Vitelliform Lesions Associated with Leptochoroid and Pseudodrusen.

OBJECTIVE: To characterize clinical and prognostic implications of leptovitelliform maculopathy (LVM), a distinctive phenotype of vitelliform lesion characterized by the coexistence of subretinal drusenoid deposits (SDDs) and leptochoroid. DESIGN: Retrospective, cohort study. SUBJECTS: The study compared patients affected by LVM with cohorts displaying a similar phenotypic spectrum. This included patients with acquired vitelliform lesions (AVLs) and those with SDDs alone. METHODS: A total of 60 eyes of 60 patients were included, of which 20 eyes had LVM, 20 eyes had AVLs, and the remaining had SDDs. Patients >50 years of age with complete medical records and multimodal imaging for ≥6 months of follow-up, including color fundus photography or MultiColor imaging, OCT, fundus autofluorescence, and OCT angiography were included. MAIN OUTCOME MEASURES: Choroidal vascularity index (CVI); proportion of late-stage complications (macular neovascularization, atrophy). RESULTS: The AVL subgroup exhibited a significantly higher CVI compared with both LVM (P = 0.001) and SDD subgroups (P < 0.001). The proportion of late-stage complications significantly differed among subgroups (chi-square = 7.5, P = 0.02). Eyes with LVM presented the greatest proportion of complications (55%) after a mean of 29.3 months, whereas the remaining eyes presented a similar proportion of complications, including 20% in the AVL group after 27.6 months and 20% in the SDD group after 36.9 months. Kaplan-Meier estimates of survival demonstrated a significant difference in atrophy development between groups (P < 0.001), with a median survival of 3.9 years for the LVM group and 7.1 years for controls. The presence of LVM correlated with a fourfold increase in the likelihood of developing complications. CONCLUSIONS: Leptovitelliform maculopathy, characterized by the association of vitelliform lesions with SDDs and leptochoroid, represents a distinct clinical phenotype in the broader spectrum of vitelliform lesions. The importance of a clinical distinction for these lesions is crucial due to their higher propensity for faster progression and elevated rate of complications, particularly atrophic conversion. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk Factors for Worsening Morphology and Visual Acuity in Eyes with Adult-Onset Foveomacular Vitelliform Dystrophy.

PURPOSE: To explore clinical risk factors and OCT features associated with worse visual acuity (VA), progression of disease, choroidal neovascularization (CNV), and atrophy in eyes with adult-onset foveomacular vitelliform dystrophy (AOFVD). DESIGN: Single-center, retrospective, observational cohort study. PARTICIPANTS: Patients seen at Duke Eye Center between January 2012 and May 2023 with a diagnosis of AOFVD confirmed via OCT and fundus autofluorescence. METHODS: Baseline and final-visit images from eyes with AOFVD were examined. Disease stage was assigned, and presence of atrophy or CNV was determined. Clinical and OCT features associated with progression to atrophy and CNV were determined using t tests and chi-square analysis. Correlation with lower VA was determined using linear regression. MAIN OUTCOME MEASURES: Association of clinical characteristics and OCT features with worse VA, progression of disease, CNV, and atrophy as determined by independent t tests, chi-square analysis, and linear regression (P < 0.05). RESULTS: One hundred one eyes (63 patients) met inclusion criteria for this study, with mean follow-up duration of 48 months (standard deviation, 31 months). Fifty-one percent of eyes progressed beyond baseline staging during follow-up; among baseline stage 1 eyes, incidence of atrophy was 0.068/person-year; incidence of CNV was 0.022/person-year. Risk factors for worse final VA were baseline presence of vitreomacular traction ([VMT], P = 0.006), ellipsoid zone attenuation (P = 0.02), and increased lesion height and width (P < 0.001). Predictors of progression include diabetes mellitus (P = 0.01), statin use (P = 0.03), presence of hyperreflective foci (P = 0.01), and increased lesion width and volume (P = 0.03 and P = 0.04, respectively). Predictors of atrophy include the baseline presence of VMT (P = 0.02), decreased choroidal thickness (P = 0.03), and greater maximal height, width, and volume of the lesion (P = 0.03, P = 0.02, and P = 0.009, respectively). Lower baseline VA (P = 0.03) and increased lesion volume (P = 0.04) were associated with CNV. CONCLUSIONS: Clinical and OCT imaging features at baseline may prove useful in stratifying patient risk for progression, atrophy, CNV, and worse VA. Features such as statin use, diabetes, baseline VA, and laterality should be accounted for. OCT features, such as lesion size, VMT, ellipsoid zone attenuation, choroidal thickness, and hyperreflective foci, may impart greater risk of poor outcomes. Future prospective analysis accounting for the time to development of atrophy and CNV is needed. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Vitelliform maculopathy: Diverse etiologies originating from one common pathway.

Vitelliform lesions (VLs) are associated with a wide array of macular disorders but are the result of one common pathway: retinal pigment epithelium (RPE) impairment and phagocytic dysfunction. VLs are defined by the accumulation of yellowish subretinal material. In the era of multimodal advanced retinal imaging, VLs can be further characterized by subretinal hyperreflectivity with optical coherence tomography and hyperautofluorescence with fundus autofluorescence. VLs can be the result of genetic or acquired retinal diseases. In younger patients, VLs usually occur in the setting of Best disease. Additional genetic causes of VL include pattern dystrophy or adult-onset vitelliform macular dystrophy. In older patients, acquired VLs can be associated with a broad spectrum of etiologies, including tractional, paraneoplastic, toxic, and degenerative disorders. The main cause of visual morbidity in eyes with VLs is the onset of macular atrophy and macular neovascularization. Histopathological studies have provided new insights into the location, nature, and lifecycle of the vitelliform material comprised of melanosomes, lipofuscin, melanolipofuscin, and outer segment debris located between the RPE and photoreceptor layer. Impaired phagocytosis by the RPE cells is the unifying pathway leading to VL development. We discuss and summarize the nature, pathogenesis, multimodal imaging characteristics, etiologies, and natural course of vitelliform maculopathies.

Choroidal structural features of acquired vitelliform lesions in non-exudative age-related macular degeneration.

PURPOSE: To define the choroidal morphological characteristics of non-exudative age-related macular degeneration (AMD) cases associated with acquired vitelliform lesions (AVLs). METHODS: This retrospective study included intermediate AMD patients with AVLs (Group1, 21eyes) and without AVLs (Group2, 21eyes). A healthy control group was (Group3, 23eyes) also included. Subfoveal choroidal thickness (SFCT), greatest basal diameter (GBD), and maximum height (MH) of the largest PED were measured on spectral domain optical coherence tomography. Internal reflectivity of PEDs and total choroidal area (TCA) were measured using ImageJ software. The TCA was binarized to the luminal area (LA) and stromal area. The choroidal vascularity index (CVI) was assessed. RESULTS: The mean SFCT, TCA, and LA were higher in Group 1 (290.3 ± 86.8 µm, 0.840 ± 0.302 mm2, 0.602 ± 0.227 mm2) than in Group 2 (215.6 ± 85.0 µm, 0.594 ± 0.183 mm2, 0.429 ± 0.139 mm2) (p = 0.014, p = 0.017, p = 0.020, respectively). There was no significant difference in the CVI measurements between Group 1 and Group 2 (p = 1.000). The mean GBD and MH of the PED was higher in Group 1 (1443 ± 595 µm, 188 ± 86 µm) than in Group 2 (851 ± 368 µm, 119 ± 38 µm) (p = <0.001, p = 0.001, respectively). Internal PED reflectivity was significantly lower in Group 1 (0.44 ± 0.21) than in Group 2 (0.66 ± 0.17) (p = <0.001). Internal PED reflectivity showed negative correlation with GBD and MH of the PED in Group 1 (r = -0.587, p = 0.005; rho = -0.448, p = 0.042, respectively). In Group 2, internal PED reflectivity had a negative correlation with MH of the PED (rho = -0.511, p = 0.018). CONCLUSION: Non-exudative AMD patients with AVLs are more prone to have a thick choroid and large hyporeflective PEDs as compared to the those without AVLs.

Acquired Vitelliform-Like Lesion in Uveitis: A case-series.

PURPOSE: To study acquired vitelliform-like lesions (AVLL) and their diagnostic and prognostic values in uveitis. PATIENTS AND METHODS: This was a retrospective case series. The clinical course, diagnostic value, and prognostic significance of AVLL were compared between uveitic patients with AVLL and uveitic patients without AVLL. RESULTS: Twelve patients (21 eyes) with both uveitis and AVLL (study group) and thirteen patients (24 eyes) without AVLL (control group) were included in the study. Macular leakage (p = .005), the presence of vasculitis (p = .01), the presence of active choroiditis (p = .01), and the presence of CME on OCT (p = .008) were significantly higher in the AVLL group compared to the control group. Best-corrected visual acuity was significantly lower at presentation (p < .001) and the last follow-up visit (p = .014) in the AVLL group. CONCLUSION: The presence of acquired vitelliform-like lesion can have both a diagnostic (uveitis as a differential diagnosis) and prognostic value in patients with different types of uveitis.

Epiretinal membrane surgery outcome in eyes with abnormalities of the central bouquet.

BACKGROUND: Clinical studies have shown that epiretinal membranes (ERM) as well as abnormalities of the central foveal bouquet (CB) can be classified in different stages according to their morphological appearance. Furthermore, visual acuity correlates with the different stages of these features. The present study evaluated how these findings change after the surgical removal of the ERM and their impact on functional outcomes. METHODS: In this retrospective study eyes with ERM were evaluated by SD-OCT scans before and after pars plana vitrectomy (PPV) with macular ERM and internal limiting membrane (ILM) peeling. CB abnormalities were classified according to their morphological appearance from stage 0 (no abnormalities) to stage 3 (acquired vitelliform lesion). ERMs were classified ranging from stage 0 (absence of ERM) to stage 4 (ERM with significant anatomic disruption of macula). Changes in morphology were correlated with visual acuity before and after surgery. RESULTS: 151 eyes were included into the study. Before surgery 27.2% (n = 41) of eyes showed CB abnormalities with stage 1 being the most common (11.9%, n = 18). Before surgery ERM was seen in all patients. The most common form was stage 1 (28.5%, n = 43), followed by stage 3 (27.8%, n = 42) and 2 (25.2%, n = 38). Only 18.5% (n = 28) presented with stage 4 ERM. The mean BCVA was 0.42 (logMAR) before and increased to 0.19 (logMAR) 8 weeks after vitrectomy (95% CI 0.20-0.28; p < 0.001). Patients who suffered from CB abnormalities had less increase in BCVA than patients who had no evidence of CB (0.28 vs. 0.14 logMAR; p < 0.001). Of all the patients with CB abnormalities at baseline, 68% had lower CB grading after the surgery (n = 28; 95% CI; p < 0.001). All patients showed an improvement of their ERM grading, with 98.7% reaching stage 0 (n = 151 vs. n = 149; 95% CI; p < 0.001). CONCLUSIONS: The study indicates that the presence of CB abnormalities correlates with worse visual function. They are furthermore associated with worse visual outcomes after PPV with ERM and ILM peeling. These findings are valuable for deciding on PPV in patients with ERM.

Spontaneous Closure of the Macular Hole in a Patient with Acquired Vitelliform Lesion.

In this paper, we report an extremely rare case of spontaneous closure of a macular hole (MH) that developed in a patient in whom acquired vitelliform lesion (AVL) occurred after vitrectomy for atopic retinal detachment (ARD). A 32-year-old male developed ARD in both eyes, and retinal reattachment was achieved after vitrectomy. Five years after surgery, optical coherence tomography showed localized serous retinal detachment (SRD) and a granular lesion with a higher brightness in the subretinal fluid, thus leading to the diagnosis of AVL. One month later, an MH developed, and a follow-up examination performed 6 weeks later revealed that the MH had spontaneously closed and the SRD decreased. In the fovea, fluorescein angiography revealed a window defect due to atrophy of the retinal pigment epithelium (RPE). These findings in this present case suggest the possibility that RPE dysfunction was involved in the development of AVL and MH.

Intraretinal hyperreflective foci in PXE-related retinopathy with acquired vitelliform lesions: a long-term follow-up.

Purposes: To describe the long-term follow-up of a patient affected by Pseudoxanthoma Elasticum (PXE) and acquired macular vitelliform lesions in both eyes. Material and methods: Case report Results: We reported the 9-year follow-up of a patient affected by PXE. We described the onset and the resolution of the vitelliform macular lesions which lasted 5 years. The vitelliform lesion appeared almost simultaneously in both eyes with an initial increase in size, even though asymmetrical. We detected the intraretinal migration of hyper-reflective foci in both eyes during the follow-up. Choroidal neovascularization (CNV) occurred in her right eye during the follow-up. Visual acuity decreased from 20/20 to 20/32 in left eye; from 20/20 to 20/100 in her right eye. Conclusions: we reported the natural history of acquired vitelliform lesion in PXE-related retinopathy describing the Intraretinal hyperreflective foci migration.

Novel Missense Mutations in BEST1 Are Associated with Bestrophinopathies in Lebanese Patients.

To identify Bestrophin 1 (BEST1) causative mutations in six Lebanese patients from three families, of whom four had a presumed clinical diagnosis of autosomal recessive bestrophinopathy (ARB) and two showed a phenotype with a single vitelliform lesion, patients were subjected to standard ophthalmic examinations. In addition, BEST1 exons and their flanking regions were amplified and sequenced by Sanger sequencing. Co-segregation and detailed bio-informatic analyses were performed. Clinical examination results were consistent with ARB diagnosis for all index patients showing multifocal vitelliform lesions and a markedly reduced light peak in the electrooculogram, including the two patients with a single vitelliform lesion. In all cases, most likely disease-causing BEST1 mutations co-segregated with the phenotype. The ARB cases showed homozygous missense variants (M1, c.209A>G, p.(Asp70Gly) in exon 3, M2, c.1403C>T; p.(Pro468Leu) in exon 10 and M3, c.830C>T, p.(Thr277Met) in exon 7), while the two patients with a single vitelliform lesion were compound heterozygous for M1 and M2. To our knowledge, this is the first study describing mutations in Lebanese patients with bestrophinopathy, where novel biallelic BEST1 mutations associated with two phenotypes were identified. Homozygous mutations were associated with multifocal lesions, subretinal fluid, and intraretinal cysts, whereas compound heterozygous ones were responsible for a single macular vitelliform lesion.

Underdeveloped RPE Apical Domain Underlies Lesion Formation in Canine Bestrophinopathies.

Canine bestrophinopathy (cBest) is an important translational model for BEST1-associated maculopathies in man that recapitulates the broad spectrum of clinical and molecular disease aspects observed in patients. Both human and canine bestrophinopathies are characterized by focal to multifocal separations of the retina from the RPE. The lesions can be macular or extramacular, and the specific pathomechanism leading to formation of these lesions remains unclear. We used the naturally occurring canine BEST1 model to examine factors that underlie formation of vitelliform lesions and addressed the susceptibility of the macula to its primary detachment in BEST1-linked maculopathies.

Adult-onset foveomacular vitelliform dystrophy: A fresh perspective.

Adult-onset foveomacular vitelliform dystrophy (AFVD) was first described by Gass four decades ago. AFVD is characterized by subretinal vitelliform macular lesions and is usually diagnosed after the age of 40. The lesions gradually increase and then decrease in size over the years, leaving an area of atrophic outer retina and retinal pigment epithelium. This process is accompanied by a loss of visual acuity. Vitelliform lesions are hyperautofluorescent and initially have a dome-shaped appearance on optical coherence tomography. The electro-oculogram and full-field electroretinogram are typically normal, indicating localized retinal pathology. Phenocopies are also associated with other ocular disorders, such as vitreomacular traction, age-related macular degeneration, pseudodrusen, and central serous chorioretinopathy. A minority of AFVD patients have a mutation in the PRPH2, BEST1, IMPG1, or IMPG2 genes. A single-nucleotide polymorphism in the HTRA1 gene has also been associated with this phenotype. Accordingly, the phenotype can arise from alterations in the photoreceptors, retinal pigment epithelium, and/or interphotoreceptor matrix depending on the underlying gene defect. Excess photoreceptor outer segment production and/or impaired outer segment uptake due to impaired phagocytosis are likely underlying mechanisms. At present, no cure is available for AFVD. Thus, the current challenges in the field include identifying the underlying cause in the majority of AFVD cases and the development of effective therapeutic approaches.

A case of Mac Tel 2 with an unusual sub macular vitelliform lesion.

METHOD: Observational case report describing the clinical, FFA, OCT and mfERG findings in an elderly female patient with atypical features of macular telangiectasia (Mac Tel 2) RESULTS: A 71-year-old lady was detected to have characteristic features of Mac Tel 2 in the left eye (LE) and a yellowish sub macular vitelliform like lesion in the right eye (RE). FFA showed ill defined hyper fluorescence in the RE and telangiectasia and parafoveal leakage typical of Mac Tel 2 in the LE. On OCT RE had hyper reflective clump of echoes subfoveally with an intact RPE and LE had foveal thinning with hypo reflective intraretinal cavities. mfERG responses were normal in the RE and reduced in the LE. During the course of 3 years LE showed natural progression while RE remained unchanged. CONCLUSION: Structural and functional evaluation of an unusual sub macular vitelliform lesion seen in association with Mac Tel 2 and its course over a period of 3 years is described. The differentiating features of this lesion from adult onset foveomacular vitelliform dystrophy (AFMD) are discussed.

Multimodal imaging of combined hamartoma of the retina and retinal pigment epithelium associated with an acquired vitelliform lesion.

BACKGROUND: We present a case of a combined hamartoma of the retina and retinal pigment epithelium associated with a subfoveal acquired vitelliform lesion induced by vitreomacular traction. The purpose of this report is to present a unifying hypothesis of these concurrent findings, as aided by multimodal imaging. CASE PRESENTATION: A 25-year-old white man presented with a 6-month history of a visual disturbance in his left eye. At presentation, ophthalmic assessment showed a combined hamartoma adjacent to his optic nerve that had caused marked corrugation within the inner retinal surface. An acquired vitelliform lesion was present in the macula with an associated epiretinal membrane as demonstrated on spectral-domain optical coherence tomography. Optical coherence tomography angiography corroborated the clinical diagnosis of combined hamartoma. CONCLUSIONS: We are not aware of previous cases of a combined hamartoma associated with an acquired vitelliform lesion. As previously proposed in acquired vitelliform lesions related to epiretinal membrane and vitreoretinal traction, we believe that macular tractional forces might interfere with retinal pigment epithelium phagocytosis of shed outer segments, leading to the occurrence of this acquired vitelliform lesion.