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Purpose To report the 10-year outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors. Design Ten-year, retrospective cohort study. Participants A total of 1046 patients who commenced treatment with anti-VEGF for nAMD. Methods Anti-VEGF–naive eyes diagnosed with nAMD that commenced treatment between November 2006 and December 2009 were identified. Data collected included the baseline demographics, visual acuity (VA), and number of intravitreal injections. Baseline fundus fluorescein angiograms and OCT images were graded for choroidal neovascularization type. OCT images were graded for central macular thickness (CMT) and the presence of fluid over the 10 years. Main Outcome Measures Change in vision at 10 years. Secondary outcomes included the proportion of eyes with 20/40 vision or better and 20/200 or worse, the proportion of eyes that were dry on OCT imaging, and the number of injections. Results Of 1046 eligible eyes, 10-year data were available for 293 (28%), which were included in the analyses. Eyes received 58.1 (standard deviation [SD], 33.6) injections during the 10 years. The mean CMT decreased from 355.5 μm (SD, 107.8 μm) to 264.2 (SD, 79.5) μm (P Conclusions On average, eyes with nAMD maintained starting VA when treated with VEGF inhibitors for 10 years. With ongoing regular treatment, a greater proportion of eyes achieved VA of 20/40 or better at 10 years than at presentation.

Purpose To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro-re-nata (PRN) regimen over 4-years in a real-life setting. Design 4-year, multicenter, retrospective comparative study PARTICIPANTS: 264 patients with treatment-naive nAMD. Methods Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n=163) or PRN (n=101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4-years and had annual fundus autofluorescence (FAF) and optical coherence tomography (OCT) imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. Main outcomes measures MA incidence and progression over 4-years, association between treatment strategy, and number of injections. Results At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (p=0.32). At year-4, 27% (34/124) and 25% (20/81) eyes without baseline MA had detectable MA, in the T&E and PRN groups respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4±0.2 and 0.4±0.1mm/year in the T&E and PRN groups, respectively (p=0. 23). Multivariate analysis for baseline predictors of MA growth demonstrated older age, poorer baseline VA and presence of RAP, had a higher risk of greater MA progression (P=0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of developing new MA during the four years of follow-up or the progression of pre-existing MA at year-4 (p=0.692). Conclusion Over four years, neither incidence nor progression of macular atrophy in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and had better visual outcomes compared to those treated with a PRN approach.

Introduction: 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 fact...

Purpose: The aim of this study was to examine 12-month outcomes of eyes switched from intravitreal ranibizumab or bevacizumab to aflibercept for cystoid macular edema due to retinal vein occlusion (RVO). Design: Retrospective, observation, case series. Methods: A retrospective study was performed assessing eyes with RVO switched to aflibercept for at least 12 months. To be included in the study, eyes had to have macular edema despite treatment for at least 6 months with bevacizumab and/or ranibizumab before the switch, central foveal thickness (CFT) ≥300 μm at time of switch, and visual acuity (VA) ≤60 early treatment of diabetic retinopathy score (ETDRS) letters (20/40 Snellen equivalent). Outcome measures included change in VA (in ETDRS letters), CFT, and interval between intravitreal injections. Results: 27 eyes of 27 patients were included in the analysis: 13 with branch RVO, and 14 with central RVO. Mean VA before switch was 54.2 ± 23.7 letters (20/80 Snellen equivalent) and mean CFT was 460.4 ± 178.2 μm. Mean number of previous anti-vascular endothelial growth factor (VEGF) injections was 29.5 ± 19.2. At 12 months, mean VA improved by 8.7 ± 13.2 letters (P

Aim The incidence and prevalence of diabetes mellitus (DM) in Australia is increasing. Thus, it is essential that practitioners appreciate the impending effect that increasing incidence of diabetes has on patients and the wider community. Accordingly, this study examines the humanistic burden of intravitreal injections for the treatment of diabetic macular oedema (DMO) among several health variables. Methods Survey data from a representative sample of Australian adults undergoing treatment for DMO were examined. Respondents participated via an online survey recruited by means of a national online consumer panel and the New South Wales and Victorian Diabetes Foundations. The online survey included questions relating to the humanistic burden of disease, such as the emotional and physical impact of intravitreal injection therapy; the practical impacts of injection therapy; and to identify potential improvements to treatment regimens. Results Sixty-five participants took part in the online survey. Of these, 49% had their most recent injection

Purpose: The current body of evidence on the efficacy and safety of anti-VEGFs for macular oedema secondary to branch retinal vein occlusion (BRVO) is steadily growing as large clinical trials and observational studies are continually completed. The aim of this meta-analysis is to analyse anatomical and functional outcomes in response to anti-VEGF therapy using evidence generated from a pooled analysis of current clinical trials and observational studies. Methods: The current meta-analysis includes treatment of BRVO with aflibercept, bevacizumab and ranibizumab from randomised controlled trials and observational studies. Inclusion criteria included peer-reviewed publications with at least a 12-month follow-up period. On literature review using multiple electronic databases (PubMed, Embase and Cochrane), 22 studies met the inclusion criteria. Baseline patient characteristics, study design, sample size and 12- and 24-month change in best corrected visual acuity (BCVA) and central foveal thickness (CFT) as measured on optical coherence tomography imaging were pooled in a meta-analysis. Data were then stratified by study design and anti-VEGF therapy in subgroup analyses. Results: A total of 1,236 eyes from 22 studies were included in this meta-analysis. Mean baseline BCVA ranged from 66 ETDRS letters (20/50 Snellen equivalent) to 35 letters (20/200 Snellen). Mean baseline CFT ranged from 406.0 to 681.0 µm. Anti-VEGF treatment demonstrated an overall mean improvement in BCVA at 12 months of 14 letters (95% CI 12.0 to 16.2, p < 0.001) and CFT reduction of 228 µm (95% CI –278.9 to –176.1, p < 0.001). The BCVA gains at 12 months were maintained to month 24 with a mean gain of 12.5 letters (95% CI 6.3 to 18.8, p < 0.001), as well as reduction of CFT of 238 µm (95% CI –336.0 to –140.2, p < 0.001). No cases of endophthalmitis or glaucoma were reported in any study. Conclusion: This meta-analysis confirms the comparable safety and efficacy of anti-VEGF therapies for patients with cystoid macular oedema secondary to BRVO. There is a need for randomised prospective comparative trials of anti-VEGF agents for BRVO.

To investigate the reliability and comparability of retinal measurements obtained with spectral-domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), confocal scanning laser ophthalmoscopy (cSLO) colour images, and fundus autofluorescence (FAF) between two multimodal imaging platforms in eyes with macular pathology and normal, healthy volunteers. This cross-sectional, multi-centre, instrument validation study recruited 94 consecutive subjects. All participants underwent a dilated examination and were scanned consecutively on the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Nidek Mirante (Nidek Co. Ltd., Gamagori, Japan) devices. Agreement between device images were evaluated from measures of the central retinal thickness (CRT), presence of segmentation and fixation imaging artefacts (IA), foveal avascular zone (FAZ) measurements; as well as sensitivity and specificity values from the detection of atrophy on fundus autofluorescence (FAF), drusen, subretinal drusenoid deposits, geographic atrophy, epiretinal membrane, fibrosis and haemorrhage on multicolour imaging, and agreement between devices and groups. Compared with reference clinical examination, sensitivity values for the identification of retinal features using sole device images ranged from 100% for epiretinal membranes to 66.7% for subretinal drusenoid deposits (SSD). Mean absolute difference for CRT between OCT devices was 3.78 μm (95% confidence interval [CI]: − 21.39 to 28.95, P = 0.809). Differences in the superficial and deep capillary plexus FAZ area on OCTA between devices were not statistically significant (P = 0.881 and P = 0.595, respectively). IAs were significantly increased in the presence of macular pathology. Comparison of retinal measurements between the OCT devices did not differ significantly. Common ultrastructural biomarkers of multiple macular pathologies were identified with high sensitivities and specificities, with good agreement between graders, indicating that they can be identified with comparable confidence in retinal imaging between the two devices.

To report the 10-year outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors.Ten-year, retrospective cohort study.A total of 1046 patients who commenced treatment with anti-VEGF for nAMD.Anti-VEGF-naïve eyes diagnosed with nAMD that commenced treatment between November 2006 and December 2009 were identified. Data collected included the baseline demographics, visual acuity (VA), and number of intravitreal injections. Baseline fundus fluorescein angiograms and OCT images were graded for choroidal neovascularization type. OCT images were graded for central macular thickness (CMT) and the presence of fluid over the 10 years.Change in vision at 10 years. Secondary outcomes included the proportion of eyes with 20/40 vision or better and 20/200 or worse, the proportion of eyes that were dry on OCT imaging, and the number of injections.Of 1046 eligible eyes, 10-year data were available for 293 (28%), which were included in the analyses. Eyes received 58.1 (standard deviation [SD], 33.6) injections during the 10 years. The mean CMT decreased from 355.5 μm (SD, 107.8 μm) to 264.2 (SD, 79.5) μm (P0.001). The median baseline VA was 60 (interquartile range [IQR], 45-70) letters, which improved by 9 (IQR, 1-14) letters after the first year of treatment (P0.001). Over the 10-year period, these initial gains were lost over time with a final VA change of +3 letters (IQR, 8-10 letters, P = 0.162). However, the proportion of eyes with VA 20/40 or better increased from 29% at baseline to 35% at 10 years (P0.001). The proportion of eyes at baseline with VA 20/200 or worse was 14% and 17% at 10 years.On average, eyes with nAMD maintained starting VA when treated with VEGF inhibitors for 10 years. With ongoing regular treatment, a greater proportion of eyes achieved VA of 20/40 or better at 10 years than at presentation.

To systematically review anatomical and functional outcomes of switching therapy from bevacizumab and/or ranibizumab to aflibercept in patients with persistent macular oedema secondary to retinal vein occlusions (RVO). A systematic search of aflibercept for the treatment of persistent macular oedema secondary to branch and central RVO was performed in EMBASE, PubMed and Cochrane databases prior to June 2017. The main outcome variables described were best-corrected visual acuity (BCVA) and central macular thickness (CMT). All results were analysed and pooled using random-effects models with 95% confidence intervals (CI). Eight studies met the inclusion criteria with a total of 137 eyes, incorporating both branch and central RVO. Meta-analysis demonstrated a nonsignificant change in BCVA at 6 and 12 months following switch to aflibercept (4.40 letters, 95% CI: -3.10 to 11.90, p = 0.25 and 3.10 letters, 95% CI: -1.74 to 7.94, p = 0.21, respectively). Significant improvement in mean CMT was observed after switch to aflibercept at 6 (-256.00 μm, 95% CI: -318.00 to -194.00, p < 0.001) but not 12 months (-118.00 μm, 95% CI: -261.00 to 25.00, p = 0.11). Switching from bevacizumab/ranibizumab to aflibercept may improve persistent macular oedema secondary to RVO. However, there may be a limitation in the potential of visual recovery.

To prospectively assess correlations between self-reported vision-related quality of life (VR-QoL) and clinical functional assessments in mild/moderate age-related macular degeneration (AMD). Cross-sectional analysis of 64 participants with bilateral mild/moderate AMD. Microperimetry (MP), flicker perimetry (FP), multifocal electroretinogram (mfERG) findings, best-corrected visual acuity (BCVA) and the National Eye Institute Visual-Function Questionnaire-25 (NEI VFQ-25) were assessed for correlation between clinical testing results and NEI VFQ-25 findings. MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p

IMPORTANCE To examine the effect of switching from intravitreal bevacizumab or ranibizumab to aflibercept in eyes with persistent macular oedema due to retinal vein occlusion (RVO). BACKGROUND We report the results of a prospective interventional study on the effect of aflibercept 2 mg in eyes with persistent macular oedema after long-term treatment with bevacizumab or ranibizumab. DESIGN Non-randomized, prospective clinical trial. PARTICIPANTS Eighteen eyes of eighteen patients were included. METHODS Eyes with persistent macular oedema despite a minimum of four previous intravitreal bevacizumab/ranibizumab injections were recruited into this 48-week trial. Three loading doses of intravitreal aflibercept were administered every 4-weeks, thereafter every 8-weeks until week 48. MAIN OUTCOME MEASURES Mean change from baseline in best corrected visual acuity (BCVA) as measured by early treatment diabetic retinopathy score (ETDRS) and central macular thickness (CMT) as measured by spectral domain optical coherence tomography (SD-OCT) at 48 weeks. RESULTS Patients had received a mean of 40.0 ± 17.8 bevacizumab/ranibizumab intravitreal injections prior to switching to aflibercept. The mean number of previous injections administered in the 12-months preceding entry into the study was 10.2 ± 2.4. Mean vision change at week 48 was +21.1 ± 5.1 ETDRS letters in the BRVO group and +18.8 ± 5.9 letters at in the CRVO group (P

PURPOSE To evaluate the current anti-vascular endothelial growth factor (anti-VEGF) treatments for macular edema due to central retinal vein occlusions. METHODS PubMed, EMBASE, the Cochrane Library were systematically searched for studies between January 2013 and July 2018. Reference lists of published articles were searched and if necessary, authors were contacted to provide additional data. Meta-analysis was performed using Comprehensive Meta-analysis software. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), injection frequency, and adverse events were evaluated. RESULTS Seventeen studies involving 1070 eyes were included in the meta-analysis. The mean differences in 12-month changes in BCVA and CFT were 14.4 ETDRS letters (P < 0.001) and -289.2 μm (P < 0.001), respectively. Visual acuity gains were maintained at 24 months (14.2 letters, P < 0.001) and CFT continued to reduce (-327.45 μm, P < 0.001). The incidence of severe adverse events was low and similar across all anti-VEGF therapies. Prospective studies administered a greater number of injections compared with retrospective studies, being 6.6 and 4.4 injections, respectively over 12 months (P < 0.001). CONCLUSIONS Intravitreal treatment with anti-VEGF agents demonstrated significant anatomical and functional gains in treating macular edema due to central retinal vein occlusions.

To report 4-year outcomes following the switch to aflibercept in treatment-resistant neovascular age-related macular degeneration (nAMD).In this prospective, open-label, non-controlled, clinical trial, 49 patients with treatment-resistant nAMD received 2 mg intravitreal aflibercept as three loading doses every 4 weeks, followed by injections every 8 weeks for the first 48 weeks, then an individualized regimen for a further 36 months, following previous treatment with ranibizumab and/or bevacizumab. Outcome measures included best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height and geographic atrophy (GA) surface area.Of the 49 patients who were initially recruited, data from 39 eyes of 39 patients were available at 48-month follow-up. Mean age was 76.7 ± 7.2 years. Over the 48 months, these eyes received a mean of 32.1 ± 5.6 injections. The mean BCVA improved significantly following 12 months of treatment (4.9 ± 9.0 ETDRS letters, p 0.001); however, this was not maintained and was similar to baseline after 48 months (mean difference -0.4 ± 13.3 letters between baseline and 48 months, p 0.001). The reduction in CRT from baseline was 170.3 ± 143.3 μm (p 0.001) with absence of macular fluid in 56% of the 39 eyes at the end of month 48. PED height reduced by a mean 77.5 ± 20.0 μm, and geographic atrophy increased by a mean of 4.1 ± 3.4 mmAflibercept is an effective alternative therapy for treatment-resistant nAMD. Good anatomical and stable functional responses are achievable with continued therapy. The lack of continued visual improvement may be representative of GA progression, reflecting the progression of late-stage nAMD in these patients.

Kimberly L Spooner,1,2 Cleopatra T Mhlanga,1 Thomas H Hong,1 Geoffrey K Broadhead,1 Andrew A Chang1,2 1Sydney Institute of Vision Science, Sydney Retina, Sydney, NSW, Australia; 2Save Sight Institute, University of Sydney, Sydney, NSW, Australia Purpose: To quantify the burden and quality of life of patients and their caregivers in a cohort of patients with neovascular age-related macular degeneration (nAMD) in an Australian clinical setting.Methods: A total of 103 patients undergoing anti-vascular endothelial growth factor (VEGF) therapy for nAMD were asked to complete questionnaires relating to the financial and time burdens of nAMD.Results: All patients completed the questionnaires. Loss in productivity due to attendance of appointments was 4.4±1.7 hours per month, with additional time lost by caregivers. Financial strain was incurred by direct medical costs associated with intravitreal assessment and injections at an average of AU$199.2±$83.1 per month. Indirect costs incurred averaged $64.8±$79.7 per month. Qualitative indirect costs due to loss of productivity for the patient, unpaid caregivers, and loss of productivity due to premature mortality were also a considerable burden. Overall mean Visual Function Questionnaire and EuroQol 5D-3L scores were correlated with visual acuity and demonstrated patients’ subjective decline in quality of vision.Conclusion: Management of nAMD carries a substantial burden on patients and caregivers. These results provide important information in understanding the effect of anti-VEGF therapy among patients with nAMD. Together with the quality-of-life burden on the patients, the management of nAMD has a significant societal impact. Keywords: burden, treatment, anti-VEGF, age-related macular degeneration, Australia, patient perspective

PURPOSE: To determine the patient-centered effectiveness of switching patients with persistent macular edema due to retinal vein occlusion (RVO) to aflibercept using the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). MATERIALS AND METHODS: Prospective study of eyes with persistent cystoid macular edema due to RVO despite regular treatment with bevacizumab or ranibizumab switched to aflibercept. Three loading doses of intravitreal aflibercept were administered every 4 weeks and thereafter every 8 weeks until week 48. Vision-related quality of life (VRQoL) using NEI-VFQ-25 was measured at baseline, 24 weeks, and 48 weeks following the switch. Baseline scores were compared to week 24 and 48 using paired t-test. Relationship between best-corrected visual acuity (BCVA) in the study eye and the NEI-VFQ-25 composite and subscale scores was investigated. RESULTS: Eighteen patients with RVO were enrolled in the study with a mean age of 70.3 ± 8.6 years. The mean change in BCVA and central macular thickness (CMT) from baseline to 48 weeks was +20.6 ± 5.2 Early Treatment of Diabetic Retinopathy Score letters and −109.2 ± 82.8 µm, respectively. VRQoL improved significantly, with an increase of mean NEI-VFQ composite score of 11.5 ± 9.5; the corresponding improvements in near and distant activities were 13.3 ± 19.4 and 8.4 ± 10.4, respectively (P < 0.001 for both). Logistic regression analysis demonstrated that BCVA gain of >15 letters and CMT < 300 µm at the end of the study predicted a higher change in VFQ-25. CONCLUSION: Switching eyes with persistent macular edema due to RVO to aflibercept resulted in significant improvement in visual function and patient satisfaction.

PURPOSE To systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD). DESIGN Systematic review and meta-analysis. METHODS Medline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs). RESULTS Of 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI -0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI -0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (-61.90 µm, 95% CI -77.10 to -46.80, P