RVO Is the Second Most Common Cause of Blindness Due to
Retinal Vascular Disease1
RVO can be an acute or chronic condition that may be associated with serious systemic disease2-4
Other risk factors
>50-year incidence increase with age2,3
Hypertension, diabetes, atherosclerosis,
Overexpression of ocular VEGF mediates destructive pathology in RVO5,6
- Stagnation of venous blood flow following occlusion leads to oxygen depletion and hypoxia5,6
- Vascular damage stimulates overexpression of VEGF, leading to angiogenesis and associated macular edema5,6
- Intraocular VEGF levels are correlated with disease severity and vision loss7,8
Systemic VEGF plays multiple roles in cellular functions, such as angiogenesis and tissue repair9,10
- Complications attributed to decreased systemic VEGF levels include hypertension, ATEs, renal dysfunction, and wound complications10
IMPORTANT SAFETY INFORMATION AND INDICATIONS
LUCENTIS is contraindicated in patients with ocular or periocular infections or hypersensitivity to ranibizumab or any of the excipients in LUCENTIS.
WARNINGS AND PRECAUTIONS
Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection technique should always be utilized when administering LUCENTIS. Patients should be monitored following the injection to permit early treatment, should an infection occur.
Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with LUCENTIS. IOP and perfusion of the optic nerve head should be monitored and managed appropriately.
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
Neovascular (wet) age-related macular degeneration
The ATE rate in the 3 controlled neovascular AMD studies during the first year was 1.9% in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% in the combined group of LUCENTIS-treated patients compared with 2.9% in patients from the control arms. In Study AMD-4, the ATE rates observed in the study during the first year were similar to rates observed in Studies AMD- 1, AMD-2, and AMD-3.
In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of LUCENTIS used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% in patients treated with 0.5 mg LUCENTIS compared to 1.1% in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)]).
Macular edema following retinal vein occlusion
The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the LUCENTIS and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS and 2 of 260 in the control arms). The stroke rate was 0.2% in the combined group of LUCENTIS-treated patients compared to 0.4% in the control arms.
Diabetic macular edema and Diabetic Retinopathy
In a pooled analysis of Studies DME-1 and DME-2, the ATE rate at 2 years was 7.2% with 0.5 mg LUCENTIS, 5.6% with 0.3 mg LUCENTIS, and 5.2% with control. The stroke rate at 2 years was 3.2% with 0.5 mg LUCENTIS, 1.2% with 0.3 mg LUCENTIS, and 1.6% with control. At 3 years, the ATE rate was 10.4% with 0.5 mg LUCENTIS and 10.8% with 0.3 mg LUCENTIS; the stroke rate was 4.8% with 0.5 mg LUCENTIS and 2.0% with 0.3 mg LUCENTIS.
Fatal events occurred more frequently in patients with DME and DR at baseline treated monthly with LUCENTIS compared with control. A pooled analysis of Studies DME-1 and DME-2 showed that fatalities in the first 2 years occurred in 4.4% of patients treated with 0.5 mg LUCENTIS, in 2.8% of patients treated with 0.3 mg LUCENTIS, and in 1.2% of control patients. Over 3 years, fatalities occurred in 6.4% of patients treated with 0.5 mg LUCENTIS and in 4.4% of patients treated with 0.3 mg LUCENTIS. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded.
Serious adverse events related to the injection procedure that occurred in <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
In clinical trials in neovascular (wet) age-related macular degeneration, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, increased IOP, vitreous detachment, and intraocular inflammation. The most common non-ocular side effects included nasopharyngitis, headache, arthralgia, and bronchitis.
In clinical trials in macular edema following retinal vein occlusion, the most common ocular side effects included conjunctival hemorrhage, eye pain, and maculopathy. The most common non-ocular side effects included nasopharyngitis, headache, influenza, and sinusitis.
In clinical trials in diabetic macular edema and diabetic retinopathy, the most common ocular side effects included conjunctival hemorrhage, cataract, increased IOP, and vitreous detachment. The most common non-ocular side effects included nasopharyngitis, anemia, and nausea.
As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS. The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.
For additional safety information, please see LUCENTIS full prescribing information.
LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with:
- Neovascular (wet) age-related macular degeneration (wAMD)
- Macular edema following retinal vein occlusion (RVO)
- Diabetic macular edema (DME)
- Diabetic Retinopathy (Non Proliferative Diabetic Retinopathy (NPDR)), Proliferative Diabetic Retinopathy (PDR) in patients with Diabetic Macular Edema (DME)
References: 1. Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res. 2008;33:111-131. 2. Yanoff M, Duker JS, eds. Ophthalmology. 2nd ed. St. Louis, MO: Mosby, Inc.; 2004. 3. Klein R, Moss SE, Meuer SM, Klein BEK. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol. 2008;126:513-518. 4. Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study. Arch Ophthalmol. 2006;124:726-732. 5. Ferrara N. Vascular endothelial growth factor. Trends Cardiovasc Med. 1993;3:244-250. 6. Lu M, Adamis AP. Molecular biology of choroidal neovascularization. Ophthalmol Clin N Am. 2006;19:323-334. 7. Noma H, Funatsu H, Yamasaki M, et al. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye. 2008;22;42-48. 8. Noma H, Funatsu H, Mimura T, et al. Increase of vascular endothelial growth factor and interleukin-6 in the aqueous humour of patients with macular oedema and central retinal vein occlusion. Acta Ophthalmol. 2010;88:646-651. 9. Wirostko B, Wong TY, Rafael Simo. Vascular endothelial growth factor and diabetic complications. Progress in Retinal and Eye Research. 2008;27:608-621. 10. Chen HX, Cleck JN. Adverse effects of anticancer agents that target the VEGF pathway. Nat. Rev. Clin. Oncol. 2009;6:465-477.