Publications by authors named "Masahiko Shimura"

98 Publications

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

Graefes Arch Clin Exp Ophthalmol 2021 Sep 3. Epub 2021 Sep 3.

Department of Ophthalmology, Kyushu University, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1007/s00417-021-05308-8DOI Listing
September 2021

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

Ophthalmic Res 2021 30;64(6):1013-1019. Epub 2021 Aug 30.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1159/000519150DOI Listing
August 2021

Effectiveness and safety of ranibizumab in patients with central retinal vein occlusion: results from the real-world, global, LUMINOUS study.

Eye (Lond) 2021 Jul 29. Epub 2021 Jul 29.

Université de Paris, Ophthalmology Department, AP-HP, Lariboisière, Saint Louis and Fondation Rothschild Hospitals, Paris, France.

Objective: To evaluate the effectiveness, treatment patterns and long-term safety of ranibizumab 0.5 mg in treatment-naïve patients with central retinal vein occlusion (CRVO) in a real-world setting.

Methods: LUMINOUS, a 5-year, global, prospective, multicentre, multi-indication, observational, open-label study, recruited treatment naïve or prior treated patients who were treated as per the local ranibizumab label. Here, we report the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), treatment exposure over year (Y) 1 and 5-year safety in treatment-naïve CRVO patients.

Results: At baseline, the mean age of treatment-naïve CRVO patients (n = 327) was 68.9 years, with a mean (Standard deviation [SD]) VA of 40.6 (23.9) letters. At Y1, patients (n = 144) had a mean (SD) VA gain from baseline of 10.8 (19.66) letters, with a mean (SD) of 5.4 (2.65) ranibizumab injections. Patients demonstrated mean (SD) VA gains of 2.7 (19.35), 11.6 (20.56), 13.9 (18.08), 11.1 (18.46) and 8.2 (24.86) letters with 1, 2-3, 4-5, 6-8 and >8 ranibizumab injections, respectively. Mean (SD) VA gains at Y1 in patients receiving loading (67.4%) and no loading dose (32.6%) was 11.9 (20.42) and 8.4 (17.99) letters, respectively. Over five years, the incidence of ocular/non-ocular adverse events (AEs) and serious AEs was 11.3%/8.6% and 1.2%/6.7%, respectively.

Conclusions: These results demonstrate the effectiveness of ranibizumab in treatment-naïve CRVO patients at Y1 with clinically meaningful VA gains and no new safety findings over five years. These findings may help inform routine practice and enable better clinical management to achieve optimal visual outcomes.
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http://dx.doi.org/10.1038/s41433-021-01702-yDOI Listing
July 2021

Role of ICAM-1 in impaired retinal circulation in rhegmatogenous retinal detachment.

Sci Rep 2021 07 28;11(1):15393. Epub 2021 Jul 28.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

Many studies have demonstrated that rhegmatogenous retinal detachment (RRD) leads to impaired retinal circulation. However, the involvement of inflammation in the RRD-induced worsening of retinal circulation was obscure. This retrospective observational study included 150 patients with primary RRD (macula-on, n = 63; macula-off, n = 87) who underwent 25-gauge microincision vitrectomy surgery (25G MIVS). Total retinal blood flow was represented by the mean blur rate (MBR) of the optic nerve head vessel, measured by laser speckle flowgraphy preoperatively and until 6 months postoperatively. Aqueous humor samples were obtained during surgery to determine cytokine concentrations by enzyme-linked immunosorbent assay. At 3 and 6 months postoperatively, there were no significant differences between eyes with macula-on RRD and fellow eyes. However, in macula-off RRD, MBR remained significantly lower in RRD eyes 6 months postoperatively (P < 0.05). Log-transformed levels of soluble intercellular adhesion molecule-1 (sICAM-1) were negatively correlated with relative MBR (r-MBR, RRD eye/fellow eye) before surgery (r =  - 0.47, P = 0.01) in macula-on, but not macula-off, RRD. Six months postoperatively, r-MBR correlated significantly with sICAM-1 levels (r =  - 0.36, P = 0.02) in macula-off RRD. ICAM-1 may play a role in RRD-induced deterioration of retinal circulation.
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http://dx.doi.org/10.1038/s41598-021-94993-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319174PMC
July 2021

Efficacy-Based Aflibercept Treatment Regimen for Central Retinal Vein Occlusion.

Ophthalmol Retina 2021 11 24;5(11):1177-1179. Epub 2021 Jun 24.

Department of Ophthalmology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan.

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http://dx.doi.org/10.1016/j.oret.2021.06.008DOI Listing
November 2021

Involvement of Cytokines in the Pathogenesis of Diabetic Macular Edema.

Int J Mol Sci 2021 Mar 26;22(7). Epub 2021 Mar 26.

Hachioji Medical Center, Department of Ophthalmology, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998, Japan.

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.
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http://dx.doi.org/10.3390/ijms22073427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036935PMC
March 2021

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

Graefes Arch Clin Exp Ophthalmol 2021 Sep 26;259(9):2597-2603. Epub 2021 Mar 26.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo, 193-0998, Japan.

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.
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http://dx.doi.org/10.1007/s00417-021-05154-8DOI Listing
September 2021

Retinal Microcirculation and Cytokines as Predictors for Recurrence of Macular Edema after Intravitreal Ranibizumab Injection in Branch Retinal Vein Occlusion.

J Clin Med 2020 Dec 26;10(1). Epub 2020 Dec 26.

Hachioji Medical Center, Department of Ophthalmology, Tokyo Medical University, Tokyo 193-0998, Japan.

Purpose: To investigate the relationship between retinal blood flow, presence or absence of recurrence of macular edema, and levels of cytokines, after intravitreal ranibizumab injection (IRI) in patients with branch retinal vein occlusion (BRVO).

Methods: In 47 patients with BRVO and macular edema, we used laser speckle flowgraphy (LSFG) to measure the relative flow volume (RFV) of the retinal arteries and veins passing through the optic disc in the occluded and non-occluded regions of the retina before and after IRI. Aqueous humor samples were obtained at the time of IRI. Levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, 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, IL-12 (p70), IL-13 and interferon-inducible 10-kDa protein (IP-10) were measured by the suspension array method. Patients were categorized into two groups on the basis of whether or not macular edema recurred at 2 months after IRI: the nonrecurrent group, = 24; and the recurrent group, = 23.

Results: In the veins of the occluded region, RFV showed a significant difference between baseline and 1 month after IRI ( < 0.001) in the recurrent group and the percent change of RFV showed a significant difference between the recurrent and nonrecurrent groups ( = 0.005). Furthermore, we found a significant negative correlation between RFV in the veins of the occluded region and aqueous levels of MCP-1, IL-8 and IP-10 at baseline ( = 0.029, = 0.035, and = 0.039, respectively). In the recurrent group, the arteries and veins of the non-occluded and occluded regions showed no significant association between RFV and the aqueous levels of any factors.

Conclusions: These findings suggested that a decrease in RFV in the veins of the occluded region might be associated with the recurrence of macular edema and that the recurrence might depend on the change in RFV in the veins of the occluded region rather than the levels of cytokines.
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http://dx.doi.org/10.3390/jcm10010058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796037PMC
December 2020

Intravitreal ranibizumab reduced ocular blood flow and aqueous cytokine levels and improved retinal morphology in patients with diabetic macular edema.

Sci Rep 2020 12 10;10(1):21713. Epub 2020 Dec 10.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo, 193-0998, Japan.

We investigated the relationship between aqueous cytokine levels, changes in ocular blood flow, and morphological and functional improvements after intravitreal ranibizumab injection (IRI) in treatment-naïve eyes with center-involving diabetic macular edema (DME). Thirty-three eligible patients with DME (33 eyes) were recruited. At the first IRI, we collected a sample of aqueous humor from each eye and measured levels of the cytokines/chemokines. Mean blur rate (MBR) was used to evaluate retinal and choroidal flow by laser speckle flowgraphy at the time of the first IRI and 1 month later. One month after IRI, both retinal and choroidal MBR had significantly decreased from baseline. The reduction ratio of the retinal MBR was significantly correlated with aqueous levels of monocyte chemotactic protein (MCP)-1 and interleukin-8, and with reduction of central macular thickness, but not with improvement of best corrected visual acuity. The reduction ratio of choroidal MBR showed no statistical correlation with any cytokine levels or changes in clinical parameters. We conclude that IRI reduces both retinal and choroidal blood flow in treatment-naïve DME. Reduction of retinal blood flow correlated with regression of morphological pathology, which is regulated by the initial aqueous levels of some cytokines.
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http://dx.doi.org/10.1038/s41598-020-78792-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728747PMC
December 2020

Cytokines and Pathogenesis of Central Retinal Vein Occlusion.

J Clin Med 2020 Oct 27;9(11). Epub 2020 Oct 27.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998, Japan.

Central retinal vein occlusion (CRVO) causes macular edema and subsequent vision loss and is common in people with diseases such as arteriosclerosis and hypertension. Various treatments for CRVO-associated macular edema have been trialed, including laser photocoagulation, with unsatisfactory results. However, when the important pathogenic role of vascular endothelial growth factor (VEGF) in macular edema was identified, the treatment of CRVO was revolutionized by anti-VEGF therapy. However, despite the success of intraocular injection of anti-VEGF agents in many patients with CRVO, some patients continue to suffer from refractory or recurring edema. In addition, the expression of inflammatory cytokines increases over time, causing more severe inflammation and a condition that is increasingly resistant to anti-VEGF therapy. This indicates that the pathogenesis of macular edema in CRVO is more complex than originally thought and may involve factors or cytokines associated with inflammation and ischemia other than VEGF. CRVO is also associated with leukocyte abnormalities and a gradual reduction in retinal blood flow velocity, which increase the likelihood of it developing from the nonischemic type into the more severe ischemic type; in turn, this results in excessive VEGF expression and subsequent neovascular glaucoma. Here, we review the role of different factors and cytokines involved in CRVO pathogenesis and propose a mechanism that holds promise for the development of novel therapies.
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http://dx.doi.org/10.3390/jcm9113457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692731PMC
October 2020

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

BMC Ophthalmol 2020 Jun 5;20(1):215. Epub 2020 Jun 5.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo, 193-0998, Japan.

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.
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http://dx.doi.org/10.1186/s12886-020-01486-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273673PMC
June 2020

Anti-VEGF Therapy Reduces Inflammation in Diabetic Macular Edema.

Ophthalmic Res 2021 26;64(1):43-49. Epub 2020 May 26.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1159/000508953DOI Listing
September 2021

Functional and anatomical changes in diabetic macular edema after hemodialysis initiation: One-year follow-up multicenter study.

Sci Rep 2020 05 8;10(1):7788. Epub 2020 May 8.

Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Yoshida, Fukui, Japan.

Diabetic nephropathy and retinopathy (DR) including diabetic macular edema (DME) are representative microvascular complications of diabetes. We conducted a retrospective multicenter study analyzing records from patients with DR (132 eyes in 70 patients) and end-stage renal diseases (ESRD) who underwent hemodialysis for the first time. We demonstrated that the central retinal thickness (CRT) values were significantly decreased (p < 0.0001), and the best-corrected visual acuity (BCVA) values were improved (p < 0.05) at 1, 3, 6, 9, and 12 months after hemodialysis initiation, in spite of a lack of specific ocular treatments for DME in 93.2% of eyes. We found a significant positive correlation in the rates of CRT changes between right and left eyes. The CRT reductions were greater in eyes with DME type subretinal detachment than in those with spongelike swelling and cystoid macular edema. The visual outcome gain was associated with the CRT reduction at 12 months in the eyes with good initial BCVA (≧20/50). Hemodialysis induction contributed to functional and anatomical improvements after 1 year, independently of initial laboratory values before the hemodialysis.
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http://dx.doi.org/10.1038/s41598-020-64798-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210956PMC
May 2020

Correction to: Current practice in the management of branch retinal vein occlusion in Japan: Survey results of retina specialists in Japan.

Jpn J Ophthalmol 2020 05;64(3):321

Kyoto University Graduate School of Medicine, Kyoto, Japan.

In the original publication, under section, BRVO treatment practice pattern, the sentence in p. 369 was published as.
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http://dx.doi.org/10.1007/s10384-020-00739-yDOI Listing
May 2020

Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention .

Br J Ophthalmol 2020 12 13;104(12):1755-1761. Epub 2020 Mar 13.

Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

Background/aims: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO).

Methods: Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment.

Results: Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term.

Conclusion: For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785163PMC
December 2020

Real-world management of treatment-naïve diabetic macular oedema in Japan: two-year visual outcomes with and without anti-VEGF therapy in the STREAT-DME study.

Br J Ophthalmol 2020 09 29;104(9):1209-1215. Epub 2019 Nov 29.

Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan.

Background/aims: To investigate real-world outcomes for best-corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve, centr-involving diabetic macular oedema (DME).

Methods: Retrospective analysis of longitudinal medical records obtained from 27 institutions specialising in retinal diseases in Japan. A total of 2049 eyes with treatment-naïve DME commencing intervention between 2010 and 2015 who were followed for 2 years were eligible. Interventions for DME included anti-vascular endothelial growth factor (VEGF) therapy, local corticosteroid therapy, macular photocoagulation and vitrectomy. Baseline and final BCVA (logMAR) were assessed. Eyes were classified by the treatment pattern, depending on whether anti-VEGF therapy was used, into an anti-VEGF monotherapy group (group A), a combination therapy group (group B) and a group without anti-VEGF therapy (group C).

Results: The mean 2-year improvement of BCVA was -0.04±0.40 and final BCVA of >20/40 was obtained in 46.3% of eyes. Based on the treatment pattern, there were 427 eyes (20.9%) in group A, 807 eyes (39.4%) in group B and 815 eyes (39.8%) in group C. Mean improvement of BCVA was -0.09±0.39, -0.02±0.40 and -0.05±0.39, and the percentage of eyes with final BCVA of >20/40 was 49.4%, 38.9%, and 52.0%, respectively.

Conclusion: Following 2-year real-world management of treatment-naïve DME in Japan, BCVA improved by 2 letters. Eyes treated by anti-VEGF monotherapy showed a better visual prognosis than eyes receiving combination therapy. Despite treatment for DME being selected by specialists in consideration of medical and social factors, a satisfactory visual prognosis was not obtained, but final BCVA remained >20/40 in half of all eyes.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577088PMC
September 2020

Change of cytokines after intravitreal ranibizumab in patients with recurrent branch retinal vein occlusion and macular edema.

Eur J Ophthalmol 2021 Jan 5;31(1):204-210. Epub 2019 Nov 5.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

Purpose: To investigate the relations of vascular endothelial growth factor, growth factors, soluble vascular endothelial growth factor receptors, and inflammatory factors to recurrence of macular edema after anti-vascular endothelial growth factor therapy in patients with branch retinal vein occlusion.

Methods: This study retrospectively investigated 17 patients with branch retinal vein occlusion who received intravitreal ranibizumab injection three times within 6 months for recurrent macular edema. Aqueous humor samples were obtained from these patients at every recurrence. Levels of soluble vascular endothelial growth factor receptor-1, soluble vascular endothelial growth factor receptor-2, vascular endothelial growth factor, placental growth factor, platelet-derived growth factor-AA, soluble intercellular adhesion molecule-1, monocyte chemoattractant protein-1, interleukin-6, interleukin-8, interleukin-12(p70), and interleukin-13 were measured by the suspension array method. Aqueous flare values were measured with a laser flare meter and central macular thickness was determined by optical coherence tomography.

Results: Mean best-corrected visual acuity and central macular thickness improved significantly over time after intravitreal ranibizumab injection, but the aqueous flare value at recurrence after intravitreal ranibizumab injection showed no significant change compared with baseline. Aqueous humor levels of soluble vascular endothelial growth factor receptor-1, soluble vascular endothelial growth factor receptor-2, vascular endothelial growth factor, platelet-derived growth factor-AA, monocyte chemoattractant protein-1, and interleukin-8 decreased significantly over time after intravitreal ranibizumab injection. However, there were no significant changes of the other five factors/cytokines (placental growth factor, soluble intercellular adhesion molecule-1, interleukin-6, interleukin-12, and interleukin-13) at recurrence after intravitreal ranibizumab injection compared with baseline.

Conclusion: These findings suggest that persistent inflammation may influence the recurrence of macular edema in branch retinal vein occlusion patients, and that adding steroid therapy might be an effective strategy for preventing recurrence.
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http://dx.doi.org/10.1177/1120672119885054DOI Listing
January 2021

Current practice in the management of branch retinal vein occlusion in Japan: Survey results of retina specialists in Japan.

Jpn J Ophthalmol 2019 Sep 19;63(5):365-373. Epub 2019 Aug 19.

Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To elucidate the current clinical practice patterns of branch retinal vein occlusion (BRVO) management by retina specialists in Japan in the era of anti-vascular endothelial growth factor (VEGF) therapy.

Study Design: A voting survey using an answer pad system.

Methods: On May 28, 2017, forty-one retina specialists were surveyed on the pathology and clinical practice of BRVO management.

Results: Most specialists (77.5%) use fundus examination and optical coherence tomography (OCT) for diagnosis of macular edema (ME) secondary to BRVO. All assess the condition of the ellipsoid zone (EZ) and external limiting membrane (ELM) and consider this a visual prognostic factor. For ME secondary to BRVO, anti-VEGF therapy is the first choice, and most specialists (82.4%) select initial injection followed by a pro re nata (PRN) regimen. For switching to other treatment options for persistent cases, combination therapy of anti-VEGF injections and laser therapy is the most common choice (35.9%), whereas 25.6% select vitreous surgery and 15.4% select adding steroid injections.

Conclusions: Our survey presents the current opinions on the diagnosis and treatment of BRVO by retina specialists in Japan, and reveals the common views about damage to the EZ/ELM as a factor of poor prognosis and anti-VEGF therapy as the first line treatment, highlighting various opinions on initiation and switching of therapy.
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http://dx.doi.org/10.1007/s10384-019-00685-4DOI Listing
September 2019

Role of Cytokines in Ranibizumab Therapy for Macular Edema in Patients with Central Retinal Vein Occlusion.

J Ocul Pharmacol Ther 2019 09 2;35(7):407-412. Epub 2019 Aug 2.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Hachioji, Tokyo, Japan.

To investigate aqueous humor levels of 11 factors/cytokines in patients with central retinal vein occlusion (CRVO) and macular edema (ME) receiving anti-vascular endothelial growth factor (VEGF) therapy, as well as correlations between changes of functional or morphological parameters and aqueous cytokine levels. In 32 CRVO patients scheduled to receive 2 consecutive doses of intravitreal ranibizumab, aqueous samples were obtained at the time of injecting each dose. Aqueous levels of VEGF, soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, platelet-derived growth factor-AA (PDGF-AA), placental growth factor (PlGF), interleukin-6, and monocyte chemotactic protein-1 (MCP-1) were measured using a suspension array. Aqueous humor levels of VEGF, sVEGFR-1, PDGF, PlGF, interleukin-6, and MCP-1 were all significantly lower at 1 month after the initial dose of intravitreal ranibizumab compared with baseline. A significant negative correlation was noted between the change of ME and the changes of aqueous humor VEGF or interleukin-6 levels after intravitreal ranibizumab. The change of VEGF also showed a significant negative correlation with improvement of visual acuity. In patients with CRVO, the changes of visual acuity and ME after intravitreal ranibizumab were associated with inhibition of intraocular VEGF production. VEGF could be a useful marker for the response of ME to treatment.
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http://dx.doi.org/10.1089/jop.2019.0011DOI Listing
September 2019

Cytokines and the Pathogenesis of Macular Edema in Branch Retinal Vein Occlusion.

J Ophthalmol 2019 2;2019:5185128. Epub 2019 May 2.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

Branch retinal vein occlusion (BRVO) is a very common retinal vascular problem in patients with lifestyle-related diseases, such as hypertension and arteriosclerosis. In patients with BRVO, development of macular edema is the main cause of visual impairment. BRVO is still a controversial condition in many respects. Over the years, various methods such as laser photocoagulation have been tried to treat macular edema associated with BRVO, but the results were not satisfactory. After vascular endothelial growth factor (VEGF) was found to have an important role in the pathogenesis of macular edema in BRVO patients, treatment of this condition was revolutionized by development of anti-VEGF therapy. Although macular edema improves dramatically following intraocular injection of anti-VEGF agents, repeated recurrence and resistance of edema is a major problem in some BRVO patients. This suggests that factors or cytokines other than VEGF may be associated with inflammation and retinal hypoxia in BRVO and that the pathogenesis of macular edema is complicated. The present review assesses the role of various factors and cytokines in the pathogenesis of macular edema associated with BRVO. We present a mechanism that is not only plausible but should also be useful for developing new therapeutic strategies.
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http://dx.doi.org/10.1155/2019/5185128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525954PMC
May 2019

Anti-vascular endothelial growth factor agent reduces inflammation in macular edema with central retinal vein occlusion.

J Inflamm (Lond) 2019 22;16. Epub 2019 May 22.

1Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo 193-0998 Japan.

Background: Correlations among the aqueous flare value (an indicator of inflammation), functional-morphologic parameters, and aqueous humor levels of growth factors/receptors and inflammatory factors/cytokines were investigated in patients with central retinal vein occlusion (CRVO) and macular edema who received intravitreal ranibizumab injection (IRI) and were followed for 6 months.

Methods: Aqueous humor levels of 11 cytokines or growth inflammatory/factors were measured in 20 CRVO patients with macular edema receiving IRI. Patients with recurrent macular edema were administered further IRI as needed. Aqueous humor levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR), and other cytokines/inflammatory factors were measured by the suspension array method. Aqueous flare values were measured with a laser flare meter and macular edema was examined by optical coherence tomography.

Results: Compared with before treatment (baseline), the aqueous flare value showed a significant decrease at both 1 month and 6 months after IRI therapy. There were significant correlations between the aqueous flare value and the aqueous levels of sVEGFR-1, placental growth factor, monocyte chemoattractant protein 1, soluble intercellular adhesion molecule-1, interleukin (IL)-6, and IL-8. In addition, a significant correlation was noted between the change of the aqueous flare value and improvement of central macular thickness at 6 months after IRI, as well as a significant correlation between the change of the aqueous flare value and improvement of best-corrected visual acuity at 6 months.

Conclusions: These findings suggest that IRI reduces inflammation and that the aqueous flare value is influenced by inflammatory factors/cytokines. In addition, the change of the aqueous flare value may be an indicator of the long-term prognosis in CRVO patients receiving IRI therapy for macular edema.
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http://dx.doi.org/10.1186/s12950-019-0214-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530041PMC
May 2019

Scleral buckling versus vitrectomy for young japanese patients with rhegmatogenous retinal detachment in the era of microincision surgery: real-world evidence from a multicentre study in Japan.

Acta Ophthalmol 2019 Aug 11;97(5):e736-e741. Epub 2019 Feb 11.

J-CREST (Japan Clinical REtina STudy group), Kagoshima, Japan.

Purpose: To evaluate real-world evidence for young Japanese patients with rhegmatogenous retinal detachment (RRD) by retrospectively examining surgical procedures and clinical outcomes in the Japan Clinical Retina Study group.

Methods: This was a multicentre retrospective study of the medical records of 562 young patients (384 males and 178 females; mean age: 33.0 ± 11.8 years) who had been diagnosed with RRD and who underwent surgical procedures in participating centres during the period between April 2013 and August 2016.

Results: The selected surgeries were scleral buckling (SB) for 295 eyes (49.7%) and pars plana vitrectomy (PPV) for 262 eyes (44.1%). Between the two surgical procedures, there was no significant difference in the primary anatomical reattachment rate (PARR, SB = 92.2%, PPV = 93.9%); improvements in vision were noted in both groups. The incidences of proliferative vitreoretinopathy and cataract formation within 1 year of PPV were 2.3% (p = 0.0047) and 6.5% (p = 0.0005), whereas they were 0% and 1.0% in the SB group, respectively.

Conclusion: Scleral buckling (SB) and PPV were chosen with almost equal frequency for young patients with RRD. Clinical outcomes for SB and PPV exhibited a similar PARR. The incidence of cataract formation after PPV may constitute an important limitation of the procedure.
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http://dx.doi.org/10.1111/aos.14050DOI Listing
August 2019

Dynamics of soluble vascular endothelial growth factor receptors and their ligands in aqueous humour during ranibizumab for age-related macular degeneration.

J Inflamm (Lond) 2018 4;15:26. Epub 2018 Dec 4.

1Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, 1163, Tatemachi, Hachioji, Tokyo, 193-0998 Japan.

Background: Intravitreal ranibizumab injection (IRI) is effective for patients with exudative age-related macular degeneration (AMD) and decreases intraocular levels of vascular endothelial growth factor (VEGF), but VEGF receptor intraocular dynamics after IRI are unclear. Therefore, we evaluated changes in the aqueous humor levels of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, and their ligands for these receptors (VEGF) patients with AMD receiving IRI.

Methods: The subjects were 24 patients with AMD (24 eyes) who received 3 doses of IRI at monthly intervals. Aqueous humor samples were obtained when each IRI dose was given (visits 0, 1, and 2 at 4-week intervals). Then the suspension array method was employed to measure sVEGFR-1, sVEGFR-2, VEGF, and placental growth factor (PlGF) in aqueous humor samples from the 24 AMD patients and 13 cataract patients (as controls). Best corrected visual acuity (BCVA; logMAR) chart and central macular thickness (CMT; optical coherence tomography) were also assessed over time.

Results: At baseline, the aqueous humor levels of sVEGFR-1, sVEGFR-2, VEGF, and PlGF were significantly higher in the AMD group than in the control group. There was a significant correlation between VEGF and PlGF or between sVEGFR-1 and sVEGFR-2. BCVA and CMT both improved significantly after IRI, and the aqueous humor levels of VEGF, PlGF, and sVEGFR-1 also decreased significantly.

Conclusions: VEGFRs may be involved in the pathogenesis of AMD. IRI improves clinical parameters in AMD patients by suppressing intraocular levels of VEGF, PlGF, and sVEGFR-1.
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http://dx.doi.org/10.1186/s12950-018-0203-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280338PMC
December 2018

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

Neuroophthalmology 2019 Dec 11;43(6):411-416. Epub 2018 Oct 11.

Department of Ophthalmology, Kyorin University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1080/01658107.2018.1526956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053975PMC
December 2019

Clinical preferences and trends of anti-vascular endothelial growth factor treatments for diabetic macular edema in Japan.

J Diabetes Investig 2019 Mar 26;10(2):475-483. Epub 2018 Oct 26.

Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Japan.

Aims/introduction: To determine the current clinical preferences of anti-vascular endothelial growth factor (VEGF) treatment protocols for diabetic macular edema (DME) in Japan.

Materials And Methods: This was a descriptive cross-sectional study. Answers to a questionnaire consisting of 16 questions were obtained from 176 of 278 (63.3%) surveyed ophthalmologists.

Results: The results showed that 81.2% preferred intravitreal injections of anti-VEGF antibodies as the first-line therapy. The most important indicators for beginning anti-VEGF therapy were: the best-corrected visual acuity in 44.3% and the retinal thickness in 30.7%. In the loading phase, 53.4% preferred a single injection, and in the maintenance phase, 75.0% preferred the pro re nata regimen. Financial limitation (85.8%) was reported as the most important difficulty in the treatment. For combination therapy with anti-VEGF treatment, panretinal photocoagulation, focal photocoagulations and a sub-Tenon steroid injection were preferred. The contraindications for anti-VEGF therapy were: prior cerebral infarction (72.7%). Regarding the use of both approved anti-VEGF agents in Japan, ranibizumab and aflibercept, 39.8% doctors used them appropriately.

Conclusions: Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.
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http://dx.doi.org/10.1111/jdi.12929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400162PMC
March 2019

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

Ophthalmologica 2019 3;241(3):161-169. Epub 2018 Sep 3.

Department of Ophthalmology, Kyusyu University Hospital, Fukuoka, Japan.

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.
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http://dx.doi.org/10.1159/000492135DOI Listing
April 2019

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

Ophthalmologica 2019 26;241(2):81-89. Epub 2018 Jul 26.

Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan.

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.
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http://dx.doi.org/10.1159/000490153DOI Listing
March 2019

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

Ophthalmic Res 2018 May 25:1-8. Epub 2018 May 25.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1159/000488494DOI Listing
May 2018

Effect of intravitreal triamcinolone acetonide injection at the end of vitrectomy for vitreous haemorrhage related to proliferative diabetic retinopathy.

Br J Ophthalmol 2018 10 17;102(10):1351-1357. Epub 2018 Jan 17.

Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Yoshida, Fukui, Japan.

Background/aims: To investigate whether intravitreal injection of triamcinolone acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy (PDR).

Methods: This prospective, multicentre, randomised study conducted at seven sites in Japan enrolled patients diagnosed as having VH following PDR. Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA at the end of the surgery. Anterior flare intensity (AFI), central retinal thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery and compared.

Results: Number of patients who completed 6 months of follow-up was 40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week (P=0.019) and 1 month (P=0.037). There were no significant differences in CRT, BCVA and IOP between the groups through the observational periods. In the cases with macular oedema >350 µm of CRT at 3 days, CRT was significantly lower in the IVTA+VIT group than in the VIT group at 1 month (P=0.041).

Conclusions: IVTA combined with vitrectomy and cataract surgery contributed to inhibit the postoperative inflammation in patients with VH due to PDR. The effect of IVTA in the reduction of diabetic macular oedema may be limited to the early stage after surgery.

Trial Registration Number: UMIN000020376, Post-results.
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http://dx.doi.org/10.1136/bjophthalmol-2017-311377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173818PMC
October 2018

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

Ophthalmic Res 2017 11;58(4):209-216. Epub 2017 Aug 11.

Department of Ophthalmology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.

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.
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http://dx.doi.org/10.1159/000478705DOI Listing
November 2017
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