In this episode of Ready, Set, Retina, Daniel Epshtein, OD, FAAO sits down with Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO, to review a geographic atrophy (GA) case report and discuss the importance of long-term care and patient education for GA patients.
Dr. Rafieetary practices at the Charles Retina Institute in Germantown, Tennessee, and is the current President of the Optometric Retina Society.
What is geographic atrophy?
Geographic atrophy is an advanced form of dry age-related macular degeneration (AMD) characterized by localized sharply demarcated atrophy of the outer retinal tissue, retinal pigment epithelium (RPE), and underlying choriocapillaris.1 Typically, GA lesions first appear in the perifoveal region and then expand to involve the fovea with time, leading to progressive and irreversible loss of visual function.
According to the Cleveland Clinic, more than 8 million people in the world have GA, with an estimated 1 million people in the US impacted by the condition.2 Further, GA affects around 20% of all people with AMD. Prior to 2023, there was no proven treatment for GA, which translated to a significant economic burden on the healthcare system and a major burden on affected patients.3
Last year, the US Food and Drug Administration (FDA) approved two interventions for GA: intravitreal pegcetacoplan (SYFOVRE, Apellis Pharmaceuticals, Waltham, MA) and avacincaptad pegol (IZERVAY, Astellas Pharma US, Northbrook, IL).4 Although both treatments are complement inhibitors, pegcetacoplan is a complement C3 inhibitor, while avacincaptad pegol is a complement C5 inhibitor.
Geographic atrophy case report
Case presentation
A 75-year-old white female patient presented to the clinic for a second opinion following recent cataract surgery in both eyes since her vision had not improved after the procedure as expected.
The patient’s medical history was remarkable for hypertension, myocardial infarction (for which she had an angioplasty and stent placement), high cholesterol, anemia, and asthma. She was also a current smoker and reported smoking around one pack per day. The patient's best-corrected visual acuity (BCVA) was 20/40 in both eyes.
Figures 1 and 2 are color fundus photography (CFP) in the right and left eye, respectively, of the patient at baseline. They show large demarcated areas of hypopigmentation caused by atrophic lesions from GA.
Figure 1: The blue arrow denotes well-demarcated hypopigmented atrophic lesions consistent with GA. (Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO)
Figure 2: The blue arrow denotes well-demarcated hypopigmented atrophic lesions consistent with GA. (Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO)
Diagnosis and management
Dr. Rafieetary diagnosed the patient with GA (i.e., ICD-10 code advanced atrophic AMD without subfoveal involvement [H35.31X3]. He added that, according to the patient, the referring eyecare practitioner (ECP) had not communicated with her about the degree of macular degeneration in her eyes.
After explaining the availability of intravitreal complement inhibitor therapies to the patient, she responded that she wasn’t interested in treatment due to her concomitant conditions and issues with accessing transportation. He noted that this conversation was over a year ago, and he hasn’t seen the patient since—which is unfortunate due to the progressive nature of GA.
Multimodal imaging of geographic atrophy
Near-infrared reflectance (NIR) imaging
Figures 3 and 4 show NIR imaging of the patient's OD and OS, respectively; as seen in the images, GA lesions show up as hyperreflective on NIR imaging.
Figure 3: Collection of hyperreflective GA lesions in the right eye. (Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO)
Figure 4: Coalesced and larger hyperreflective GA lesions in the left eye. (Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO)
Optical coherence tomography (OCT)
As AMD is a disease of the outer retina, Dr. Rafieetary emphasized the importance of evaluating the RPE, ellipsoid zone, and outer nuclear layer (ONL) on OCT imaging. ONL degeneration is particularly worth noting because it indicates the loss of photoreceptors.
In addition, he noted the absence of the choroid (seen below as choroidal hypertransmission on OCT) suggests that from this point on the patient will likely experience worsening vision due to GA progression. Dr. Rafieetary also identified areas of incomplete RPE and outer retina atrophy (iRORA) and complete RPE and outer retina atrophy (cRORA) on the patient’s OCT imaging.
He then highlighted the hyperreflective foci on the patient’s OCT imaging and explained that sometimes these can be detected as hyperpigmentation during clinical examinations. Of note, studies have found that the number and volume of hyperreflective foci are associated with an increased risk of atrophy in patients with AMD.5,6
Figure 5: OCT imaging OD that shows hyperreflective foci, outer retinal atrophy, and choroidal hypertransmission.
Figure 5: Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO.
Figure 6: OCT imaging OS that demonstrates hyperreflective foci and choroidal hypertransmission.
Figure 6: Courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO.
GA progression: Multimodal imaging from 12 years prior
Dr. Rafieetary noted that this case made him reflect on the timeline that ECPs tend to see patients in—which is typically relatively short (ex., 1 to 6 months or 1 year). He added that it can be challenging to follow up with patients over longer periods of time (i.e., 5 to 10 years) to monitor progressive diseases like AMD or GA.
He recommended that optometrists consider the patient’s long-term health at routine visits and proactively educate patients on the impact of diet and lifestyle choices on their future ocular health, similar to how a financial advisor factors in long-term calculations for investments.
He also noted that risk factors, such as sleep apnea, obesity, hypertension, high cholesterol, and smoking, are important to consider when determining if patients have a higher risk of progressing to GA. Dr. Epshtein remarked that in his clinical experience, many patients with advanced AMD tend to have concomitant cardiovascular disease.
Carousel 1 shows the patient’s NIR imaging from 12 years ago and the most recent NIR imaging, highlighting the development of GA lesions.
Carousel: Images courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO.
Carousel 2 shows the patient’s OCT imaging from 12 years ago and the most recent OCT imaging, revealing an increase in choroidal hypertransmission and hyperreflective foci due to GA progression.
Carousel 2: Images courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO.
Carousel 3 shows the patient’s color fundus photography from 12 years ago and the most recent CFP, demonstrating the progression of drusen to geographic atrophy OS.
Carousel 3: Images courtesy of Mohammad Rafieetary, OD, FAAO, FORS, ABO, ABCMO.
When to bring up complement inhibitor therapies with GA patients
Dr. Rafieetary mentioned complement inhibition therapy to this patient because she was beginning to experience diminished visual function, had a high risk of disease progression, and would likely experience a reduction in quality of life without intervention.
When explaining the benefits of complement inhibition therapies to a patient with multifocal lesions, he remarked that instead of the patient beginning to notice changes to their vision in 2 to 3 years, the timeline would potentially be extended to 7 or 10 years—and in 10 years other interventions may be developed to reverse or address the retinal tissue damage.
Conclusion
Takeaways for optometrists treating GA patients include:
- Identify relevant risk factors that predispose patients to GA progression, such as smoking, hypertension, cardiovascular disease, high cholesterol, obesity, and sleep apnea
- Look for biomarkers on multimodal imaging, including NIR, OCT, CFP, and fundus autofluorescence (FAF)
- Consider patient education and treatments for both the patient’s short- and long-term ocular health
- Introducing complement inhibition therapies to patients early empowers them to make informed medical decisions and gives them some level of hope
