Overview
Adult-onset vitelliform macular dystrophy (AVMD) is a macular dystrophy presenting in the 4th–6th decade with a characteristic egg-yolk (vitelliform) lesion at the fovea, caused by mutations in BEST1, PRPH2, IMPG1, or IMPG2. Unlike Best disease (which presents in childhood), AVMD has a later onset and generally milder course. Visual acuity is often preserved until the lesion enters the vitelliruptive or atrophic stage. It is frequently misdiagnosed as AMD.
Genetics
Multiple causative genes. BEST1 mutations cause both Best disease (childhood) and AVMD (adult onset). PRPH2 and IMPG1/2 are also common causes. All autosomal dominant.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| BEST1 | 11q12.3 | AD | Bestrophin-1; allelic with Best disease; most common AVMD gene |
| PRPH2 | 6p21.1 | AD | Peripherin-2; allelic with RP and pattern dystrophy |
| IMPG1 | 6q14.2 | AD | Interphotoreceptor matrix proteoglycan 1 |
| IMPG2 | 3q12.3 | AD/AR | Interphotoreceptor matrix proteoglycan 2 |
Clinical Presentation
Vitelliform stage
- Egg-yolk lesion at fovea
- Often asymptomatic or mild metamorphopsia
- Near-normal visual acuity
Vitelliruptive stage
- Lesion breaks up ('scrambled egg')
- Visual acuity begins to decline
- Metamorphopsia worsens
Atrophic/CNV stage
- Geographic atrophy or CNV
- Significant central vision loss
- Peripheral vision preserved
Diagnosis
- Fundus: Characteristic vitelliform lesion at fovea
- OCT: Subretinal hyperreflective material
- FAF: Hyperautofluorescent vitelliform lesion
- EOG: Reduced Arden ratio (in BEST1-associated cases)
- Genetic testing: BEST1, PRPH2, IMPG1/2 sequencing
Current Research & Treatment
Anti-VEGF for CNV. BEST1 gene therapy is in clinical trials (NCT03001310 — AAV2-hBEST1). The Best Disease Gene Therapy Program at University of Iowa is a leading research center.
Active Clinical Trials
The following active clinical trials are investigating treatments for Adult-Onset Vitelliform Macular Dystrophy. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.