Comparison between two multimodal imaging platforms: Nidek Mirante and Heidelberg Spectralis.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

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-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four 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 undergone annual fundus autofluorescence (FAF) and 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: Macular atrophy incidence and progression over 4 years, association between treatment strategies, 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 = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed 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 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation 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 new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA 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 achieved better visual outcomes compared with those treated with a PRN approach.

Prospective study of aflibercept for the treatment of persistent macular oedema secondary to retinal vein occlusions in eyes not responsive to long-term treatment with bevacizumab or ranibizumab.

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 < .001 for both groups). Mean decrease in CMT was 87.6 ± 48.8 µm and 191.0 ± 128.3 µm, in the BRVO and CRVO groups, respectively (P < .001). Using linear regression analyses, a higher number of previous intravitreal ranibizumab/bevacizumab injections and thicker pre-switch CMT were correlated with greater visual gains. CONCLUSION AND RELEVANCE: Switching to aflibercept from bevacizumab or ranibizumab in eyes with persistent macular oedema due to RVO can lead to functional and anatomical improvement. This effect was more obvious in eyes with a greater CMT prior to the switch.

Does functional assessment predict everyday visual functioning? Visual function testing and quality of life in mild/moderate age-related macular degeneration.

PURPOSE: 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). METHODS: 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. RESULTS: MP findings in the better eye were weakly correlated with NEI VFQ-25 subscales for colour, general, near and distance vision (p < 0.05 and R2 < 0.3 for all). FP findings and mfERG response density were not correlated with any subscale, apart from mfERG ring 1 response density and general health (p < 0.05, R2 = 0.41). mfERG latency was weakly correlated with general vision in the better eye in rings 2 and 4 (p < 0.05, R2 < 0.2). CONCLUSION: Functional assessment in mild/moderate AMD is at best, weakly correlated with patient-reported VR-QoL. Despite the growing awareness of the importance of VR-QoL outcomes in improving patient outcomes and satisfaction, surrogate markers of these outcomes remain elusive, and testing of VR-QoL in regular clinical settings remains difficult.

Current Outcomes of Anti-VEGF Therapy in the Treatment of Macular Oedema Secondary to Branch Retinal Vein Occlusions: A Meta-Analysis.

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.

Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

BACKGROUND: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice. METHODS: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion's margins from serial OCT images and growth rates were calculated. RESULTS: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions. CONCLUSIONS: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

Long-term outcomes of anti-VEGF treatment of retinal vein occlusion.

BACKGROUND/OBJECTIVES: To analyze the long-term outcomes of eyes with retinal vein occlusion (RVO) 8 years after commencing treatment with anti-vascular endothelial growth factor (VEGF) agents. SUBJECTS/METHODS: Retrospective, multicentre study of 221 eyes diagnosed with RVO, which were commenced on anti-VEGF therapy between 2009 and 2011. VA and CRT were recorded at baseline and at subsequent annual time points. The mean number of injections administered each year and the incidence of adverse events were recorded. RESULTS: Of a total of 221 eyes which commenced treatment with anti-VEGF agents for RVO, 95 were diagnosed with BRVO and 126 with CRVO. 8-year data were available for 94 eyes (43%). The mean age of patients was 65.1 ± 12.0 years. Mean VA improved from baseline by 16.9 letters, (57.8-74.7 letters), (P < 0.001). For BRVO eyes, mean VA improved from 60.5 to 74.8 letters (p < 0.001) and for CRVO eyes from 52.0 to 66.4 letters (p < 0.001). In all RVO eyes, there was a reduction in mean CRT from 501.0 to 249.1 µm; in BRVO eyes from 472.4 to 284.7 µm and in CRVO eyes from 533.9 to 267.5 µm. In the 8th year after starting treatment, eyes with RVO were receiving a mean of four injections. CONCLUSION: Good long-term outcomes of VEGF inhibition for eyes with RVO were found in this study. Patients maintained a gain of 3-lines of vision 8-years after the commencing therapy. This encouraging result contrasts with long-term studies of patients with neovascular age-related macular degeneration, where initial gains are lost over time.

Patient-reported outcomes from a phase IV study of aflibercept in patients with refractory retinal vein occlusions.

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.

Optical-coherence tomography angiography and ultrawide-field angiography findings in eyes with refractory macular edema secondary to retinal vein occlusion switched to aflibercept: A subanalysis from a 48-week prospective study.

PURPOSE: To evaluate anatomical changes on ultra-wide-field fluorescein-angiography and optical coherence angiography (OCT-A) among a cohort with treatment-resistant macular edema secondary to retinal vein occlusions (RVO) switched to aflibercept. MATERIALS AND METHODS: Patients with persistent macular edema despite previous bevacizumab and/or ranibizumab were switched to aflibercept in a 48-week prospective trial. Ultra-wide-field fluorescein angiography (UWFFA) and OCT-A were performed at baseline, week-24 and week-48. The ischemic index was calculated from UWFFA and the areas of vascular perfusion. The foveal avascular zone (FAZ) were quantitatively evaluated on OCT-A. RESULTS: Eighteen patients (mean age, 70.3±8.6 years) were recruited. Mean central macular thickness (CMT) was significantly reduced at 48-weeks compared to baseline (-87.6±48.8 µm, P < 0.001 and -191.0±128.3µm, P < 0.001 among BRVO and CRVO eyes, respectively). The mean baseline ischemic index as measured on Optos wide-field angiography was 10.9%±8.3 and decreased to 5.7%±4.2 (P = 0.028), at week 48. The mean FAZ areas of the SCP and DCP reduced by -0.06 ± 0.12 mm 2 and -0.17± 0.45 mm 2 , respectively. FAZ area on OCT-A was stable in eyes with stable or improved vision but increased in size in eyes with baseline macular ischemia and those with lower gains in BCVA at week 48 (R 2 =0.719, P = 0.05 and R 2 =0.516, P = 0.01). CONCLUSION: There was a reduction in macular edema measured on OCT at 48-weeks in eyes switched to aflibercept with chronic macular edema due to retinal vein occlusion. There was also a reduction in retinal ischemia as measured using UWFFA.

Long-term Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration: The LATAR Study: Report 1: Ten-Year, Real-World Outcomes.

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-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. 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 < 0.001). 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 (P < 0.001). 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 (P < 0.001). The proportion of eyes at baseline with VA 20/200 or worse was 14% and 17% at 10 years. 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.

Effects of Switching to Aflibercept in Treatment Resistant Macular Edema Secondary to Retinal Vein Occlusion.

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 ±â€Š23.7 letters (20/80 Snellen equivalent) and mean CFT was 460.4 ±â€Š178.2 µm. Mean number of previous anti-vascular endothelial growth factor (VEGF) injections was 29.5 ±â€Š19.2. At 12 months, mean VA improved by 8.7 ±â€Š13.2 letters (P < 0.01) and mean CFT decreased by 180.9 ±â€Š207.7 µm compared with baseline (P < 0.01). Mean injection interval increased by 1.6 ±â€Š2.0 weeks to 6.9 ±â€Š1.2 weeks, but this was not statistically significant (P = 0.18). CONCLUSIONS: In our small retrospective study, eyes switched to intravitreal aflibercept for persistent cystoid macular edema (CME) due to RVO improved vision and macular thickness; however, larger prospective studies are required to validate our findings.

A meta-analysis of patients with treatment-resistant macular oedema secondary to retinal vein occlusions following switching to aflibercept.

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.

Current Outcomes of Anti-VEGF Therapy in the Treatment of Macular Edema Secondary to Central Retinal Vein Occlusions: A Systematic Review and Meta-Analysis.

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.

Five-year outcomes of retinal vein occlusion treated with vascular endothelial growth factor inhibitors.

PURPOSE: Report 5-year outcomes of patients receiving anti-vascular endothelial growth factor (VEGF) for the treatment of macular oedema secondary to retinal vein occlusion (RVO. METHODS: Retrospective review of eyes with RVO which initiated anti-VEGF treatment. Data including age, gender, visual acuity (VA) and injection numbers were obtained from medical records. Optical coherence tomography scans were graded for presence or absence of macular oedema and central foveal thickness (CFT). Macular perfusion was assessed on fundus fluorescein angiography by masked graders. RESULTS: 68 eyes (31 branch RVO, BRVO; 35 central RVO, CRVO and 2 hemi-RVO) with 5 years of follow-up after initiation of anti-VEGF treatment. Mean change in VA at 5 years was + 9.6 ± 21.6 letters among CRVO eyes and + 14.2 ± 15.6 letters among eyes with BRVO (p=0.001). Vision of 20/40 or better was achieved in 65 % of treated eyes. The proportion of eyes with a three-line improvement of vision (15 letters) at 5 years was 22 %. Mean CFT decreased by 257.6 ± 249.8 µm in eyes with CRVO and 145.6 ± 143.3 µm in eyes with BRVO. CONCLUSION: The results confirm good long-term outcomes can be achieved with anti-VEGF therapy for RVO.

Burden Of Treatment Among Patients Undergoing Intravitreal Injections For Diabetic Macular Oedema In Australia.

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 <1 month prior to completing the survey. The mean age was 52.5 years, with the majority of patients in full-time work. A substantial proportion of participants had several comorbidities, with a significantly high Charlson comorbidity index of 2.7. Participants reported the main burden of DMO care was the direct cost of medical treatment and the time burden demanded upon their carers. Results suggest that the overall burden is significant for those with diabetes and increases as additional complications of diabetes occur. CONCLUSION: These results suggest that treatment strategies for DMO should consider clinical, humanistic and economic burden and patients should be educated on the roles of complications in disease outcomes. Less frequent treatment regimens could also reduce the economic burden and assist in decreasing the effect on health care resources, relevant to the escalation in the prevalence of diabetes.

Long-term outcomes of switching to aflibercept for treatment-resistant neovascular age-related macular degeneration.

PURPOSE: To report 4-year outcomes following the switch to aflibercept in treatment-resistant neovascular age-related macular degeneration (nAMD). METHODS: 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. RESULTS: 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 mm2 (p < 0.01) over the 48 months. CONCLUSION: Aflibercept 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.

The burden of neovascular age-related macular degeneration: a patient's perspective.

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.

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis.

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<0.001 and -50.00 µm, 95% CI -63.20 to -36.80, P<0.001 at 6 and 12 months, respectively). CONCLUSION: Pooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.