| Domain | Key points | Quantitative data | Key source (include DOI/URL + year) |
|---|---|---|---|
| Definition / classification | AOFVD/AFVD is a retinal pattern dystrophy characterized by subfoveal vitelliform material on fundus exam and multimodal imaging; often bilateral; slow progression but can lead to vision loss from CNV or macular atrophy. Debate persists about strict inclusion among pattern dystrophies because inheritance is often not clearly autosomal dominant. Synonyms used in the literature include adult vitelliform macular degeneration, adult macular vitelliform degeneration, pseudovitelliform macular degeneration, adult-onset foveomacular pigment epithelial dystrophy, adult foveomacular vitelliform dystrophy, and adult vitelliform macular dystrophy. (pqac-00000026, pqac-00000034, pqac-00000028) | Approximate prevalence reported as 1:7,400 to 1:8,200; AFVD described as the common phenotype among pattern dystrophies. (pqac-00000026, pqac-00000028, pqac-00000033) | Nipp et al., 2023, Front. Ophthalmol., DOI: 10.3389/fopht.2023.1237788, https://doi.org/10.3389/fopht.2023.1237788; Jaskoll et al., 2024, IOVS, DOI: 10.1167/iovs.65.13.53, https://doi.org/10.1167/iovs.65.13.53 |
| Epidemiology / onset | Most patients are diagnosed between ages 50–70, although reported onset ranges extend from ~30 to 80 years; AFVD is frequently misdiagnosed as AMD. (pqac-00000027, pqac-00000035) | Mean age in one 2023 case series: 62.75 years (12 patients, 19 eyes). In the 2024 genetics cohort: AFVD mean age 73 ± 10 years (n=50). (pqac-00000037, pqac-00000033) | Tesfaw & Bernstein, 2023, JOECSA, DOI: 10.64666/joecsa.2023.81, https://doi.org/10.64666/joecsa.2023.81; Jaskoll et al., 2024, https://doi.org/10.1167/iovs.65.13.53 |
| Gene evidence: PRPH2 | PRPH2 encodes peripherin-2, important for rod/cone outer segment disc formation and stabilization. It is the most commonly reported mutated gene in AOFVD but is not present in most cases; some authors consider it more of a predisposing factor in many patients than a universal monogenic cause. Pattern dystrophies are mainly autosomal dominant, and PRPH2 is associated with almost all pattern dystrophies. (pqac-00000035, pqac-00000023, pqac-00000039) | Reported to account for only 2%–18% of AOFVD patients. (pqac-00000027, pqac-00000035) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, DOI: 10.24190/issn2564-615x/2017/s1.27, https://doi.org/10.24190/issn2564-615x/2017/s1.27 |
| Gene evidence: BEST1 | BEST1 (formerly VMD2) encodes bestrophin-1, an RPE-predominant transmembrane protein involved in ion channel function and intracellular calcium signaling. BEST1 mutations are classic for Best disease and have also been reported in some AOFVD/AVMD cases; some late-onset mild cases may represent mild Best disease. However, BEST1 mutations are absent in most AOFVD patients, so AFVD remains largely a clinical diagnosis with no formal genetic-testing guideline. (pqac-00000035, pqac-00000025, pqac-00000023) | In a testing-focused review, BEST1 variants were reported as common in AVMD: 96% with positive family history and 50%–70% of sporadic cases, but this estimate comes from the testing review context and not all clinically defined AOFVD cohorts. (pqac-00000022) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, https://doi.org/10.24190/issn2564-615x/2017/s1.27 |
| Gene evidence: IMPG1 | IMPG1 and IMPG2 encode extracellular/interphotoreceptor matrix proteins involved in retinal adhesion. Primary genetic evidence shows IMPG1 mutations cause vitelliform macular dystrophies, including both autosomal dominant and autosomal recessive forms. Reported IMPG1 variants include missense, splice-site, and nonsense changes; disease mechanism implicates impaired interphotoreceptor matrix biology. (pqac-00000017, pqac-00000018, pqac-00000016) | In familial AOFVD patients lacking PRPH2/BEST1 mutations, IMPG1/2 mutations were found in 4/49 (~8%); likely <8% among all AOFVD. Primary IMPG1 report identified recurrent p.Leu238Arg and additional c.807+1G>T, p.Leu154Pro, p.Arg507*. (pqac-00000027, pqac-00000017) | Manes et al., 2013, Am J Hum Genet, DOI: 10.1016/j.ajhg.2013.07.018, https://doi.org/10.1016/j.ajhg.2013.07.018; Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788 |
| Gene evidence: IMPG2 | IMPG2 is also implicated in AOFVD/AVMD and, like IMPG1, encodes an extracellular matrix protein important for retinal adhesion/interphotoreceptor matrix structure. Evidence supports its contribution in a minority of cases and in familial disease lacking PRPH2/BEST1 mutations. (pqac-00000035, pqac-00000023, pqac-00000007) | Combined IMPG1/IMPG2 frequency in familial AOFVD without PRPH2/BEST1 mutations: 4/49 (~8%). (pqac-00000027) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Abeshi et al., 2017, https://doi.org/10.24190/issn2564-615x/2017/s1.27 |
| Clinical stage 1: Vitelliform | Classic “egg-yolk” lesion: yellowish-white, rounded, centered on the fovea. OCT shows dome-shaped homogeneous subretinal hyperreflective material between RPE and neurosensory retina. FAF is hyperautofluorescent. FA shows a non-fluorescent central spot with a hyperfluorescent spoked ring and no leakage. (pqac-00000036, pqac-00000029, pqac-00000003) | In one 2023 series, 10/19 eyes were stage I. (pqac-00000037) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81 |
| Clinical stage 2: Pseudohypopyon | Layering of vitelliform material within the lesion. OCT shows two zones: upper hyporeflective/optically clear space and lower homogeneous hyperreflective material; intraretinal pseudocysts may occur. FAF shows hyperautofluorescent inferior half and hypoautofluorescent superior half. FA may show a “stars-in-the-sky” appearance. The optically clear space may help distinguish AFVD from neovascular AMD. (pqac-00000036, pqac-00000037, pqac-00000002) | In one 2023 series, 5/19 eyes were stage II; optically clear subretinal spaces were seen in 6/19 eyes overall, including 5 pseudohypopyon eyes; 4/5 pseudohypopyon eyes had intact IS/OS interfaces. (pqac-00000037) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81 |
| Clinical stage 3: Vitelliruptive | “Scrambled egg” stage with breakup and reabsorption of the lesion. OCT shows fragmented vitelliform material with mixed hyper-/hyporeflective spaces, hyperreflective clumps, and increasing photoreceptor loss/ellipsoid zone disruption. FAF becomes hypoautofluorescent; FA may retain a “stars-in-the-sky” pattern. (pqac-00000036, pqac-00000029, pqac-00000003) | In one 2023 series, 4/19 eyes were stage III; IS/OS disruption was seen in 8/19 eyes total, including 4 stage III eyes. (pqac-00000037) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81 |
| Clinical stage 4: Atrophic | Final stage after lesion resorption; not all eyes with lesion resorption become atrophic. OCT shows widespread photoreceptor-layer loss and RPE atrophy/cRORA. FAF is hypoautofluorescent. FA shows late hyperfluorescence of the atrophic area; color photography may show pale fundus/visible choroidal vessels. (pqac-00000036, pqac-00000035) | No atrophic eyes were present in the 19-eye 2023 Ethiopian series. (pqac-00000000, pqac-00000002) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81 |
| Imaging / differential diagnosis | SD-OCT and OCTA are central for diagnosis and for distinguishing AFVD from AMD and Best disease. OCTA may detect CNV not seen on FA; one cited example detected CNV in 1/8 eyes on OCTA not seen on FA. EOG and full-field ERG are often normal or only mildly abnormal, supporting focal rather than generalized dysfunction. (pqac-00000005, pqac-00000004, pqac-00000001) | OCTA-detected CNV missed by FA: 1/8 eyes in one cited report. In the 2023 19-eye series, presenting VA ranged from 20/100 to 20/20. (pqac-00000005, pqac-00000037) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Tesfaw & Bernstein, 2023, https://doi.org/10.64666/joecsa.2023.81 |
| Prognosis / complications | Visual course is often relatively benign, but decline is greater with stage progression, CNV, or macular atrophy. Reported complications include CNV, macular atrophy, PED, retinal folds, macular coloboma, and RPE aperture. (pqac-00000005, pqac-00000036) | Example natural-history data: in 28 eyes followed 1–5 years, 10 stable, 11 worse, 4 improved; progression to vitelliruptive/atrophic stages reduced BCVA from 20/50 to 20/104 versus minimal change when stable at vitelliform stage (20/36 to 20/39). CNV prevalence around 15% is reported in review summaries. (pqac-00000005, pqac-00000001) | Nipp et al., 2023, https://doi.org/10.3389/fopht.2023.1237788; Jabłoński & Mackiewicz, 2026, https://doi.org/10.5114/oku/215545 |
| 2024 development: AFVD genetic overlap with AMD/complement | A 2024 IOVS study examined non-monogenic AFVD and found partial genetic overlap with AMD, especially in complement-related loci, while major AMD loci such as ARMS2/HTRA1 were not similarly associated with AFVD. The study suggests complement dysregulation may contribute to a subset of AFVD and raises complement inhibition as a future research direction. (pqac-00000008, pqac-00000010, pqac-00000011, pqac-00000033) | Cohort: 50 AFVD, 917 AMD, 432 controls; 52 AMD-linked SNPs tested. AFVD-associated loci vs controls: CFH rs570618 OR 2.73 (95% CI 1.32–5.73; P=0.01); C2/CFB/SKIV2L rs116503776 OR 0.31 (0.14–0.71; P=0.0036); rs114254831 OR 0.41 (0.22–0.74; P=0.0025); MIR6130/RORB rs10781182 OR 0.13 (0.06–0.25; P<0.0001) vs controls and OR 0.19 (0.10–0.34; P<0.0001) vs AMD. Complement GRS OR 1.42 (1.04–1.95; P=0.03); other-pathways GRS OR 0.46 (0.21–0.98; P=0.04). Plasma complement activation did not differ significantly among AFVD, AMD, and controls. (pqac-00000008, pqac-00000010, pqac-00000011, pqac-00000033) | Jaskoll et al., 2024, Invest. Ophthalmol. Vis. Sci., DOI: 10.1167/iovs.65.13.53, https://doi.org/10.1167/iovs.65.13.53 |


*Table: This table condenses the most evidence-supported findings on adult-onset foveomacular vitelliform dystrophy, including nomenclature, genetics, multimodal imaging stages, prognosis, and the major 2024 complement-genetics development. It is useful as a high-density reference for disease knowledge-base curation.*