This narrative review aims to explore the correlation between choroidal thickness (CT), broader choroidal changes, and the development and progression of vitelliform lesions, with a focus on their potential modulatory role-whether primary or secondary- through mechanisms involving choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction. CT was found to be significantly increased in various vitelliform maculopathies, including adult-onset foveomacular vitelliform dystrophy (AOFVD), Best disease, autosomal recessive bestrophinopathy, age-related macular degeneration (AMD), and pachychoroid disease spectrum (PDS) disorders. Notably, increased subfoveal CT was associated with the presence and progression of subretinal hyperreflective material and subretinal fluid in AOFVD and Best disease. In PDS disorders, choroidal thickening, pachyvessels, and choroidal vascular hyperpermeability were identified as key contributors to RPE dysfunction and vitelliform lesion formation. Conversely, leptovitelliform maculopathy was characterised by thinner choroid in association with reticular pseudodrusen or subretinal drusenoid deposits. An important feature is CC dysfunction, which is often associated with pachyvessels, even in the absence of a clear pachychoroid-related phenotype or choroidal thickening. These findings underscore the importance of CT evaluation in clinical practice and highlight the need for further research to elucidate the complex relationship between CT and vitelliform maculopathies.

To assess the outcomes and safety of cataract surgery in Adult-Onset Foveomacular-Vitelliform dystrophy (AFVD) patients. This retrospective study analyzed eyes with AFVD that underwent cataract surgery in a tertiary center, comparing them with eyes affected by none and neovascular age-related macular degeneration (NVAMD). Data included demographics, best-corrected visual acuity LogMAR (VA), eye examination results, and optical coherence tomography (OCT) results. The primary outcome was improvement in VA. A secondary outcome was AFVD progression such as the development of choroidal neovascularization (CNV) or retinal atrophy. The cohort included 83 eyes (18 with AFVD, 27 with none-NV AMD, and 38 with NVAMD). AFVD eyes showed significant improvement in VA±SD from pre-surgery (0.60 ± 0.34) to 1 month (0.23 ± 0.11; P < 0.0001) and 12 months post-operatively (0.26 ± 0.12; P < 0.0001). No cases of CNV or major AFVD progression changes were observed over 12 months of follow up. However, at last follow-up (62.20 ± 39.30 months) there was increased proportion of atrophic AFVD (44.40% compared to 5.50% at baseline; P = 0.10). No difference was found comparing VA improvement one month after surgery of none-NV AMD, NVAMD and AFVD (AFVD = 0.37 ± 0.36, none-NV AMD = 0.47 ± 0.68, NVAMD = 0.28 ± 0.37; P = 0.29). In the none-NV AMD group, one eye developed CNV ten months post-operatively and another eye demonstrated worsening retinal atrophy one-month post-surgery. In the NVAMD group, 9 eyes developed retinal atrophy at last follow up. Cataract surgery in AFVD eyes led to significant visual acuity improvement and demonstrated good safety with no new CNV or retinal atrophy. The similar visual improvement across the AFVD, none-NV AMD and NVAMD groups suggests the procedure's efficacy and safety for AFVD patients.

To describe the clinical and multimodal imaging findings of two siblings with different vitelliform phenotypes associated with a novel IMPG1 gene deletion. Case series of two siblings. Patients underwent standard optical coherence tomography (OCT), fundus color and short-wavelength fundus autofluorescence (SW-FAF) imaging, fluorescein angiography, and genetic testing for a panel of inherited retinal disorders. A 43-year-old brother and his 41-year-old sister were found to have bilateral vitelliform lesions. The brother presented with single bilateral foveal lesions whereas his asymptomatic sister had multifocal extrafoveal lesions. OCT imaging demonstrated classic subretinal vitelliform lesions in various stages. SW-FAF confirmed that the lesions were hyperautofluorescent. Genetic testing identified an identical heterozygous exon 7 deletion of IMPG1 in both patients. Segregation of a novel deletion in exon 7 of IMPG1 in a family with a vitelliform macular dystrophy, together with a previously reported similar phenotype in patients with heterozygous nucleotide changes within this region of the gene supports the pathogenicity of this variant. Intrafamilial variability in the topography of the lesions with multifocality in one of the siblings suggests retina-wide abnormalities with individual modifiers modulating disease expression.

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

Adult-onset foveomacular vitelliform dystrophy (AFVD) shares phenotypic similarities with age-related macular degeneration (AMD). The genetic factors associated with AFVD are unknown in >80% of cases. This study evaluated the association of known AMD genetic risk variants with AFVD and compared systemic complement activation in these conditions. Clinical, imaging, and genetic data were collected from 50 patients with AFVD (men/women = 25/25, mean age ± SD 73 ± 10 years), 917 patients with AMD (men/women = 377/540, mean age ± SD 77 ± 9 years), and 432 unaffected healthy controls (men/women = 202/230, mean age ± SD 71 ± 8 years). Genotyping focused on 52 single nucleotide polymorphisms (SNPs) linked to AMD. Weighted genetic risk scores (GRS) for 19 complement system associated variants, 7 lipid metabolism associated variants, the remaining 26 variants (other pathways GRS), and for all 52 variants (global score) were derived and correlated with phenotype. Of the 52 SNPs evaluated, CFH (rs570618) and C2/CFB/SKIV2L (rs116503776 and rs114254831) were associated with AFVD compared with healthy controls (odds ratio [OR] = 2.73, 95% confidence interval [CI] = 1.32-5.73, P = 0.01; OR = 0.31, 95% CI = 0.14-0.71, P = 0.0036; and OR = 0.41, 95% CI = 0.22-0.74, P = 0.0025, respectively). MIR6130/RORB (rs10781182) was negatively associated with AFVD compared with the healthy controls (OR = 0.13, CI = 0.06-0.25, P < 0.0001) and AMD (OR = 0.19, CI = 0.10-0.34, P < 0.0001). Regression analysis showed complement GRS was positively associated with AFVD compared with controls (OR = 1.42, 95% CI = 1.04-1.95, P = 0.03), whereas the other pathways' GRS was negatively associated (OR = 0.46, 95% CI = 0.21-0.98, P = 0.04). AMD was positively associated with the complement score, global score, and ARMS2/HTRA1 compared with controls. Non-monogenic AFVD is associated with AMD risk alleles in the complement cascade, but not in other pathways. Further research is needed to explore complement inhibition for AFVD.