Journal List > J Korean Ophthalmol Soc > v.50(2) > 1008466

Kim, Park, Lee, Lee, and Oum: Short-term Safety and Efficacy of Intravitreal Bavacizumab Injection

Abstract

Purpose

To evaluate the short-term safety and efficacy of intravitreal bevacizumab (Avastin®) injection for various conditions.

Methods

The medical records of 257 eyes of 251 patients who underwent intravitreal bevacizumab injections were reviewed. Central retinal thickness on optical coherence tomography and visual acuity before injections, at 1 week, 1 month, 2 months and 3 months after injections were analyzed.

Results

The patients included age-related macular degeneration (89 eyes), diabetic macular edema (67 eyes) and retinal vascular occlusion (57 eyes). The number of injections was twice in 82 eyes, 3 times in 23 eyes and 4 times in 2 eyes. In total, 391 injections were performed. Best corrected visual acuity increased significantly at 3 months (p=0.033) and central retinal thickness decreased by 1 month and was maintained until 3 months after the first injection (p<0.001). No serious drug-related ocular or systemic adverse incidents including endophthalmitis, glaucoma, retinal detachment, hypertension or myocardial infarction were identified.

Conclusions

The intravitreal bevacizumab injection was safe and efficient for macular edema in this short-term study.

References

1. Senger DR, Connolly DT, Van de Water L, et al. Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res. 1990; 50:1774–8.
2. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1977; 18:4–25.
crossref
3. Kvanta A, Algvere PV, Berglin L, Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1996; 37:1929–34.
crossref
4. Kliffen M, Sharma HS, Mooy CM, et al. Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol. 1997; 81:154–62.
crossref
5. Gragoudas ES, Adamis AP, Cunningham ET Jr, et al. Pegaptanib for neovascular age-related macular defeneration. N Engl J Med. 2004; 351:2805–16.
6. Boyer DS, Antoszyk AN, Awh CC, et al. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology. 2007; 114:246–52.
crossref
7. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006; 19:361–72.
8. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006; 355:1432–44.
crossref
9. Gordon MS, Cunnigham D. Managing patients treated with bavacizumab combination therapy. Oncology. 2005; 69:25–33.
10. Skillings JR, Johnson DH, Miller K, et al. Arterial throm-boembolic events (ATEs) is a pooled analysis of 5 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy. J Clin Oncol. 2005; 23:3019.
11. Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherencetomography findings after an intravitreal injection of bavacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2005; 36:331–5.
12. Rosenfeld PJ, Fung AE, Puliafito VA. Optical coherence tomography findings after an intravitreal injection of bavacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging. 2005; 36:336–9.
13. Rich RM, Rosenfeld PJ, Puliato CA, et al. Short-term safety and efficacy of intravitreal bevacizumab (avastin) for neovascular age-related macular degeneration. Retina. 2006; 26:495–511.
crossref
14. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. 2006; 26:383–90.
crossref
15. Haritoglou C, Kook D, Neubauer A, et al. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina. 2006; 26:999–1005.
crossref
16. Costa RA, Jorge R, Calucci D, et al. Intravitreal bevacizumab (avastin) for central and hemicentral retinal vein occlusions: IBeVO study. Retina. 2007; 27:141–9.
17. Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, et al. Pan-American Collaborative Retina Study Group. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology. 2007; 114:743–50.
18. Fung AE, Rosenfeld PJ, Reichel E. The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol. 2006; 90:1344–49.
crossref
19. Mordenti J, Cuthbertson RA, Ferrara N, et al. Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration. Toxicol Pathol. 1999; 27:536–44.
crossref
20. Ferrara N, Hillan KJ, Novotony W. Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun. 2005; 333:328–35.
crossref
21. Han DP. Intravitreal human immune globulin in a rabbit model of Staphylococcus aureus tozin-mediated endophthalmitis:a potential adjunct in the treatment of endophthalmitis. Trans Am Ophthalmol Soc. 2004; 102:305–20.
22. Michels S, Rosenfeld PJ, Puliafito CA, et al. Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration twelve-week results of an uncontrolled open-label clinical study. Ophthalmology. 2005; 112:1035–47.
23. Rosenfeld PJ, Brown DM, Heier JS, et al. MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006; 355:1419–31.
24. Brown DM, Kaiser PK, Michels M, et al. ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006; 355:1432–44.

Figure 1.
Changes in best corrected visual acuity through 3 months; AMD=age-related macular degeneration; RVO=retinal vascular occlusion; DME=diabetic macular edema; PCV=polypoid choroidal vasculopathy.
jkos-50-219f1.tif
Figure 2.
Frequency distribution of changes in visual acuity in different diseases; AMD=age-related macular degeneration; RVO=retinal vascular occlusion; DME= diabetic macular edema; PCV=polypoid choroidal vasculopathy.
jkos-50-219f2.tif
Figure 3.
Changes in central retinal thickness through 3 months; AMD=age-related macular degeneration; RVO=retinal vascular occlusion; DME=diabetic macular edema; PCV=polypoid choroidal vasculopathy.
jkos-50-219f3.tif
Figure 4.
Changes in best corrected visual acuity and macular thickness on OCT for 3 months after injection of bevacizumab according to number of injection.
jkos-50-219f4.tif
Figure 5.
Changes in best corrected visual acuity and macular thickness on OCT for 3 months after injection of bevacizumab according to the dose.
jkos-50-219f5.tif
Figure 6.
A case of subfoveal classic choroidal neovascularization (CNV) in age-related macular degeneration.(A) Fluorescein angiography (FA) image at baseline shows hyperfluorescent leakage. Best corrected visual acuity was 0.16. (B) Optical coherence tomography (OCT) image demonstrates CNV lesion and retinal edema. Central retinal thickness was 311 µm. (C) At postinjection 3 months, leakage decreased on FA image. (D) Retinal edema was resolved on OCT. Central retinal thickness was 159 µm. Visual acuity was unchanged as 0.16.
jkos-50-219f6.tif
Figure 7.
A case of branched retinal vein occlusion (BRVO). (A) Fluorescein angiography (FA) image at the first visit before treatment shows venous occlusion at superior vascular arcade. Best corrected visual acuity was 0.16(B) Optical coherence tomography (OCT) image demonstrates multiple cystic edema of the macula. Central retinal thickness was 660 µm. (C) FA image after intravitreal triamcinolone injection and grid/focal laser treatment. (D) OCT image demonstrates preexisting macular edema. Central retinal thickness was 440 µm. (E) At 3 months after Avastin injection, FA image shows no leakage. (F) Central retinal thickness at month 3 was 214 µm, cystoid macular edema subsided. Visual acuity improved to 0.32.
jkos-50-219f7.tif
Table 1.
Disease distribution and number of injections (* p<0.05)
No of Eyes No. of injections
Total Average
1 2 3 4
Age-related macular degeneration 89 38 38 12 1 154 1.7
Diabetic macular edema 67 55 9 3 0 82 1.2*
Retinal vascular occlusion 57 32 19 6 0 88 1.5
Polypoid choriovasculopathy 18 9 6 2 1 31 1.7
Others 26 16 10 0 0 36 1.4
Total 257 150 82 23 2 391 1.5
Table 2.
Injection numbers and frequency according to doses of the first injection
1.25 mg 2.5 mg Total
Eyes 194 63 257
Average 1.5 1.5 1.5
Interval (weeks) 7.9 8.0 7.9
Table 3.
Rates of specific adverse incidents
No (%)
1.25 mg 2.5 mg Total (%)
Subconjunctival hemorrhage 31 (10.5) 10 (10.4) 41 (10.5)
Transient irritation, SPK 15 (5.1) 8 (8.3) 23 (5.9)
Increased intraocular pressure 1 (0.3) 4 (4.2) 5 (1.3)
Endophthalmitis 0 0 0
Retinal detachment 0 0 0
A/C inflammation and uveitis 0 (0.0) 1 (1.0) 1 (0.4)
Elevation of blood pressure 0 0 0
Myocardial infarction 0 0 0
Cerebrovascular attack 0 0 0
Death 0 0 0
TOOLS
Similar articles