Adult vitelliform dystrophy (AVD), also known as adult-onset foveomacular vitelliform dystrophy, is an acquired macular condition that typically presents in middle-aged or older adults. It is a slowly progressive disorder that causes central visual disturbances, often taking the form of subtle vision loss or metamorphopsia. Because its clinical presentation and fundus appearance can resemble age-related macular degeneration (AMD), AVD is sometimes misdiagnosed. However, these are distinct conditions, differing in their genetic background, pathological mechanisms, natural history, and management strategies.
Overview of Adult Vitelliform Dystrophy
AVD is part of a group of conditions called pattern dystrophies, which involve dysfunction of the retinal pigment epithelium (RPE). Most cases are associated with mutations in the PRPH2 gene (formerly known as the RDS gene), which encodes peripherin-2, a protein involved in the structure of photoreceptor outer segments. AVD typically appears between the ages of 40 and 60, with no significant sex predilection, and is usually bilateral but may be asymmetric in appearance.
The hallmark lesion in AVD is a yellow, round or oval, subretinal deposit at the fovea that resembles an “egg yolk.” This lesion results from the accumulation of lipofuscin-like material between the photoreceptors and the RPE. Over time, this material can become fragmented or reabsorbed, resulting in variable degrees of retinal atrophy and, occasionally, mild scarring.
Clinical Presentation
Patients with AVD often present with mild visual symptoms. These may include:
Blurred central vision
Metamorphopsia (distorted vision)
Difficulty with reading or recognizing faces
Some individuals remain asymptomatic, and the condition may be discovered incidentally during routine eye exams. Visual acuity is usually well preserved in early stages, and many patients maintain functional central vision for years.
Funduscopically, the early lesion appears as a well-circumscribed, yellow, foveal deposit. As the disease progresses, the lesion may go through different phases:
Vitelliform stage: the “egg yolk” appearance
Pseudohypopyon stage: layering of material within the lesion, giving a fluid level appearance
Vitelliruptive stage: fragmentation of the deposit, resembling a “scrambled egg”
Atrophic stage: degeneration of overlying photoreceptors and underlying RPE
In some cases, patients may develop choroidal neovascularization (CNV), but this is relatively rare compared to AMD.
Diagnostic Workup
AVD diagnosis is based on clinical examination, supported by multimodal imaging. Optical coherence tomography (OCT) shows subretinal hyperreflective material in the foveal region, often dome-shaped in early disease, with potential disruption of the ellipsoid zone and retinal thinning in later stages.
Fundus autofluorescence (FAF) is a useful tool, as the vitelliform material is rich in lipofuscin and therefore shows hyperautofluorescence. As the lesion breaks down, the autofluorescence pattern becomes more heterogeneous or reduced.
Fluorescein angiography (FA) may show blocked fluorescence corresponding to the lesion in early stages, with possible staining or transmission defects in later stages.
Unlike in Best vitelliform macular dystrophy, the electrooculogram (EOG) in AVD is typically normal or only mildly abnormal, helping to distinguish the two.
In some cases, genetic testing may be used to confirm mutations in the PRPH2 gene, although this is not required for routine diagnosis and management.
Management and Prognosis
There is currently no definitive treatment for AVD. Management is supportive and involves regular monitoring with OCT and visual acuity testing to assess for progression or the development of complications such as CNV. In rare cases where CNV does occur, anti-VEGF therapy may be indicated, similar to that used in AMD.
The prognosis in AVD is generally favorable. Most patients retain good central vision for many years, and severe visual loss is uncommon. Vision decline, when it does occur, tends to be gradual and is usually due to atrophy in the vitelliruptive or atrophic stages.
Overview of Age-Related Macular Degeneration
Age-related macular degeneration is a leading cause of irreversible vision loss in the elderly. It typically occurs after the age of 60 and is classified into dry (non-neovascular) and wet (neovascular) forms. Dry AMD is characterized by the presence of drusen—extracellular deposits between the RPE and Bruch’s membrane—and may progress to geographic atrophy. Wet AMD, on the other hand, involves the growth of abnormal blood vessels beneath the retina, leading to fluid leakage, hemorrhage, and scar formation.
AMD has a complex etiology involving both genetic and environmental factors. Mutations in genes such as CFH and ARMS2 increase susceptibility, while modifiable risk factors include smoking, hypertension, and diet.
Key Differences Between AVD and AMD
Although AVD and AMD may appear similar on fundoscopic examination, there are important differences between the two conditions. One of the most significant distinctions is age of onset. AVD typically presents in middle-aged individuals, whereas AMD is primarily a disease of those over 60. Additionally, AVD is often linked to inherited mutations, particularly in the PRPH2 gene, while AMD is associated with polygenic risk and lifestyle factors.
The fundus appearance in AVD features a single, well-defined, yellow lesion in the fovea that may break up over time. In contrast, AMD is associated with multiple drusen, pigmentary changes, and, in advanced stages, geographic atrophy or neovascular membranes.
Imaging findings also differ. On OCT, AVD shows subretinal hyperreflective deposits with relatively preserved retinal layers early in the disease. AMD often shows drusen beneath the RPE, RPE detachment, or intraretinal/subretinal fluid in the neovascular form. FAF imaging in AVD typically shows strong central hyperautofluorescence, while AMD shows patchy areas of hypo- and hyperautofluorescence, especially in geographic atrophy.
In terms of prognosis, AVD tends to be more benign, with relatively stable central vision and slow progression. AMD, particularly the neovascular form, can lead to rapid and severe central vision loss if untreated. While AVD usually does not require intervention, wet AMD is treated with intravitreal anti-VEGF injections. The AREDS supplements, often recommended for intermediate or advanced dry AMD, have no established benefit in AVD.
Lastly, complications such as CNV are common in wet AMD but rare in AVD, making this another key differentiating point when considering treatment options.
Conclusion
Adult vitelliform dystrophy is a rare, inherited macular condition that is often mistaken for age-related macular degeneration due to overlapping clinical features. However, the two disorders differ in age of onset, genetic background, lesion characteristics, imaging findings, prognosis, and management. Recognizing these differences is crucial to avoid misdiagnosis, prevent unnecessary treatments, and provide accurate counseling. Patients with AVD generally retain good visual function for many years, and careful monitoring is usually sufficient. In contrast, AMD—especially in its neovascular form—requires active intervention to prevent vision loss. By distinguishing these conditions based on clinical and imaging features, ophthalmologists can ensure appropriate care and optimize outcomes for their patients.