Vitelliform Lesions Research Articles

Retinal structure in young patients aged 10years or less with Best vitelliform macular dystrophy.

Our aim was to analyze retinal structure in young patients with Best disease with reference to future gene therapy. This was a retrospective observational spectral domain optical coherence tomography study of four patients aged 10years or less with Best disease. Findings ranged from subtle thickening at the level of the retinal pigment epithelium-photoreceptor interdigitation line, to subretinal fluid and precipitate-like changes at the level of the photoreceptor outer segments, and further to choroidal neovascularization. The photoreceptor innersegment ellipsoid layer could be visualized seemingly undisturbed above the vitelliform lesions, except in the case of choroidal neovascularization. Clinical variability is evident even among young patients aged 10years or less with Best disease. The earliest structural alterations seem to occur at the level of the retinal pigment epithelium-photoreceptor interdigitation line. The photoreceptor inner segment seems to be unaffected unless choroidal neovascularization develops, which seems promising regarding future gene therapy.

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.

Paraneoplastic Vitelliform Retinopathy in Metastatic Cutaneous Melanoma: A Case Series

Paraneoplastic vitelliform retinopathy is a rare condition associated with metastatic melanoma. Like melanomaassociated retinopathy (MAR), it can cause nyctalopia and progressive vision loss; however, unlike MAR, the fundus shows multifocal, yellow-orange vitelliform lesions beneath the neurosensory retina and at the level of the retinal pigment epithelium, as well as areas of subretinal fluid in the macula. The treatment of paraneoplastic vitelliform retinopathy is aimed at the underlying metastatic melanoma but unfortunately has a poor prognosis, with most patients succumbing to their disease. We report two cases of paraneoplastic vitelliform retinopathy in patients with metastatic cutaneous melanoma.

Paraneoplastic Cloudy Vitelliform Submaculopathy in Primary Vitreoretinal Lymphoma

To describe the nature and evolution of paraneoplastic cloudy vitelliform submaculopathy in patients with primary vitreoretinal lymphoma and propose a mechanism for its development and course. Retrospective, observational case series. Three patients presenting with unilateral cloudy vitelliform submaculopathy based on clinical examination, fundus autofluorescence, fluorescein angiography, and spectral-domain optical coherence tomography (SD OCT) imaging and ultimately diagnosed with primary vitreoretinal lymphoma and/or primary central nervous system lymphoma were analyzed. In all 3 patients, cloudy vitelliform submaculopathy appeared with hazy indistinct yellow subretinal material resembling the vitelliform lesions found in acute exudative paraneoplastic polymorphous vitelliform maculopathy, although with less distinct appearance and without intense hyper-autofluorescence. In all 3 patients, cloudy vitelliform submaculopathy was transient, showed spontaneous regression within 3 months, and preceded the diagnosis of lymphoma, suggestive of a paraneoplastic process. The diagnosis of primary vitreoretinal lymphoma and/or primary central nervous system lymphoma was made within 6 months with classic features of new intraretinal or sub-retinal pigment epithelium infiltration of lymphoma in the peripheral retina (n = 2) and hyperintense lesions on brain magnetic resonance imaging (n = 2). With SD OCT imaging, the cloudy vitelliform subretinal lesions appeared as hyperreflective debris above the retinal pigment epithelium band in all 3 eyes, and were associated with an irregularly thickened and rippled retinal pigment epithelium band in 2 eyes. Resolution of the cloudy submacular lesions resulted in outer retinal atrophic changes in all 3 eyes. Paraneoplastic cloudy vitelliform submaculopathy, a form of lymphoma-associated retinopathy, can precede the diagnosis of primary vitreoretinal lymphoma or primary central nervous system lymphoma and can regress spontaneously, leaving outer retinal abnormalities.

SUBRETINAL HYPERREFLECTIVE EXUDATION ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION

To describe the multimodal imaging findings of subretinal hyperreflective exudation (SHE) observed in association with choroidal neovascularization and to distinguish SHE from other forms of subretinal hyperreflective material (SHM) seen in patients with age-related macular degeneration and other macular disorders. A retrospective study on 46 eyes of 42 patients with SHE associated with Types 1, 2, and 3 choroidal neovascularization secondary to neovascular age-related macular degeneration. Patients were examined using multimodal imaging, including color photography, near-infrared reflectance imaging, spectral domain optical coherence tomography, fluorescein angiography, fundus autofluorescence imaging, and indocyanine green angiography. Clinical and imaging characteristics were evaluated at baseline, after the initiation of intravitreal antivascular endothelial growth factor therapy, and during the resolution of SHE. Forty-five of the 46 eyes were treatment naive. The mean ± SD age at the first detection of SHE was 77.2 ± 10.1 years. The mean ± SD follow-up was 2.1 ± 0.6 years. Fluorescein angiography was performed in 42 eyes and demonstrated leakage and/or staining of underlying or adjacent choroidal neovascularization but not of the SHE itself in all eyes. On fluorescein angiography, SHE was transparent in 29 eyes and blocking in 7 eyes. In 32 eyes, SHE showed isoautofluorescence on fundus autofluorescence imaging, and in 8 eyes, SHE showed varying degrees of hyperautofluorescence. Indocyanine green angiography was performed in eight eyes and demonstrated hyperfluorescence of SHE in seven eyes. In eight eyes, SHE was the only evidence of neovascular activity. All eyes having follow-up (42 eyes) showed resolution of the subretinal material with partial or full reconstitution of the ellipsoid zone after a median of 2 injections range (1-16 injections). Subretinal hyperreflective exudation persisted for a median of 9 weeks (range, 4-60 weeks) after the initiation of treatment. The mean visual acuity before treatment was 0.619 (20/83), and it improved to 0.380 (20/48) (P = 0.03) after the resolution of SHE. Subretinal hyperreflective exudation differs from other types of SHM based on the findings from multimodal imaging. This novel type of SHM likely represents a sign of active neovascular age-related macular degeneration distinct from subretinal fluid, hemorrhage, neovascular tissue, lipid, pigment hyperplasia, subretinal fibrosis, and the SHM observed with acquired vitelliform lesions. Intravitreal antivascular endothelial growth factor agents can be used to successfully resolve SHE, often resulting in better visual outcomes in eyes manifesting this form of exudation.

A Case of Neurosyphilis Revealed by Acute Exudative Polymorphous Vitelliform Maculopathy

The authors report the case of a healthy 56-year-old man presenting with bilateral vision loss. Clinical features were consistent with the diagnosis of acute exudative polymorphous vitelliform maculopathy (AEPVM). The patient returned 10 days later with bilateral anterior granulomatous uveitis, and the inflammatory work-up revealed treponemal antibodies in the serum and spinal fluid, consistent with a diagnosis of active neurosyphilis. The patient received standard treatment for neurosyphilis with intravenous penicillin G. Two months later, the intraocular inflammation had resolved, but the resolution of the vitelliform lesions was more gradual. An immune process could be a plausible explanation for these clinical findings. Clinicians should be aware that syphilis can produce AEPVM.

Quantitative Fundus Autofluorescence and Optical Coherence Tomography in Best Vitelliform Macular Dystrophy

Quantitative fundus autofluorescence (qAF), spectral domain optical coherence tomography (SD-OCT) segmentation, and multimodal imaging were performed to elucidate the pathogenesis of Best vitelliform macular dystrophy (BVMD) and to identify abnormalities in lesion versus nonlesion fundus areas. Sixteen patients with a clinical diagnosis of BVMD were studied. Autofluorescence images (30°, 488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The grey levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density, to yield qAF. Horizontal SD-OCT scans were obtained and retinal layers manually segmented. Additionally, color and near-infrared reflectance (NIR-R) images were registered to AF images. All patients were screened for mutations in BEST1. In three additional BVMD patients, in vivo spectrofluorometric measurements were obtained within the vitelliform lesion. Mean nonlesion qAF was within normal limits for age. Maximum qAF within the lesion was markedly increased compared with controls. By SD-OCT segmentation, outer segment equivalent thickness was increased and outer nuclear layer thickness decreased in the lesion. Changes were also present in a transition zone beyond the lesion border. In subclinical patients, no abnormalities in retinal layer thickness were identified. Fluorescence spectra recorded from the vitelliform lesion were consistent with those of retinal pigment epithelial cell lipofuscin. Based on qAF, mutations in BEST1 do not cause increased lipofuscin levels in nonlesion fundus areas.

En face enhanced depth imaging optical coherence tomography features in adult onset foveomacular vitelliform dystrophy

Our purpose was to describe the different morphological features in adult onset foveomacular vitelliform dystrophy (AOFVD), using en face enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). Thirty eyes of 22 consecutive patients presenting with diagnosis of AOFVD were enrolled. Diagnosis of AOFVD was concluded based on fundus examination, autofluorescence imaging, fluorescein angiography and SD-OCT. En face OCT imaging was obtained with the Spectralis EDI SD-OCT; 97 inverted sections (nine averaged B-scans per image) were acquired. On en face OCT, vitelliform lesions appeared as regular concentric rings of different reflectivity. From the periphery to center of the ring, we observed: (1) the hypereflective ring representing the inner segment/ outer segment (IS/OS) junction, which was continuous in 23 out of 30 eyes, and (2) a well-detectable hyporeflective ring between the IS/OS junction and vitelliform material in 20 out of 30 eyes; the innermost composant of the lesion was hypereflective, and it corresponded to vitelliform material. In eight out of 30 eyes, a hyporeflective "croissant"-shaped lesion with inferior concavity in the upper part of the hyperreflective material was present. Hypereflective retinal pigment epithelium (RPE) elevations or bumps were detected in 25 out of 30 eyes. These areas of focal RPE thickening or bumps appeared to be intensely hypereflective on infrared reflectance imaging. En face imaging of the retina helps visualizing the distribution of vitelliform material in AOFVD. The sedimentation of vitelliform lesions is characterized by a upper "croissant"-shaped hypoflectivity. The bumps/thickening of RPE appeared as hypereflective lesions on IR imaging.

Clinical Findings of Acquired Vitelliform Lesions Associated With Retinal Pigment Epithelial Detachments

To study clinical findings associated with acquired vitelliform lesions in retinal pigment epithelial detachments (PEDs). Retrospective, interventional, consecutive case series. We retrospectively reviewed 32 eyes of 24 patients (22 men, 2 women; age range [mean], 58-85 [73.7] years) with acquired vitelliform lesions. All eyes had acquired vitelliform lesions in the central macula associated with a serous PED at baseline. Of the 32 eyes, 30 (93.8%) were observed for 12 months, 26 (81.3%) for 24 months, and 17 (53.1%) for 36 months. The mean logarithm of the minimal angle of resolution best-corrected visual acuity (BCVA) levels were 0.19 at month 12, 0.28 at month 24, and 0.25 at month 36, none of which differed significantly from baseline. The mean changes in the BCVA were declines of 0.38, 1.29, and 1.21 lines at months 12, 24, and 36, respectively. Of 7 eyes treated with 3 consecutive monthly intravitreal injections of ranibizumab, the serous PEDs remained in all 7 eyes and the mean changes of BCVA were a decline of 2.40 lines 12 months after the first injection and a decline of 3.58 lines at the final visit. In the 24 untreated eyes, the mean change in the BCVA was a decline of 0.25 line at the final visit, which differed significantly (P = .021) compared with that of the treated eyes at the final visit. Intravitreal injections of ranibizumab were ineffective because of the absence of resolution of the PEDs and the declines in VA.

Ranibizumab for choroidal neovascularization following atrophic involution of adult-onset foveomacular vitelliform dystrophy.

Purpose: We report a case of adult-onset foveomacular vitelliform dystrophy (AOFVD) complicated with atrophic involution and subsequent choroidal neovascularization (CNV) and treated with intravitreal ranibizumab. Design: Case Report Methods: A 71-year-old woman diagnosed with AOFVD experienced a progression of the vitelliform lesion to the atrophic stage in her left eye immediately after cataract surgery. Best corrected visual acuity (BCVA) decreased from 0.5 to 0.16. Ten months later, the patient was referred with new worsening of her visual acuity (0.05) and metamorphopsia. The spectral-domain optical coherence tomography (SD-OCT) confirmed the presence of type 2 CNV next to the atrophic area. The patient was treated with 2 monthly injections of ranibizumab. Results: SD-OCT images improved significantly and her BCVA increased to 0.20 associated with subjective improvement of metamorphopsia. Conclusion: Ranibizumab may be effective for CNV in patients with AOFVD.

Multimodal Imaging of Acquired Vitelliform Lesion Diagnosed at Pseudohypopyon Stage

Purpose. To present a case study of a monocular acquired vitelliform lesion, studied with multimodal fundus imaging (spectral-domain-optical coherence tomography, fundus autofluorescence, and fluorescein angiography) with a followup of three years. Case Report. An asymptomatic macular lesion was detected on a 64-year-old man. Fundus exam revealed a macular lesion with an apparent horizontal level associated with multiple round small whitish lesions, suggestive of cuticular drusen. He was studied with autofluorescence of the fundus (FAF), fluorescein angiography (FA), spectral domain-optical coherence tomography (SD-OCT), and electrooculogram. The findings were compatible with the diagnosis of acquired vitelliform lesion, associated with cuticular drusen. After one year, the visual acuity decreased to 20/50, without identifiable alterations of the FAF, FA, or SD-OCT. Three years later, fundoscopy and imaging showed an evolution to a state similar to vitelli disruptive phase of Best disease with an improvement of visual acuity to 20/25. We report the results of FAF, FA, and SD-OCT at this stage. Conclusion. Acquired vitelliform lesions associated with cuticular drusen can present as a pseudohypopyon lesion, and the evolution to the atrophic phase can be associated with an improvement of visual acuity.

Unusual presentation of residual subretinal fluid composition after surgery for acute rhegmatogenous retinal detachment

The purpose of this paper is to report an unusual case of accumulation of residual subretinal fluid after surgery for acute rhegmatogenous retinal detachment, sparing the fovea. A 28-year-old male presented with a four-day history of acute visual loss in his right eye secondary to bulbous rhegmatogenous retinal detachment, sparing the fovea. The patient underwent an uneventful pars plana vitrectomy and scleral buckling procedure. At four weeks postoperatively (after complete gas resorption), the visual acuity was 20/40. However, the patient complained of blurred vision. A dilated fundus examination showed a fat retina and the presence of multiple yellowish subretinal deposits resembling vitelliform lesions in the macula. Some lesions were encroaching on the fovea, and were connected via a tract to a previous horseshoe tear with evidence of a thin layer of subretinal fluid. The patient symptoms persisted for one year postoperatively. However, the retina remained fat with evidence of retinal pigment epithelium mottling and faint scars corresponding to previous lesions. Persistent subretinal fluid with thick subretinal precipitate can occur even after successful surgery for acute retinal detachment sparing the fovea and cause visual dysfunction.

Best's vitelliform macular dystrophy associated with choroidal neovascularization

Case reportWe report the case of a child with a sudden loss of vision of the left eye. Ophthalmoscopic examination revealed vitelliform lesions in both foveal centers, as well as an adjacent hemorrhage in his left eye. Fluorescein angiography confirmed the presence of a neovascular membrane in his left eye. The electrooculogram showed disease. According to complementary studies the patient was diagnosed with Best's disease associated with choroidal neovascularization. DiscussionThe diagnosis of Best's vitelliform macular dystrophy is often a casual finding as visual acuity tends to remain stable for long periods of time. A sudden deterioration in vision may suggest complications, such as choroidal neovascularization.

Progression of an Acquired Vitelliform Lesion to a Full-Thickness Macular Hole Documented by Eye-Tracked Spectral-Domain Optical Coherence Tomography

Progression of an Acquired Vitelliform Lesion to a Full-Thickness Macular Hole Documented by Eye-Tracked Spectral-Domain Optical Coherence Tomography

ACQUIRED VITELLIFORM LESION ASSOCIATED WITH LARGE DRUSEN

The purpose of this study was to describe the association of acquired vitelliform lesion (AVL) and large drusen in patients with non-neovascular age-related macular degeneration. A retrospective review of clinical examination and multimodal imaging data of patients with AVL and large drusen seen over a 12-month period was performed. Acquired vitelliform lesion was defined as subretinal accretion of hyperautofluorescent yellowish material within the macular region not due to vitelliform macular dystrophy. Large drusen were diagnosed by the presence of mounded deposits in the subretinal pigment epithelial space between the retinal pigment epithelium and the Bruch membrane using multimodal imaging analysis (color photography, autofluorescence, and spectral domain optical coherence tomography). Thirteen eyes of 9 white patients with a mean age of 74 years were observed to have AVL associated with large drusen. The median visual acuity was 20/60. All AVLs were hyperautofluorescent and were located in the subretinal space between the retinal pigment epithelium and the photoreceptor inner segment/outer segment junction. The AVL in this series had similar color, autofluorescence, and optical coherence tomographic findings as the AVL seen in association with cuticular drusen and subretinal drusenoid deposits. Acquired vitelliform lesions, which have previously been related to cuticular drusen and subretinal drusenoid deposits, can occur in association with large drusen. Abnormalities leading to drusen formation or processes that function in parallel to these may be causative in AVL formation.

A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy

To determine the genetic basis of early onset autosomal recessive Best vitelliform macular dystrophy (arBVMD) in a family with three affected children. Clinical and family-based genetic study. Seven subjects making up a family with three children affected by Best vitelliform macular dystrophy were studied. Standard ophthalmic exam with dilated ophthalmoscopy and imaging were performed in each individual. The eleven exons of BEST1 were directly sequenced. All three affected children have the clinical characteristic features of Best vitelliform macular dystrophy: large macular vitelliform lesions, scattered vitelliform lesions along the arcades and in the peripheral retina, and an accumulation of serous retinal fluid. A novel compound heterozygous mutation in the BEST1 gene was found in the three affected individuals (L41P and I201T). The unaffected parents and children only harbor one heterozygous mutation. arBVMD can be caused by the compound heterozygous mutation L41P and I201T in the BEST1 gene.

Distrofia macular viteliforme de Best asociada a neovascularización coroidea

Case reportWe report the case of a child with a sudden loss of vision of the left eye. Ophthalmoscopic examination revealed vitelliform lesions in both foveal centers, as well as an adjacent hemorrhage in his left eye. Fluorescein angiography confirmed the presence of a neovascular membrane in his left eye. The electrooculogram showed disease. According to complementary studies the patient was diagnosed with Best's disease associated with choroidal neovascularization. DiscussionThe diagnosis of Best's vitelliform macular dystrophy is often a casual finding as visual acuity tends to remain stable for long periods of time. A sudden deterioration in vision may suggest complications, such as choroidal neovascularization.

Peripapillary choroidal neovascularization in best disease.

Best disease is an autosomal dominant retinal dystrophy with a variable phenotypic expression. Clinically, it is characterized by a vitelliform lesion in the macula because of the deposition of yellow material in a dome-shaped configuration, believed to be lipofuscin that accumulates within and beneath the retinal pigment epithelium. Best disease is occasionally complicated by the development of choroidal neovascularization (CNV), which typically occurs in the macula. We report a case of peripapillary CNV in Best disease. Interventional case report. A 12-year-old boy who was previously diagnosed with Best disease was treated with reduced fluence photodynamic therapy for subfoveal CNV in the right eye. After 2 months, he presented with peripapillary CNV in the left eye, which was treated with repeated sessions of reduced fluence photodynamic therapy. Ophthalmologists must be aware that peripapillary CNV may occasionally complicate Best disease and can be successfully treated with photodynamic therapy.

Three-dimensional Distribution of the Vitelliform Lesion, Photoreceptors, and Retinal Pigment Epithelium in the Macula of Patients With Best Vitelliform Macular Dystrophy

To describe the anatomical phenotypes of Best vitelliform macular dystrophy (BVMD) with spectral-domain optical coherence tomography (SD-OCT) in a large series of patients with confirmed mutations in the BEST1 gene. In our retrospective observational case series, we assessed 15 patients (30 eyes) with a clinical diagnosis of vitelliform macular dystrophy who were found to have mutations in the BEST1 gene. Color fundus photographs and SD-OCT images were evaluated and compared with those of 15 age-matched controls (30 eyes). Using a validated 3-dimensional SD-OCT segmentation algorithm, we calculated the equivalent thickness of photoreceptors and the equivalent thickness of the retinal pigment epithelium for each patient. The photoreceptor equivalent thickness and the retinal pigment epithelium (RPE) equivalent thickness were compared in all patients, in a region of the macula outside the central lesion for patients with BVMD and outside the fovea in control patients. Paired t tests were used for statistical analysis. The SD-OCT findings revealed that the vitelliform lesion consists of material above the RPE and below the outer segment tips. Additionally, drusen-like deposition of sub-RPE material was notable, and several patients exhibited a sub-RPE fibrotic nodule. Patients with BVMD had a mean photoreceptor equivalent thickness of 28.3 μm, and control patients had a mean photoreceptor equivalent thickness of 21.8 μm, a mean difference of 6.5 μm (P < .01), whereas the mean RPE equivalent thickness was not statistically different between patients with BVMD and control patients (P = .53). The SD-OCT findings suggest that vitelliform material is located in the subretinal space and that BVMD is associated with diffuse photoreceptor outer segment abnormalities overlying a structurally normal RPE. These findings provide new insight into the pathophysiology of BVMD and thus have implications for the development of therapeutic interventions.

Evolution of Spectral Domain Optical Coherence Tomography changes in Adult Onset Vitelliform Dystrophy

Vitelliform macular dystrophy is an autosomal dominant disorder with variable penetrance and expressivity. It was first described by Friedrich Best1 in 1905 with a complete description of various stages of this disease. Adult-onset vitelliform dystrophy, which was first described by Gass2 in 1974, differs from classic vitelliform dystrophy in that the vitelliform lesion may have a variable evolution. It manifests with bilateral mild to moderate visual loss of late onset. Electrooculogram (EOG) is normal to slightly abnormal. It is an important differential diagnosis for wet AMD where antiVEGF therapy has little or no benefit.3-5 Optical coherence tomography (OCT) is a useful tool to evaluate and document different stages of this disease. In this report, we documented OCT changes in a patient through different stages of the disease over a follow-up of 10 months.