MyVisionTest News Archive
Feb 26, 2012
Risk score for geographic atrophy
Researchers have developed a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen.
Choroidal neovascularization (CNV) and geographic atrophy (GA) are two forms of end-stage AMD. GA is responsible for about 10% of the severe vision loss attributed to the AMD, and affects approximately 900,000 persons in the United States. Anti-vascular endothelial growth factor (Anti-VEGF) therapy has been proven to be highly effective in reducing the vision loss in patients with CNV. Although several agents to prevent the development or arrest the progression of GA are currently under investigation in clinical trials, none have yet been shown to be effective.
GA progresses gradually over time, and the causes of GA are largely unknown. However, data from large observational studies and clinical trial cohorts have consistently identified age, current smoking status, hypertension, drusen size or area, and pigmentary changes as risk factors. Recent investigations have identified genes associated with GA, including Complement Factor H, Complement Factor B, LOC387715 and Complement C3 variant. More recently, night vision as assessed by a 10-item questionnaire was found to be highly predictive of the development of GA, independent of other established risk factors.
Methods & Results
The study included 1052 participants from the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT) with ≥10 large (>125 µm) drusen and visual acuity ≥20/40 in each eye.
In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 µm] > 1 disc area), GA (>175 µm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk.
Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for <7 points to 15% for ≥12 points. The 5-factor risk score predicted development of GA moderately well with the area under the receiver operating characteristic curve (AUC) 0.76 (95% confidence interval [CI], 0.71-0.81) for end point GA; 0.76 (95% CI, 0.71-0.80) for CGA, and 0.68 (95% CI, 0.65-0.72) for any GA. Prediction from the risk score without the night vision score had lower AUCs (range, 0.67-0.72).
Discussion & Conclusions
A 15-point GA risk score was developed using five easily accessible risk factors that predicts moderately well the 5-year risk of endpoint GA, CGA and any GA. This predictive power is similar to the predictive power of the Framingham risk score for coronary heart disease, similar to the recently developed risk score for glaucoma and also similar to the prediction of advanced AMD using demographic and environmental variables. When the score is computed without consideration of night vision there is a decrease in prediction power.
To our knowledge, this is the first study to develop risk scores specifically for predicting GA rather than CNV and GA combined. Data from CAPT is especially well-suited for developing a model for GA because participants had substantial drusen burden (each eye have at least 10 large drusen (≥125 µ)), were followed prospectively at least 5 years, and had yearly color photographs taken by certified photographers with interpretation at a central reading center.
The GA risk scores we developed may improve the design and analysis of clinical trials to prevent GA. Progression from drusen to GA takes years, and only a small percentage of AMD patients will develop GA even among those starting with bilateral large drusen (6.8% for endpoint GA in CAPT participants, and 6% for CGA in AREDS participants). The night vision questionnaire may be used when screening patients to more finely stratify patients by risk of developing GA than is possible with knowledge of only age, cigarette smoking, hypertension, presence of large drusen or pigmentation changes.
The GA risk scores also provide an easy way for ophthalmologists to estimate the 5-year risk of developing GA among their AMD patients. These estimates may help in explaining the implications of newly detected signs of early AMD to patients.
Our risk score was developed from readily available risk factors, and it does not consider other risk factors that are more difficult to obtain, specifically the genetic risk factors. Complement Factor H, Complement Factor B, LOC387715 and complement C3 variant were recently found to be associated with risk of GA. Including these genetic risk factors and other risk factors (such as dietary or supplemental antioxidant intake) in the risk score development may improve its predictive power for GA. Seddon et al recently developed a comprehensive predictive model for advanced AMD (CNV and GA combined) based on both genetic, demographic and environmental variables, and found that the AUC (c-statistic) improved from 0.73 to 0.83 when genetic data was included in the prediction model.
In summary, the GA risk scores developed from the CAPT data discriminated several levels of risk and provided accurate estimates of risk for the CAPT participants. If the discrimination and accuracy are validated in other independent groups of patients, they will provide useful tools for identifying high risk patients for clinical trials for prevention of GA and for GA risk assessment of AMD patients.
Read more...
Ophthalmology. 2011 Feb;118(2):332-8
Tags: dry AMD, genetics, risk factors, prognosis, geographic atrophy
Researchers have developed a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen.Choroidal neovascularization (CNV) and geographic atrophy (GA) are two forms of end-stage AMD. GA is responsible for about 10% of the severe vision loss attributed to the AMD, and affects approximately 900,000 persons in the United States. Anti-vascular endothelial growth factor (Anti-VEGF) therapy has been proven to be highly effective in reducing the vision loss in patients with CNV. Although several agents to prevent the development or arrest the progression of GA are currently under investigation in clinical trials, none have yet been shown to be effective.
Methods & Results
The study included 1052 participants from the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT) with ≥10 large (>125 µm) drusen and visual acuity ≥20/40 in each eye.
In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 µm] > 1 disc area), GA (>175 µm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk.
Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for <7 points to 15% for ≥12 points. The 5-factor risk score predicted development of GA moderately well with the area under the receiver operating characteristic curve (AUC) 0.76 (95% confidence interval [CI], 0.71-0.81) for end point GA; 0.76 (95% CI, 0.71-0.80) for CGA, and 0.68 (95% CI, 0.65-0.72) for any GA. Prediction from the risk score without the night vision score had lower AUCs (range, 0.67-0.72).
Discussion & Conclusions
A 15-point GA risk score was developed using five easily accessible risk factors that predicts moderately well the 5-year risk of endpoint GA, CGA and any GA. This predictive power is similar to the predictive power of the Framingham risk score for coronary heart disease, similar to the recently developed risk score for glaucoma and also similar to the prediction of advanced AMD using demographic and environmental variables. When the score is computed without consideration of night vision there is a decrease in prediction power.
To our knowledge, this is the first study to develop risk scores specifically for predicting GA rather than CNV and GA combined. Data from CAPT is especially well-suited for developing a model for GA because participants had substantial drusen burden (each eye have at least 10 large drusen (≥125 µ)), were followed prospectively at least 5 years, and had yearly color photographs taken by certified photographers with interpretation at a central reading center.
The GA risk scores we developed may improve the design and analysis of clinical trials to prevent GA. Progression from drusen to GA takes years, and only a small percentage of AMD patients will develop GA even among those starting with bilateral large drusen (6.8% for endpoint GA in CAPT participants, and 6% for CGA in AREDS participants). The night vision questionnaire may be used when screening patients to more finely stratify patients by risk of developing GA than is possible with knowledge of only age, cigarette smoking, hypertension, presence of large drusen or pigmentation changes.
The GA risk scores also provide an easy way for ophthalmologists to estimate the 5-year risk of developing GA among their AMD patients. These estimates may help in explaining the implications of newly detected signs of early AMD to patients.
Our risk score was developed from readily available risk factors, and it does not consider other risk factors that are more difficult to obtain, specifically the genetic risk factors. Complement Factor H, Complement Factor B, LOC387715 and complement C3 variant were recently found to be associated with risk of GA. Including these genetic risk factors and other risk factors (such as dietary or supplemental antioxidant intake) in the risk score development may improve its predictive power for GA. Seddon et al recently developed a comprehensive predictive model for advanced AMD (CNV and GA combined) based on both genetic, demographic and environmental variables, and found that the AUC (c-statistic) improved from 0.73 to 0.83 when genetic data was included in the prediction model.
In summary, the GA risk scores developed from the CAPT data discriminated several levels of risk and provided accurate estimates of risk for the CAPT participants. If the discrimination and accuracy are validated in other independent groups of patients, they will provide useful tools for identifying high risk patients for clinical trials for prevention of GA and for GA risk assessment of AMD patients.
Read more...
Ophthalmology. 2011 Feb;118(2):332-8
