwent a single IVBr. AFI and central retinal thickness (CRT) were measured using a laser flare meter and spectral-domain optical coherence tomography, respectively, at weeks 0 and 6. RESULTS: Sixty-five patients (phakia, 37 eyes; pseudophakia, 28 eyes) were enrolled. Six weeks after IVBr, CRT and best-corrected visual acuity significantly improved (p < 0.0001). AFI (p = 0.0003) and age (p = 0.0054) were significantly higher in patients with pseudophakic eyes than those with phakic eyes. The AFI of the phakic eyes decreased after IVBr (p = 0.043). As the AFI before injection is higher (p = 0.0363) and the age is lower (p = 0.0016), the AFI decreases after IVBr. There was a significant positive correlation between the rates of change in CRT and AFI (p = 0.024). CONCLUSION: After IVBr, AFI decreases in phakic eyes but not in pseudophakic eyes. The age, AFI and CRT before injection and changes of CRT are involved in the change in AFI after IVBr.

Effects of Intravitreal Ranibizumab Injection to Treat Macular Edema due to Central Retinal Vein Occlusion on Choroidal Findings and Functional-Morphological Parameters.

INTRODUCTION: Little research has examined the effects of anti-vascular endothelial growth factor therapy on subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare, and humor levels of growth and inflammatory factors in patients with macular edema due to central retinal vein occlusion (CRVO). METHODS: In 58 patients with macular edema due to CRVO treated by intravitreal ranibizumab injection (IRI), we retrospectively assessed best-corrected visual acuity (BCVA, assessed as the logarithm of the minimum angle of resolution [logMAR]), 8 aqueous factors (by suspension array), mean blur rate (MBR; estimated by laser speckle flowgraphy as a measure of choroidal blood flow), aqueous flare (with a laser flare meter), and SCT and central macular thickness (CMT; by optical coherence tomography). RESULTS: After 4 weeks, IRI resulted in a significant improvement in BCVA and CMT and a significant reduction in SCT, choroidal MBR, and aqueous flare. SCT was significantly positively correlated with placental growth factor and significantly negatively correlated with platelet-derived growth factor-AA, and change in SCT was significantly negatively correlated with change in BCVA (logMAR). Aqueous flare was significantly negatively correlated with SCT. CONCLUSION: Growth and inflammatory factors may be associated with SCT, and changes in SCT may be associated with changes in BCVA after IRI to treat macular edema due to CRVO.

Effects of Intravitreal Ranibizumab Injection on Peripheral Retinal Microcirculation and Cytokines in Branch Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow.

Role of Novel Inflammatory Factors in Central Retinal Vein Occlusion with Macular Edema.

Background and Objectives: To investigate associations among the aqueous humor levels of novel inflammatory factors, including FMS-related tyrosine kinase 3 ligand (Flt-3L), fractalkine, CXC chemokine ligand 16 (CXCL-16), and endocan-1; the severity of macular edema in central retinal vein occlusion (CRVO); and the prognosis of CRVO with macular edema after antivascular endothelial growth factor (VEGF) therapy. Materials and Methods: Aqueous humor was obtained during anti-VEGF treatment with intravitreal ranibizumab injection (IRI) in patients with CRVO and macular edema (n = 19) and during cataract surgery in patients with cataracts (controls, n = 20), and the levels of VEGF and novel inflammatory factors were measured. Macular edema was evaluated by central macular thickness (CMT) and neurosensory retinal thickness (TNeuro), and improvement was evaluated by calculating the percentage change in CMT and TNeuro from before to 1 month after IRI. Results: The levels of VEGF and the novel inflammatory factors were significantly higher in the CRVO group, and the levels of Flt-3L, CXCL-16, and endocan-1 were significantly correlated with each other and with the aqueous flare value. Baseline levels of Flt-3L, CXCL-16, and endocan-1 had a significantly negative correlation with the change in CMT, and the baseline level of CXCL-16 was significantly negatively correlated with the change in TNeuro. Conclusions: Relations among novel inflammatory factors should be further investigated. These findings may help improve understanding of macular edema in CRVO patients and aid the development of new treatments targeting novel inflammatory factors.

Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY).

PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS). RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

RELATIONSHIP BETWEEN CHOROIDAL FINDINGS AND GROWTH FACTORS, CYTOKINES, AND OTHER INFLAMMATORY MEDIATORS AFTER INTRAVITREAL RANIBIZUMAB INJECTION IN PATIENTS WITH MACULAR EDEMA SECONDARY TO BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To examine possible associations between subfoveal choroidal thickness (SCT), choroidal blood flow, aqueous flare value, and aqueous humor levels of multiple growth factors, cytokines, and other inflammatory mediators in patients with branch retinal vein occlusion and macular edema who received antivascular endothelial growth factor (anti-VEGF) therapy. METHODS: We recruited 65 patients with macular edema due to branch retinal vein occlusion who received intravitreal ranibizumab injection and measured aqueous levels of eight factors by the suspension array method. Furthermore, we evaluated choroidal blood flows by laser speckle flowgraphy and quantified them as the mean blur rate and measured aqueous flare values using a laser flare meter and SCT and central macular thickness by optical coherence tomography. RESULTS: At 1 month after intravitreal ranibizumab injection, central macular thickness was significantly improved and SCT, choroidal mean blur rate, and aqueous flare value were significantly decreased. SCT was significantly correlated with vascular endothelial growth factor and placental growth factor, and the change in both SCT and central macular thickness was significantly correlated with the change in aqueous flare value. However, only SCT was significantly negatively correlated with the aqueous flare value. CONCLUSION: Growth factors seem to play a role in SCT. In macular edema with branch retinal vein occlusion, antivascular endothelial growth factor agents may decrease SCT by reducing inflammation.

Intravitreal ranibizumab improves macular sensitivity in patients with central retinal vein occlusion and macula edema.

BACKGROUND: Patients with central retinal vein occlusion (CRVO) and macular edema often are treated by intravitreal ranibizumab injection (IRI). The role of changes in macular sensitivity in the positive effects of IRI on visual functions is unclear. Therefore, we assessed the relationship between macular sensitivity and improvement of visual functions. METHODS: We included 15 eyes of 15 patients with treatment-naïve CRVO and followed patients for 6 months after pro re nata IRI. IRI was repeated if the central macular thickness was greater than or equal to 300 µm. Microperimetry-3 was used to measure macular sensitivity within the central 1-mm, 3-mm, and 6-mm fields before and monthly for 6 months after IRI. RESULTS: IRI significantly improved mean macular sensitivity over time within the central 1-mm, 3-mm, and 6-mm fields (all P < 0.001). None of the fields showed significant differences in the change of mean macular sensitivity between patients with little improvement in best corrected visual acuity (BCVA; i.e., in patients with a change in logarithm of the minimum angle of resolution [logMAR] BCVA < 0.3) and those with marked improvement in BCVA (change in logMAR BCVA > 0.3). The mean macular sensitivity before IRI showed correlations with the improvement of macular sensitivity in every field. CONCLUSION: These findings suggest that IRI improves macular sensitivity in patients with CRVO and macular edema independent of any improvement in BCVA and that macular sensitivity before treatment is associated with improvement of macular sensitivity after treatment.

Effects of ranibizumab on growth factors and mediators of inflammation in the aqueous humor of patients with diabetic macular edema.

PURPOSE: The study aims to investigate changes in the aqueous humor levels of 8 growth factors and inflammatory mediators after intravitreal ranibizumab injection (IRI) and the relationship between these substances and functional-morphological parameters in patients with diabetic macular edema (DME). METHODS: We recruited 25 patients with DME who were scheduled to receive 2 doses of IRI at monthly intervals. At baseline and 1 month after IRI, we measured aqueous levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, and interferon-gamma inducible protein 10 (IP-10) by the suspension array method. Central macular edema (CMT) or macular volume (MV) was examined by optical coherence tomography before and 1 month after IRI, and the improvement of macular edema was evaluated by calculating the percent change of CMT or MV. RESULTS: Aqueous humor levels of VEGF, PlGF, PDGF-AA, and IP-10 were significantly decreased 1 month after IRI (P < 0.001, P = 0.002, P = 0.002, and P = 0.005, respectively). In addition, the baseline aqueous humor levels of PlGF, MCP-1, and IL-6 were significantly correlated with the improvement in best corrected visual acuity (P = 0.036, P = 0.024, and P = 0.049, respectively). The baseline aqueous humor level of sICAM-1 was significantly negatively correlated with the change in CMT (P = 0.005), and the baseline aqueous humor levels of VEGF and PlGF were significantly correlated with the change in MV (P = 0.020 and P = 0.003, respectively). Furthermore, the percentage reduction in VEGF after IRI was significantly correlated with the change in MV (P = 0.037). CONCLUSIONS: Our findings suggest that the change in aqueous humor levels of VEGF, PlGF, and ICAM-1 in DME may not only be an anatomic response but also a potential therapeutic target. CLINICAL TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry. The registration number is UMIN000030301.

Anti-VEGF Therapy Reduces Inflammation in Diabetic Macular Edema.

PURPOSE: Correlations among the aqueous flare value (an indicator of inflammation), several functional-morphologic parameters, and aqueous humor levels of multiple cytokines or inflammatory factors were investigated in patients with diabetic macular edema (DME) receiving intravitreal rani-bizumab injection (IRI). METHODS: Aqueous humor levels of 12 cytokines, growth factors, or inflammatory factors were measured in 46 DME patients who received IRI. Vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR), and the other cytokines/inflammatory factors were measured by the suspension array method. In addition, aqueous flare values were measured with a laser flare meter, and central macular thickness (CMT) was examined by optical coherence tomography. RESULTS: At 1 month after IRI therapy, the aqueous flare value showed a significant decrease compared with before treatment (baseline). Significant correlations were noted between the aqueous flare value and the aqueous humor levels of 6 factors/cytokines, including sVEGFR-1, placental growth factor, monocyte chemoattractant protein 1, soluble intercellular adhesion molecule-1, interleukin (IL)-6, and interferon-inducible 10-kDa protein (IP-10). There was also a significant correlation between the change in aqueous flare value and improvement in CMT 1 month after IRI. CONCLUSIONS: These findings suggest that IRI reduces subclinical inflammation and that the aqueous flare value is influenced by inflammatory factors/cytokines. In addition, the change in the aqueous flare value may be an indicator of the response of CMT to IRI in patients with DME.

Retinal Blood Flow as a Predictor of Recurrence of Macular Edema after Intravitreal Ranibizumab Injection in Central Retinal Vein Occlusion.

INTRODUCTION: To investigate the relationship between retinal blood flow and the presence or absence of macular edema (ME) recurrence after intravitreal ranibizumab injection (IRI) in patients with central retinal vein occlusion (CRVO). METHODS: We reviewed the medical records of 16 eyes with ME associated with CRVO. All eyes had received pro re nata IRI. Repeat IRI was performed if the central macular thickness was ≥300 µm. At 12 months, patients without additional IRI in the past 6 months were assigned to the resolved group, and those with additional IRI, to the recurrence group. We used laser speckle flowgraphy (LSFG) to measure the mean blur rate (MBR) of the optic disc before and after IRI. RESULTS: Ten of the 16 eyes were assigned to the resolved group, and the other 6 eyes to the recurrence group. At several visits in the 12 months after IRI, MBR was significantly higher in the resolved group than in the recurrence group. Percent change of MBR (%Δ MBR) from baseline was significantly higher in the resolved group than in the recurrence group at 1 month (initial %Δ MBR) and 11 and 12 months. Multivariate stepwise analysis showed that the initial %Δ MBR was significantly and negatively correlated with the number of IRIs. DISCUSSION/CONCLUSION: These findings suggest that determining %Δ MBR in LSFG may be a useful way to determine the likelihood of ME recurrence in CRVO patients.

Involvement of Cytokines in the Pathogenesis of Diabetic Macular Edema.

Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood-retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments.

Relationship between retinal blood flow and cytokines in central retinal vein occlusion.

BACKGROUND: We evaluated the relationship between retinal blood flow and aqueous humor levels of cytokines/growth factors in patients with central retinal vein occlusion (CRVO). METHODS: In an observational study, 64 eyes of 64 CRVO patients were examined before anti-vascular endothelial growth factor (VEGF) therapy. Blood flow was assessed in large vessels around and at the optic disk by determining the mean blur rate using laser speckle flowgraphy. Aqueous humor samples were obtained from the patients during anti-VEGF therapy and levels of the following molecules were measured by the suspension array method: soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, VEGF, plancental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13. RESULTS: The mean blur rate of the affected eye was significantly lower than that of the unaffected eye. The mean blur rate showed a significant negative correlation with the log-transformed aqueous humor levels of PlGF, sICAM-1, and IL-8, but not VEGF. CONCLUSIONS: These findings suggest that retinal blood flow velocity might be more strongly correlated with inflammatory factors than VEGF in patients with nonischemic CRVO and macular edema.

Phase II/III Clinical Trial of Sub-Tenon Injection of Triamcinolone Acetonide (WP-0508ST) for Diabetic Macular Edema.

PURPOSE: To assess the efficacy and safety of sub-Tenon injection of triamcinolone acetonide (WP-0508ST) for the patients with diabetic macular edema (DME). METHODS: This multicenter, randomized, double-masked, comparative, controlled study was performed in 95 patients with DME. The patients were randomly divided into 20 mg WP-0508ST, 40 mg WP-0508ST, and control groups. RESULTS: A significant improvement in central macular thickness (CMT) was observed (p < 0.001) at 12 weeks after a single sub-Tenon injection of 20 mg WP-0508ST. The 40 mg group also demonstrated improvement in CMT, but the difference was not significant. In addition, the best-corrected visual acuity was improved in both the 20 mg and 40 mg groups at 12 weeks. The major side effects were increased intraocular pressure (9.4% in the 20 mg group and 13.3% in the 40 mg group) and lenticular opacity (6.3% in the 20 mg group and 10.0% in the 40 mg group). However, none of the patients with increased intraocular pressure required surgery. CONCLUSION: The efficacy and tolerability of WP-0508ST in the treatment of DME were confirmed, and 20 mg was determined to be the optimal dose.

Aqueous Humor Levels of Cytokines in Patients with Age-Related Macular Degeneration.

PURPOSE: To compare aqueous humor levels of various cytokines between patients with age-related macular degeneration (AMD) and cataract patients. METHODS: Thirteen eyes with wet-type AMD (AMD group) and 14 eyes with cataract (cataract group) were studied. Aqueous humor levels of 11 factors (vascular endothelial growth factor receptors, growth factors, and inflammatory factors) were measured by the suspension array method. RESULTS: Aqueous humor levels of vascular endothelial growth factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, and inflammatory factors (monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, and IL-8) were significantly higher in the AMD group than in the cataract group (all p < 0.05). In contrast, aqueous humor levels of placental growth factor (PGF), tumor necrosis factor-α, soluble intercellular adhesion molecule (sICAM)-1, IL-12 (p70), and IL-13 showed no significant difference between the two groups. There were significant correlations between sVEGFR-1 or sVEGFR-2 levels and some of the inflammatory molecules (PGF, sICAM-1, MCP-1, IL-6, and IL-8). CONCLUSIONS: These findings suggest that various cytokines/growth factors involved in inflammation and angiogenesis may be associated with the pathogenesis of AMD.

Increased Microcirculation on Optic Nerve Head by Laser Speckle Flowgraphy at Early Stage of Leber Hereditary Optic Neuropathy.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder predominantly affecting young men. Characteristic features of an early stage of LHON are peripapillary telangiectatic microangiopathy with optic disc hyperaemia and swelling of the retinal nerve fibre layers. We evaluated the microcirculation of the optic nerve head (ONH) by laser speckle flowgraphy (LSFG) in a 79-year-old man and a 36-year-old woman with LHON. The ONH microcirculation of the tissue area was markedly increased in the early stage in both patients. LSFG may be a useful noninvasive method to suspect individuals to have an early stage of LHON.

Comparing Cytokine Kinetics between Ranibizumab and Aflibercept in Central Retinal Vein Occlusion with Macular Edema.

PURPOSE: To investigate dynamic changes in aqueous humor levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), and inflammatory factors in patients receiving intravitreal ranibizumab injection (IRI) or intravitreal aflibercept injection (IAI) to treat central retinal vein occlusion (CRVO) with macular edema. METHODS: In 22 CRVO patients scheduled to receive 3 doses of ranibizumab (11 eyes) or aflibercept (11 eyes) at monthly intervals, aqueous samples were collected at the time of intravitreal injection. The concentrations of VEGF, PlGF, soluble intercellular adhesion molecule-1, monocyte chemotactic protein (MCP)-1 (CCL2), platelet-derived growth factor-AA, interleukin (IL)-6, IL-8 (CXCL8), IL-12(p70) (IL12B), and IL-13 in aqueous samples were measured by the suspension array method. RESULTS: Visual acuity and foveal thickness improved significantly in both the IRI group and the IAI group. In addition, aqueous levels of VEGF and PlGF as well as MCP-1 and IL-6 decreased significantly over time in both groups. These parameters did not significantly differ between both groups. CONCLUSIONS: In CRVO patients, both ranibizumab and aflibercept achieved similar improvement in clinical parameters and similar reductions in aqueous VEGF, PlGF, MCP-1, and IL-6 levels.

Dynamics of Inflammatory Factors in Aqueous Humor during Ranibizumab or Aflibercept Treatment for Age-Related Macular Degeneration.

PURPOSE: To evaluate the dynamic changes of the aqueous humor levels of inflammatory factors between patients receiving intravitreal ranibizumab injection (IRI) and aflibercept injection (IAI) in patients with exudative age-related macular degeneration (AMD). METHODS: The study was performed on 30 eyes with AMD that were scheduled to receive 3 doses of IRI (15 eyes) or IAI (15 eyes) at monthly intervals. Aqueous humor samples were collected when injection was done. The concentrations of VEGF, monocyte chemoattractant protein 1 (MCP-1), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, and IL-8 were measured in aqueous humor samples from the 30 AMD patients and 10 cataract patients (as controls) by the suspension array method. RESULTS: Aqueous levels of the inflammatory factors (MCP-1, PDGF-AA, IL-6, and IL-8) were significantly correlated with each other. In both the IRI-treated eyes and the IAI-treated eyes, visual acuity and central macular thickness improved significantly, and the aqueous level of VEGF showed a significant decrease. In IAI-treated eyes, the aqueous levels of MCP-1 and PDGF-AA were significantly decreased at 2 months. CONCLUSIONS: These findings suggest that the inflammatory factors are involved in the pathogenesis of AMD and also the possibility that the interaction between these inflammatory factors and IRI or IAI is different.

Aqueous Humor Levels of Soluble Vascular Endothelial Growth Factor Receptor and Inflammatory Factors in Diabetic Macular Edema.

Aqueous levels of soluble vascular endothelial growth factor receptor (sVEGFR) and inflammatory factors were measured in 35 patients (37 eyes) with diabetic macular edema (DME) receiving anti-vascular endothelial growth factor (VEGF) therapy. Aqueous levels of growth factors (VEGF, placental growth factor [PlGF], and platelet-derived growth factor AA [PDGF-AA]), sVEGFR-1 and -2, soluble intercellular adhesion molecule 1, monocyte chemotactic protein (MCP)-1, interleukin (IL)-6, -8, -12, and -13, and interferon-inducible 10-kDa protein (IP-10) were significantly higher in the DME group than in the nondiabetic control group. The sVEGFR-2 level was significantly correlated with the neurosensory retinal thickness, as well as with the levels of growth factors (VEGF and PDGF-AA) and inflammatory factors (MCP-1, IL-6, and IL-8). Three growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other, as were sVEGFR-1 or -2 and the inflammatory factors (MCP-1, IL-6, IL-8, and IP-10). These findings suggest that sVEGFRs and growth/inflammatory factors have an important role in DME.

POSSIBLE MOLECULAR BASIS OF BEVACIZUMAB THERAPY FOR MACULAR EDEMA IN BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: To investigate changes in the aqueous humor levels of 11 factors/cytokines (including vascular endothelial growth factor [VEGF] receptors, growth factors, and inflammatory factors) after intravitreal injection of bevacizumab (IVB), as well as the relationship between changes of these factors and improvement of macular edema in patients with branch retinal vein occlusion and macular edema. METHODS: In 29 patients with branch retinal vein occlusion who received IVB twice for macular edema at monthly intervals, aqueous humor samples were obtained during IVB. Levels of VEGF, soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor, soluble intercellular adhesion molecule-1, monocyte chemotactic protein 1, platelet-derived growth factor-AA, and interleukin (IL)-6, IL-8, IL-12 (p70), and IL-13 were measured by the suspension array method. Foveal thickness was examined by optical coherence tomography before and 1 month after IVB, and the improvement of macular edema was evaluated by calculating the percent change of foveal thickness. RESULTS: Aqueous humor levels of sVEGFR-1, VEGF, monocyte chemotactic protein 1, and IL-6 showed a significant decrease at 1 month after IVB compared with baseline (P = 0.013, P < 0.001, P = 0.047, and P = 0.019, respectively). There was a significant negative correlation between the change of sVEGFR-1 or platelet-derived growth factor-AA after IVB and the improvement of macular edema (P = 0.004 and P = 0.036, respectively). CONCLUSION: These findings suggest that improvement of macular edema by IVB is related to inhibition of sVEGFR-1 and platelet-derived growth factor-AA, but not VEGF, in patients with branch retinal vein occlusion. Soluble VEGF receptor-1 and platelet-derived growth factor-AA might be useful indicators of the response of macular edema.

Changes of retinal flow volume after intravitreal injection of bevacizumab in branch retinal vein occlusion with macular edema: a case series.

BACKGROUND: Although intravitreal injection of bevacizumab (IVB) is effective for macular edema in patients with branch retinal vein occlusion (BRVO), the changes of retinal hemodynamics remain unclear. We investigated retinal hemodynamic changes in BRVO patients after IVB by performing laser speckle flowgraphy (LSFG). METHODS: In 35 BRVO patients with macular edema, the relative flow volume (RFV) of the retinal artery and vein passing through the optic disc was measured in both the occluded and non-occluded regions of the retina before IVB and 1 month after IVB by LSFG. The ischemic region of retina was measured with the Scion Image program and the severity of retinal ischemia was assessed by dividing the non-perfused area by the disc area. RESULTS: Macular edema improved significantly by 1 month after IVB. The venous RFV ratio showed a significant increase in the non-occluded region at 1 month after IVB. There was a significant negative correlation between the venous RFV ratio and the severity of retinal ischemia in the occluded region. On the other hand, arterial RFV ratio showed no significant change after IVB in either the occluded or non-occluded region. In addition, there was no significant correlation between the arterial RFV ratio and the severity of retinal ischemia in either the occluded or non-occluded region. CONCLUSIONS: These results suggest that an increase of retinal venous outflow after IVB may possibly influence the resolution of macular edema and that the response of venous outflow after IVB depends on the severity of retinal ischemia in the occluded region.