Endothelial Growth Factor Agents Research Articles

Risk of dialysis in patients receiving intravitreal anti-vascular endothelial growth factor treatment: a population-based cohort study.

We utilized the Longitudinal Health Insurance Database which was stemmed from the Taiwan's National Health Insurance Research Database to conduct a retrospective cohort study investigating the risk of becoming dialysis dependent after receiving intravitreal anti-vascular endothelial growth factor (VEGF) agents for retinal diseases. Patients newly receiving intravitreal ranibizumab or aflibercept from 2000 to 2017 for age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic macular edema, retinal vein occlusions, or myopic choroid neovascularization were included as the study group, and patients with same retinal diseases but did not receive intravitreal anti-VEGFs served as controls extracted by age- and sex-matched (1:4) and further propensity score matching (PSM). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the risk of dialysis. A cohort of 2447 anti-VEGF users and 2447 controls by PSM were evaluated. Higher dialysis risks were observed among patients newly receiving anti-VEGF agents compared to controls (adjusted HR: 1.849; 95% CI: 1.378–2.482) in the PSM cohort. For subgroup analysis, patients newly receiving anti-VEGF treatment for diabetic macular edema had significant risk (adjusted HR: 1.834; 95% CI: 1.448–2.324) of becoming dialysis-dependent, while patients in other subgroups demonstrated similar risks as the controls. In conclusion, intravitreal anti-VEGF agents might increase the risk of becoming dialysis-dependent, especially in patients who are treated for diabetic macular edema.

Short-term changes in retinal and choroidal relative flow volume after anti-VEGF treatment for neovascular age-related macular degeneration

The effects of anti-vascular endothelial growth factor (anti-VEGF) agents on the native ocular vasculature are poorly understood. This pilot study aimed to assess short-term changes in retinal and choroidal perfusion after anti-VEGF treatment for neovascular exudative age-related macular degeneration (nAMD) using the relative flow volume (RFV) parameter derived from laser speckle flowgraphy. Ten treatment-naïve nAMD patients underwent measurements of mean, maximum, minimum, and differential RFV within a retinal arteriolar segment and a choroidal vessel segment outside the neovascular area. Measurement of retinal RFV (rRFV), choroidal RFV (cRFV), and subfoveal choroidal thickness (SCT) was repeated 9 and 35 days after a single anti-VEGF injection. The treatment caused a statistically significant decrease in the mean rRFV, mean cRFV, and SCT during the follow-up (p < 0.05). At the intermediate visit, the mean cRFV and SCT were − 17.6% and − 6.4% compared to baseline, respectively. However, at the final measurement, the mean cRFV was not different from the baseline value, which indicated waning of the anti-VEGF effect. In conclusion, a single anti-VEGF injection in treatment-naïve nAMD resulted in a decrease in retinal arteriolar and choroidal perfusion, according to the RFV parameter, which is a promising tool to simultaneously assess retinal and choroidal perfusion changes in response to anti-VEGF therapy.

Emerging Treatment Modalities for Neovascular Age-Related Macular Degeneration: A Systematic Overview.

Neovascular age-related macular degeneration (nAMD) represents a leading cause of irreversible visual loss affecting the quality of life of millions of elderly patients worldwide. Although the introduction of intravitreal injections with anti-vascular endothelial growth factors (anti-VEGF) agents has revolutionized the management of nAMD, their effectiveness and ultimate success are limited by several therapeutic challenges. Consequently, real-world efficacy appears significantly inferior to that reported by randomized controlled trials. Therefore, further innovative, long-term treatment options are essential to improve the prognosis and outcome of nAMD therapy. Emerging pharmacological therapies for nAMD and those currently in clinical trials are reviewed and their mechanism of action, safety, and efficacy are discussed. The evidence presented herein has been collected from online databases PubMed, Cochrane library, and the ClinicalTrials.gov site. A number of promising technologies and novel anti-VEGF therapies are currently being tested and some have already reached phaseIII trials. Anti-VEGF agents with enhanced durability and possibly efficacy, gene therapy, angiogenic targets, alternative drug delivery routes such as sustained delivery implants, drug carriers, and encapsulated cell technology are currently being explored. We briefly discuss the potential value of these options. Several options may optimize future nAMD management. On the basis of current, albeit limited evidence, the most promising technology to reach clinical practice soon appears to be the sustained drug delivery options, which may improve visual outcome and reduce the socioeconomic burden of nAMD.

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

PurposeThe 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.MethodsThis 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).ResultsThe 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).ConclusionMERCURY 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.

Analyses of the effects of persistent subretinal fluid on visual/anatomic outcomes according to the type of macular neovascularization during the relaxed treat-and-extend protocol in age-related macular degeneration patients

BackgroundTo analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients.MethodsPatients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type.ResultsSeventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type.ConclusionsUsing a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

Neovascular age-related macular degeneration: A review of findings from the real-world Fight Retinal Blindness! registry.

The use of vascular endothelial growth factor (VEGF) inhibitors has revolutionised the treatment of neovascular age‐related macular degeneration (nAMD) since the pivotal Phase III studies demonstrated their efficacy more than 10 years ago. The Fight Retinal Blindness! project was developed to track the treatment outcomes of patients with nAMD in real‐world practice. Data from this registry have been used to answer several clinically relevant questions related to the treatment of nAMD including the effect of under‐treatment, the comparative effectiveness of different anti‐vascular endothelial growth factor agents, long‐term treatment outcomes, identifying optimal treatment regimens and the rate and outcomes of rare adverse events. Observational studies are a valuable complement to the shortcomings of clinical trials and a combination of data from real‐world settings and clinical trials are necessary to provide evidence on how to achieve the best outcomes for individual patients with nAMD.

Ranibizumab for the treatment of diabetic retinopathy

ABSTRACT Introduction: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus and the leading cause of blindness in young adults. Prior to anti-vascular endothelial growth factor (anti-VEGF) agents, the treatment of DR was based on control of systemic factors and laser photocoagulation. Over the past decade, the use of anti-VEGF agents has revolutionized the treatment of DR, including diabetic macular edema (DME). Areas covered: Ranibizumab has been proven to be effective for the treatment of DME in large clinical trials, while patients in these studies have been assessed in terms of DR severity change. In this review, evidence from randomized trials regarding the use of ranibizumab for DR treatment is presented. Expert opinion: A comprehensive presentation of randomized clinical trials evaluating ranibizumab for DR indicates that it is effective and safe, offering improvement of DR severity in both non-proliferative and proliferative forms. However, there is no general consensus regarding the exact treatment regimen in patients with DR, while the effect of ranibizumab on the progression of retinal ischemia remains unclear.

Retinal venous pressure is decreased after anti-VEGF therapy in patients with retinal vein occlusion\u2013related macular edema

PurposeThe pathomechanism leading to retinal vein occlusion (RVO) is unclear. Mechanical compression, thrombosis, and functional contractions of veins are discussed as the reasons for the increased resistance of venous outflow. We evaluated changes in the retinal venous pressure (RVP) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent to determine the effect on RVO-related macular edema.MethodsTwenty-six patients with RVO-related macular edema (16 branch RVOs [BRVOs] and 10 central RVOs [CRVOs], age 72.5 ± 8.8 years) who visited our hospital were included in this prospective study. Visual acuity (VA), intraocular pressure (IOP), central retinal thickness (CRT) determined by macular optical coherence tomography, and RVP measured using an ophthalmodynamometer were obtained before intravitreal injection of ranibizumab (IVR) and 1 month later.ResultsComparison of the BRVOs and CRVOs showed that VA was significantly improved by a single injection in BRVOs (P < 0.0001; P = 0.1087 for CRVOs), but CRT and RVP were significantly decreased without significant difference in IOP after the treatment in both groups (P < 0.0001).ConclusionThe anti-VEGF treatment resulted in a significant decrease in the RVP, but the RVP remained significantly higher than the IOP. An increased RVP plays a decisive role in the formation of macula edema, and reducing it is desirable.

Predictors of persistent disease activity following anti-VEGF loading dose for nAMD patients in Singapore: the DIALS study

BackgroundTo determine the frequency of persistent disease activity following 3 loading doses of anti- vascular endothelial growth factor (VEGF) agents, and the anatomic and demographic predictors of early persistent disease activity among patients with neovascular age-related macular degeneration (nAMD).MethodsIn a retrospective real-world cohort study, 281 consecutive patients with nAMD were reviewed at baseline and after 3 anti-VEGF injections for pre-defined indicators of disease activity. Optical coherence tomography (OCT) features such as subretinal fluid, intraretinal cysts and intraretinal fluid were assessed by reading-center certified graders. Multiple logistic regression was performed on demographic and anatomic factors.ResultsAt month 3, 66.1% of patients had persistent disease activity. The best-corrected visual acuity (BCVA) improvement was 0.16 LogMAR for those with no disease activity compared to 0 for patients with persistent activity (p < 0.001). The significant risk factors for persistent activity at 3 months were male gender (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32–0.93, p = 0.025), intraretinal cysts at baseline (OR 2.95, 95% CI 1.67–5.20, p < 0.001) and subretinal fluid at baseline (OR 3.17, 95% CI 1.62–6.18, p = 0.002). At 3 months, 58% of patients had features of activity on OCT. Patients with intraretinal cysts and intraretinal fluid at baseline had worse BCVA at month 3 compared to patients without these OCT features (0.69 vs. 0.43, p < 0.001, and 0.62 vs. 0.43, p < 0.001, respectively).ConclusionsIn a real-world study, 66.1% of nAMD patients have persistent disease activity after the initial loading dose, with poorer BCVA compared to those without. Baseline OCT features (intraretinal cysts and subretinal fluid) are useful predictors of persistent disease activity at month 3.

Brolucizumab: an evolution in treatment for neovascular age-related macular degeneration

ABSTRACTIntroduction: The treatment paradigm for neovascular age-related macular degeneration (nAMD) has had a profound shift over the past 15 years with the advent of anti-vascular endothelial growth factor (VEGF) agents. However, the ability to sustain optimal visual outcomes is challenging with disease chronicity and treatment burden. Brolucizumab, a single-chain antibody fragment targeting all isoforms of VEGF, is a new molecule with properties that allow for less frequent doses of anti-VEGF to be administered with low systemic exposure.Areas covered: The authors will provide a comprehensive review of the current literature and clinical trial data surrounding brolucizumab in the treatment of nAMD, while comparing it with other emerging therapies.Expert opinion: Brolucizumab is a novel anti-VEGF inhibitor, with Phase I, II, and III trial data indicating safety, tolerability, and efficacy for the treatment of nAMD when given 12-weekly. Precision dosing with brolicizumab may best achieve the opportunity for vision improvement and maintenance of vision gains, while potentially maintaining patients on manageable dosing intervals with disease stability, improved treatment adherence, and reduced burden.

Intraocular pharmacokinetics of anti-vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil-filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study.

Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5mg/0.05ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6months postoperatively. The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p<0.05). With the same drug dose, subretinal injection (5.49±6.11μg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42±0.46μg/ml, p=0.001) 4weeks after the treatment. The mean residence time last (MRT0-t ) by subretinal injection (11.57±0.83days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10±1.00days, p<0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6months postoperatively (p=0.028) while the BCVA did not improve significantly by intravitreal injection (p=0.715). The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.

P4568Effect of intravitreal anti-vascular endothelial growth factor therapy on aortic stiffness and serum interleukin-6 levels in hypertensive patients with age-related macular degeneration

Abstract Purpose Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults over 65 years old and it is associated with moderate to severe arterial hypertension and increased aortic stiffness. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, can reverse the symptoms of neovascular (wet) AMD. We sought to investigate whether intravitreal anti-VEGF therapy may influence aortic elastic properties of hypertensive patients with AMD. Methods 54 hypertensive patients with exudative (“wet”) AMD received intravitreal ranibizumab (0.5mg) and blood pressure (BP) and carotid-femoral pulse wave velocity (PWV) were measured at baseline (approximately 2 days before the first injection), 24 h after the first and second injection (time interval between the injections: 1 month) and 1 month after the second injection. Serum levels of high sensitivity interleukin-6 (hsIL-6) were measured at three time points (baseline, first injection, 1 month after the second injection). Results Systolic BP decreased by 3.2 mmHg and by 3.0 mmHg after the first and second injection respectively and remained decreased (by 2.6 mmHg) 1 month after the second injection (overall p=0.07, by ANOVA). The changes in diastolic BP were minimal (overall p=0.74). Ranibizumab injection caused a significant decrease of PWV after the first (by 0.34 m/s) and the second injection (by 0.31 m/s). Furthermore, as upper figure shows, PWV remained decreased 1 month after the second injection. Among the treated naïve eyes, 45 (83%) had a good response to ranibizumab while 9 (17%) were poor responders. Interestingly, PWV decreased significantly in good responders to AMD therapy (overall p=0.004) whereas, it increased in poor responders (overall p=0.21) over the study period. In responders to therapy serum hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 pg/ml, overall p=0.02, lower figure). The levels of hsIL-6 increased in poor responders (overall p=0.54). Ranibizumab, PWV and serum hsIL-6 levels Conclusions This is the first study showing that intravitreal administration of ranibizumab, a anti-VEGF used for improvement of wet AMD was associated with a beneficial acute and mid-term systematic effect on aortic elastic properties. Changes in systemic inflammatory activation may be involved. The findings have important implications for assessing the effect of anti-VEGF interventions on cardiovascular performance in hypertensive patients with exudative AMD.

Utilization of Apatinib-Loaded Nanoparticles for the Treatment of Ocular Neovascularization.

The current treatment of ocular neovascularization requires frequent intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents that cause severe side effects. The purpose of this study is to prepare and characterize a novel nanoscale delivery system of apatinib for ocular neovascularization. The optimized formulation showed a particle size of 135.04 nm, polydispersity index (PDI) of 0.28 ± 0.07, encapsulation efficiency (EE) of 65.92%, zeta potential (ZP) of -23.70 ± 8.69 mV, and pH of 6.49 ± 0.20. In vitro release was carried out to demonstrate a 3.13-fold increase in the sustainability of apatinib-loaded nanoparticles versus free apatinib solution. Cell viability and VEGFA and VEGFR2 expression were analyzed in animal retinal pigment epithelial (ARPE-19) cells. The results confirmed the hypothesis that apatinib nanoparticles decreased toxicity (1.36 ± 0.74 fold) and efficient VEGF inhibition (3.51 ± 0.02 fold) via VEGFR2 mediation.

An efficacy comparison of anti-vascular growth factor agents and laser photocoagulation in diabetic macular edema: a network meta-analysis incorporating individual patient-level data

BackgroundThis was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment.MethodsAn updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with ≥10 and ≥ 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network).ResultsThirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90–8.52 ETDRS letters), ≥15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12–4.20), and ≥10 ETDRS letter loss (OR 0.25, 95% CrI 0.05–0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26–10.61 ETDRS letters) (IPD and aggregate random-effects model).ConclusionsThis NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA.

The effect of ranibizumab and aflibercept treatment on the prevalence of outer retinal tubulation and its influence on retreatment in neovascular age-related macular degeneration

BackgroundWe aimed to analyze the differences in the prevalence of outer retinal tubulation (ORT) in neovascular age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents, either aflibercept or ranibizumab. Our further aim was to examine the changes in the frequency of injections of ranibizumab before and after ORT appearance.MethodsTwo hundred thirty six eyes of 230 patients were included in the study (184 eyes treated with ranibizumab by pro re nata regimen (PRN), 52 eyes with aflibercept bimonthly) and followed for 6–24 months. Using optical coherence tomography (OCT), the first appearance of ORT was documented, and fixed time point evaluations were also made every six months to determine the existence of ORT. The number of injections, the presence or absence of subretinal hyperreflective material (SHRM) at treatment initiation and visual acuity were also noted.ResultsThe survival analysis with Cox proportional hazard model showed no significant difference between the ranibizumab and aflibercept groups in relation to the development of ORT (p = 0.79, hazard ratio 0.92). In the PRN treated ranibizumab group the number of injections showed significant decrease after ORT development (p = 0.004). When SHRM was present at treatment initiation the chance of developing ORT was 2.75 and 11.14 times higher in the ranibizumab and aflibercept groups, respectively.ConclusionsThe prevalence of ORT increased over time independently from the chosen anti-VEGF drug. Our results suggest that upon the appearance of ORT a decrease in retreatments can be expected.

Long-term efficacy and safety of anti-VEGF therapy in retinitis pigmentosa: a case report

BackgroundRetinitis pigmentosa (RP), a neurodegenerative disease, is occasionally accompanied by choroidal neovascularization (CNV) and cystoid macular oedema. It is presently treated with repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. However, there are concerns regarding long-term inhibition of VEGF by the use of these agents, especially in cases involving neurodegenerative diseases, since VEGFs have a neuroprotective effect. Currently, there are no reports on the long-term safety of anti-VEGF therapy in patients with RP.Case presentationIn this report, we describe the case of a 56-year-old female patient with CNV associated with RP who was treated with anti-VEGF therapy for 8 years. She had autosomal dominant RP with a heterozygous PRPH2 mutation (c.410G > A) and complained of metamorphopsia in her left eye. Examinations revealed CNV with serous retinal detachment. She was treated with as-needed injections for 2 years; however, she experienced a recurrence. Therefore, we switched to a bimonthly regimen that was continued for 6 years. In total, the patient received 34 injections of various types of anti-VEGFs over 8 years. No recurrences were noted during that time, and we have not detected any negative effects concerning the progression of visual field loss in comparison with the fellow eye.ConclusionsNo negative effects related to the progression of visual field loss were observed during continuous treatment with anti-VEGF agents for 8 years in our patient.

The safety of trifluridine and tipiracil for the treatment of metastatic colorectal cancer

ABSTRACTIntroduction: TAS102 is an oral thymidine-based nucleoside analog that has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) previously treated with, or not candidates for, available therapies including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-vascular endothelial growth factor (VEGF) agents and, if RAS wild-type, anti-epidermal growth factor receptor (EGFR) therapy. The pivotal RECOURSE phase III trial demonstrated a significant improvement in disease control rate, progression-free survival (PFS), and overall survival (OS) as compared with placebo in patients with refractory mCRC.Areas covered: This manuscript aims to review the clinical development of TAS102 in CRC, with a particular focus on safety, and to provide some perspective regarding its role in clinical practice. A literature search was conducted of MEDLINE and EMBASE databases for published studies (January 2004–December 2016) using the search terms TAS102, trifluridine–tipiracil, metastatic or advanced CRC, clinical trial, toxicity, safety, pharmacology, pharmacokinetics, and therapy.Expert opinion: TAS102 significantly improves survival of patients with refractory mCRC and has manageable toxicity. An expanding role in the treatment of CRC is expected for TAS102 in the near future, as its favorable safety profile makes TAS102 a suitable drug to be combined with other cytotoxic and targeted agents.

Increasing rates for certification of visual impairment at Royal Cornwall Hospital Trust: An audit series

The audit series investigated how rates of Certification of Visual Impairment (CVI) at Royal Cornwall Hospital Trust (RCHT) performed when compared against Public Health England (PHE) indices. Our aim was to assess whether CVI rates could be improved by promoting clinician awareness. We collected CVI data for Sight Impairment (SI) and Severe Sight Impairment (SSI) from a prospective MS Excel database maintained at RCHT for all certifications between 1 August 2014 and 31 July 2016. Annual local certification rates were compared to regional and national rates using data from Public Health Outcomes Framework (PHOF) for glaucoma, age-related macular degeneration (ARMD), and diabetic eye disease. We found that overall rates of certification were above both those of the South West region and England; however, certifications for ARMD and glaucoma fell below the regional and national rates. Reasons for this may include variations in ethnicity, introduction of anti-vascular endothelial growth factor (anti-VEGF) agents, and/or the potential delay in CVI completion while under treatment for ARMD. We concluded that raising awareness among clinicians did not prove a satisfactory intervention to improve certification rates. In response to these findings, RCHT and a local charity, iSight Cornwall, have jointly funded an Eye Clinic Liaison Officer (ECLO) to enhance the certification process. This is expected to deliver immediate service improvement. Considerable overlap in dual diagnoses presents a problem in interpretation of CVI data, which could be targeted by the implementation of electronic certification.

Ranibizumab versus aflibercept for the treatment of vascularized pigment epithelium detachment due to age-related macular degeneration.

To compare the efficacy and safety of two intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, ranibizumab and aflibercept, for the treatment of vascularized pigment epithelium detachment (vPED) due to age-related macular degeneration (AMD) in a follow-up time of 12months. Participants in this study were 71 patients (71 eyes) with vPED due to AMD, who were treated with intravitreal 0.5mg ranibizumab (n=38) or 2.0mg aflibercept (n=33) and had at least 12-month follow-up. All patients underwent best-corrected visual acuity (BCVA) measurement and optical coherence tomography at baseline and at every visit. The PED height, the presence of subretinal fluid (SRF), intraretinal fluid and diffuse macular edema (DME) were recorded at each visit. There was a statistically significant difference in BCVA between the two groups at month 12 in favor of aflibercept. However, both agents were found to improve or stabilize BCVA in the majority of patients at the end of the follow-up. The change in PED height did not differ significantly between the two groups at the end of the follow-up with similar number of injections. At month 12, there was a significant improvement in SRF presence in both groups compared to baseline. Although aflibercept was found to be superior to ranibizumab regarding BCVA improvement, both agents showed anatomical effectiveness with significant reduction in PED height and SRF absorption in patients with vPED due to AMD.

Paying attention to the prognosis guiding effects of CNV dynamic changes based-OCT angiography in neovascular age-related macular degeneration after antiangiogenic therapy

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is a first line therapy for neovascular age-related macular degeneration (nAMD). However, how to predict the respond for anti-VEGF treatment is still a challenge in clinic practice.Optical coherence tomography angiography (OCTA) can offer dynamic following-up for choroidal neovascularization (CNV) in nAMD after antiangiogenic therapy.The change of vascular morphology based on OCTA enriches the novel theory of prognosis for tveatment of nAMD and can be considered as a biomarker of neovascularization in vivo, which can help us to evaluate the activity of CNV and understand the mechanism of anti-VEGF resistance.So, OCTA should be a standard strategy during the diagnosis, treatment and follow-up of nAMD.We should pay more attention to the guiding significance in the prognosis evaluation of nAMD basis on character of vascular morphology by OCTA following antiangiogenic therapy. Key words: Tomography, optical coherence; Age-related macular degeneration, neovascular/drug therapy; Choroidal neovascularization/drug therapy; Prognosis; Vascular endothelial growth factor; Optical coherence tomography angiography