Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Experience With Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration

Lingmin He, MD, MS; Ruwan A. Silva, MD; Noel Ayoub, BS; Darius M. Moshfeghi, MD; Theodore Leng, MD, MS

Abstract

BACKGROUND AND OBJECTIVE:

Describe visual and anatomic outcomes of eyes with exudative age- related macular degeneration (AMD) after treatment with aflibercept.

PATIENTS AND METHODS:

Eyes treated with intravitreal injections of aflibercept for exudative AMD were retrospectively reviewed to compare visual acuity and central subfield thickness (CST) on optical coherence tomography.

RESULTS:

A total of 142 eyes receiving aflibercept were previously treated with bevacizumab or ranibizumab intravitreal injections. Baseline vision was 20/73 ± 5.18 lines when switched to aflibercept. It improved by 0.2 ± 1.91 lines (P =.14) after three injections but decreased by 0.45 ± 2.9 lines (P = .06) after 1 year of follow-up. The reduction in CST was 9.9 ± 46.5 µm (P = .06) after three injections and grew to 19.3 ± 50.6 µm (P = .002), a statistically significant amount, after 1 year.

CONCLUSION:

Switching to aflibercept resulted in no clinically significant differences in visual acuity after 1 year. There was a significant reduction in CST, but this may not be clinically significant.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:542–549.]

From the Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California.

Dr. Moshfeghi did not participate in the editorial review of this manuscript.

The authors report no relevant financial disclosures.

Address correspondence to Theodore Leng, MD, MS, Byers Eye Institute at Stanford, 2452 Watson Court, Palo Alto, CA 94303; email: tedleng@stanford.edu.

Received: December 13, 2013
Accepted: March 12, 2015

Abstract

BACKGROUND AND OBJECTIVE:

Describe visual and anatomic outcomes of eyes with exudative age- related macular degeneration (AMD) after treatment with aflibercept.

PATIENTS AND METHODS:

Eyes treated with intravitreal injections of aflibercept for exudative AMD were retrospectively reviewed to compare visual acuity and central subfield thickness (CST) on optical coherence tomography.

RESULTS:

A total of 142 eyes receiving aflibercept were previously treated with bevacizumab or ranibizumab intravitreal injections. Baseline vision was 20/73 ± 5.18 lines when switched to aflibercept. It improved by 0.2 ± 1.91 lines (P =.14) after three injections but decreased by 0.45 ± 2.9 lines (P = .06) after 1 year of follow-up. The reduction in CST was 9.9 ± 46.5 µm (P = .06) after three injections and grew to 19.3 ± 50.6 µm (P = .002), a statistically significant amount, after 1 year.

CONCLUSION:

Switching to aflibercept resulted in no clinically significant differences in visual acuity after 1 year. There was a significant reduction in CST, but this may not be clinically significant.

[Ophthalmic Surg Lasers Imaging Retina. 2015;46:542–549.]

From the Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California.

Dr. Moshfeghi did not participate in the editorial review of this manuscript.

The authors report no relevant financial disclosures.

Address correspondence to Theodore Leng, MD, MS, Byers Eye Institute at Stanford, 2452 Watson Court, Palo Alto, CA 94303; email: tedleng@stanford.edu.

Received: December 13, 2013
Accepted: March 12, 2015

Introduction

The FDA approval of aflibercept (Eylea; Regeneron Pharmaceuticals, Tarrytown, NY) in November 2011 based on the VIEW 1 and 2 trials has spurred extensive interest in further elucidating its optimal use.1 The drug has been shown in in vitro studies to have a higher binding affinity for the A isoform of vascular endothelial growth factor (VEGF-A) than ranibizumab, the affinity-matured agent that has been established as one of the current standard-of-care agents for the treatment of exudative age-related macular degeneration (AMD).2,3 Additionally, the aflibercept molecule binds to isoforms of the VEGF-B molecule and placental growth factor and has a longer half-life in the eye than does ranibizumab.4,5 This has led to its FDA label for dosing every 8 weeks after three monthly initial loading doses, the regimen that was shown to have non-inferior visual acuity endpoints to monthly ranibizumab in clinical trials.1,4

Since aflibercept was introduced, physicians have been switching their patients to it in an attempt to extend the treatment period, reduce the risk of multiple intravitreal injections, or achieve improved treatment efficacy for choroidal neovascularization that had been refractory to other anti-VEGF agents. Several institutions have recently published their initial experience with switching patients to aflibercept.6–8 The results so far seem to indicate that the visual stability and potential improvements in anatomic outcomes can be achieved in switching patients. This study seeks to report outcomes for all patients receiving intravitreal aflibercept at our institution to determine whether switching agents impacted the final visual or anatomic outcomes.

Patients and Methods

After institutional review board approval for this retrospective comparative case series, billing records were obtained for patients receiving intravitreal aflibercept to treat exudative AMD (ICD-9 code 362.52) between November 2011 and February 2013 at the Byers Eye Institute at Stanford. Six different retinal specialists administered these injections. Medical records and retinal imaging were then reviewed until March 2013 for patient age, sex, laterality of injected eye, and number and time frame of previous intravitreal injections. Patients were excluded if they had fewer than three intravitreal injections of aflibercept in the past year, had a confounding cause of fluid (eg, diabetic macular edema, severe epiretinal membrane, vein occlusion, central serous chorioretinopathy, or posterior uveitis), a confounding cause of vision loss (eg, optic neuropathy), or switched intravitreal medications during the study period.

Patients were then divided into groups of those who were treatment-naïve and those who had previously received anti-VEGF infections. Patients who received previous bevacizumab (Avastin; Genentech, South San Francisco, CA) and previous ranibizumab (Lucentis; Genentech) intravitreal injections were analyzed separately and together.

Patients’ response to intravitreal injections based on Snellen visual acuity and anatomic response based on the central subfield thickness (CST) measured by spectral-domain optical coherence tomography (SD-OCT) (Cirrus; Carl Zeiss Meditec, Dublin, CA) were tracked after the first three injections and then 1 year after the switch. Visual acuity was converted to the logarithm of the minimum angle of resolution (log-MAR) for analysis as has been previously described.9 A paired t test was used for statistical comparisons tracking the changes experienced by patients. A P value of .025 or less was considered significant with use of the Bonferroni correction for two primary outcomes of visual acuity and CST at 1 year after switching from either anti-VEGF. Power calculations at 80% showed that 73 eyes were needed to detect a one-line difference in visual acuity, and 11 eyes were needed to detect a 100-µm difference in CST.

Additionally, an exploratory analysis of patients who received any previous intravitreal injections was performed to group eyes by the strategy the treating physician used after making the switch to aflibercept. They were classified as receiving “standard therapy” of three monthly loading doses and then repeated injections every 8 weeks for those who received “less than standard” (ie, fewer intravitreal injections than they would have received under the standard therapy) or “more than standard” (ie, more intravitreal injections than they would have received if treated with standard therapy). An unpaired t test was used to compare treatment strategies. CST measurements were included in the analysis only if a baseline value was available and an SD-OCT was performed at either the visit following three injections or after 1 year.

Results

A total of 198 patients were identified as having received an intravitreal injection of aflibercept from review of billing records. Figure 1 shows the proportion of patients excluded and those monitored for this study. A total of 181 eyes were included in the study, of which 38 had no previous treatment and 142 were previously injected with an anti-VEGF agent.

Proportion of patients included in and excluded from study participation.

Figure 1.

Proportion of patients included in and excluded from study participation.

The 36 patients (38 eyes) who were anti-VEGF–naïve had an average age of 81.64 ± 8.84 years. Of these, 17 were men and 19 were women. The average vision at the start of aflibercept intravitreal injections was 20/102 ± 6.71 lines. These patients experienced an improvement in vision of 1.45 ± 4.29 lines (P =.05) after 1 year (7.73 ± 1.91 injections over 12.15 ± 1.86 months). Figure 2A displays the logMAR vision after three injections and after 1 year compared to baseline for this group of eyes. SD-OCT measurements of CST showed a significant improvement naïve from a baseline of 341.91 ± 136.90 µm to 236.34 ± 43.66 µm after three injections (P = .002), an improvement that persisted after 1 year. Figure 2B displays these results.

(A) Vision after three injections and after 1 year compared to baseline in the anti-VEGF–naïve group. (B) Central subfield thickness measurements showed a significant improvement from a baseline of 341.91 ± 136.90 µm to 236.34 ± 43.66 µm after three injections (P = .002), an improvement that persisted after 1 year.

Figure 2.

(A) Vision after three injections and after 1 year compared to baseline in the anti-VEGF–naïve group. (B) Central subfield thickness measurements showed a significant improvement from a baseline of 341.91 ± 136.90 µm to 236.34 ± 43.66 µm after three injections (P = .002), an improvement that persisted after 1 year.

There were 56 men and 65 women (142 eyes) previously treated with anti-VEGF agents, on average 82.90 ± 8.15 years old. They had previously received 17.46 ± 10.07 intravitreal injections (range: 3 to 46) during a period of 23.38 ± 13.84 months (range: 3 to 52 months), with 19.71% (28 eyes) receiving intravitreal injections over more than 3 years.

On average, patients who were switched started with visual acuity of 20/73 ± 5.17 lines and improved to 20/69 ± 5.20 lines after three injections (P =.14). After 1 year (12.57 ± 1.32 months), they received 7.51 ± 1.65 intravitreal injections, and visual acuity deteriorated to 20/82 ± 6.12 lines (P = .06). This was a decline of 0.70 ± 2.51 lines when compared to the three-injection vision (P = .001). Figure 3A shows the vision at each time point studied compared to baseline for these eyes. The 27 eyes that previously received bevacizumab had 16.44 ± 8.55 prior intravitreal injections during a period of 24.67 ± 13.49 months. The 115 eyes previously receiving ranibizumab had 17.70 ± 10.41 intravitreal injections over 23.07 ± 13.97 months. Visual acuity changes in these eyes were not different from baseline after three intravitreal injections or after 1 year (P > .11). A summary of the visual acuity results after three injections and at the last visit for each category of previous treatment is presented in Table 1 along with the number of patients available for analysis. Power calculations showed that 116 eyes were needed to detect a one-line difference in vision.

(A) Vision at each study time point compared to baseline for eyes previously treated with anti-VEGF agents. (B) Central subfield thickness measurements compared to baseline for each patient switched to aflibercept.

Figure 3.

(A) Vision at each study time point compared to baseline for eyes previously treated with anti-VEGF agents. (B) Central subfield thickness measurements compared to baseline for each patient switched to aflibercept.

Changes in Visual Acuity in Study Groups

Table 1:

Changes in Visual Acuity in Study Groups

The CST compared to baseline for each patient switched to aflibercept can be seen in Figure 3B. After three intravitreal injections of aflibercept, CST decreased by −9.9 ± 46.5 µm (P = .06). After 1 year, the decrease of −19.3 ± 50.6 µm was statistically significant (P = .002). Table 2 displays the mean thickness and change from baseline for all categories of previous treatment, along with the number of eyes with SD-OCT available for analysis.

Change in Central Subfield Thickness in Each Study Group

Table 2:

Change in Central Subfield Thickness in Each Study Group

Of the eyes that received previous injections, 82 were treated with standard therapy of aflibercept: three monthly loading doses and bimonthly doses thereafter. Thirty-four eyes were treated with less than standard therapy, undergoing intravitreal injections spaced further apart, and 26 were treated with “more than standard,” meaning monthly or intravitreal injections every 6 weeks. The visual acuity outcomes for these eyes are shown in Table 3, with no difference in outcomes between any of the treatment strategies (P > .17). CST measurements are compared in Table 4, again showing no difference between eyes receiving any of the strategies (P > .23). However, fewer eyes had scans by 1 year, with less than 30 eyes available for this comparison.

Visual Acuity Results for Each Treatment Strategy Compared

Table 3:

Visual Acuity Results for Each Treatment Strategy Compared

Central Subfield Thickness Results for Each Treatment Strategy Compared

Table 4:

Central Subfield Thickness Results for Each Treatment Strategy Compared

Discussion

In this retrospective observational case series, we studied the visual acuity and anatomic outcomes for all patients who had been administered aflibercept since its approval for clinical use at a single academic vitreoretinal practice with six physicians. Theoretically, the higher binding affinity for the VEGF receptor allows for a longer interval between intravitreal injections (bimonthly) and may enable better efficacy in patients with refractory fluid or tachyphylaxis to other agents.

Our results for eyes that had not received any previous treatment are comparable to those from the VIEW 1 and VIEW 2 studies. Eyes demonstrated significant improvements in both visual acuity and anatomic outcomes during the year that they were observed. The average improvement was 1.45 ± 4.29 lines (P = .05) at the 1-year follow-up visit compared to 8.4 letters in the combined VIEW 1 and 2 data after 12 months.1 We found a reduction in CST of 129.2 ±143.5 µm, which is also very similar to the trial data.

Previous groups have published their initial experience with switching patients from bevacizumab and ranibizumab to aflibercept to investigate whether better efficacy could be achieved in refractory cases. A group from the University of Iowa studied switched patients after the three monthly loading injections of aflibercept and showed that they had stable vision and a decrease of approximately 65 µm in CST.6 A group from Emory University followed up patients 4 months after they switched and showed that visual acuity and macular volume significantly decreased in more than half of eyes having partial or full resolution of macular fluid.7 A third group, from the Massachusetts Eye and Ear Infirmary, also monitored patients after three to four injections and reported an improvement in anatomic outcomes and stable visual acuity.8 Finally, a large retinal group in New York analyzed outcomes of switching patients with pigment epithelial detachments and found improvements in visual acuity and anatomic outcomes in the 33 patients 6 months after initiation of consecutive injections of aflibercept.10

Here, outcomes for patients who had previously been treated with an anti-VEGF agent compared favorably to those in previous studies. After the initial three injections, vision was stable with even a trend toward slight improvement (0.2 ± 1.91 lines; P = .14), and CST was reduced by 9.9 ± 46.5 µm (P = .06). The clinical significance of these improvements is unclear, because clinical trials have used a 100-µm increase in fluid as the threshold for re-injection in as-needed treatment arms.11,12

Previous studies did not monitor patients much beyond the initial three injections. After longer follow-up of 1 year (7.51 ± 1.65 injections over 12.57 ± 1.32 months), we saw a reversal of some of the gains observed after three injections (2.96 ± 0.18 injections over 4.32 ± 1.13 months). While there was no statistically significant change compared to baseline vision, there was a mean decline of 0.45 ± 2.77 lines (P = .06) even while the mean CST declined by 19.3 ± 50.6 µm (P = .002). When the 1-year vision was compared to the vision after three injections, there was a significant decline of 0.70 ± 2.51 lines (P = .001). However, there was no difference in CST measurements between the 1-year and three-injection visit (P = .16) Recently, the SEVEN-UP trial monitored patients 7 to 8 years after entry into the original trials with intravitreal injections of ranibizumab and found that while 43% of the patients had stable vision compared to baseline, there was a mean overall decline by 8.6 letters.13

Although we used Snellen visual acuities and not ETDRS letters, the threshold for a clinically significant outcome in previous trials has been a change of five ETDRS letters, or one line of vision.12,14–17 The decline in vision we detected is therefore likely not clinically significant, although in line with the SEVEN-UP trial, it suggests that there may be a gradual decline over time in a proportion of these patients despite treatment.

A possible explanation for a decrease in the visual acuities reported here is that patients may have been undertreated. However, our average number of injections in patients who switched to aflibercept was 7.51 ± 1.65 over a period of 12.57 ± 1.32 months, which is the number of intravitreal injections that would be expected with the standard therapy of three loading injections (months 1 to 3) and then bimonthly injections (four injections over months 5 to 12). The VIEW, ANCHOR, and MARINA trials monitoring treatment-naïve patients receiving aflibercept or ranibizumab over 1 year show maintenance of visual acuity with strict treatment criteria and follow-up,1,3,18 and the CATT and IVAN studies have shown some decline in vision, which may not be clinically significant, when patients are treated on an as-needed basis.15,19 The FDA package insert for aflibercept indicates that it may be used as frequently as monthly even though there were no data showing additional efficacy with the more frequent dosing.20 At baseline when switched, approximately 70% of eyes already had some amount of residual fluid, suggesting that the patients were either inadequately treated with the other anti-VEGF agents or recalcitrant to treatment. The 2013 practice patterns survey by the American Society of Retina Specialists showed that most U.S. physicians will attempt three to six injections before switching to a different anti-VEGF agent, using presence of fluid as the main determinant of efficacy of treatment.21 Our study used this guideline for switching and suggests that while SD-OCT measurements of CST quantitatively showed significant improvement, qualitatively there were still many instances of residual fluid. It is possible that fluid may not completely resolve despite a maximal attempt to resolve the fluid.

Additionally, our study explored the difference in treatment outcomes based on the strategy that physicians chose, whether it be the “standard” three monthly loading doses followed by injections every 8 weeks or if they had more or less frequent injections. Patients who were being treated more frequently than the standard therapy would more likely have refractory disease, and those treated less often likely had more indolent disease. We did not find differences in visual acuity or CST between any of the treatment strategies, although our sample sizes were only powered to detect a two-line difference in visual acuity and a 100-µm difference in thickness. It was not suf-ficiently powered to detect smaller differences. Additionally, the injections were not necessarily given in the regular intervals in which they were intended, potentially making the difference between actual treatments received minimal. The VIEW 1 and 2 trials did detect a difference in treatment strategies, with patients initially who received monthly injections having better visions, leading to adoption of the “standard” therapy.1,4 Potentially, this suggests that in a real-world setting when patients often reschedule appointments or miss injections, treatment frequencies other than the “standard therapy” can be as effective.

Ideally, the questions raised and the conclusions suggested by this retrospective review will be further investigated in a randomized, prospective manner with strict adherence to injection strategies and criteria for treatment across multiple sites in order to determine the optimal role for aflibercept. So far, aflibercept seems to be a promising new addition to our armamentarium for treating exudative AMD.

References

  1. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537–2548. doi:10.1016/j.ophtha.2012.09.006 [CrossRef]
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  4. 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. doi:10.1016/j.ajo.2012.04.020 [CrossRef]
  5. Ohr M, Kaiser PK. Intravitreal aflibercept injection for neovascular (wet) age-related macular degeneration. Expert Opin Pharmacother. 2012;13(4):585–591. doi:10.1517/14656566.2012.658368 [CrossRef]
  6. Bakall B, Folk JC, Boldt HC, et al. Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol. 2013;156(1):15–22 e11 doi:10.1016/j.ajo.2013.02.017 [CrossRef]
  7. Ho VY, Yeh S, Olsen TW, et al. Short-term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor inhibitors. Am J Ophthalmol. 2013;156(1):23–28 e22. doi:10.1016/j.ajo.2013.02.009 [CrossRef]
  8. Yonekawa Y, Andreoli C, Miller JB, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol. 2013;156(1):29–35 e22. doi:10.1016/j.ajo.2013.03.030 [CrossRef]
  9. Holladay JT. Proper method for calculating average visual acuity. J Refract Surg. 1997;13(4):388–391.
  10. Kumar N, Marsiglia M, Mrejen S, et al. Visual and anatomical autcomes of intravitreal aflibercept in eyes with persistent subfoveal fluid despite previous treatments with ranibizumab in patients with neovascular age-related macular degeneration. Retina. 2013;33(8):1605–1612. doi:10.1097/IAE.0b013e31828e8551 [CrossRef]
  11. Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009;148(1):43–58 e41. doi:10.1016/j.ajo.2009.01.024 [CrossRef]
  12. Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study. Ophthalmology. 2011;118(4):663–671. doi:10.1016/j.ophtha.2010.12.019 [CrossRef]
  13. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120(11):2292–2299. doi:10.1016/j.ophtha.2013.03.046 [CrossRef]
  14. Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119(7):1399–1411. doi:10.1016/j.ophtha.2012.04.015 [CrossRef]
  15. Martin DF, Maguire MG, Fine SL, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119(7):1388–1398. doi:10.1016/j.ophtha.2012.03.053 [CrossRef]
  16. Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897–1908. doi:10.1056/NEJMoa1102673 [CrossRef]
  17. Mitchell P, Korobelnik JF, Lanzetta P, et al. Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials. Br J Ophthalmol. 2010;94(1):2–13. doi:10.1136/bjo.2009.159160 [CrossRef]
  18. Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N. Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. Ophthalmology. 2006;113(4):623–632.e1. doi:10.1016/j.ophtha.2006.01.027 [CrossRef]
  19. Chakravarthy U, Harding SP, Rogers CA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet. 2013;382(9900):1258–1267. doi:10.1016/S0140-6736(13)61501-9 [CrossRef]
  20. Center for Drug Evaluation and Research. Eylea Label. 2013. Report No. 125387Orig1s000.
  21. Stone TW, Mittra RA. ASRS 2013 Preferences and Trends Membership Survey. Chicago, IL; 2013.

Changes in Visual Acuity in Study Groups

GroupBaselineAfter Three InjectionsAfter 1 Year
Treatment-naiven = 38n = 38n = 38
  Snellen vision20/101 ± 6.71 lines20/84 ± 6.41 lines20/71 ± 5.34 lines
  Change in vision compared to baseline0.83 ± 2.55 lines1.45 ± 4.29 lines
  P value.05.05

Prior bevacizumabn = 27n = 27n = 26
  Snellen vision20/59 ± 4.75 lines20/58 ± 4.79 lines20/69 ± 5.71 lines
  Change in vision compared to baseline0.06 ± 1.05 lines−0.67 ± 2.94 lines
  P value.78.26

Prior ranibizumabn = 115n = 115n = 114
  Snellen vision20/77 ± 5.27 lines20/72 ± 5.30 lines20/85 ± 6.22 lines
  Change in vision compared to baseline0.28 ± 2.1 lines−0.40 ± 2.74 lines
  P value.15.12

Any prior injectionn = 142n = 142n = 140
  Snellen vision20/73 ± 5.18 lines20/69 ± 5.20 lines20/82 ± 6.12 lines
  Change in vision compared to baseline0.24 ± 1.91 lines−0.45 ± 2.77 lines
  P value.14.06

Change in Central Subfield Thickness in Each Study Group

GroupBaselineAfter Three InjectionsAfter 1 Year
Treatment-naïven = 32n = 32n = 26
  Central subfield thickness (microns)341.9 ± 136.9236.3 ± 43.7237.3 ± 51.3
  Change in thickness compared to baseline−105.6 ± 140.0−129.2 ± 143.5
  P value.0002.001

Prior bevacizumabn = 25n = 24n = 19
  Central subfield thickness (microns)252.12 ± 41.52237.13 ± 41.50284.8 ± 221.9
  Change in thickness compared to baseline−11.2 ± 39.17.1 ± 45.7
  P value.19.51

Prior ranibizumabn = 64n = 57n = 52
  Central subfield thickness (microns)248.31 ± 56.02239.96 ± 58.93227.9 ± 44.0
  Change in thickness compared to baseline−9.5 ± 49.4−23.8 ± 52.0
  P value.15.002

Any prior injectionn = 90n = 81n = 70
  Central subfield thickness (microns)248.59 ± 52.40239.1 ± 54.11230.92 ± 45.47
  Change in thickness compared to baseline−9.9 ± 46.5−19.3 ± 50.6
  P value.06.002

Visual Acuity Results for Each Treatment Strategy Compared

Standard*Less Than Standard*More Than Standard*
n = 82n = 34n = 26
Baseline visual acuity20/78 ± 5.33 lines20/56 ± 4.05 lines20/84 ± 5.87 lines
  Comparison to more than standard therapyP = .78P = .18
  Comparison to less than standard therapyP = .17

n = 82n = 34n = 26
Visual acuity after three injections20/73 ± 5.38 lines20/59 ± 4.1 lines20/72 ± 5.9
  Comparison to more than standard therapyP = .97P = .49
  Comparison to less than standard therapyP = .36

n = 82n = 33n = 25
Visual acuity after 1 year20/88 ± 6.28 lines20/66 ± 5.11 lines20/86 ± 7.2 lines
  Comparison to more than standard therapyP = .94P = .49
  Comparison to less than standard therapyP = .31

Central Subfield Thickness Results for Each Treatment Strategy Compared

Standard*Less Than Standard*More Than Standard*
n = 39n = 30n = 25
Baseline central subfield thickness (microns)241.9 ± 41.3255.2 ± 69.1248.6 ± 46.4
  Comparison to more than standard therapyP = .55P = .69
  Comparison to less than standard therapyP = .33

n = 36n = 27n = 20
Central subfield thickness after three injections (microns)229.8 ± 45.2242.5 ± 56.3247.9 ± 66.9
  Comparison to more than standard therapyP = .23P = .76
  Comparison to less than standard therapyP = .32

n = 28n = 23n = 21
Central subfield thickness at last visit (microns)227.1 ± 47.7237.4 ± 44.8228.9 ± 44.6
  Comparison to more than standard therapyP = .90P = .53
  Comparison to less than standard therapyP = .44

10.3928/23258160-20150521-05

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