Bevacizumab vs Dexamethasone for Macular Edema With BRVO
Bevacizumab vs Dexamethasone for Macular Edema With BRVO
This study compared the results of intravitreal bevacizumab given on a monthly PRN basis versus dexamethasone implants given at 6-month intervals on a PRN basis for macular oedema secondary to BRVO. The results showed that as needed injections of 1.25 mg of bevacizumab provided sustained visual and anatomical improvement comparable with dexamethasone implants for up to 5 months, but bevacizumab treatment showed superior anatomic outcome at postoperative 6 months in terms of improvement in CFT. However, there was statistically no significant difference of logMAR BCVA change between the IVB and IVD groups. At 12 months, both the IVB and IVD groups achieved similar improvement of logMAR BCVA and CFT. Regarding the percentage of patients gaining at least two or three Snellen lines, results showed that both the IVB group and the IVD group achieved similar outcomes, and there was no significant difference between the two groups at 12-month follow-up.
Recently, the BRAVO study proved the efficacy of monthly injections of ranibizumab during the first 6 months for the treatment of macular oedema associated with BRVO. However, continuous monthly injection of ranibizumab can be quite burdensome for patients due to its high cost and the need for repeated injections. Intravitreal bevacizumab injections administered on an as needed basis can be a practical alternative for these patients and have been shown to have comparable functional and anatomical outcomes in comparison with monthly ranibizumab injections. Additionally, a prolonged-release dexamethasone implant, administered at 6-month intervals, proved to be effective for the treatment of macular oedema associated with retinal vein occlusion. Despite the widespread use of both intravitreal bevacizumab administered as needed and dexamethasone implants, there is little data on which to compare the efficacy of these two specific treatment modalities. Our study showed that the IVB group attained a mean improvement of 0.23±0.40 logMAR units at postoperative 12 months, comparable with previous studies reporting mean visual improvement ranging from 0.26 to 0.44 logMAR units at 6 months after as needed IVB injections. Similarly, IVD injections resulted in a visual gain of 0.19±0.34 logMAR units at 12 months. Regarding CFT improvement, the IVB group achieved a mean reduction of 160.09±124.68 μm, slightly lower than the findings in previous studies, which ranged from 184 to 219 μm. Likewise, the CFT improvement from baseline was 140.67±151.14 μm in the IVD group at the 12-month follow-up. We observed the greatest degree of CFT improvement during the first month after the initial injection in both groups. Subsequent injections in the IVB group, while improving CFT, mostly sustained the benefit gained from the initial injection. This pattern of macular oedema improvement was consistent with previous findings.
Dexamethasone implants were originally expected to last for 6 months, as the 12-month data from the original phase III study of GENEVA also reported similar outcomes at fixed 6-month dosing schedules. Since then, many studies have reported that repeated injections were needed at around 4–5 months after initial injection, implying that intravitreal dexamethasone implants may not last for the expected 6 months, as was previously suggested by the re-treatment protocol in the GENEVA trial. Our results also showed a decrease in effect noted at 5 and 6 months in the IVD group in terms of CFT improvement; however, at postoperative 12 months, there was no significant differences of functional and anatomical outcomes between the two groups. However, it may be reasonable to perform additional injections of either repeated dexamethasone implants or bevacizumab at some point between 5 and 6 months in the IVD group to sustain the visual and anatomical benefits attained from the initial injection of the dexamethasone implant, rather than merely waiting until 6 months for re-evaluation of macular oedema. In one pilot study that compared the efficacy of three consecutive monthly intravitreal bevacizumab injections versus dexamethasone implants, no significant differences were found between the two treatments in terms of BCVA and CFT at 6 months. The study included re-treatment with bevacizumab or dexamethasone implants at 4 months, and more than 90% (10 of the 11 eyes) required a second injection of dexamethasone implant at 4 months, whereas 36% (3 of the 8 eyes) required a further injection of bevacizumab.
BRVO with macular ischaemia were excluded, as these patients had a lower likelihood of visual improvement after the treatment, similar to the exclusion criteria used in the GENEVA study. Furthermore, anti-VEGF therapy could compromise the retinal circulation, thereby potentially worsening macular ischaemia in the long term, particularly after repeated anti-VEGF injections.
During the study, there were no significant complications associated with either intravitreal injection of bevacizumab or dexamethasone implants, such as development of cataract, increased IOP >21 mm Hg or endophthalmitis, and there were no differences of safety profiles between the medications.
There were several limitations to the study. Due to the retrospective nature of the study, only the patients who were given IVD at 6-month intervals were included, and the inability to re-treat patients with IVD before 6 months during the follow-up may not correspond well enough to the current clinical practice pattern. Also, as this was a retrospective study, patients were not randomised in terms of whether they received bevacizumab or dexamethasone implants; moreover, dexamethasone implants were not available in Korea until its approval for use in 2012. Hence, patients who visited our clinic for treatment of BRVO-associated macular oedema before its approval were treated with bevacizumab, while dexamethasone implant injection began to be used after its approval in 2012. BCVA was only measured in Snellen visual acuity, and the study was also limited by the short study duration of only 12 months and the difference in the size of the two study groups. The absence of significant complications such as persistent IOP elevation or visual loss due to cataract may be attributable to the relatively smaller number of patients enrolled in the IVD group and the short-term follow-up of only 12 months. If more patients had been enrolled with a longer follow-up, there might have been a higher incidence of complications associated with the use of IVD such as IOP elevation or visual loss due to cataract.
In conclusion, monthly PRN injections of 1.25 mg of bevacizumab provided sustained visual and anatomical improvements that were comparable with dexamethasone implants given PRN at 6-month intervals, particularly in terms of improvement in logMAR BCVA and CFT at 12 months. Further studies with more patients and a longer follow-up are warranted in the future.
Discussion
This study compared the results of intravitreal bevacizumab given on a monthly PRN basis versus dexamethasone implants given at 6-month intervals on a PRN basis for macular oedema secondary to BRVO. The results showed that as needed injections of 1.25 mg of bevacizumab provided sustained visual and anatomical improvement comparable with dexamethasone implants for up to 5 months, but bevacizumab treatment showed superior anatomic outcome at postoperative 6 months in terms of improvement in CFT. However, there was statistically no significant difference of logMAR BCVA change between the IVB and IVD groups. At 12 months, both the IVB and IVD groups achieved similar improvement of logMAR BCVA and CFT. Regarding the percentage of patients gaining at least two or three Snellen lines, results showed that both the IVB group and the IVD group achieved similar outcomes, and there was no significant difference between the two groups at 12-month follow-up.
Recently, the BRAVO study proved the efficacy of monthly injections of ranibizumab during the first 6 months for the treatment of macular oedema associated with BRVO. However, continuous monthly injection of ranibizumab can be quite burdensome for patients due to its high cost and the need for repeated injections. Intravitreal bevacizumab injections administered on an as needed basis can be a practical alternative for these patients and have been shown to have comparable functional and anatomical outcomes in comparison with monthly ranibizumab injections. Additionally, a prolonged-release dexamethasone implant, administered at 6-month intervals, proved to be effective for the treatment of macular oedema associated with retinal vein occlusion. Despite the widespread use of both intravitreal bevacizumab administered as needed and dexamethasone implants, there is little data on which to compare the efficacy of these two specific treatment modalities. Our study showed that the IVB group attained a mean improvement of 0.23±0.40 logMAR units at postoperative 12 months, comparable with previous studies reporting mean visual improvement ranging from 0.26 to 0.44 logMAR units at 6 months after as needed IVB injections. Similarly, IVD injections resulted in a visual gain of 0.19±0.34 logMAR units at 12 months. Regarding CFT improvement, the IVB group achieved a mean reduction of 160.09±124.68 μm, slightly lower than the findings in previous studies, which ranged from 184 to 219 μm. Likewise, the CFT improvement from baseline was 140.67±151.14 μm in the IVD group at the 12-month follow-up. We observed the greatest degree of CFT improvement during the first month after the initial injection in both groups. Subsequent injections in the IVB group, while improving CFT, mostly sustained the benefit gained from the initial injection. This pattern of macular oedema improvement was consistent with previous findings.
Dexamethasone implants were originally expected to last for 6 months, as the 12-month data from the original phase III study of GENEVA also reported similar outcomes at fixed 6-month dosing schedules. Since then, many studies have reported that repeated injections were needed at around 4–5 months after initial injection, implying that intravitreal dexamethasone implants may not last for the expected 6 months, as was previously suggested by the re-treatment protocol in the GENEVA trial. Our results also showed a decrease in effect noted at 5 and 6 months in the IVD group in terms of CFT improvement; however, at postoperative 12 months, there was no significant differences of functional and anatomical outcomes between the two groups. However, it may be reasonable to perform additional injections of either repeated dexamethasone implants or bevacizumab at some point between 5 and 6 months in the IVD group to sustain the visual and anatomical benefits attained from the initial injection of the dexamethasone implant, rather than merely waiting until 6 months for re-evaluation of macular oedema. In one pilot study that compared the efficacy of three consecutive monthly intravitreal bevacizumab injections versus dexamethasone implants, no significant differences were found between the two treatments in terms of BCVA and CFT at 6 months. The study included re-treatment with bevacizumab or dexamethasone implants at 4 months, and more than 90% (10 of the 11 eyes) required a second injection of dexamethasone implant at 4 months, whereas 36% (3 of the 8 eyes) required a further injection of bevacizumab.
BRVO with macular ischaemia were excluded, as these patients had a lower likelihood of visual improvement after the treatment, similar to the exclusion criteria used in the GENEVA study. Furthermore, anti-VEGF therapy could compromise the retinal circulation, thereby potentially worsening macular ischaemia in the long term, particularly after repeated anti-VEGF injections.
During the study, there were no significant complications associated with either intravitreal injection of bevacizumab or dexamethasone implants, such as development of cataract, increased IOP >21 mm Hg or endophthalmitis, and there were no differences of safety profiles between the medications.
There were several limitations to the study. Due to the retrospective nature of the study, only the patients who were given IVD at 6-month intervals were included, and the inability to re-treat patients with IVD before 6 months during the follow-up may not correspond well enough to the current clinical practice pattern. Also, as this was a retrospective study, patients were not randomised in terms of whether they received bevacizumab or dexamethasone implants; moreover, dexamethasone implants were not available in Korea until its approval for use in 2012. Hence, patients who visited our clinic for treatment of BRVO-associated macular oedema before its approval were treated with bevacizumab, while dexamethasone implant injection began to be used after its approval in 2012. BCVA was only measured in Snellen visual acuity, and the study was also limited by the short study duration of only 12 months and the difference in the size of the two study groups. The absence of significant complications such as persistent IOP elevation or visual loss due to cataract may be attributable to the relatively smaller number of patients enrolled in the IVD group and the short-term follow-up of only 12 months. If more patients had been enrolled with a longer follow-up, there might have been a higher incidence of complications associated with the use of IVD such as IOP elevation or visual loss due to cataract.
In conclusion, monthly PRN injections of 1.25 mg of bevacizumab provided sustained visual and anatomical improvements that were comparable with dexamethasone implants given PRN at 6-month intervals, particularly in terms of improvement in logMAR BCVA and CFT at 12 months. Further studies with more patients and a longer follow-up are warranted in the future.
Source...