MyVisionTest News Archive
Jun 22, 2009
Avastin for neovascular AMD: 2-year results
A new study of patients with neovascular age-related macular degeneration (AMD) treated with intravitreal Avastin (bevacizumab) on an as-needed basis over 2 years finds that 43% of patients experienced a 3-line or more improvement in visual acuity (VA) and an average of 4.9 injections were administered over the 24-month follow-up period.
In the MARINA and ANCHOR trials, monthly intravitreal injection of Lucentis (ranibizumab) prevented vision loss and improved average VA over a 2 year follow-up period in patients with wet AMD. The Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular AMD Treated with intraOcular Ranibizumab (PrONTO) Study suggested that less frequent treatment with Lucentis using a variable-dosing regimen is possible if patients are monitored closely for recurrences with OCT.
Avastin is a monoclonal antibody against all isoforms of VEGF. It is approved by the FDA for the treatment of colorectal cancer. In 2005, the first report of the intravitreal use of Avastin for choroidal neovascularization (CNV) was published. Since then, there have been many short-term retrospective and prospective studies suggesting that Avastin is safe and effective for the treatment of neovascular AMD. Although not approved by the FDA for intraocular use, the low cost of Avastin makes it appealing for the treatment of neovascular ocular diseases.
Methods and Results
The current study is a continuation of a 1-year prospective, open-label, nonrandomized clinical study. All 51 patients (51 eyes) with subfoveal CNV resulting from AMD that completed the first year of follow-up agreed to continue in the study for a second year. In the initial treatment phase, intravitreal Avastin (2.5 mg) was given at baseline, and then two additional monthly injections were given if the macula was not dry on OCT. The criteria for reinjection were presence of fluid in the macula, increased central retinal thickness (CRT) of at least 100 µm, loss of at least 5 letters of vision associated with increased fluid in the macula, new classic CNV, or new macular hemorrhage.
Mean baseline BCVA was 45.7 letters (Snellen equivalent, 20/125). By month 24, mean BCVA was 54.3 letters (Snellen equivalent, 20/80) with a mean gain of 8.4 letters from baseline (P = .001). There was no statistically significant difference between mean BCVA at 12 months (53.1 letters) and 24 months (P = .35). Compared with baseline, 47 eyes (92.2%) avoided losing 15 letters of BCVA by 24 months. Forty-one eyes (82.4%) avoided losing any letters of BCVA, 22 eyes (43.1%) gained at least 15 letters, and 6 eyes (11.8%) gained at least 30 letters by 24 months. Four eyes lost more than 15 letters of vision during the first 12 months. Although they maintained a dry macula, they gradually began to lose vision and to show progressive subfoveal fibrosis or retinal pigment epithelial (RPE) atrophy. Mean baseline CRT was 327.4 µm. By month 24, mean CRT was 246.6 µm and had decreased by 80.8 µm compared with baseline (P < .001). There was no significant difference between mean CRT at 12 months (227.8 µm) and 24 months (P = .19). An average of 3.4 injections (range, 1 to 8) was given in the first 12 months, and this decreased to 1.5 injections (range, 0 to 7) during the second year (P < .001). No serious ocular or systemic side effects were noted.
Of the 51 eyes, 4 showed a partial response at the initiation of therapy that increased to 7 by the end of the first 12 months. During the next 12 months, an additional 7 eyes began to show a partial response. There was no statistically significant difference between complete responders and partial responders with respect to mean BCVA and CRT at baseline and 24 months. Partial responders received a mean of 6.8 injections over 24 months vs 4.3 injections for complete responders (P = .009).
Discussion and Conclusions
This treatment regimen resulted in a rapid gain in VA and decrease in CRT after the first month with stability and minor fluctuations over the remainder of the study. Lesion size showed a more gradual improvement during the first year and stabilized over the second year. It may be that intravitreal Avastin rapidly improves macular anatomy by decreasing leakage from the CNV and by inhibiting further angiogenesis. Mature vessels in CNV probably do not respond to anti-VEGF therapy and may explain why the CNV does not resolve completely. Similar to our findings at 12 months, good baseline VA and smaller lesions generally resulted in better VA at 24 months.
With OCT it was possible to detect most recurrences on OCT before any change in VA or other clinical findings. Fewer treatments were necessary during the second year, and some eyes required no treatments at all. These eyes tended to have a larger lesion at baseline with more fibrous tissue. Smaller lesions consisted primarily of active CNV that may have required anti-VEGF therapy for a longer period of time to stabilize.
A concerning finding was the number of partial responders, which seems to increase with time. Longer follow-up is necessary to determine if VA in partial responders will deteriorate and if the number of partial responders will continue to increase. Possible mechanisms for resistance to anti-VEGF therapy include a change to alternative pathways of angiogenesis that do not rely on VEGF-A or a change in the CNV to more mature VEGF-independent vessels.
In conclusion, intravitreal Avastin for neovascular AMD over 24 months achieved functional stability with anatomic improvement. The treatment seems to be safe and well tolerated. However, it may be needed indefinitely, and some eyes may continue to deteriorate despite anatomic improvement. The issue of tachyphylaxis may become more prominent with repeated injections. Further studies are necessary to confirm the long-term efficacy and safety of this treatment.
Read more...
Am J Ophthalmol 2009;148:59–65
Tags: Avastin, dosing strategy, wet AMD, clinical trial, PrONTO, tachyphylaxis
A new study of patients with neovascular age-related macular degeneration (AMD) treated with intravitreal Avastin (bevacizumab) on an as-needed basis over 2 years finds that 43% of patients experienced a 3-line or more improvement in visual acuity (VA) and an average of 4.9 injections were administered over the 24-month follow-up period.In the MARINA and ANCHOR trials, monthly intravitreal injection of Lucentis (ranibizumab) prevented vision loss and improved average VA over a 2 year follow-up period in patients with wet AMD. The Prospective Optical Coherence Tomography (OCT) Imaging of Patients with Neovascular AMD Treated with intraOcular Ranibizumab (PrONTO) Study suggested that less frequent treatment with Lucentis using a variable-dosing regimen is possible if patients are monitored closely for recurrences with OCT.
Methods and Results
The current study is a continuation of a 1-year prospective, open-label, nonrandomized clinical study. All 51 patients (51 eyes) with subfoveal CNV resulting from AMD that completed the first year of follow-up agreed to continue in the study for a second year. In the initial treatment phase, intravitreal Avastin (2.5 mg) was given at baseline, and then two additional monthly injections were given if the macula was not dry on OCT. The criteria for reinjection were presence of fluid in the macula, increased central retinal thickness (CRT) of at least 100 µm, loss of at least 5 letters of vision associated with increased fluid in the macula, new classic CNV, or new macular hemorrhage.
Mean baseline BCVA was 45.7 letters (Snellen equivalent, 20/125). By month 24, mean BCVA was 54.3 letters (Snellen equivalent, 20/80) with a mean gain of 8.4 letters from baseline (P = .001). There was no statistically significant difference between mean BCVA at 12 months (53.1 letters) and 24 months (P = .35). Compared with baseline, 47 eyes (92.2%) avoided losing 15 letters of BCVA by 24 months. Forty-one eyes (82.4%) avoided losing any letters of BCVA, 22 eyes (43.1%) gained at least 15 letters, and 6 eyes (11.8%) gained at least 30 letters by 24 months. Four eyes lost more than 15 letters of vision during the first 12 months. Although they maintained a dry macula, they gradually began to lose vision and to show progressive subfoveal fibrosis or retinal pigment epithelial (RPE) atrophy. Mean baseline CRT was 327.4 µm. By month 24, mean CRT was 246.6 µm and had decreased by 80.8 µm compared with baseline (P < .001). There was no significant difference between mean CRT at 12 months (227.8 µm) and 24 months (P = .19). An average of 3.4 injections (range, 1 to 8) was given in the first 12 months, and this decreased to 1.5 injections (range, 0 to 7) during the second year (P < .001). No serious ocular or systemic side effects were noted.
Of the 51 eyes, 4 showed a partial response at the initiation of therapy that increased to 7 by the end of the first 12 months. During the next 12 months, an additional 7 eyes began to show a partial response. There was no statistically significant difference between complete responders and partial responders with respect to mean BCVA and CRT at baseline and 24 months. Partial responders received a mean of 6.8 injections over 24 months vs 4.3 injections for complete responders (P = .009). Discussion and Conclusions
This treatment regimen resulted in a rapid gain in VA and decrease in CRT after the first month with stability and minor fluctuations over the remainder of the study. Lesion size showed a more gradual improvement during the first year and stabilized over the second year. It may be that intravitreal Avastin rapidly improves macular anatomy by decreasing leakage from the CNV and by inhibiting further angiogenesis. Mature vessels in CNV probably do not respond to anti-VEGF therapy and may explain why the CNV does not resolve completely. Similar to our findings at 12 months, good baseline VA and smaller lesions generally resulted in better VA at 24 months.
With OCT it was possible to detect most recurrences on OCT before any change in VA or other clinical findings. Fewer treatments were necessary during the second year, and some eyes required no treatments at all. These eyes tended to have a larger lesion at baseline with more fibrous tissue. Smaller lesions consisted primarily of active CNV that may have required anti-VEGF therapy for a longer period of time to stabilize.
A concerning finding was the number of partial responders, which seems to increase with time. Longer follow-up is necessary to determine if VA in partial responders will deteriorate and if the number of partial responders will continue to increase. Possible mechanisms for resistance to anti-VEGF therapy include a change to alternative pathways of angiogenesis that do not rely on VEGF-A or a change in the CNV to more mature VEGF-independent vessels.
In conclusion, intravitreal Avastin for neovascular AMD over 24 months achieved functional stability with anatomic improvement. The treatment seems to be safe and well tolerated. However, it may be needed indefinitely, and some eyes may continue to deteriorate despite anatomic improvement. The issue of tachyphylaxis may become more prominent with repeated injections. Further studies are necessary to confirm the long-term efficacy and safety of this treatment.
Read more...
Am J Ophthalmol 2009;148:59–65
