Aflibercept Treatment for Patients With Exudative AMD
Aflibercept Treatment for Patients With Exudative AMD
Forty-six patients enrolled directly from the SAVE trial into the TURF trial between April and September 2012. Baseline demographics and clinical findings are described in Table 1 . Forty-five of 46 (98%) patients completed the 6-month trial. At baseline, patients had received a mean of 42 (range 19–67) prior anti-VEGF intravitreal treatments including a mean of 21 (range 13–24) prior 2.0 mg ranibizumab treatments out of a maximum 24 during the immediately preceding 24 months of the SAVE trial. Median time from prior anti-VEGF treatment to the first aflibercept treatment was 28 days (mean 33.3, range 28 to 68 days).
At enrolment, mean BCVA was 74.2 ETDRS letters (Snellen equivalent 20/32, range 41–91, 20/100–20/16). BCVA remained stable throughout the 6-month trial with no significant fluctuation; at month 6, mean change was +0.2 ETDRS letters (range −10 to +13, p=0.71) (figure 1). At 6 months, 4 eyes (9%) improved by ≥5 ETDRS letters and 1 eye (2%) improved by ≥10 ETDRS letters, gaining 13 letters within the first month of treatment; PRN retreatment was required at both PRN visits in 3 of 4 of these patients, while 1 patient received neither PRN retreatment. At month 6, 4 eyes (9%) lost ≥5 letters or more with 1 eye (2%) receiving neither PRN retreatment and losing 10 letters associated with collapse of a pigment epithelial detachment (PED) and progression of geographic atrophy (figure 2A); PRN retreatment was required at both PRN visits in 2 of 4 of these patients, and 2 patients received neither PRN retreatment. No patient lost >15 letters BCVA.
(Enlarge Image)
Figure 1.
Change in mean best-corrected visual acuity (best corrected visual acuity (BCVA); Early Treatment Diabetic Retinopathy Study (ETDRS) letters) over 6 months with standard error (SE) bars.
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Figure 2.
Case examples. Baseline late-phase fluorescein angiograms (FA) with associated spectral domain optical coherence tomography (SD-OCT) orientations (white dashed line) followed by sequential SD-OCT images at baseline (left), 1 month (centre) and 6 months (right). (A) flattening of pigment epithelial detachment (PED) from baseline associated with retinal pigment epithelial and outer retinal atrophy. (B) flattening of PED with residual subretinal fluid under the fovea at month 6.
At enrolment, mean CST was 347 μm (range 188–565 μm). Mean CST improved significantly from baseline at all study visits including −23.6 μm at month 1 (−5%, range −384 to +32 μm), and −27.3 μm at month 6 (−6%, range −381 to +59 μm, p=0.018) (figure 3).
(Enlarge Image)
Figure 3.
Change in central subfield thickness (spectral domain optical coherence tomography (SD-OCT)) over 6 months with standard error (SE) bars. Central subfield thickness was evaluated monthly as well as 7 days after the first aflibercept treatment.
CST decreased >10% in 9 of 46 patients (19.6%) at month 3, and in 7 of 45 patients (15.6%) at month 6. For these eyes, the mean decrease in CST at month 6 was −149 μm (−31%, range −48 to −381 μm). Of the 7 patients with CST decrease >10% at month 6, 4 had complete, or near complete, resolution of PED (figure 2B); 94% of the decrease in CST in these patients was realised within the first 2 months of aflibercept treatment. At month 3, no patient gained >10% CST, but at month 6, 2 patients gained >10% CST, gaining either significant subretinal (60 μm) or intraretinal (92 μm) fluid after not receiving a PRN injection.
In total, 71 of 90 (79%) possible PRN injections were administered and a mean of 5.6 aflibercept injections out of the minimum 4 and maximum 6 total injections were administered. PRN retreatment was required at both PRN visits in 33 of 46 (72%) patients due to SD-OCT findings, and neither of the PRN injections were given in 8 of 46 (17%) patients. At months 3 and 6, 17 (37%) and 10 (22%) patients had no intraretinal, subretinal, or sub-RPE fluid, respectively.
Ocular and systemic adverse events are reported in Table 2 . There were no cases of endophthalmitis, intraocular inflammation, new subretinal haemorrhage, or traumatic cataract. In total, three patients were noted to have increased geographic atrophy (3/46, 7%). No systemic arterial thromboembolic events were identified. One (1/46, 2%) patient died at month 5 related to complications of acute onset leukaemia.
Results
Patient Characteristics
Forty-six patients enrolled directly from the SAVE trial into the TURF trial between April and September 2012. Baseline demographics and clinical findings are described in Table 1 . Forty-five of 46 (98%) patients completed the 6-month trial. At baseline, patients had received a mean of 42 (range 19–67) prior anti-VEGF intravitreal treatments including a mean of 21 (range 13–24) prior 2.0 mg ranibizumab treatments out of a maximum 24 during the immediately preceding 24 months of the SAVE trial. Median time from prior anti-VEGF treatment to the first aflibercept treatment was 28 days (mean 33.3, range 28 to 68 days).
Visual Outcomes
At enrolment, mean BCVA was 74.2 ETDRS letters (Snellen equivalent 20/32, range 41–91, 20/100–20/16). BCVA remained stable throughout the 6-month trial with no significant fluctuation; at month 6, mean change was +0.2 ETDRS letters (range −10 to +13, p=0.71) (figure 1). At 6 months, 4 eyes (9%) improved by ≥5 ETDRS letters and 1 eye (2%) improved by ≥10 ETDRS letters, gaining 13 letters within the first month of treatment; PRN retreatment was required at both PRN visits in 3 of 4 of these patients, while 1 patient received neither PRN retreatment. At month 6, 4 eyes (9%) lost ≥5 letters or more with 1 eye (2%) receiving neither PRN retreatment and losing 10 letters associated with collapse of a pigment epithelial detachment (PED) and progression of geographic atrophy (figure 2A); PRN retreatment was required at both PRN visits in 2 of 4 of these patients, and 2 patients received neither PRN retreatment. No patient lost >15 letters BCVA.
(Enlarge Image)
Figure 1.
Change in mean best-corrected visual acuity (best corrected visual acuity (BCVA); Early Treatment Diabetic Retinopathy Study (ETDRS) letters) over 6 months with standard error (SE) bars.
(Enlarge Image)
Figure 2.
Case examples. Baseline late-phase fluorescein angiograms (FA) with associated spectral domain optical coherence tomography (SD-OCT) orientations (white dashed line) followed by sequential SD-OCT images at baseline (left), 1 month (centre) and 6 months (right). (A) flattening of pigment epithelial detachment (PED) from baseline associated with retinal pigment epithelial and outer retinal atrophy. (B) flattening of PED with residual subretinal fluid under the fovea at month 6.
Anatomic Outcomes
At enrolment, mean CST was 347 μm (range 188–565 μm). Mean CST improved significantly from baseline at all study visits including −23.6 μm at month 1 (−5%, range −384 to +32 μm), and −27.3 μm at month 6 (−6%, range −381 to +59 μm, p=0.018) (figure 3).
(Enlarge Image)
Figure 3.
Change in central subfield thickness (spectral domain optical coherence tomography (SD-OCT)) over 6 months with standard error (SE) bars. Central subfield thickness was evaluated monthly as well as 7 days after the first aflibercept treatment.
CST decreased >10% in 9 of 46 patients (19.6%) at month 3, and in 7 of 45 patients (15.6%) at month 6. For these eyes, the mean decrease in CST at month 6 was −149 μm (−31%, range −48 to −381 μm). Of the 7 patients with CST decrease >10% at month 6, 4 had complete, or near complete, resolution of PED (figure 2B); 94% of the decrease in CST in these patients was realised within the first 2 months of aflibercept treatment. At month 3, no patient gained >10% CST, but at month 6, 2 patients gained >10% CST, gaining either significant subretinal (60 μm) or intraretinal (92 μm) fluid after not receiving a PRN injection.
In total, 71 of 90 (79%) possible PRN injections were administered and a mean of 5.6 aflibercept injections out of the minimum 4 and maximum 6 total injections were administered. PRN retreatment was required at both PRN visits in 33 of 46 (72%) patients due to SD-OCT findings, and neither of the PRN injections were given in 8 of 46 (17%) patients. At months 3 and 6, 17 (37%) and 10 (22%) patients had no intraretinal, subretinal, or sub-RPE fluid, respectively.
Adverse Events
Ocular and systemic adverse events are reported in Table 2 . There were no cases of endophthalmitis, intraocular inflammation, new subretinal haemorrhage, or traumatic cataract. In total, three patients were noted to have increased geographic atrophy (3/46, 7%). No systemic arterial thromboembolic events were identified. One (1/46, 2%) patient died at month 5 related to complications of acute onset leukaemia.
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