Vascular endothelial growth factors in retinal and choroidal neovascular diseases

Figures & data

Figure 1. Normal anatomy of the eye.

Table I. Statistics of visual impairment in developed countries and the world. Modified from WHO global data on visual impairment in the year 2002. Sample of Western countries includes Australia, Denmark, Finland, Iceland, Ireland, Italy, Netherlands, UK, and USA.

Region	Western countries	World
No. of blind people (millions)	2.02	36.86
Prevalence of blindness, %	0.23	0.57
No. of blind people (millions) by age (years)
<15	0.05	1.37
15–49	0.39	5.18
>50	1.59	30.31
No. of people with low vision (millions)	11.35	124.25
Prevalence of low vision, %	1.23	2.00
No. of visually impaired (millions)	13.37	161.12
AMD as a cause of blindness, %	50.00	8.70
Diabetic retinopathy as a cause of blindness, %	17.00	4.80

Figure 2. VEGF family and VEGF receptors.

Figure 3. A: Moderate non-proliferative diabetic retinopathy with hard exudates (large arrows), soft exudates (small arrows), and microaneurysms (arrowheads). B: Proliferative diabetic retinopathy and neovascularization in the optic disc.

Figure 4. Consequences of hyperglycaemia.

Figure 5. Wet form of age-related macular degeneration with oedema, CNV (arrows), and haemorrhages (arrowheads). A: Fundus photograph. B: Fluorescein angiography image in the 30 s time point.

Figure 6. Consequences of wet AMD.

Table II. Clinical trials for anti-VEGF therapy.

Trial; No. of patients	Disease	Injection protocol	Drug; Dosage	Control	Results (time point)
VISION; 1186	AMD; All lesions	IVT every 6 weeks	Pegaptanib; 0.3/1.0/3.0 mg	Sham	31%–37% stable vision, 4%–6% gained >3 lines (12 months)
MARINA; 716	AMD; Minimally classic/occult CNV	IVT monthly	Ranibizumab; 0.3/0.5 mg	Sham	95% stable vision, 26%–34% gained >3 lines (12 months)
ANCHOR; 423	AMD; Predominantly classic CNV	IVT monthly	Ranibizumab; 0.3/0.5 mg	Sham + PDT every 3 months if needed	96% stable vision, 35%–40% gained >3 lines (12 months)
FOCUS; 162	AMD; Predominantly classic CNV	IVT monthly + PDT	Ranibizumab; 0.5 mg	PDT every 3 months	90% stable vision
HORIZON; 853	AMD; Previously treated patients in MARINA, ANCHOR, FOCUS	IVT monthly	Ranibizumab; 0.5 mg		Mean loss of vision 2–5 letters, 3% gained >3 lines, 7%–14% lost >3 lines (12 months)
PIER; 182	AMD; All lesions	IVT monthly × 3, re-treatment every 3 months	Ranibizumab; 0.3/0.5 mg	Sham	83%–90% stable vision, 12%–13% gained >3 lines (12 months)
Pronto; 37	AMD	IVT monthly × 3, re-treatment as needed (9.9 injections over 24 months)	Ranibizumab; 0.5 mg	–	43% gained >3 lines (24 months)
Case series (Adepegba 2010) 78	AMD	IVT monthly × 3, re-treatment as needed (3 + PRN)	Ranibizumab; 0.5 mg	IVT monthly if needed (PRN)	89%–93%% stable vision, 29% gained >3 lines (3 + PRN) versus 12.9% (PRN group) (12 months)
Case series (Spaide 2006); 266	AMD	IVT monthly	Bevacizumab; 1.25 mg	–	95% stable vision, 38% gained > 3 lines (3 months)
READ; 126	DR; Macular oedema	IVT at 0, 1, 3, 5 months	Ranibizumab; 0.5 mg	Focal laser/ Laser and ranibizumab at 0,3 months	22% gained >3 lines (6 months)
Case series (Avery 2006); 32	DR; Proliferative retinopathy	IVT monthly	Bevacizumab; 6.2/12.5/62.0/125/625 μg/1.25 mg	–	59%–82% resolution of leakage of neovascularization (2 months)
Case series (Macugen Diabetic Retinopathy Study Group 2006); 172	DR; Macular oedema	IVT every 6 weeks	Pegaptanib; 0.3/1.0/3.0 mg	Sham	90%–98% stable vision, 18% gained >3 lines (9 months)
BRAVO	Branch retinal vein occlusion	IVT monthly	Ranibizumab; 0.3/0.5 mg	Sham	61% gained >3 lines (6 months)
CRUISE	Central retinal vein occlusion	IVT monthly	Ranibizumab; 0.3/0.5 mg	Sham	48% gained >3 lines (6 months)
Case series (Stahl 2007); 21	Retinal vein occlusion	IVT single	Bevacizumab; 1.25 mg	–	100% stable vision, 33% gained > 3 lines (6 weeks)
Case series (Mintz-Hittner 2008); 11	ROP; Moderate and severe stage 3	IVT single	Bevacizumab; 0.625 mg	–	No need for laser therapy during the follow-up (13–85 weeks)

IVT = intravitreal.

Table III. Clinical trials for new anti-VEGF agents.

Trial; No. of patients	Disease	Injection protocol	Drug; Dosage	Control	Results
CLEAR-IT-1; 51	AMD; Lesion size <12 disc areas, >50% active CNV	IVT single	Aflibercept; 0.05/0.15/0.5/1.0/ 2.0/4.0 mg	–	95% stable vision, 50% of 2.0/4.0 mg group gained >3 lines (3 months)
VIEW; 1200	AMD	IVT every 4 or 8 weeks	Aflibercept; 0.5/2.0 mg	Ranibizumab; 0.5 mg	?
DA VINCI; 219	DR/Macular oedema	IVT monthly/3 IVT monthly (0, 1, 2), followed by IVT every 8 weeks or as needed (PRN)	Aflibercept; 0.5/2.0 mg	Focal laser	Mean gain of vision 8.5–11.4 letters (6 months)
CARE; 129	AMD; Predominantly or minimally classic CNV	IVT; At base-line and week 6	Bevasiranib; 0.2/1.5/3.0 mg	–	Mean loss of vision 4.1–6.9 letters (3 months)
RACE; 48	DR; Macular oedema	IVT monthly	Bevasiranib	–	No change in visual acuity
CARBON; 496	AMD	IVT ranibizumab 0.5 mg monthly × 3, followed by IVT every 8 weeks	Bevasiranib; 1.0/2.0/2.5 mg	Ranibizumab; 0.5 mg	?
Sirna-027; 26	AMD	IVT single	siRNA for VEGFR-1; 0.1/0.2/0.4/0.8/1.2/1.6 μg	–	92% stable vision, 19% gained >3 lines (3 months)

IVT = intravitreal.