الفهرس 
AGE RELATED MACULAR DEGENERATION: PREVALENCE, RISK FACTORS AND DIAGNOSISOnly 14 pages are availabe for public view
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Abstract
Age related macular degeneration (AMD) is the most common cause of legal blindness and visual disability among the elderly in developed countries. Early identification of AMD susceptibility and implementation of preventive measures are important management strategies.
In early AMD, visual loss is generally mild and often asymptomatic. Conversely, patients with neovascular AMD can have rapid, profound visual loss within days to weeks as a result of subretinal hemorrhage or fluid accumulation secondary to CNV.
Examination of the fundus, preferably using a stereoscopic viewing method (slit-lamp biomicroscopy), shows the presence of drusen, pigmentary, exudative, haemorrhagic or atrophic changes affecting the macula.
Standard diagnostic modalities including fundus flourescein angiography (FFA) and optical coherence tomography (OCT) can detect CNV in clinical stages even when vision is still not affected.
Previously many methods of treatment were used in the management of neovascular AMD including; Argon laser photocoagulation, photodynamic therapy alone or in combination with intravitreal steroids or in combination with intravitreal anti vascular endothelial growth factor (anti-VEGF). Later on, anti-VEGF agents were used in the management.
Vascular endothelial growth factor is a prime regulator of angiogenesis with diverse roles, both physiological as well as pathological during development and adulthood.
The physiological response is seen in healing wounds with restoration of blood flow, maintaining female reproductive cycle, and formation of placenta with fetal development. While tumor growth, neovascular age related macular degeneration and various proliferative retinopathies are the prime example of its pathological response.
Angiogenic cascade is believed to be initiated due to hypoxia with release of VEGF, FGF and other growth factors. These factors bind to endothelial cells of nearby capillaries thereby activating them. The activated endothelial cells proliferate, migrate and release various proteases. These enzymes increase permeability of basement membrane. The migrating endothelial cells also form new blood vessels in formerly avascular space. These newly formed vessels are fragile causing leakage and bleeding with promotion of scar tissue formation resulting in visual loss.
Bevacizumab is a humanized full length monoclonal antibody to all isoforms of VEGF – A. It is FDA approved as intravenous infusion in combination with chemotherapy for metastatic colorectal cancer. It prevents VEGF from binding to its receptors. It is safe and non toxic drug to the retina that can be used for the treatment of exudative AMD.
Rosenfeld et al. in 2005 and 2006 had reported the use of bevacizumab systemically and intravitreally in the treatment of macular degeneration. Then, Intravitreal bevacizumab has been used extensively for the treatment of macular edema and neovascularization in diseases such as diabetic retinopathy, age related macular degeneration, retinal vein occlusion and neovascular glaucoma through Inhibition of VEGF related angiogenesis.
Intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age related macular degeneration. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age related macular degeneration who are losing vision secondary to macular neovascularization.
There are different treatment regimens that can be used for intravitreal injection of anti vascular endothelial growth factor in the treatment of exudative AMD including: standard and individualized regimens.
The standard treatment regimen consists of monthly injection for at least 24 months, while individualized treatment regimens include:
1. Quarterly treatment Regimen: in which patients receive anti-VEGF agents once per month for the first three months followed thereafter by doses once every three months.
2. Treat and observe Regimen: in which patients receive anti-VEGF agents once per month for the first three months followed thereafter by doses once every month as-needed.
3. Treat and extend regimen: in which patients receive anti-VEGF agents once per month for the first three months followed thereafter by injections at increasing intervals by two weeks per visit.
4. The pro re nata regimen: in which patients receive anti-VEGF agents once followed thereafter by doses once every month as-needed.
It is obvious that a monthly treatment is an expensive and burdensome ordeal. Treat and observe approach obviates the need for high number of injections per year, but still has the cost of monthly examinations. Treat and extend regimen provides fewer patient visits and fewer treatments compared with monthly dosing. And the equation is ”which treatment regimen is better?”.
Our study was a prospective randomized clinical trial where the patients were complaining from subfoveal CNV with their visual acuity 3/60 or better and their age above 55 years. All of them were subjected to complete ophthalmological examination, flourecein angiography and OCT.
This study included 30 patients with neovascular AMD categorized into three groups (10 in each group); treat and extend, treat and observe & pro re nata groups. They were 16 females (53.3%) and 14 males (46.7%). Their age ranged from 60 to88 years with a mean of 72.3 ± 7.99 years.
The primary outcome measure was the mean change of BCVA in lines and the secondary outcome measures include: mean change of CRT, average number of injections per year and local or systemic side effects.
Visual acuity improved when compared from baseline to 1 year in all three study groups. At 1 year, treat and extend protocol was superior to both treat and observe and PRN protocols for the difference in the mean change in visual acuity score. The comparison between treat and observe protocol and PRN protocol was inconclusive, so neither superiority nor inferiority was established between the two study groups.
At 1 year, the mean increases in BCVA were 2.1 ± 0.4 lines in the treat and extend protocol treatment group, 1.5 ± 0.3 lines in the treat and observe protocol treatment group and 0.7 ± 0.6 lines in the PRN protocol treatment group.
At 1 year, the mean decrease in the central retinal thickness was 134.2 ± 31.7 μm in the treat and extend protocol treatment group, 119.9 ± 31.5 μm in the treat and observe protocol treatment group and 55.7 ± 26.8 μm in the PRN protocol treatment group.
Also, there was no statistically significant difference between treat and extend protocol and treat and observe protocol for the difference in the mean change in CRT and both of them were superior to PRN protocol.
The number of injection treatments ranged from 2 to10 injections per year with a mean of 5.83 ± 2.4 injections. Subgroup analysis; the mean number of treatments was 8.1 ± 0.966 for the treat and extend protocol treatment group, 6 ± 1.885 for the treat and observe protocol treatment group and 3.4 ± 0.966 for the PRN protocol treatment group.
Overall, there was a balance among the 3 treatment groups in the rates of ocular and systemic adverse events in the study eyes.