Geographic atrophy (GA) represents an advanced form of age-related macular degeneration (AMD), accounting for a significant portion of vision loss within the population. The prevalence of GA worldwide is estimated to be about 5 million people, while in the United States, the disease affects approximately 1 million people, with 160,000 new cases occurring each year.1,2
The average age of a patient with GA is 79 years.3 For every decade after 50 years of age, the prevalence quadruples from 0.15 to 2.91% at 80 years of age.4 The incidence of GA is projected to increase in the coming decades, due in part because of a surge in the aging population—the so-called "silver tsunami"—but also because of the present burgeoning awareness of this unique disease state.5
Understanding the many nuanced aspects of GA, including its pathophysiological development, course and prognosis, key features and findings, risk factors, and options for disease management can be somewhat overwhelming, especially for those without extensive experience managing retinal conditions.
What you need to know about the flashcard challenge
That’s why we assembled a team of top retinal experts in optometry to create this unique and innovative learning tool, designed to help clinicians sharpen their diagnostic skills and improve their confidence in referring patients with suspected GA.
Here, we’ll present a series of virtual “flashcards” depicting a representative diagnostic image and/or a clinical scenario in order to sharpen your clinical acumen in a fun and engaging way. Just like in school, you’ll have the opportunity to test your knowledge and decision-making skills from the comfort of your home, office, or your favorite GA study spot!
We hope that you’ll find this to be an engaging and helpful exercise, and one that will help you gain confidence while refining your expertise in recognizing and diagnosing patients with GA.
Diagnosing GA and understanding risk factors
A history of smoking significantly increases the risk of developing GA. Current smokers have a fourfold higher risk of developing late AMD as compared to non-smokers, while past smokers have a threefold higher risk of GA than non-smokers.6,7
The number of pack-years smoked is also a major factor in determining the risk of GA.8,9 Even if a patient already has AMD, it will progress faster if they continue to smoke.
A history of cardiovascular disease has also been noted to increase the risk of developing late AMD by 2.2x.10 It has also been noted that patients with AMD are at a higher risk of developing cardiovascular disease, further exemplifying the commonalities between these two multifactorial complex diseases.
Tracking GA progression
The median time for a patient with extra-foveal GA to develop center-involving GA is 2.5 years.11 As GA encroaches on the fovea, visual function decreases, and the risk of symptomatic vision loss increases.
When diagnosing extra-foveal GA, it is important to monitor these patients carefully (every 3 to 6 months) to monitor for progression and referral to a retinal specialist to consider treatment with complement inhibition therapy. The risk of a unilateral GA patient developing GA in the fellow eye within 12 months is 30%.12
GA patients with a fundus autofluorescence (FAF) pattern that includes hyper-FAF are at higher risk for developing more rapidly progressing GA.12 It is thought that the hyper-FAF area represents a “sick RPE,” which is more likely to atrophy.
Patients with banded patterns of hyper-FAF (as in the patient above) or diffuse patterns of hyper-FAF are more likely to develop rapidly progressing GA as compared to patients with no hyper-FAF or focal hyper-FAF patterns.12
It is important to detect GA early on in the disease process because early treatment will likely lead to better visual outcomes.
Identifying GA biomarkers
iRORA is considered a precursor to cRORA and is defined by:13
- Choroidal hypertransmission
- RPE attenuation or disruption
- Overlying photoreceptor degeneration
- Can not fulfill criteria for cRORA
Hyperreflective foci (HRF) are highly reflective lesions visualized with OCT. HRF are thought to represent RPE cells that have migrated anteriorly. These lesions may correlate to focal areas of pigment hypertrophy in AMD patients. The presence of HRF in AMD patients is an independent risk factor for the development of GA.14
Hyporeflective wedges are triangular wedge-shaped areas of decreased reflectivity noted within the outer retina that can only be visualized with OCT.15 Hyporeflective wedges are thought to represent damaged photoreceptors and are associated with progression to GA.
Subretinal drusenoid deposits (SDDs) confer a greater risk factor for the development of GA than soft drusen.15 SDD are extracellular deposits located above the RPE as compared to soft drusen which are located below the RPE.
Treating GA
The complement pathway is a part of the innate immune system which induces an inflammatory response to combat infection. The complement cascade can be initiated by 3 different pathways: the classical, lectin, and alternative.16
Dysregulation of the complement pathway has been associated with pathological retinal/RPE inflammation and retinal/RPE cell damage/death.16 Complement pathway inhibition with IZERVAY (avacincaptad pegol) and SYFOVRE (pegcetacoplan) has been shown to slow down the progression of GA.
Currently, there is no way to reverse RPE/retinal atrophy or vision loss from GA. Similar to glaucoma management, our goal as eyecare providers is to detect GA patients early in the disease process and consider treatment with IZERVAY (avacincaptad pegol) or SYFOVRE (pegcetacoplan) to help preserve their vision for as long as possible.
When discussing complement inhibition therapy, there are some important adverse events to keep in mind:
- Increased risk of choroidal neovascularization
- The use of intravitreal complement inhibition in GA patients increases the risk of choroidal neovascularization from 3 to 4% to 7 to 12%.17,18
- Risk of retinal vasculitis
- No cases of retinal vasculitis have been reported with the use of IZERVAY (avacincaptad pegol).17
- 14 eyes of 13 patients have developed retinal vasculitis after treatment with SYFOVRE (pegcetacoplan).19
- Risk of ischemic optic neuropathy
- No cases of ischemic optic neuropathy have been reported with the use of IZERVAY (avacincaptad pegol).17
- 1.7% (dosed every month) and 0.2% (dosed every other month) of patients developed ischemic optic neuropathy after treatment with SYFOVRE (pegcetacoplan).18
