Age-related macular degeneration (AMD) remains an uncurable progressive disease. Even patients with early and intermediate stage AMD may suffer visual deficits such as reduced best corrected visual acuity, metamorphopsias, decreased contrast sensitivity, and delayed dark adaptation. If patients progress to advanced stages of disease, they can be left with debilitating central vision loss inhibiting their abilities to drive and perform tasks of daily living. Advanced stage AMD is categorized as exudative or atrophic. In exudative AMD, formation of macular neovascularization (MNV) can quickly lead to submacular scarring and photoreceptor atrophy. In advanced atrophic AMD, formation of geographic atrophy (GA) leads to progressively enlarging areas of retinal pigment epithelium (RPE) and photoreceptor atrophy.   

Historically, treatment of AMD centered around lifestyle modifications, appropriate vitamin supplementation, and treatment of MNV with anti-VEGF injections. In the United States Recent FDA approval of intravitreal complement factor inhibitors for the treatment of GA has changed the conversation for patients with advanced atrophic AMD. These patients now have a treatment option that can slow down the progression of GA and maintain their central vision longer. This innovation makes it highly important to identify and properly educate patients with GA about these treatment options.

This case demonstrates the progression of intermediate stage AMD to advanced atrophic AMD over the course of 9 years, showing imaging characteristics that imply greater risk of conversion to advanced AMD and highlighting how to identify GA on optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging.

In 2012, a 70-year-old white female presented to clinic for evaluation of her AMD. She felt her vision was good and had 20/20 visual acuity OD and OS. She did not smoke and did not have any systemic vascular diseases such as hypertension. She focused a lot of energy on her diet which was heavy in fresh vegetables such as spinach and kale, and she generally tried to avoid sugary or processed foods. She was faithfully taking AREDS 2 vitamin supplements, wore sunglasses when she was outdoors, and used an Amsler grid daily.

While the patient was doing very well to mitigate modifiable risk factors, her imaging showed higher risk of conversion to advanced stage disease. (Image 1 and 2) On the OCT cross section scans, both eyes had large sized drusen (yellow arrows). These large drusen created hyper-autofluorescence on the FAF. Data from the AREDS trials showed that patients with large sized drusen are at higher risk of developing advanced stage AMD than those without. Those with large drusen in both eyes had 12% chance of developing advanced stage AMD over 5 years.1 In addition to having large sized drusen in both eyes, she also had a type of drusen described as reticular pseudodrusen (RPD) or subretinal drusenoid deposits. On FAF RPD typically present as small hypo-autofluorescent spots distributed in a reticular pattern. They are also seen well on infrared or near infrared reflectance imaging. On OCT, they can be seen as small hyper-reflective projections that sit on top of the RPE. The blue arrows on the FAF and near IR photos point towards regions of RPD. The blue arrows on the cross-section OCT scans point to individual RPD. Patients with RPD tend to have worse visual function and have higher risk to develop advanced AMD, particularly through the development of GA. Their risk of advance AMD is even higher than those with just large sized drusen.2-5

The patient was educated about her higher risk of developing advanced AMD but was encouraged that she was taking all steps possible at that time to preserve her vision. The patient wished to follow up with her primary optometrist and return if necessary. 

In 2021, the patient was referred back for re-evaluation due to decreased visual acuity in the OD. Her best corrected acuity OD had dropped to 20/80. OS best corrected acuity was 20/25. She felt this change had been fairly dramatic over the last few months, and she was noticing distortion on her Amsler grid in the OD. Since 2012, she had been diligent about observing a healthy diet and lifestyle, taking AREDS 2 supplements, and wearing sunglasses when outdoors. Sudden vision changes in those with AMD are very concerning for development of MNV, but her imaging showed a different story. 

When comparing the OCT cross section scans from 2012 to 2021, there was significant regression of the large sized drusen that were present in 2012. Sudden and dramatic regressions of large drusenoid PEDs can be a precursor to development of GA.6-9 In place of the large drusen centrally in the OD, there was prominent hyper transmission of light into the choroid: a sign of RPE atrophy associated with GA development.10 There was also clear atrophy of the RPE, loss of the photoreceptor integrity line (PIL), and dehiscence and disorganization of the outer nuclear layer (ONL). Essentially, the acuity change in the OD was from development of GA. On OCT GA will present with hyper-transmission defects into the choroid, loss of the RPE and PIL, atrophy/thinning of the ONL, and caving downward of the inner retinal layers.11 

On FAF, GA will present as regions of hypo-autofluorescence.11 The FAF’s in 2021 both showed presence of multiple patches of GA (dark patches on the FAF). The GA centrally in the OD was somewhat masked by the normal macular pigment (which makes the area dark) and imaging quality at this exam. The red arrows on the OCT cross section scans and the FAF point to corresponding areas of GA. 

The FAF and near IR photos in 2021 showed increased regions of RPD (blue arrows). In addition, the OCT cross section scan of the OS shows atypical cone shaped drusen deposits with patchy internal reflectivity (green arrows). These have been described as conical debris or ghost drusen and are highly associated with presence or development of advanced atrophic AMD.12

This change of disease over the course of 9 years was discussed with the patient. This type of conversion is not an easy one to have with a patient: her visual acuity had dropped in the OD and she had paracentral GA in the OS—and there was nothing more that could be done for the disease at the time. The patient was encouraged; however, that promising treatments for GA may be approved.

This brings us to the current year, 2023. The patient’s acuity has fortunately maintained 20/80 OD and 20/25 OS; however, there has been increase in GA area during this time OU. This patient is an ideal candidate for newly approved intravitreal complement inhibitors that have been shown to slow down GA progression and maintain vision longer. It is critical to identify patients with GA and have conversations about new treatment options. This patient is highly motivated to begin treatment as soon as possible.   

Lastly, always remember that patients with visual decline from uncurable sources who struggle with ADL’s should be educated about low vision options and resources in your area.  


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