Ryosuke Motohashi

Intravitreal Ranibizumab and Aqueous Humor Factors/Cytokines in Major and Macular Branch Retinal Vein Occlusion

Aqueous humor levels of cytokines and growth/inflammatory factors were measured in 38 patients with macular edema who had major branch retinal vein occlusion (BRVO) or macular BRVO and were treated with intravitreal ranibizumab injection (IRI). Patients with recurrence of macular edema received further IRI as needed. Aqueous humor levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1), and other cytokines/factors were measured. Compared with major BRVO, macular BRVO was associated with lower aqueous humor levels of sVEGFR-1, its ligands (VEGF and placental growth factor), and other growth/inflammatory factors (platelet-derived growth factor-AA, monocyte chemotactic protein-1, soluble intercellular adhesion molecule-1, interleukin-6, and interleukin-8). The mean number of IRI over 6 months was significantly lower in the macular BRVO group than in the major BRVO group. These findings suggest that macular BRVO requires fewer IRI than major BRVO and is associated with lower aqueous humor levels of various growth/inflammatory factors and cytokines.

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.

Optic neuritis and acute anterior uveitis associated with influenza A infection: a case report

Background A few reports have described ocular complications of influenza A infection, such as impaired ocular movement, parasympathetic ocular nerve, keratitis, macular lesion, and frosted branch angiitis. We encountered a rare case of acute anterior uveitis and optic neuritis associated with influenza A infection. Case presentation A 70-year-old man presented with symptoms of upper respiratory tract infection. A rapid diagnostic test showed a positive result for influenza A. At the same time, he developed ocular symptoms including blurred vision with optic disk edema and hemorrhage in the left eye, and bilateral red eyes. Multiplex polymerase chain reaction performed on aqueous humor sample detected no viral infection. Visual field testing with a Goldmann perimeter showed central and paracentral scotomas in the left eye. In addition to antiviral agent (oseltamivir phosphate 75 mg), the patient was prescribed topical prednisolone acetate ophthalmic suspension eye drops every 5 hours and high-dose intravenous methylprednisolone 1,000 mg daily for 3 days. Two months later, his best-corrected visual acuity improved to 20/50 with regression of visual field defects in his left eye. Conclusion We report a case of bilateral acute anterior uveitis and unilateral optic neuritis concomitant with influenza A infection. Topical and systemic corticosteroids were effective to resolve acute anterior uveitis and neuritis. Analysis of aqueous humor sample suggested that acute anterior uveitis and optic neuritis in this case were not caused by influenza A virus infection per se but by autoimmune mechanism.

Cytokines and Recurrence of Macular Edema after Intravitreal Ranibizumab in Patients with Branch Retinal Vein Occlusion

The aqueous humor levels of cytokines and growth/inflammatory factors were measured in 46 branch retinal vein occlusion (BRVO) patients with macular edema (ME) who were treated with intravitreal ranibizumab injection (IRI). Patients with recurrence of ME received further IRI as needed. The number of IRIs was significantly correlated with age, baseline best-corrected visual acuity, and baseline central macular thickness (CMT), as well as the baseline aqueous levels of 5 cytokines/factors (soluble vascular endothelial growth factor receptor-1, platelet-derived growth factor-AA [PDGF-AA], soluble intercellular adhesion molecule-1, interleukin-6 [IL-6], and IL-8). Multivariate linear regression analysis with stepwise selection confirmed that age, baseline CMT, and baseline PDGF-AA level were independent determinants of the number of IRIs. These findings suggest that inflammatory factors may influence the recurrence of ME in BRVO patients, and that PDGF-AA might be a useful indicator of the number of IRIs required to control ME.

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 cytokine and growth factor levels indicate response to ranibizumab for diabetic macular oedema

Background/Aims To investigate the relations between aqueous humour levels of cytokines/growth factors and treatment response to intravitreal ranibizumab (IVR) for diabetic macular oedema (DME) Methods Sixty-eight eyes of 68 patients with treatment-naïve centre-involved DME, central macular thickness (CMT) greater than 400 μm and visual acuity (VA) worse than logMAR 0.3 were recruited. Each patient received monthly IVR injection (0.5 mg/0.05 mL) until CMT was reduced to below 300 μm. Additional IVR was given to maintain CMT below 300 μm during the clinical course of 6 months with monthly follow-up. Aqueous concentrations of cytokines/chemokines and growth factors were measured using samples obtained just before first IVR injection. CMT and VA were monitored monthly for up to 6 months. The number of monthly IVR injections given during the 6-month study period was also recorded. Results Twenty-four eyes showed CMT <300 μm soon after the first IVR injection (good responders), while 12 eyes did not reach the goal after six consecutive injections (poor responders). Baseline CMT and VA were not significantly different between the two groups. However, the good responders showed significant increases in baseline aqueous concentrations of vascular endothelial growth factor (VEGF), placenta growth factor, soluble VEGF receptor-1 (sVEGFR1), monocyte chemoattractant protein-1, intercellular adhesion molecule-1, interleukin 6 and inducible protein-10, but not of sVEGFR2, compared with poor responders. Conclusions Response to ranibizumab treatment for DME appears to be associated with aqueous concentrations of VEGFR1 family and certain inflammatory cytokines, but not with clinical parameters.