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Background: To assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab., Methods: Patients with pDME on chronic anti-vascular endothelial growth factor therapy that were switched to faricimab and received at least three injections at our institution between April 2022 and May 2023 were included in this study. Patients were excluded if they had complete response to previous treatment but were switched to extend treatment intervals if they had steroid or laser treatment for DME within 6 months prior to switch. Clinical and imaging data were extracted from the electronic medical record. Central foveal thickness (CFT) and Snellen visual acuity (VA) were obtained before and after three intravitreal faricimab injections. Generalised estimating equations were used to analyse the change in CFT and VA., Result: During the study period, 69 eyes of 53 patients met inclusion criteria. The mean age was 68.6±9.0 years. The mean number of injections prior to switch was 18.1±16.0. Pre-switch mean logarithm of the minimal angle of resolution VA was 0.40±0.30 (Snellen equivalent 20/50) and 0.38±0.27 (Snellen equivalent 20/48) after three faricimab injections (p=0.397). Mean CFT improved from 380±155 microns to 323±147 microns (p<0.001). No ophthalmic or systemic adverse events occurred during the study period., Conclusions: Intravitreal faricimab can improve anatomic outcomes while maintaining visual acuity in eyes with pDME previously treated with anti-VEGF therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To investigate the outcomes of intravitreal aflibercept and gas injections for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV)., Methods: We retrospectively reviewed the medical records of 22 eyes with SMH secondary to PCV that underwent intravitreal aflibercept and 100% perfluoropropane (0.3-0.5 mL) followed by 3-day prone positioning from August 2013 through November 2020. The primary outcome measure was best-corrected visual acuity (BCVA) at 12 months., Results: The average SMH size was 13.0 ± 9.7 (range, 2.0-37.8) disc diameter. The complete, partial, and no displacement of the SMH was observed in 8 (36%) eyes, 9 (41%) eyes, and 5 (23%) eyes, respectively. The BCVA (logarithm of the minimum angle of resolution) continuously improved significantly from 0.81 ± 0.41 (Snellen equivalent, 20/125) at baseline to 0.48 ± 0.44 (20/60), 0.33 ± 0.39 (20/43), and 0.28 ± 0.45 (20/38), at 3, 6, and 12 months, respectively (P = 0.01 for 3 months; P < 0.001 for 6 and 12 months). The BCVA improved by 3 or more lines in 14 eyes (64%). Two eyes (9%) developed visually significant vitreous hemorrhage, and 1 (5%) eye developed rhegmatogenous retinal detachment; all were successfully treated with vitrectomy. The better BCVA at 12 months tended to be associated with lower height of the SMH at baseline (R 2  = 0.171, P = 0.056) and a greater displacement of SMH (R 2  = 0.244, P = 0.069). Worse BCVA at 12 months was associated with anticoagulant medication (P < 0.001)., Conclusions: Intravitreal aflibercept and gas injections are effective and relatively safe for SMH associated with PCV, resulting in significant visual improvement., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To compare chorioretinal atrophy (CRA) progression in myopic choroidal neovascularization (mCNV) between intravitreal injections of ranibizumab (IVR) and aflibercept (IVA) in the eyes with mCNV., Methods: Thirty eyes (28 patients) with treatment-naïve mCNV were included in this study. IVR or IVA was administered for up to 1 year. The best-corrected visual acuity (BCVA) was measured, and fundus photographs and fundus autofluorescence were obtained before and 1, 3, 6, and 12 months after the initial treatment. The clinical characteristics including the macular choroidal thickness in various areas and CRA progression were compared between the drugs. The clinical characteristics and macular choroidal thicknesses were compared between eyes with and without CRA progression., Results: The BCVA improved significantly (p < 0.05 for all comparisons) from 0.44 to 0.26, 0.19, 0.20, and 0.17 after 1, 3, 6, and 12 months, respectively. CRA progressed in 12 (40%) eyes over 1 year. The CRA progression did not differ significantly between aflibercept and ranibizumab. The foveal choroid was significantly (p = 0.0043) thinner in aflibercept-treated eyes compared with ranibizumab-treated eyes at 1 year. Subfoveal CNV tended to cause CRA progression more frequently at 1 year, although this did not reach significance., Conclusions: IVA to treat mCNV caused more severe thinning of the foveal choroid than ranibizumab; however, no significant difference was seen in CRA progression between the drugs and the choroidal thickness should not be associated with CRA progression. The CNV location may predict CRA progression after anti-vascular endothelial growth factor therapy for mCNV.

Purpose: To investigate vascular perfusion and foveal avascular zone area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) after intravitreal aflibercept therapy in central retinal vein occlusion eyes and their association with best-corrected visual acuity., Methods: Thirty-five subjects with central retinal vein occlusion and macular edema were evaluated. After macular edema resolution following intravitreal aflibercept, subjects underwent optical coherence tomography angiography to measure SCP and DCP perfusion and the foveal avascular zone within a 3 × 3-mm area. Correlations between best-corrected visual acuity and optical coherence tomography angiography measurements were examined., Results: After intravitreal aflibercept therapy, mean retinal vascular area was 3.41 ± 0.74 mm in the SCP and 3.25 ± 0.91 mm in the DCP. Foveal avascular zone area was 1.03 ± 1.04 mm in the SCP and 1.78 ± 1.73 mm in the DCP. Improved best-corrected visual acuity was significantly associated with better SCP and DCP perfusion (both P < 0.001) and with smaller SCP and DCP foveal avascular zone areas (both P < 0.001). Additionally, SCP and DCP perfusion were negatively correlated with macular edema before treatment (P < 0.05) and ischemia (determined via pretreatment fluorescein angiography, P < 0.05), and positively correlated with photoreceptor integrity (P < 0.001)., Conclusion: Patients with better retinal perfusion and less retinal ischemia are associated with better visual outcomes after aflibercept in eyes with central retinal vein occlusion.

Purpose: To investigate the changes in the retinal microvasculature during the course of anti-VEGF therapy in eyes with macular edema due to retinal vein occlusion (RVO) and their association with visual outcomes., Methods: The vessel density (VD) and foveal avascular zone (FAZ) area in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were quantitatively measured by optical coherence tomography angiography (OCTA) in 48 consecutive eyes with RVO before and 1, 3, 6, 9, and 12 months after anti-VEGF therapy. Anti-VEGF therapy was performed either with ranibizumab or aflibercept following a pro re nata (PRN) regimen. The correlation between post-treatment best-corrected visual acuity (BCVA) and changes in the retinal microvasculature evaluated by OCTA were assessed., Results: The BCVA improved significantly at 12 months (P < 0.001). Better BCVA at 12 months was significantly associated with a better VD in the SCP and DCP both at baseline (R2 = 0.524, P < 0.001 and R2 = 0.457, P < 0.001, respectively) and at 12 months (R2 = 0.521, P < 0.001 and R2 = 0.662, P < 0.001, respectively). Overall, both VD and FAZ did not change significantly during the 12 months. However, the progression of nonperfusion was observed in the SCP in 6 (13%) eyes and in the DCP in 10 (21%) eyes. The number of macular edema recurrence was significantly associated with a decrease in the VD (P = 0.006 [SCP] and P < 0.001 [DCP]) and less visual gain (P = 0.02) after treatment., Conclusions: Anti-VEGF therapy maintains retinal perfusion in most patients with RVO. Preserving retinal perfusion is crucial for better visual outcomes.

Angiogenesis plays a crucial role in tumor growth, with an undisputed contribution of resident endothelial cells (EC) to new blood vessels in the tumor. Here, we report the definition of a small population of vascular-resident stem/progenitor-like EC that contributes predominantly to new blood vessel formation in the tumor. Although the surface markers of this population are similar to other ECs, those from the lung vasculature possess colony-forming ability in vitro and contribute to angiogenesis in vivo These specific ECs actively proliferate in lung tumors, and the percentage of this population significantly increases in the tumor vasculature relative to normal lung tissue. Using genetic recombination and bone marrow transplant models, we show that these cells are phenotypically true ECs and do not originate from hematopoietic cells. After treatment of tumors with antiangiogenic drugs, these specific ECs selectively survived and remained in the tumor. Together, our results established that ECs in the peripheral vasculature are heterogeneous and that stem/progenitor-like ECs play an indispensable role in tumor angiogenesis as EC-supplying cells. The lack of susceptibility of these ECs to antiangiogenic drugs may account for resistance of the tumor to this drug type. Thus, inhibiting these ECs might provide a promising strategy to overcome antiangiogenic drug resistance. Cancer Res; 76(11); 3200-10. ©2016 AACR., (©2016 American Association for Cancer Research.)

Aims: To assess the long-term efficacy of intravitreal bevacizumab for recurrent leakage owing to the residual branching vascular networks in polypoidal choroidal vasculopathy after photodynamic therapy., Methods: Forty-five eyes with exudative branching vascular networks were treated with intravitreal bevacizumab and followed for at least 24 months. Original polypoidal lesions had been treated successfully with previous photodynamic therapy in all eyes. The best-corrected visual acuity and retinal morphological changes were assessed retrospectively., Results: Exudative branching vascular networks were characterised as occult choroidal neovascularisation (38 eyes) or classic choroidal neovascularisation (7 eyes) on fluorescein angiography. Intravitreal bevacizumab maintained or improved vision in 38 eyes (84%) over 12 months and in 36 eyes (80%) over 24 months, although the mean visual acuity at 12 and 24 months did not differ significantly compared with baseline. Complete resolution of macular fluid was achieved continuously in 26 eyes (58%) during 24 months. Sixteen eyes (36%) responded once to treatment but became unresponsive to additional injections for recurrent exudation. Three eyes (7%) were refractory to treatment throughout follow-up. Cystoid macular oedema eventually developed in 10 eyes and was a poor prognostic sign for visual outcome., Conclusion: Intravitreal bevacizumab improved the retinal morphology and maintained vision over 1 year in most eyes with recurrent fluid owing to persistent abnormal vascular networks in polypoidal choroidal vasculopathy. The therapeutic response, however, may decrease during the second year.

It is widely accepted that blood vessels in the tumor microenvironment are immature because mural cell (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion., (© 2011 Japanese Cancer Association.)

Purpose: To evaluate the clinical outcomes and biologic effects on the aqueous humor concentrations of vascular endothelial growth factor (VEGF) in patients with neovascular glaucoma (NVG) treated with intravitreal bevacizumab (IVB)., Methods: Twenty-nine consecutive patients (35 eyes) treated with 1.0- or 0.1-mg injections of IVB for NVG between January and December 2009 were enrolled in this retrospective, interventional pilot study. The visual prognosis and changes in intraocular pressure (IOP) were followed for >6 months after the initial injection. Aqueous humor samples were obtained at the initial IVB injection from all study eyes and 1 week after the first injection in eyes undergoing a second intervention to measure the VEGF concentration., Results: The VEGF concentrations in the 35 eyes significantly correlated (r=0.535, P<0.001) with the pretreatment IOP. The mean reductions of the VEGF levels 1 week after IVB did not differ significantly between the 1.0- and 0.1-mg groups (P=0.738). Despite more repeated injections in the 0.1-mg group and additional medical or surgical interventions in both groups, both dosages inhibited the neovascular activity. The ability to control the IOP after IVB did not differ significantly between groups at 1 week (P=0.625) and 6 months (P>0.99). Visual improvements also did not differ significantly between groups during the 6-month follow-up (P=0.437)., Conclusions: Aqueous humor levels of VEGF were significantly correlated with the IOP. Low-dose (0.1 mg) IVB was as effective as the currently used higher dose (1.0 mg) for treating NVG within at least 6 months after the initial injection.

Purpose: To compare the visual outcomes and retreatment rate of single injection of intravitreal bevacizumab followed by pro re nata (PRN) treatment and three monthly injections of intravitreal bevacizumab followed by PRN treatment for myopic choroidal neovascularization., Methods: Thirty-one consecutive eyes of 31 patients with myopic choroidal neovascularization were retrospectively evaluated. Nineteen eyes were treated with a single injection + PRN and 12 eyes with 3 monthly injections + PRN. The best-corrected visual acuity 12 months after the initial injection, logarithm of the minimum angle of resolution gain from baseline, recurrence rate, and number of injections were statistically compared., Results: Baseline best-corrected visual acuity (logarithm of the minimal angle of resolution) was 0.42 ± 0.31 in the single injection + PRN group and 0.47 ± 0.29 in the 3 monthly injections + PRN group (P = 0.64). The best-corrected visual acuity improved significantly at 3, 6, and 12 months in both groups (P < 0.05 at each time point). Mean logarithm of the minimal angle of resolution gain at 3, 6, and 12 months did not differ significantly between groups. The single injection + PRN group required significantly fewer intravitreal bevacizumab treatments (P = 0.005). The rate of recurrence and choroidal neovascularization persistence did not differ significantly between groups., Conclusion: Compared with 3 monthly injections followed by PRN, single injection followed by PRN for myopic choroidal neovascularization required fewer injections and produced a similar visual outcome over 12 months.

Purpose: To compare the efficacy of photodynamic therapy (PDT) with or without intravitreal bevacizumab injection for polypoidal choroidal vasculopathy., Design: Retrospective, comparative, interventional case series., Methods: We included 146 eyes of 146 patients with treatment-naïve polypoidal choroidal vasculopathy including the subfoveal region treated with PDT monotherapy or combined with intravitreal bevacizumab injection. Treatments were chosen according to the time period. For eyes that received combination therapy, bevacizumab (1.25 mg) was administrated 1 day before PDT. All eyes were followed up for at least 12 months. Ophthalmic evaluations, including measurement of the best-corrected visual acuity and optical coherence tomography, were performed at every visit. Indocyanine green angiography and fluorescein angiography were performed every 3 months., Results: Sixty-one eyes were treated with PDT combined with bevacizumab and 85 eyes were treated with PDT monotherapy. The mean best-corrected visual acuity was significantly better in the combined treatment group than in the monotherapy group at 3 months (P = .0016), 6 months (P = .028), 9 months (P = .038), and 12 months (P = .048). However, lesions resolved in 78.7% of eyes in the combined group and in 75.3% in the monotherapy group; the recurrence rates were 43.8% and 40.6%, respectively, and did not differ significantly. The rate of development of subretinal hemorrhage within 1 month from the initial treatment was significantly lower in the combined group than in the PDT monotherapy group (4.5% vs 17.7%; P = .023)., Conclusions: Photodynamic therapy combined with bevacizumab injection offers significantly better early visual outcomes than PDT alone. Combined treatment did not affect the resolution and recurrence of lesions; however, it decreased the rate of development of PDT-related hemorrhages., (2010 Elsevier Inc. All rights reserved.)

Purpose: To compare the visual outcomes of intravitreal bevacizumab (Avastin; Genentech Inc, South San Franciso, California, USA) and sub-Tenon triamcinolone acetonide (TA) for choroidal neovascularization attributable to pathologic myopia (mCNV)., Design: Retrospective, comparative, interventional case series., Methods: Fifty-four consecutive eyes of 53 patients with mCNV treated with either sub-Tenon TA or intravitreal bevacizumab in an institutional setting were included. Twenty eyes were treated with sub-Tenon TA and 34 eyes were treated with intravitreal bevacizumab. The main outcome measures included best-corrected visual acuity (BCVA) 12 months after the initial injection and logarithm of the minimum angle of resolution gain from baseline compared with analysis of covariance (ANCOVA)., Results: At 12 months, the BCVA improved by 1.9 lines in the intravitreal bevacizumab group and worsened by 0.3 lines in the sub-Tenon TA group. Thus, the intravitreal bevacizumab group had significantly greater visual improvement than the sub-Tenon TA group (P < .01). Statistical analysis (ANCOVA) revealed that age (P = .01), pretreatment BCVA (P < .01), and the treatment choice (intravitreal bevacizumab or sub-Tenon TA; P < .01) correlated significantly with the BCVA and the BCVA gain at 12 months. The refractive error was of borderline significance (P = .06)., Conclusions: Although this study is limited because of its retrospective nature, intravitreal bevacizumab seems to result in a more favorable visual outcome than sub-Tenon TA in the treatment of mCNV. Patient age, the BCVA before treatment, and the refractive error must be considered to initiate the treatment.

Purpose: To report new indocyanine green angiographic (ICGA) findings after intravitreal bevacizumab (IVB) for myopic choroidal neovascularization (mCNV)., Cases Report: Three eyes of three patients with mCNV were examined with fluorescein angiography (FA) and ICGA using Heidelberg Retinal Angiograph 2 and the conventional fundus camera before and after IVB. The cessation of angiographic leakage on FA was achieved in all eyes (100%) after IVB, however the hypofluorescent line delineating the margin of the neovascular tissue appeared in ICGA seemingly according to the contraction of mCNV. It was not detected either on FA or ICGA with the conventional camera. This hypofluorescence line enlarged over the time., Conclusion: The contraction-associated hypofluorescence line, namely marginal crack line, indicates the early damage of retinal pigment epithelium and seems to lead to expanding macular chorioretinal atrophy typically seen in mCNV.

Purpose: To investigate the feasibility and efficacy of microincision vitrectomy surgery (MIVS) combined with intravitreal bevacizumab (IVB) as a surgical adjunct for treating traction retinal detachment (TRD) secondary to severe proliferative diabetic retinopathy (PDR)., Design: Retrospective, comparative, consecutive, interventional case series., Participants: Seventy-one eyes of 59 consecutive patients who underwent primary vitrectomy for diabetic TRD and were followed up for more than 6 months after surgery., Methods: Eyes that received IVB (1 mg) as a preoperative adjunct followed by MIVS (IVB/MIVS group) from November 2005 through December 2007 were compared with eyes that underwent conventional 20-gauge pars plana vitrectomy (20-g PPV group) from September 2003 through October 2005., Main Outcome Measures: Primary and ultimate anatomic success, intraoperative and postoperative complications, and final visual success with at least 6 months of follow-up., Results: This series included 38 eyes (33 patients) in the IVB/MIVS group and 33 eyes (26 patients) in the 20-g PPV group. The primary and ultimate anatomic success rates (95% vs. 91% and 100% in both groups, respectively) and the mean visual acuity changes did not differ significantly between groups; the surgical time and intraoperative bleeding in the IVB/MIVS group decreased significantly compared with the 20-g PPV group (P<0.001). The rate of visual improvement of 3 lines or more at the 6-month follow-up was 68% in the IVB/MIVS group and 49% in the 20-g PPV group, respectively. Progression of the preexisting TRD after IVB occurred in 7 eyes (18%). Absence of previous laser photocoagulation (P = 0.025) and the presence of a ring-shaped fibrovascular membrane (P = 0.013) were relevant findings in eyes with these IVB-induced complications., Conclusions: Intravitreal bevacizumab plus MIVS offers comparable anatomic success compared with conventional 20-gauge PPV in patients with TRD resulting from severe PDR. This technique shortens the surgical time with fewer intraoperative complications and favorable visual recovery. However, caution should be taken because of rapid progression of the preexisting TRD after IVB in some patients., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To evaluate the biologic efficacy of intravitreal bevacizumab (IVB) for iris neovascularization (INV) or neovascular glaucoma (NVG) in patients with ischemic retinal disorders., Design: Retrospective, consecutive, interventional case series., Participants: Thirty patients (41 eyes) with INV or NVG secondary to ischemic retinal disorders., Methods: Patients received IVB (1 mg) as the initial treatment for INV or NVG and were followed up for at least 6 months. Ophthalmic evaluations included measurement of visual acuity and intraocular pressure (IOP), a complete ophthalmic examination, and fluorescein angiography. Patients were divided into 3 subgroups: INV without elevated IOP (INV group), NVG with an open angle (O-NVG group), and NVG with angle closure (C-NVG group) for outcomes analysis., Main Outcome Measures: The controllability of IOP by IVB, incidence of recurrence, and requirement for surgery to treat NVG., Results: No significant ocular or systemic adverse events developed during follow-up (range, 6-22 months; mean, 13.3 months). The mean IOP levels were 14.7, 31.2, and 44.9 mmHg at baseline in the INV, O-NVG, and C-NVG groups, respectively. In the INV group (9 eyes), the INV regressed or resolved after 1 injection. Iris neovascularization recurred in 4 eyes by 6 months and stabilized after repeated injections without IOP elevation. In the O-NVG group (17 eyes), rapid neovascular regression with successful IOP normalization (