الفهرس 
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Abstract
Age-related macular degeneration is a multifactorial neurodegenerative disease of the photoreceptors and retinal pigment epithelieum (RPE) in the human macula affecting the elderly persons worldwide.According to the WHO in 2012, AMD ranked 3rd globally as a cause of blindness after cataract and glucoma. It is a common cause of visual impairment in individuals over the age of 50 years.
Risk factors for AMD are heterogenous including cigarette smoking, hypertension , nutritional and epigenetic factors.
There is an extensive support for a strong genetic component in the pathogenesis of AMD based on familial aggregation and linkage studies.
Neovascularization is an important component of the pathophysiology of the disease. The vascular endothelial growth factor (VEGF-A) is a major player in the control of angiogenesis.
The human VEGF gene polymorphisms such as (VEGF-1154 G>A) in the promotor region and VEGF+405 G>C) in the 5`UTR are common in the VEGF gene.
The most effective treatment for AMD is intravitral injection of anti-VEGF agents. These drugs (by several mechanisms)inhibit neovascularization.
This study aimed to investigate the role of- 1154G>A and +405G>C VEGF gene polymorphisms as possible riskfactors for AMD and to evaluate their role in the response of patients to anti-VEGF therapy among the studied sample.
Fifty patients were included in the study (≥50years of age) with pre diagnosed AMD from those referred to the Ophthalmology Department, Alexandria Main University Hospital.
The control group included 64 healthy volunteer with matched age and sex. All the patients were subjected to structural questionnaire including age, sex, smoking status, consanguinity, medical history (HTN, DM, heart disease), onset of the disease, family history, ophthalmological examination including visual acuity, fundus examination and OCT parameters pre and post intraviteral injection.
The patients and control groups were assessed. Blood samples were obtained from patients and control, DNA extraction and PCR-RFLP were then performed to assess the VEGF-1154 G>A and VEGF +405G>C polymorphisms in relation to AMD.
The results of the present study was as follow: the age of the studied patients ranged from 50-82 years, patients above 60 years were higher(70%) than those below 60 years (30%). There was no statistical significance compared to the control group.
Females were slightly higher (52%) than males (48%). Regarding the smoking status, the frequency of smokers was higher (78%) compared with nonsmokers (22%). There was statistical significant difference implying a strong association between smoking and the development of AMD.
Hypertension was found in 80% of patients compared to 24% of the control, there was statistical significant difference between the 2 groups which indicates HIN as an important risk factor for AMD.
The frequency of patients with history of heart disease was 26% compared to 10.9% of the control group and there was statistical significance among the two groups.
DM was found in 26% of patients, on the other hand, 74% were non-diabetic. There was no statistical significant difference between patients and control.
The VEGF-1154 G>A polymorphism was found as (26%, 70%, and 4%) for the genotypes GG, GA and AA respectively in patients compared to (45.3%, 51.6% and 3.1%) for the genotypes GG, GA and AA respectively among the control group. There was no statistical significant association observed between VEGF-1154 G>A and AMD in the 2 groups.
The VEGF +405G>C polymorphism was found as (52%, 46% and 2%) for the genotypes GG, GC and CC respectively compared to (54.7%, 37.5% and 7.8%) for the genotypes GG, GC and CC respectively in the control group. There was no statistical significant association observed between VEGF +405G>C and AMD.
Visual acuity and OCT parameters were statistically significant when compared pre and post intervention.
Among the studied group, thirty six patients (72%) were responders to intravitrealLucentis injection compared to (28%) were classified as non-responders.
Comparing factors among responders and non-responders revealed that age was statistically significant, implying an association between age and response to intervention.
A statistical significant association was observed between the VEGF +405G>C and response to therapy. Also there was a statistical significant association between the onset of the disease ranged from (4-36 month) with median 11 and response to treatment.