Real-world visual acuity outcomes between ranibizumab and aflibercept in treatment of neovascular amd in a large us data set

ABSTRACT PURPOSE To examine 12-month real-world visual acuity outcomes and treatment patterns in neovascular age-related macular degeneration (nAMD) eyes, including those with pigment

epithelial detachment (PED), receiving ranibizumab or aflibercept. PATIENTS AND METHODS Electronic medical records were used to identify ranibizumab or aflibercept-treated nAMD eyes with 12

months follow-up from first prescription. The primary objective was to compare mean change in visual acuity (VA) between index and month 12, in eyes treated with ranibizumab and aflibercept

to assess the non-inferiority of ranibizumab _vs_ aflibercept using a −5 letter non-inferiority margin. The number of injections and non-injection visits during follow-up were key secondary

objectives. RESULTS A total of 3350 ranibizumab and 4300 aflibercept treatment-naive eyes were included. At month 12, mean change from index in VA letter score was −0.30 for ranibizumab and

−0.19 for aflibercept (_P_=0.81). The adjusted difference of mean change was −0.14 (−0.79 to 0.51) (_P_=0.67) (generalized estimating equations method) confirming the non-inferiority of

ranibizumab. Eyes received a similar number of injections during follow-up. The mean (±SD) number of ranibizumab and aflibercept injections were 6.70 (±2.54) and 7.00 (±2.40), respectively

(_P_<0.0001). In PED eyes, the mean (±SD) change between baseline to month 12 was 1.25 (±11.3) for ranibizumab and −0.39 (±13.3) for aflibercept (adjusted between-group difference 1.80

(−0.71 to 4.30; _P_=0.16)) achieved with a mean (±SD) 7.85 (±2.68) ranibizumab and 7.47 (±2.45) aflibercept injections, (_P_=0.11). CONCLUSIONS Ranibizumab and aflibercept treatment yielded

comparable VA outcomes in nAMD eyes, including those with PED, with similar treatment patterns over 12 months in real-world clinical practice. SIMILAR CONTENT BEING VIEWED BY OTHERS

LONG-TERM OUTCOMES OF THE OBSERVE-AND-PLAN REGIMEN IN TREATING NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A RETROSPECTIVE REAL-LIFE ANALYSIS Article Open access 10 May 2025 VISUAL OUTCOME

FOLLOWING INITIATION OF FIRST INJECTION VERSUS AFTER THREE MONTHLY DOSES OF AFLIBERCEPT 2 MG FOR TREATMENT NAÏVE AGE-RELATED MACULAR DEGENERATION TO INFORM CLINICAL TRIAL DESIGNS: PRECISE

REPORT NO. 6 Article 12 May 2025 EFFECTIVENESS OF BEVACIZUMAB STEP THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION Article 20 September 2022 INTRODUCTION Age-related macular

degeneration (AMD) is a chronic, degenerative eye disease causing pathological changes in the macular region of the retina and is the most common cause of permanent vision impairment and

loss in older adults.1, 2, 3 Despite accounting for only about 10% of AMD cases, neovascular AMD (nAMD) is responsible for 80–90% of severe vision loss in AMD patients.3 nAMD is

characterized by retinal thickening and the growth and leakage of new blood vessels resulting in scarring of the macula and irreversible loss of central vision. Intravitreal anti-vascular

endothelial growth factor (anti-VEGF) agents are now the established standard of care for nAMD.4 Approved in the United States in 2006, and the European Union in 2007 following the pivotal

MARINA and ANCHOR phase III trials, ranibizumab was a major breakthrough in the treatment of nAMD5 achieving VA improvement by approximately seven and eleven letters, respectively, on the

Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 12 months, which was generally maintained up to 24 months.6, 7 Subsequent studies highlighted that individualized treatment

strategies could optimize outcomes and treatment frequency. Ninety-three percent patients receiving individualized ranibizumab dosing for 24 months in the HARBOR study achieved similar

visual acuity outcomes compared to monthly dosing.8 Aflibercept was approved in the United States in November 2011 and in European Union in November 2012 following demonstration of

non-inferiority of 8-weekly aflibercept to monthly ranibizumab in the VIEW 1 and 2 studies.9 Aflibercept recommended dosing in nAMD is three monthly loading doses, followed by injection once

every 8 weeks.10 Occurring in up to 62% eyes with advanced AMD, retinal pigment epithelial detachment (PED) is an important marker of disease severity and predictor of vision loss in AMD

patients.11 Although evidence from small, non-comparative studies suggests that both ranibizumab and aflibercept may be effective in reversing the anatomical changes associated with PED,12,

13, 14, 15, 16 there is limited evidence of effectiveness in visual acuity outcomes in PED patients.17, 18, 19 Real-world evidence (RWE) studies to date suggest that ranibizumab and

aflibercept are not dosed according to recommendations and patients generally receive fewer doses than label recommendations.20, 21, 22 The consequences of individualized dosing on visual

acuity outcomes in the real world is unclear. Using US electronic medical records (EMR), this study examines visual acuity linked to real-world treatment patterns in a large cohort of nAMD

patients. METHODS INFORMATION SOURCE A retrospective, comparative, non-randomized cohort study of real-world ocular treatment with intravitreal injections of ranibizumab or aflibercept in

nAMD patients was performed using data extracted from a standardized EMR system in the United States. Consistent with the US Code of Federal Regulations (45 CFR 164.514(e)), this EMR source

constitutes a ‘limited data set’ in which all-patient identifiers have been completely removed and site and clinician data pseudo-anonymized. On this basis, formal ethics approval is not

required. Data were extracted for the period 1 January 2011–30 June 2015. PATIENTS Treatment-naive adult patients (aged ≥21 years) were included if they had a diagnosis of nAMD (recorded as

ICD-9-CM code 362.52) and ≥1 ranibizumab or aflibercept injection between 01 July 2011 and 30 June 2014. This first injection date was defined as the index date. Eyes were required to have a

nAMD diagnosis on or within 6 months pre-index, no record of anti-VEGF therapy 180 days pre-index and at least 1 year of post-index follow-up data. Eyes were required to have had ≥1

quantifiable VA (not: light perception, no light perception, invalid) reading on or within 30 days of the index date and ≥1 quantifiable VA reading eligible to be included as the month 12

reading. Eligible VA readings at month 12 were defined as any time between day 300 and day 420 post-index. Eyes which (in addition to nAMD) recorded ICD-9-CM 362.42 (serous PED) and 362.43

(hemorrhagic PED) were classified as having PED. Eyes were excluded if they received any anti-VEGF treatment within 6 months prior to the index date or if discontinuation occurred, defined

as a gap of more than 180 days between study injections or VA assessments during the follow-up period, or if anti-VEGF therapy was switched during the 12 months of follow-up. STUDY DESIGN

AND ANALYSES The primary objective was to compare mean change in VA (letters) between index and month 12 in treatment-naive eyes receiving ranibizumab or aflibercept. Secondary objectives

included: the proportion of eyes gaining or losing ≥0, ≥5, ≥10 and ≥15 letters between index and month 12; the mean number of injections per eye during the first 12 months of treatment

(follow-up period), and in the first 2 months after index injection (loading period). Non-injection visits were defined as those visits without study drug injection but during which either

visual acuity or intraocular pressure was measured or when optical coherence tomography or fluorescein angiography was utilized. Subgroup analysis included eyes stratified by baseline VA

<69 and ≥69 letters (~≥20/40, a threshold for driving ability in United States) and eyes with PED. Visual acuity recorded as Snellen fraction was adjusted for partially read lines and

converted to approximate ETDRS letter scores as described previously,23 except ‘count fingers’ was treated as one letter. Age was collected in 5-year bands up until the maximum (90+ years).

SAMPLE SIZE Based on observations in a previous trial with ranibizumab and aflibercept in nAMD,9 which reported a mean (standard deviation (SD)) change in BCVA at month 12 of 7.9 (15.0) with

aflibercept and 8.1 (15.3) with ranibizumab, the sample size for the VA outcome analysis for non-inferiority of ranibizumab _vs_ aflibercept was calculated assuming no difference, a

non-inferiority limit of −5 letters, and a significance level of 0.05. Assuming a common SD of 15.0, 154 eyes were determined to be needed to achieve at least 90% power. STATISTICAL ANALYSIS

The eye was defined as the unit of analysis. Calculations were performed using SAS 9.1 statistical package. All eligible eyes with 12-month follow-up data post-index were assessed for all

outcomes. Descriptive statistics included mean (SD), median, or range, where appropriate. _P_-values using _χ_2 testing for categorical variables and the Wilcoxon rank-sum test for

continuous variables were reported. A _P_-value of <0.05 was considered statistically significant. The primary comparison of the study was a test of non-inferiority of ranibizumab _vs_

aflibercept, based on the primary outcome, using a margin of non-inferiority of 5 letters. A general linear model (GLM) of analysis of covariance (ANCOVA) was used to compare the two study

groups. Mean difference in VA (letters) score at month 12 was the dependent variable. A generalized estimating equations (GEE) method was also used to account for demographic and clinical

characteristics (including age and baseline VA) as well as repeated measurements in cases of bilateral treatment clustering at the patient level. The GEE data are presented throughout. A

two-sided Wilcoxon rank-sum test was used to compare numbers of injections and visits. Logistic regression models, adjusting for baseline VA, were used to compare binary change in VA letter

score (the relative odds of gaining/losing ≥5, ≥10 and ≥15 letters at month 12). Tests were not adjusted for multiple comparisons. SENSITIVITY ANALYSES For month 12 measurements, a

sensitivity analysis expanding the window to ±3 months was performed. To investigate the impact of requiring eyes to have 12 months follow-up, the baseline characteristics of eyes

discontinuing treatment or switching anti-VEGF therapy were also considered. RESULTS STUDY POPULATIONS A total of 3350 ranibizumab and 4300 aflibercept-treated treatment-naive eyes were

included in the study. Of these 253 ranibizumab-treated eyes and 203 aflibercept-treated eyes were classified as PED. Figure 1 shows the study flow chart incorporating exclusion rules.

Baseline characteristics were generally balanced between ranibizumab and aflibercept cohorts. Treatment-naive ranibizumab patients were slightly older than aflibercept patients (47.3% _vs_

39.9%, respectively, were aged >85 years) with slightly lower baseline mean study eye VA (57.5 (±21.2) _vs_ 58.5 (±20.7); _P_=0.025). PED ranibizumab patients were also slightly older

than their aflibercept counterparts (49.0% _vs_ 38.0%, respectively, were aged >85 years) with a higher proportion of female patients (71.2% _vs_ 58.0%; _P_=0.007) (Table 1). Overall,

15.4% of eyes (17.5% ranibizumab _vs_ 13.4% aflibercept) discontinued therapy during follow-up. Eyes discontinuing treatment (compared to those with 12 months follow-up) were generally older

with a higher proportion in 90+ age bracket (28.8% _vs_ 22.7%) and had poorer baseline vision in the study eye (mean (±SD) VA 50.0 (±24.9) _vs_ 58.1 (±20.9); _P_<0.0001). An additional

12.5% of eyes (17.0% ranibizumab _vs_ 8.3% aflibercept) switched anti-VEGF therapy and were therefore excluded. These eyes had similar baseline visual acuity compared to the non-switchers

(mean (±SD) 57.8 (19.8) _vs_ 58.1 (20.9)). Among the switchers, baseline VA was comparable by index treatment (mean (±SD) 57.8 (19.8) _vs_ 57.8 (19.9)), with a smaller decrease in VA from

baseline to switch for switchers from ranibizumab (mean (±SD) −1.0 (13.9) _vs_ −1.5 (15.2)). VISUAL ACUITY Ranibizumab and aflibercept-treated eyes achieved similar visual acuity outcomes

over 12 months. At month 12, the mean (±SD) change from baseline in VA letter score (primary objective) was −0.30 (±14.8) for ranibizumab and −0.19 (±14.7) for aflibercept. Non-inferiority

was confirmed by virtue of the lower boundary of the confidence interval (−0.79) being greater than the negative of the non-inferiority margin (5) (adjusted between-group difference −0.14,

95% CI: −0.79 to 0.51, _P_=0.67) (Figure 2a). This was confirmed in a sensitivity analysis in which the window for the month 12 measurement was expanded to ±3 months (adjusted difference

−0.22, 95% CI: −0.86 to 0.43, _P_=0.51). In the PED subgroup, at month 12, the mean (±SD) change from baseline was 1.25 (±11.3) for ranibizumab and −0.39 (±13.3) for aflibercept (adjusted

between-group difference 1.80, 95% CI: −0.71 to 4.30, _P_=0.16) (Figure 2b). Ranibizumab and aflibercept also achieved similar visual acuity outcomes in eyes stratified by baseline VA. Eyes

with a lower baseline VA (<69 letters) achieved greater improvement with either treatment than eyes with a high baseline VA (≥69 letters). In the lower-baseline VA subpopulation, the mean

(±SD) change in VA letter score between index and month 12 was similar for ranibizumab and aflibercept (+1.3 (±17.2) _vs_ +1.9 (±17.3), respectively; adjusted difference −0.51, 95% CI:

−1.49 to 0.47, _P_=0.31). In the high baseline VA subpopulation, the mean (±SD) change in VA letter score between index and month 12 was similar for ranibizumab and aflibercept (−2.8 (±9.3)

_vs_ −3.2 (±9.1), respectively; adjusted difference 0.42, 95% CI: −0.24 to 1.08, _P_=0.21) (Figure 2c). The proportion of eyes achieving predefined VA thresholds, defined as gain or loss of

≥0, ≥5, ≥10, ≥15 VA letters at month 12 compared to baseline, was similar for both treatment groups (Figure 3). TREATMENT PATTERNS During the 12-month post-index follow-up period,

ranibizumab and aflibercept-treated eyes received a similar number of injections. The mean (±SD) number of injections was 6.70 (±2.54) _vs_ 7.00 (±2.40) for ranibizumab and aflibercept eyes,

respectively (_P_<0.0001). The mean number of injections per eye was similar regardless of baseline VA and agent received (Figure 4). In the subgroup of patients with PED, the mean (±SD)

number of injections per eye was similar for both agents in the 12-month follow-up period (ranibizumab 7.85 (±2.68) _vs_ aflibercept 7.47 (±2.45)) (_P_=0.11) highlighting that PED eyes had

on average one injection more than non-PED eyes during the first 12 months of treatment (Figure 4). Within the loading period of follow-up (defined as the first 2 months post-index), of a

possible maximum of three injections, the mean (±SD) number of injections administered was 1.76 (±0.60) for ranibizumab and 1.78 (±0.56) for aflibercept (Figure 4). The number of injections

in the loading period was also similar by agent across subgroups (Figure 4). The mean (±SD) number of non-injection visits was 2.15 for both ranibizumab (±2.86) and aflibercept (±3.08)

(_P_=0.12) during the 12-month follow-up period (_P_=0.12). DISCUSSION This is the first US EMR-based retrospective study to compare both treatment frequency and outcomes with ranibizumab

and aflibercept in nAMD. Results show, despite differences in the label-recommended dosing, comparable numbers of ranibizumab and aflibercept injections are administered in the first year of

therapy in the United States with no clinically relevant differences in visual acuity outcome at 12 months. On this basis, the non-inferiority of ranibizumab to aflibercept, the primary

test of the study, was achieved. Alternative models used for comparison of the primary outcome (GLM of ANCOVA similarly concluded non-inferiority, as did the sensitivity analysis expanding

window to ±3 months for the month 12 measurement. Of note was the maintenance of visual acuity in patients with both high (≥69 letters) as well as low (<69 letters) baseline visual acuity

over 12 month’s follow-up. The former group are often excluded or under-represented in clinical trials (for example in VIEW 1 and VIEW 2 clinical trials, enrollment was restricted to

patients with baseline VA of ≤73 letters.9 The maintenance visual acuity in this cohort is supportive of the much advocated early detection and treatment in nAMD to ensure nAMD eyes remain

in the best health state for a greatest duration of time.24, 25 With a mean 7.0 doses in the 12-month follow-up period, data from this study suggest that in clinical practice aflibercept is

being administered at a similar frequency to clinical trials (7.5 doses in VIEW 1 and VIEW 2 trials).9 With a mean 6.7 doses in the first year of treatment and 2.15 non-injection visits,

this study suggests that ranibizumab is generally being dosed flexibly with injection frequency comparable to previous clinical studies, which have reported a mean 12.6 ranibizumab

injections over 2 years and 7.7 over 1 year26, 27 although higher than in previously reported real-world studies (mean 5.7 injections in year 1). Recent claims database analyses have also

shown similar dosing of ranibizumab and aflibercept in treatment-naive nAMD patients with 4.9 _vs_ 5.2 and 5.8 _vs_ 5.5 injections, respectively, over 12 months.20, 22 The higher number of

injection visits in this study perhaps reflects the more complete picture of treatment provided by EMR compared to claims databases due to potential gaps in claims reporting or

identification or claim adjudication at clinic level. Of key clinical and patient relevance, this study demonstrates that with comparable dosing, ranibizumab and aflibercept were equally

effective in maintaining visual acuity in real-world clinical practice. The essentially stable VA during follow-up in this study contrasts with gains reported in clinical trials such as

CATT, HARBOR, and VIEW trials.9 Differences in VA outcomes between RWE studies and clinical trials are not unexpected and most likely reflect the narrow population and significant exclusion

criteria in clinical trials. RWE studies would allow inclusion of eyes with a wider range of CNV lesions (for example, larger lesions) as well as those with structural damage at the fovea

and may include confounders such as cataract, which would be excluded from clinical trials. Further, visual acuities recorded here are not equivalent to refracted protocol-standardised

visual acuity measurements seen in clinical trials and as such may show fewer letters gained compared with a clinical trial-recorded visual acuity measurement. There is limited prospective

data with which to guide treatment for PEDs and these patients are generally excluded from clinical trials and not analyzed as a subgroup. Ranibizumab and aflibercept were equally effective

in stabilizing VA over 12 months and with similar efficacy to that in non-PED patients suggesting anti-VEGF therapy is a viable treatment option in PED patients and is in agreement with a

further comparative short-term study.28 Of note is the relatively low proportion of PED eyes identified in this study. At 6% of eyes in the study, this is considerably lower than would be

expected. Indeed, PEDs are seen in up to 62% of eyes with advanced AMD.11 This potential under-representation is likely due to the lack of granularity in ICD-9 coding for PED. The ICD-9

codes 362.42 and 362.43 used to classify PED in this analysis refer only to serous and hemorrhagic PEDs, respectively, and hence other PED subtypes including fibrovascular and drusenoid

PEDs, which might be expected to account for ~90% of PEDs29 were not necessarily captured. Serous PEDs comprise ~10% of all PEDs in nAMD29 and in this context, the 6% rate of PED

identification in this study is consistent with expectations for the frequency of this subtype in nAMD. Therefore, while in this study ranibizumab and aflibercept show similar efficacy in

PED, their relative efficacy in fibrovascular and drusenoid PED remain to be determined, especially as fibrovascular PED has been demonstrated to be more difficult to treat with anti-VEGF

agents and with poorer visual outcomes than serous PED.30 It has been hypothesized that the wider binding capacity of aflibercept (VEGF-A, VEGF-B, and PIGF) coupled to its higher affinity

for VEGF compared to ranibizumab might result in improved efficacy.31, 32, 33, 34 However, results here suggest that these properties do not translate into improvements in patient-relevant

visual functioning as captured by VA in real-world clinical practice. Furthermore, this study highlights that the potential capacity advantage offered by 8-weekly aflibercept compared to

monthly ranibizumab does not translate to real-world clinical practice, where treatment patterns with the two agents are similar, crucially with similar visual acuity outcomes. To our

knowledge, this is the first comparative US EMR-based retrospective study to compare outcomes and treatment frequency with ranibizumab and aflibercept in nAMD. The standardized EMR database

used utilizes data entered as part of routine clinical care, which allowed data evaluation in a detailed and consistent manner from a large number of geographically diverse practices in

United States. Although in the study itself, data collection was retrospective (introducing inherent biases such as misclassification, treatment bias, and confounding) data fields were

predefined before any data collection started and were entered prospectively and is reflective of real-world daily clinical practice rather than of protocol-driven clinical trials. It is

important to continue to explore long-term outcomes of anti-VEGF treatment in nAMD given the chronic nature of the disease. However, it is possible that any differences in treatment may not

have been manifest at 12 month’s follow-up. An extended study with longer follow-up would address this. There was a high proportion of eyes lost to follow-up due to both treatment

discontinuation and switching anti-VEGF treatment. Discontinuing eyes were generally older with poorer VA at index, which are associated with an increased mortality rate and reduced gains in

visual acuity. Possibly patients with poorer visual acuity outcomes might discontinue or switch treatment thus confounding our results. The direction of any confounding would depend both on

the differential discontinuation rates between treatments (ranibizumab is higher) and trend in visual acuity at switch (aflibercept has a larger decrease). The high discontinuation rate in

this study has been described before in real-world studies of anti-VEGF treatment in nAMD.35 Additional reasons for discontinuation might include inconvenience and/or discomfort associated

with intravitreous injection and a perceived lack of benefit35 or death. Regular intravitreal injections are associated with a significant treatment burden for patients, caregivers, and

physicians, which is often unsustainable in clinical practice.36 Visual acuity post-switch for eyes that switched treatment was available but not analyzed in this study. A companion analysis

for switchers with 12 months on the switch treatment found a comparable change in VA at 12 months post-switch (mean (SD) VA change −1.56 (13.4) ranibizumab to aflibercept switchers _vs_

0.21 (19.2) aflibercept to ranibizumab switchers; _P_=0.55) (manuscript in preparation). nAMD generally occurs in those aged 50 or over. However, eyes from patients aged <50 were included

in this study (0.2% of those analyzed). This finding raises the possibility of misclassification/miscoding of these younger patients, however, it is unlikely that the study results were

impacted. Further limitations also include the loss of sensitivity associated with conversion of Snellen vision recorded in this study to ETDRS letters, limited data on choroidal

neovascularization classification as well as limited systemic medical history of participants and lack of match-control. The latter could be addressed with larger study cohorts in the

future. An additional limitation is the lack of detail in ICD-9 classification for PEDs resulting in potential misclassification and potentially the majority of PED eyes remaining

uncaptured. CONCLUSIONS This study represents, to our knowledge, the largest EMR database analysis comparing both treatment patterns and visual outcomes between ranibizumab and aflibercept.

Despite differences in their approved treatment regimens, in real-world clinical practice, ranibizumab and aflibercept-treated nAMD eyes receive similar numbers of injections and achieve

similar visual acuity outcomes in the first year of treatment. In addition, this study shows that anti-VEGF therapy is effective in maintaining vision in patients with high visual acuity not

normally assessed in phase 3 clinical trials and further supports the early detection and treatment paradigm in nAMD to ensure maintenance of visual function of the eye. REFERENCES * Ambati

J, Fowler BJ . Mechanisms of age-related macular degeneration. _Neuron_ 2012; 75 (1): 26–39. Article  CAS  Google Scholar  * Congdon N, O’Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS

_et al_. Causes and prevalence of visual impairment among adults in the United States. _Arch Ophthalmol_ 2004; 122 (4): 477–485. Article  Google Scholar  * Quillen DA . Common causes of

vision loss in elderly patients. _Am Fam Physician_ 1999; 60 (1): 99–108. CAS  PubMed  Google Scholar  * Kovach JL, Schwartz SG, Flynn Jr HW, Scott IU . Anti-VEGF treatment strategies for

wet AMD. _J Ophthalmol_ 2012; 2012: 786870. Article  Google Scholar  * Dedania VS, Bakri SJ . Current perspectives on ranibizumab. _Clin Ophthalmol_ 2015; 9: 533–542. CAS  PubMed  PubMed

Central  Google Scholar  * Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T . Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular

degeneration: two-year results of the ANCHOR study. _Ophthalmology_ 2009; 116 (1): 57–65.e5. Article  Google Scholar  * Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY _et

al_. Ranibizumab for neovascular age-related macular degeneration. _N Engl J Med_ 2006; 355 (14): 1419–1431. Article  CAS  Google Scholar  * Ho AC, Busbee BG, Regillo CD, Wieland MR, Van

Everen SA, Li Z _et al_. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. _Ophthalmology_ 2014;

121 (11): 2181–2192. Article  Google Scholar  * Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD _et al_. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular

degeneration. _Ophthalmology_ 2012; 119 (12): 2537–2548. Article  Google Scholar  * https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.pdf. * Coscas F, Coscas G, Souied E,

Tick S, Soubrane G . Optical coherence tomography identification of occult choroidal neovascularization in age-related macular degeneration. _Am J Ophthalmol_ 2007; 144 (4): 592–599. Article

  Google Scholar  * Broadhead GK, Hong T, Zhu M, Li H, Schlub TE, Wijeyakumar W _et al_. Response of pigment epithelial detachments to intravitreal aflibercept among patients with

treatment-resistant neovascular age-related macular degeneration. _Retina_ 2015; 35 (5): 975–981. Article  CAS  Google Scholar  * Iordanous Y, Powell AM, Mao A, Hooper PL, Eng KT, Schwartz C

_et al_. Intravitreal ranibizumab for the treatment of fibrovascular pigment epithelial detachment in age-related macular degeneration. _Can J Ophthalmol_ 2014; 49 (4): 367–376. Article 

Google Scholar  * Panos GD, Gatzioufas Z, Petropoulos IK, Dardabounis D, Thumann G, Hafezi F . Effect of ranibizumab on serous and vascular pigment epithelial detachments associated with

exudative age-related macular degeneration. _Drug Des Dev Ther_ 2013; 7: 565–569. Article  CAS  Google Scholar  * Patel KH, Chow CC, Rathod R, Mieler WF, Lim JI, Ulanski LJ 2nd _et al_.

Rapid response of retinal pigment epithelial detachments to intravitreal aflibercept in neovascular age-related macular degeneration refractory to bevacizumab and ranibizumab. _Eye_ 2013; 27

(5): 663–667. Article  CAS  Google Scholar  * Wolf A, Ruping J, Neubauer AS, Mayer W, Ulbig M, Haritoglou C _et al_. Alterations of vascular pigment epithelium detachments associated with

age-related macular degeneration during upload with intravitreal ranibizumab. _Retina_ 2013; 33 (9): 1843–1849. Article  CAS  Google Scholar  * Freeman WR, Kozak I, Yuson RM, Nigam N, Cheng

L, Mojana F . Prognosti implications of pigment epithelial detachment in bevacizumab (avastin)-treated eyes with age-related macular degeneration and choroidal neovascularization. _Retina_

2011; 31 (9): 1812–1818. Article  CAS  Google Scholar  * Introini U, Torres Gimeno A, Scotti F, Setaccioli M, Giatsidis S, Bandello F . Vascularized retinal pigment epithelial detachment in

age-related macular degeneration: treatment and RPE tear incidence. _Graefes Arch Clin Exp Ophthalmol_ 2012; 250 (9): 1283–1292. Article  Google Scholar  * Ritter M, Bolz M, Sacu S, Deak GG,

Kiss C, Pruente C _et al_. Effect of intravitreal ranibizumab in avascular pigment epithelial detachment. _Eye_ 2010; 24 (6): 962–968. Article  CAS  Google Scholar  * Ferreira A, Sagkriotis

A, Olson M, Lu J, Makin C, Milnes F . Treatment frequency and dosing interval of ranibizumab and aflibercept for neovascular age-related macular degeneration in routine clinical practice in

the USA. _PLoS ONE_ 2015; 10 (7): e0133968. Article  Google Scholar  * Holekamp NM, Liu Y, Yeh WS, Chia Y, Kiss S, Almony A _et al_. Clinical utilization of anti-VEGF agents and disease

monitoring in neovascular age-related macular degeneration. _Am J Ophthalmol_ 2014; 157 (4): 825–33.e1. Article  Google Scholar  * Johnston SS, Wilson K, Huang A, Smith D, Varker H, Turpcu A

. Retrospective analysis of first-line anti-vascular endothelial growth factor treatment patterns in wet age-related macular degeneration. _Adv Ther_ 2013; 30 (12): 1111–1127. Article  CAS

  Google Scholar  * Gregori NZ, Feuer W, Rosenfeld PJ . Novel method for analyzing snellen visual acuity measurements. _Retina_ 2010; 30 (7): 1046–1050. Article  Google Scholar  * Rauch R,

Weingessel B, Maca SM, Vecsei-Marlovits PV . Time to first treatment: the significance of early treatment of exudative age-related macular degeneration. _Retina_ 2012; 32 (7): 1260–1264.

Article  Google Scholar  * Schwartz R, Loewenstein A . Early detection of age related macular degeneration: current status. _Int J Retina Vitreous_ 2015; 1: 20. Article  Google Scholar  *

Busbee BG, Ho AC, Brown DM, Heier JS, Suner IJ, Li Z _et al_. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular

degeneration. _Ophthalmology_ 2013; 120 (5): 1046–1056. Article  Google Scholar  * Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ . Ranibizumab and bevacizumab for

neovascular age-related macular degeneration. _N Engl J Med_ 2011; 364 (20): 1897–1908. Article  CAS  Google Scholar  * Dirani A, Ambresin A, Marchionno L, Decugis D, Mantel I . Factors

influencing the treatment response of pigment epithelium detachment in age-related macular degeneration. _Am J Ophthalmol_ 2015; 160 (4): 732–8.e2. Article  Google Scholar  * Lee SY, Stetson

PF, Ruiz-Garcia H, Heussen FM, Sadda SR . Automated characterization of pigment epithelial detachment by optical coherence tomography. _Invest Ophthalmol Vis Sci_ 2012; 53 (1): 164–170.

Article  Google Scholar  * Baba T, Kitahashi M, Kubota-Taniai M, Oshitari T, Yamamoto S . Two-year course of subfoveal pigment epithelial detachment in eyes with age-related macular

degeneration and visual acuity better than 20/40. _Ophthalmologica_ 2012; 228 (2): 102–109. Article  Google Scholar  * Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW . Aflibercept for

age-related macular degeneration: a game-changer or quiet addition? _Am J Ophthalmol_ 2012; 154 (2): 222–226. Article  CAS  Google Scholar  * Chong V . Biological, preclinical and clinical

characteristics of inhibitors of vascular endothelial growth factors. _Ophthalmologica_ 2012; 227 (Suppl 1): 2–10. Article  CAS  Google Scholar  * Papadopoulos N, Martin J, Ruan Q, Rafique

A, Rosconi MP, Shi E _et al_. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. _Angiogenesis_ 2012; 15

(2): 171–185. Article  CAS  Google Scholar  * Rakic JM, Lambert V, Devy L, Luttun A, Carmeliet P, Claes C _et al_. Placental growth factor, a member of the VEGF family, contributes to the

development of choroidal neovascularization. _Invest Ophthalmol Vis Sci_ 2003; 44 (7): 3186–3193. Article  Google Scholar  * Curtis LH, Hammill BG, Qualls LG, DiMartino LD, Wang F, Schulman

KA _et al_. Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 medicare beneficiaries. _Am J Ophthalmol_ 2012; 153 (6): 1116–24.e1. Article  Google

Scholar  * Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R _et al_. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related

macular degeneration. _Br J Ophthalmol_ 2015; 99 (2): 220–226. Article  Google Scholar  Download references ACKNOWLEDGEMENTS Novartis Pharma AG, Basel, Switzerland funded this study. Medical

writing support was provided by Jonathan Askham at Wellmera AG and was funded by Novartis. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Eye Unit, University Hospital Southampton NHS

Foundation Trust, Southampton, UK A Lotery * Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK A Lotery * QuintilesIMS, Cambridge, MA, USA R

Griner * Novartis Pharma AG, Basel, Switzerland A Ferreira & F Milnes * Retinal Consultants of Arizona LTD, Phoenix, AZ, USA P Dugel Authors * A Lotery View author publications You can

also search for this author inPubMed Google Scholar * R Griner View author publications You can also search for this author inPubMed Google Scholar * A Ferreira View author publications You

can also search for this author inPubMed Google Scholar * F Milnes View author publications You can also search for this author inPubMed Google Scholar * P Dugel View author publications You

can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A Lotery. ETHICS DECLARATIONS COMPETING INTERESTS PD is a consultant to Alcon, Genentech,

Novartis Pharma AG, and Ophthotech. AL has received travel support from Bayer and attended advisory boards for Novartis and Bayer. AF and FM are employees of Novartis. RG is an employee of

QuintilesIMS. QuintilesIMS received funding from Novartis to conduct the study. RIGHTS AND PERMISSIONS This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0

International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the

material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit

http://creativecommons.org/licenses/by-nc-nd/4.0/ Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Lotery, A., Griner, R., Ferreira, A. _et al._ Real-world visual acuity

outcomes between ranibizumab and aflibercept in treatment of neovascular AMD in a large US data set. _Eye_ 31, 1697–1706 (2017). https://doi.org/10.1038/eye.2017.143 Download citation *

Received: 01 March 2017 * Accepted: 13 June 2017 * Published: 21 July 2017 * Issue Date: December 2017 * DOI: https://doi.org/10.1038/eye.2017.143 SHARE THIS ARTICLE Anyone you share the

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