Evaluation of plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab and aflibercept for exudative age-related macular degeneration

Background

To evaluate the plasma vascular endothelial growth factor (VEGF) levels after one intravitreal injection of aflibercept or ranibizumab in patients with exudative age-related macular degeneration (AMD).

Methods

Twenty-four Japanese with exudative AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation were included. Fourteen patients received an intravitreal injection of aflibercept, and ten patients received an intravitreal injection of ranibizumab. Plasma VEGF levels were evaluated within 7 days before the intravitreal injections and 1 day, 1 week, and 1 month after the intravitreal injection.

Results

In the ranibizumab group, the mean plasma VEGF levels were 245.7?±?233.4 pg/ml before the injection, 246.6?±?304.8 pg/ml after 1 day, 217.8?±?212.9 pg/ml after 1 week, and 260.0?±?290.1 pg/ml after 1 month. The plasma VEGF levels did not decrease significantly in patients in the ranibizumab group at any time point. In the aflibercept group, the mean plasma VEGF levels were 280.0?±?170.3 pg/ml before the intravitreal injection and 8.2?±?12.9 pg/ml after 1 day, 9.1?±?9.1 pg/ml after 1 week, and 41.9?±?41.4 pg/ml after 1 month (p?Conclusion Intravitreally injected aflibercept reduced plasma VEGF over at least 1 month. In contrast, intravitreal injection of ranibizumab did not cause a significant reduction in the plasma VEGF levels.     

Aqueous vascular endothelial growth factor and ranibizumab concentrations after monthly and bimonthly intravitreal injections of ranibizumab for age-related macular degeneration

Purpose

To evaluate vascular endothelial growth factor (VEGF) and ranibizumab concentrations in eyes with age-related macular degeneration (AMD) after monthly and bimonthly intravitreal ranibizumab (IVR) injections.

Methods

Aqueous humor samples were obtained from 26 eyes with AMD before and after IVR injections. Nine eyes received three monthly injections and 17 eyes received two bimonthly injections. The VEGF and ranibizumab concentrations were measured by enzyme-linked immunosorbent assay.

Results

The aqueous VEGF concentrations in the monthly injection group decreased below the lowest detectable limit in eight of nine eyes 1 month after the first injection and seven of nine eyes 1 month after the second injection (P?<?0.001, mean baseline value, 94.7 pg/ml); the aqueous VEGF concentrations in the bimonthly injection group decreased below the lowest detectable limit in two of 17 eyes 2 months after the first injection (P?<?0.001, mean baseline value, 152.4 pg/ml). The mean aqueous ranibizumab concentrations with monthly injections were 71.2 ng/ml 1 month after the first injection, and 96.3 ng/ml 1 month after the second injection. The mean aqueous ranibizumab concentrations in the bimonthly injection group were 2.5 ng/ml in 15 of 17 eyes, and below the lowest detectable limit in two of 17 eyes 2 months after the first injection.

Conclusions

In this pilot study with limited follow-up, intravitreal injection of ranibizumab can suppress aqueous VEGF completely for 1 month in most cases. Its effect does not last for 2 months enough to suppress VEGF completely in most cases, although aqueous VEGF at 2 months after intravitreal injection of ranibizumab is less than that before injection in most cases.     

Comparison of the efficacy of aflibercept,ranibizumab, and bevacizumab in an RPE/choroid organ culture

Purpose

Anti-VEGF treatment is the therapy of choice in age-related macular degeneration and is also applied in diabetic macular edema or retinal vein occlusion. Recently, aflibercept has been approved for therapeutic use. In this study, we investigate the efficacy of aflibercept in comparison with the VEGF-antagonists ranibizumab and bevacizumab in RPE/choroid organ cultures.

Methods

RPE/choroid organ cultures were prepared from freshly slaughtered pigs’ eyes. Organ cultures were treated with 125 μg/ml aflibercept, ranibizumab, or bevacizumab, and the VEGF content of the supernatant was evaluated over the course of 7 days. Additionally, the minimal concentration of VEGF inhibition was evaluated in organ cultures, measured after 6 h of application.

Results

Aflibercept was able to completely inhibit VEGF detection for 6 h at a minimal concentration of 0.031 μg/ml, in contrast to bevacizumab (3.9 μg/ml) and ranibizumab (0.244 μg/ml). A statistically significant VEGF inhibition compared to control could be found for aflibercept and ranibizumab down to and including 0.031 μg/ml, while bevacizumab was significantly reduced compared to control down to a concentration of 0.244 μg/ml and again at 0.061 μg/ml. Inhibition of VEGF after a single aflibercept application of 125 μg/ml could be found over the course of 7 days, with some VEGF detectable at the 7th day. In contrast, VEGF was detectable after 72 h of ranibizumab treatment and some VEGF could already be found 12 h after bevacizumab treatment.

Conclusions

In conclusion, aflibercept displays a prolonged VEGF inhibition, confirming its effectiveness but also raising concerns about possible side effects of long-term usage.     

Factors influencing the exudation recurrence after cataract surgery in patients previously treated with anti-vascular endothelial growth factor for exudative age-related macular degeneration

Purpose

To investigate factors influencing exudation recurrence following cataract surgery in patients already treated with anti-vascular endothelial growth factor (VEGF) agents for exudative age-related macular degeneration (AMD).

Methods

A retrospective review of medical records was performed for patients who underwent cataract surgery and had been previously treated with anti-VEGF for exudative AMD. Visual acuity was examined before surgery and 1 and 6 months after surgery. The time between diagnosis and surgery, and the exudation-free period before surgery were examined and compared between patients who had exudation recurrence and those that did not.

Results

Thirty-nine eyes of 39 patients were included in analyses. The logarithm of the minimum angle of resolution visual acuity was 1.02?±?0.58 and had significantly improved 1 month (0.81?±?0.62, P?P?=?0.001) following surgery. Both the diagnosis-to-surgery period (P?=?0.001) and the preoperative exudation-free period (P?Conclusions Cataract surgery was beneficial in patients previously treated with anti-VEGF for exudative AMD. Our data suggests that cataract surgery should be performed after a sufficiently long exudation-free period to minimize exudation recurrence. But larger prospective studies are required to draw definitive clinical guidelines.     

Increased serum VEGF and b-FGF in Graves’ ophthalmopathy

Background

Graves’ ophthalmopathy (GO) is thought to be an inflammatory disorder of autoimmune background. The aim of this study is to investigate the involvement of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) in patients with Graves’ ophthalmopathy (GO).

Methods

Serum concentrations of VEGF and b-FGF of 48 GO patients, 30 Graves’ hyperthyroid disease (GD) patients without ophthalmopathy, and 30 healthy controls were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Patients with GO were subdivided into two groups according to clinical activity scores (CAS): a score of 3 or less is considered as inactive (CAS?≤?3, inactive GO, n?=?14), and 4 or more is considered active eye disease (CAS?≥?4, active GO; n?=?34). All of the patients with active GO underwent corticosteroid therapy.

Results

The concentrations of serum VEGF and b-FGF were significantly higher in patients with GO and in those with GD than in controls. The serum levels of VEGF and b-FGF in patients with active GO were higher than those in patients with inactive GO and those in GD patients (P?VEGF and b-FGF concentratison were significantly correlated with CAS in GO patients (p?VEGF and b-FGF levels in corticosteroid-responsive patients (CAS decreases ≥3 after treatment) decreased significantly after corticosteroid treatment (P?P?Conclusion The results suggest that serum VEGF and b-FGF levels were increased in patients with active GO and could reflect the degree of ocular inflammatory activity.     

Effect of aflibercept in insufficient responders to prior anti-VEGF therapy in neovascular AMD

Purpose

Evaluation of three aflibercept injections at 4-week intervals in patients with neovascular AMD showing an “insufficient anatomic response” to prior anti-VEGF therapy with ranibizumab or bevacizumab.

Methods

The retrospective analysis included 96 eyes that had received at least three intravitreal 0.5 mg ranibizumab or 1.25 mg bevacizumab injections over a period of no more than 4 months prior to switching to aflibercept. In addition, the selected eyes had to have evidence of persisting or increasing sub- or intraretinal fluid, observed in optical coherence tomography (OCT). All patients received a loading dose of three intravitreal 2 mg aflibercept injections at 4-week intervals. Evaluation included central retinal thickness (CRT) and maximum pigment epithelium (PED) height measured by spectral domain OCT and best-corrected visual acuity (BCVA) prior to the switch of therapy and 4 weeks after the third aflibercept injection.

Results

A significant reduction of mean CRT (?39 μm; p?p?p?=?0.061). The further analysis did not show any correlation of the change in CRT, maximum PED, and BCVA with the number of prior anti-VEGF treatments.

Conclusion

Retinal edema and PEDs regressed significantly after switching to aflibercept in patients insufficiently responding to prior therapy with ranibizumab or bevacizumab. No correlation could be found with regard to the number of prior treatments.     

The relationship between serum levels of angiogenin, bFGF, VEGF, and ocular involvement in patients with Behçet’s disease

Objectives

The aim of this study was to investigate the possible role of angiogenin, vascular endothelial growth factor, (VEGF) and basic fibroblast growth factor (bFGF) in the pathogenesis of BD.

Design and methods

Sixty-five patients with BD and 21 healthy control subjects were included in the study, and serum angiogenin, bFGF, and VEGF concentrations were measured by using in-vitro enzyme immunoassay (ELISA) kits according to the manufacturer’s instructions.

Results

The median serum angiogenin level was significantly higher in patients with BD (391.8; range:151.6–594.8 pg/ml) than controls (298.8; range:241.9–449.6 pg/ml) (p?=?0.001). The levels were similar in both ocular and non-ocular BD patients (p?=?0.537). The mean serum bFGF level was higher in patients with BD (38.8?±?12.3 pg/ml) than controls (33.2?±?11.3 pg/ml); the median serum VEGF level was also higher in BD patients (239.7; range:53–991.3 pg/ml) than controls (189.4; range:53.6–357.9 pg/ml). But these differences were not statistically significant. Serum bFGF and VEGF levels were also not different statistically in ocular and non-ocular Behçet’s patients. There was no statistically significant relationship between serum angiogenin, bFGF, and VEGF levels and the presence of active eye disease or anatomic location of uveitis. While there was a correlation of borderline significance in angiogenin levels between the patients with anterior uveitis and panuveitis (p?=?0.053), we did not obtain any correlation between serum angiogenin, bFGF, and VEGF levels and the duration of BD.

Conclusions

This study suggests that angiogenin may be associated with pathophysiology of BD, and highlights the need of further investigation of the role of angiogenin, bFGF, and VEGF serum levels in BD susceptibility and its clinical manifestations.     

Predictive value of VEGF A and VEGFR2 polymorphisms in the response to intravitreal ranibizumab treatment for wet AMD

Background

To determine whether gene polymorphisms of the vascular endothelial growth factor A (VEGF A) and its receptor (VEGFR) influence the response to a variable-dosing treatment regimen with ranibizumab for age-related macular degeneration.

Methods

This prospective cohort study included 94 patients (94 eyes) with exudative age-related macular degeneration (AMD) treated with ranibizumab. Patients underwent a 1-year treatment as in the Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration (SUSTAIN). Injections were administered monthly during 3 months to all the patients diagnosed of neovascular AMD; reinjections were made when a patient lost 5 letters on the Early Treatment Diabetic Retinopathy Study chart or gained 100 μm in central subfield retinal thickness measured by OCT. Genotypes (VEGF A (rs 699947, rs833061) and VEGFR (rs 2071559)) were analyzed using TaqMan probes. Best-corrected visual acuity (BCVA), subjective improvement, and macular thickness measured with OCT values were compared with VEGF A and VEGFR genotypes. Multiple regression analysis was used to assess the statistical significance.

Results

We found statistically significant differences in allelic distribution of VEGF A rs833061 polymorphism in relation with the response to intravitreal ranibizumab regarding to visual acuity improvement [p?=?0,.34; OR: 1.619 (1.098–2.386)]. Patients carrying “protector” genotype CC had higher probability of best corrected visual acuity improvement. When we analyzed VEGF A rs699947 polymorphism we found that patients expressing AA genotype had a higher chance of increasing their best corrected visual acuity [p:0,022; OR 1,532 (1,015–2,313)]. We did not find statistically significant differences reagarding VEGFR rs2071559 polymorphism and treatment response.

Conclusions

Polymorphisms of VEGF A seem to influence the different response to antiangiogenic treatment in patients with AMD in our population, although further investigation is needed to know the mechanisms of this relationship.     

Increased intravitreous interleukin-18 correlated to vascular endothelial growth factor in patients with active proliferative diabetic retinopathy

Purpose

To determine the intravitreous levels of interleukin-18 (IL-18) and vascular endothelial growth factor (VEGF) in patients with proliferative diabetic retinopathy (PDR) and to ascertain their association with PDR activity.

Methods

Thirty eyes of 30 diabetic patients with PDR were divided into two groups (active PDR, n?=?17; quiescent PDR, n?=?13). Fifteen eyes of 15 non-diabetic patients (macular hole, n?=?9; epiretinal membrane, n?=?6) served as controls. All vitreous fluid samples were obtained during vitrectomy. IL-18 and VEGF were measured by enzyme-linked immunosorbent assay. Serum glycosylated hemoglobin as well as the basic demographic data was documented.

Results

Both IL-18 and VEGF levels were higher in patients with PDR than control (P?<?0 .01 and P?<?0 .01, respectively). Both IL-18 and VEGF in active PDR were higher than those in quiescent PDR (P?=?0.048 and P?=?0.03, respectively). A significant positive correlation (Spearman rank correlation coefficient (r _s)?=?0.502, P?=?0.005) between IL-18 and VEGF was observed in all PDR patients but not in the control. The correlation between VEGF and IL-18 was even stronger in the subgroup of active PDR (r _s?=?0.684; P?=?0.002), whereas no significant correlation was found in the subgroup of quiescent PDR (r _s?=?0.049; P?=?0.873).

Conclusions

Both intravitreous IL-18 and VEGF were elevated in patients with PDR, which were closely correlated in active PDR. IL-18 may contribute to retinal angiogenesis by acting together with or via VEGF, and become the potential therapeutic target for treatment of PDR.     

Two-year results of combined intravitreal ranibizumab and photodynamic therapy for polypoidal choroidal vasculopathy

Background

To clarify the efficacy of combined therapy with intravitreal ranibizumab injections and photodynamic therapy (PDT) in patients with symptomatic polypoidal choroidal vasculopathy (PCV).

Methods

We retrospectively reviewed 57 treatment-naïve eyes of 57 patients. Thirty-two patients were treated with standard fluence PDT (PDT group), and 25 patients were treated with three consecutive monthly intravitreal injections of ranibizumab and standard fluence PDT (ranibizumab plus PDT group). All patients were followed for at least 24 months.

Results

In the ranibizumab plus PDT group, the mean best-corrected visual acuity (BCVA) levels of decimal (logMAR equivalent) significantly improved from 0.30 (0.52) at baseline to 0.55 (0.26) at 24 months (P?<?0.001). In the PDT group, the BCVA levels stabilized from 0.26 (0.58) at baseline to 0.25 (0.60) at 24 months. The mean changes in the BCVA in the ranibizumab plus PDT group and the PDT group were improvement of 2.63 lines and decline of 0.16 lines respectively (P?=?0.010). The mean number of PDTs at 24 months in the ranibizumab plus PDT group and the PDT group were 1.4 and 2.6 respectively. Increased subretinal hemorrhages were seen in eight (18.0 %) eyes, all of which were belonging to the PDT group.

Conclusions

Combined intravitreal ranibizumab and PDT was significantly more effective in maintaining and improving VA for PCV patients compared with PDT monotherapy over 24 months.     

Anti-angiogenic effect of KH902 on retinal neovascularization

Purpose

KH902 is a fusion protein derived from the extracellular domains of vascular endothelial growth factor (VEGF) receptors 1 and 2 and the Fc portion of immunoglobulin G1 (IgG1). Retinopathy of prematurity (ROP) is an eye disease that affects premature babies who have received intensive neonatal care, and the disorganization of retinal blood vessels may result in scarring and retinal detachment. This study was designed to examine the inhibitory effects of KH902 on mice with oxygen-induced retinopathy (OIR), one of the animal models of ROP.

Methods

Human umbilical vein endothelial cells (HUVECs) were used for an in vitro study, and the C57BL/6 J OIR mouse model was used for an in vivo study. HUVECs were incubated with KH902 or a VEGF- and KH902-containing medium. Cell proliferation, migration, apoptosis, and tube formation were measured with BrdU incorporation, Transwell, flow cytometry, and Matrigel assays. C57BL/6 J mice were exposed to 75 % oxygen from postnatal day 7 (P7) to P12, after which the mice were brought to room air and intravitreously injected with KH902. At P18, the mice were perfused with fluorescein isothiocyanate (FITC)-dextran and Evans Blue, and flat-mounted retinas were used to measure the non-perfused and leakage areas. The data were analyzed with GraphPad Prism 5.0 software.

Results

In vitro, KH902 dose-dependently inhibited HUVEC proliferation in general culture medium and in VEGF₁₆₅-containing medium at different time points. Moreover, KH902 inhibited HUVEC migration and tube formation and induced HUVEC apoptosis. In vivo, an intravitreous injection of KH902 reduced the retinal non-perfused area from 34 % in the control group to 19 % in the treatment group and significantly reduced the retinal leakage area from 18 % to 9 %.

Conclusion

KH902 had marked inhibitory effects on angiogenesis both in vitro and in vivo. These data suggest that KH902 could serve as an innovative pharmaceutical agent to prevent retinal neovascularization (NV) and as a strategy for the treatment of ROP.     

Effects of vitreomacular adhesion on ranibizumab treatment in Japanese patients with age-related macular degeneration

Purpose

To investigate the effects of vitreomacular adhesion (VMA) on intravitreal ranibizumab treatment in Japanese patients with exudative age-related macular degeneration (AMD).

Methods

This was a retrospective comparative study that included 123 eyes from 123 patients with exudative AMD. The presence or absence of VMA was examined by spectral domain optical coherence tomography. The association of VMA with best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 3, 6, and 12 months after ranibizumab treatment was evaluated.

Results

In the group of eyes without VMA [VMA(?)], the mean BCVA was 0.41 logMAR at baseline and significantly improved to 0.28, 0.30, and 0.29 logMAR at 3, 6, and 12 months following the initiation of treatment (P < 0.0001, <0.0001, <0.0001), respectively. In the group of eyes with VMA [VMA(+)], the mean BCVA was 0.42 logMAR at baseline, and there was no improvement at any of the measurement time-points during the follow-up period [0.39, 0.40, and 0.39 logMAR at 3, 6, and 12 months (P = 0.53, 0.75, 0.67), respectively]. The mean baseline CRT in the VMA(?) and VMA(+) groups was 326 and 370 µm, respectively, decreasing to 195 and 293 µm (P < 0.0001 and P = 0.0070), respectively, at 12 months. A better baseline BCVA was associated with poor visual response to intravitreal ranibizumab.

Conclusions

Our study of Japanese patients with AMD managed in real-world clinical practice revealed that both VMA and BCVA at baseline were associated with a poor visual response to intravitreal ranibizumab. These results are in agreement with previously reported findings for other ethnic groups.     

Two-year results of combined intravitreal anti-VEGF agents and photodynamic therapy for retinal angiomatous proliferation

Purpose

To clarify the efficacy of a combination of intravitreal anti-vascular endothelial growth factor (VEGF) injections and photodynamic therapy (PDT), over 24 months, for patients with symptomatic retinal angiomatous proliferation (RAP).

Methods

We retrospectively reviewed 13 treatment-naïve eyes of 12 patients (7 men, 5 women; age range (mean), 63–92 (77) years) treated with intravitreal bevacizumab (IVB) plus PDT as initial treatment. Retreatment was performed with IVB plus PDT until February 2009 or intravitreal ranibizumab and PDT from March 2009.

Results

Mean best-corrected visual acuity (BCVA) significantly improved from 0.26 at baseline to 0.40 at 24 months (P = 0.013). The mean improvement in BCVA at 24 months from baseline was 1.79 lines. The central retinal thickness decreased significantly from 431 to 142 microns at 24 months (P < 0.0001). Complete occlusion of the retinal–retinal anastomosis was achieved in seven of the 10 eyes at 24 months. The mean number of PDT treatments during 24 months was 2.8 and the mean number of injections was 3.4. Geographic atrophy was seen in four eyes without significant decline of VA at 24 months.

Conclusion

Combined anti-VEGF and PDT for RAP patients effectively maintained or improved VA and reduced exudation, without severe adverse events, over 24 months.     

Growth factor combinations modulate human retinal pigment epithelial cell proliferation

PURPOSE: Retinal pigment epithelial (RPE) cell proliferation is an important step in the pathogenesis of ocular diseases such as proliferative retinopathy. Growth factors play a major role in modulating the development and progression of these diseases. The aim of this study was to examine the effects of single growth factors as compared to growth factor combinations on the stimulation of RPE cell proliferation. METHODS: Human RPE cells were treated with 10 ng/ml IGF-1, PDGF, bFGF, EGF, VEGF, and TGFbeta(2), or with the combination of each of the growth factors. RPE cell proliferation was determined by [(3)H]-thymidine incorporation after growth factor stimulation for 24 hr. RESULTS: RPE cell proliferation was significantly increased when PDGF and bFGF were combined as compared to the single growth factor (p<0.005). There was a decrease in DNA synthesis for combined growth factors as compared to the single growth factor for IGF-1 plus TGFbeta(2) (p<0.05), IGF-1 plus VEGF (p<0.005), PDGF plus TGFbeta(2) (p<0.005), VEGF plus TGFbeta(2) (p<0.005 as compared to VEGF), and bFGF plus TGFbeta( 2) (p = 0.01 as compared to bFGF). The remaining growth factor combinations showed no significant synergistic effect on human RPE cell proliferation. CONCLUSIONS: These data lead to the implication that DNA synthesis in human RPE cell culture is synergistically affected by certain growth factor combinations, but not by all of them. This observation may be important for a better understanding of growth factor interactions occuring in proliferative diseases in the eye.     

Hyperthermia-induced upregulation of vascular endothelial growth factor in retinal pigment epithelial cells is regulated by mitogen-activated protein kinases

Purpose

Localized application of hyperthermia is a potential treatment for retinal diseases. Vascular endothelial growth factor (VEGF) derived from the retinal pigment epithelium (RPE) is implicated in a variety of retinal pathologies. As it has been recently shown that hyperthermia may induce VEGF in the RPE, the aim of this study was to investigate hyperthermia-induced VEGF secretion and the pathways of hyperthermal VEGF upregulation in the RPE.

Material and methods

The human RPE cell line (Arpe-19) was exposed to 40°, 42°, 45° and 50 °C for one, five and 15 min. Cell viability was evaluated using a trypan blue exclusion assay, VEGF secretion was evaluated by an enzyme-linked immunosorbent assay ELISA) and VEGF expression was investigated using a Western blot. Involvement of mitogen-activated protein kinase (MAPK) pathways (ERK1/2, JNK, p38) and transient receptor potential vanilloid (TRPV) channels on VEGF induction was investigated using commercially available inhibitors (U0126, SB203580, SP600125, ruthenium red). Expression and phosphorylation of MAPKs was investigated using a Western blot.

Results

Hyperthermia induces time- and temperature-dependent cell death in human RPE cells. VEGF expression and secretion is induced by hyperthermia in a time- and temperature-dependent manner mediated by p38 and to a lesser degree by JNK. TRPV channels seem to play a minor role in regulation of hyperthermia-induced VEGF secretion.

Conclusions

Hyperthermia induces temperature-dependent secretion of VEGF in the RPE, which is mediated by p38 and, to a lesser extent, JNK. This may lead to undesired effects from hyperthermal treatment of retinal diseases.     

Comparison between ranibizumab and aflibercept for macular edema associated with central retinal vein occlusion

Purpose

We compared the efficacy of bimonthly intravitreal injections of ranibizumab (IVR) with that of bimonthly intravitreal injections of aflibercept (IVA) in two prospective, consecutive groups of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).

Patients and Methods

Eyes with ME after CRVO received either bimonthly IVR (ranibizumab group; n = 13) or IVA (aflibercept group; n = 13) injections and were followed monthly for 6 months. Three patients in the ranibizumab group and two in the aflibercept group were lost to follow-up and excluded from the study. The best-corrected visual acuity (BCVA), central foveal thickness (CFT) on optical coherence tomography, and aqueous vascular endothelial growth factor (VEGF) concentrations were evaluated before and after treatment.

Results

From baseline to month 6, significant improvements occurred in mean logMAR BCVA (ranibizumab group: 0.78–0.47; p < 0.05; aflibercept group: 0.74–0.54; p < 0.05) and mean CFT (ranibizumab group: 685–311 µm; p < 0.05; aflibercept group: 695–230 µm; p < 0.05). Fluctuations in CFT were seen at months 2, 4, and 6 in the ranibizumab group. Mean aqueous VEGF concentration decreased from baseline to month 2 in the ranibizumab group (509.9–348.2 pg/ml) and aflibercept group (412.1 pg/ml to undetectable limits in eight of 11 eyes and to 13.6, 15.6, and 24.1 pg/ml in the other three eyes, respectively).

Conclusions

There was no significant improvement of visual acuity in one group compared with another; VEGF may not be completely neutralized by bimonthly injections of ranibizumab.

     

Patterns of ranibizumab and aflibercept treatment of central retinal vein occlusion in routine clinical practice in the USA

Background

The intravitreal anti-vascular endothelial growth factor treatments ranibizumab and aflibercept have proven efficacy in clinical trials, but their real world usage in central retinal vein occlusion (CRVO) has not been assessed. We therefore evaluated the treatment patterns of both drugs in a US claims database.

Methods

The IMS Integrated Data Warehouse was used to identify the patients with CRVO in the USA with claims for ranibizumab or aflibercept between 24 September 2012 and 31 March 2014 with at least 12 months follow-up. Patients were required to have had no anti-VEGF treatment code for 6 months before index (‘treatment-naive''). Mean numbers of injections and non-injection visits to a treating physician were compared with patients receiving these treatments.

Results

Patient characteristics were similar for patients receiving ranibizumab (n=206) or aflibercept (n=79) at index. The mean (±SD) numbers of injections received by patients treated with ranibizumab or aflibercept were 4.4±2.8 and 4.7±2.9 (P=0.38), respectively; the total number of patient visits to their treating physician was 7.3±3.7 and 7.0±2.9 (P=0.52), respectively. For patients receiving one or more injections (n=238), the mean interval between injections was 55.1 days (ranibizumab) and 54.2 days (aflibercept; P=0.44).

Conclusions

Our results suggest that, in routine clinical practice, patients receive a comparable number of injections in the first year of treatment with ranibizumab or aflibercept. This may have implications for commissioning and service development of CRVO care pathways.     

Influence of seasonal sunlight intensity and iris color on the anti-VEGF therapy for neovascular age-related macular degeneration

Purpose

To investigate the influence of seasonal light intensity and patients'' iris color on the visual recovery after anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD).

Methods

The visual acuity of 555 eyes (529 patients) with neovascular AMD was evaluated after intravitreal injections of either ranibizumab or bevacizumab in respect to global radiation intensity and iris color.

Results

The functional results during anti-VEGF therapy revealed a seasonal oscillation with a negative correlation between visual recovery and global radiation intensity (R²=−0.756, P=0.004). Although the influence of the sunlight intensity on the visual recovery was significant after the first injection, this effect vanished within the continuous course of treatment. Regarding the improvement of functional recovery depending on iris color, dark-colored eyes (16.0%) gained 8.5±10.0 letters after the first injection and 9.9±12.8 letters after the second injection, compared with 3.4±8.6 letters and 4.4±11.0 letters in light-colored eyes (84.0%), respectively (P=0.005 and P=0.019).

Conclusions

Our results indicate that seasonal sunlight intensity and iris color might influence the visual recovery of neovascular AMD patients undergoing anti-VEGF therapy. Our findings may be used as suggestions to refine individual anti-VEGF therapy regimens, especially in patients with light-colored eyes.     

Ranibizumab treatment administered as needed for occult and minimally classic neovascular membranes in age-related macular degeneration

Purpose

To report the clinical experience of intravitreal ranibizumab administered as needed for the treatment of neovascular age-related macular degeneration (AMD).

Methods

We retrospectively reviewed the charts of 41 patients (41 eyes) with occult and minimally classic neovascular membrane in AMD. Patients received intravitreal injections (0.5 mg) of ranibizumab and were monitored monthly for 12 months. Forty-one eyes were retreated at the discretion of the treating physician on an as-needed basis after the first injection, instead of initially giving three monthly injections. The main outcomes measured were change in mean visual acuity and central retinal thickness, and the total number of injections received by patients during the 12 months.

Results

At 12 months, the mean logarithm of the minimum angle of resolution (logMAR) visual acuity improved by 0.078 logMAR units (P = 0.046) and the mean central retinal thickness decreased by 85.7 ??m (P < 0.001). Thirty of 41 eyes (73.2%) avoided any loss of vision, and 20 eyes (48.8 %) showed improved visual acuity. A mean of 4.07 injections were given over the 12 months.

Conclusions

Ranibizumab administered on an as-needed basis may stabilize visual acuity in patients with neovascular AMD.