Stage-dependent choriocapillaris impairment in Best vitelliform macular dystrophy characterized by optical coherence tomography angiography.
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SUBMITTER: Jauregui R
PROVIDER: S-EPMC8275766 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeIn patients diagnosed with Best vitelliform macular dystrophy (BVMD), quantitative fundus autofluorescence (qAF), near-infrared fundus autofluorescence (NIR-AF), and spectral-domain optical coherence tomography (SD-OCT) were used to elucidate pathogenic mechanisms.MethodsFourteen patients heterozygous for BEST1 mutations were recruited. qAF was analyzed using short-wavelength fundus autofluorescence (SW-AF) images. Mean gray levels (GL) were determined in nonlesion areas (7 to 9° eccentricity) and adjusted by GL measured in an internal fluorescent reference. NIR-AF images (787 nm; sensitivity of 96) were captured and saved in non-normalized mode. Horizontal SD-OCT images also were acquired and BVMD was staged according to the OCT findings.ResultsIn the pre-vitelliform stage, NIR-AF imaging revealed an area of reduced fluorescence, whereas in the vitelliruptive stage, puncta of elevated NIR-AF signal were present. In both SW-AF and NIR-AF images, the vitelliform lesion in the atrophic stage was marked by reduced signal. At all stages of BVMD, nonlesion qAF was within the 95% confidence intervals for healthy eyes. Similarly, the NIR-AF intensity measurements outside the vitelliform lesion were comparable to the healthy control eye. SD-OCT scans revealed a fluid-filled detachment between the ellipsoid zone and the hyperreflectivity band attributable to RPE/Bruch's membrane.ConclusionsNIR-AF imaging can identify the pre-vitelliform stage of BVMD. Mutations in BEST1 are not associated with increased levels of SW-AF outside the vitelliform lesion. Elevated SW-AF within the fluid-filled lesion likely reflects the inability of RPE to phagocytose outer segments due to separation of RPE from photoreceptor cells, together with progressive photoreceptor cell impairment.
| S-EPMC6735800 | biostudies-literature
Project description:PurposeSwept-source optical coherence tomography angiography (SS-OCTA) was used to measure the age-dependent changes in macular choriocapillaris (CC) flow deficits (FDs) in normal eyes.DesignA prospective, cross-sectional study.MethodsSubjects with normal eyes ranging in age from their 20s to their 80s were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000, Carl Zeiss Meditec, Dublin, California, USA). Both 3 × 3-mm and 6 × 6-mm scans were used to image the macular CC. Visualization of the CC and quantification of FDs were performed using a previously validated algorithm. The percentage of FDs (FD%) in the central 1-mm circle (C1), 1.5-mm rim (R1.5), and 2.5-mm circle (C2.5) from the 3 × 3-mm and 6 × 6-mm scans and FD% in the 2.5-mm rim (R2.5) and 5-mm circle (C5) from the 6 × 6-mm scans were measured and correlated with age and axial length.ResultsA total of 164 subjects were enrolled, with at least 10 subjects from each decade of life. No meaningful correlations were found between FD% and axial length (|r| < 0.30). FD% in all fields increased with increasing age (all r > 0.50; all P < .001); however, the greatest increases were found in the central macula C1 regions and the smallest increases in the peripheral macula R2.5 regions.ConclusionsIn normal aging, the FD% increased with age across the central 5 mm of the macula, but the greatest increase was found in the central 1-mm region of the macula.
| S-EPMC6513331 | biostudies-literature
Project description:ImportanceImaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging.ObjectiveTo investigate multiple en face image averaging on OCTA images of the choriocapillaris.Design, setting, and participantsObservational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016.ExposuresAll participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images.Main outcome and measureVessel caliber measurement.ResultsSeventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P < .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P < .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P < .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images.Conclusions and relevanceMultiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.
| S-EPMC5710392 | biostudies-literature
Project description:ImportanceNovel therapies for choroideremia, an X-linked recessive chorioretinal degeneration, demand a better understanding of the primary site(s) of cellular degeneration. Optical coherence tomography angiography allows for choriocapillaris (CC) imaging. We compared the extent of structural alterations of the CC, retinal pigment epithelium, and photoreceptors with multimodal imaging.ObservationsIn a clinical case series conducted from September 15, 2014, through February 5, 2015, 14 eyes of 7 male patients with choroideremia (median age, 34 years [interquartile range, 15-46 years]; age range, 13-48 years), 4 eyes of 2 women with choroideremia carrier state (both in mid-50s), and 6 eyes of 6 controls (median age, 42.5 years [interquartile range, 33-55 years]; age range, 24-55 years) underwent multimodal imaging with optical coherence tomography angiography and electroretinography. The mean (SD) macular CC density was 82.9% (13.4%) in patients with choroideremia, 93.0% (3.8%) in female carriers, and 98.2% (1.3%) in controls. The mean (SD) CC density in affected eyes was higher in regions with preserved (92.6% [5.8%]) vs absent (75.9% [12.6%]) ellipsoid zone (mean difference, 16.7%; 95% CI, 12.1% to 21.3%; P < .001). Seventeen of 18 eyes of the patients and carriers had outer retinal tubulations forming pseudopod-like extensions from islands of preserved ellipsoid zone. Outer retinal tubulations were associated with absence of underlying retinal pigment epithelium and were longer (r = -0.62; 95% CI, -0.84 to -0.19; P < .001) and more numerous (r = -0.71; 95% CI, -0.91 to -0.27; P < .001) in more severely affected eyes.Conclusions and relevanceThese findings suggest that regional changes in CC density correlate with photoreceptor structural alterations in choroideremia. Although closely coupled, the results suggest that retinal pigment epithelium loss is more extensive than photoreceptor loss.
| S-EPMC4978125 | biostudies-literature
Project description:Importance:Whether optical coherence tomography angiography (OCT-A) outperforms OCT to detect glaucoma remains inconclusive. Objective:To compare (1) the diagnostic performance for detection of glaucoma and (2) the structure-function association between inner macular vessel density and inner macular thickness. Design, Setting, and Participants:This cross-sectional study included 115 patients with glaucoma and 35 healthy individuals for measurements of retinal thickness and retinal vessel density, segmented between the anterior boundary of internal limiting membrane and the posterior boundary of the inner plexiform layer, over the 3 × 3-mm2 macula using swept-source OCT. All participants were Chinese. Visual sensitivity corresponding to the 3 × 3-mm2 macular region was expressed in unlogged 1/lambert for investigation of the structure-function associations. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (AUCs). The study was conducted between January 12, 2016, and December 12, 2016. Main Outcomes and Measures:Area under the receiver operating characteristic curve and R2 analysis. Results:Of the 115 patients with glaucoma, 42 (36.5%) were women (mean [SD] age, 53.5 [13.4] years); of the 35 individuals with healthy eyes, 25 (71.4%) were women (age, 60.6 [5.9] years). Inner macular vessel density and thickness were 4.3% (95% CI, 2.4%-6.1%) and 21.1 μm (95% CI, 17.4-24.9 μm) smaller, respectively, in eyes with glaucoma compared with healthy eyes. The AUC of mean inner macular thickness for glaucoma detection was greater than that of mean inner macular vessel density (difference, 0.17; 95% CI, 0.01-0.31; P = .03). At 90% specificity, the sensitivity of mean inner macular thicknesses for detection of glaucoma was greater than that of mean inner macular vessel densities (difference, 29.2%; 95% CI, 11.5%-64.6%; P = .02). The strength of the structure-function association was stronger for mean inner macular thickness than mean inner macular vessel density in the linear (difference in R2 = 0.38; 95% CI, 0.22-0.54; P < .001) and nonlinear (difference in R2 = 0.36; 95% CI, 0.21-0.51; P < .001) regression models. Conclusions and Relevance:In this study, OCT measurement of inner macular thickness shows a higher diagnostic performance to detect glaucoma and a stronger structure-function association than the currently used OCT-A measurement of inner macular vessel density. These findings may suggest that OCT-A of the macula has a limited role in the diagnostic evaluation of glaucoma.
| S-EPMC6142951 | biostudies-literature
Project description:Demonstrating the utility of adaptive optics scanning light ophthalmoscopy (AOSLO) to assess outer retinal structure in Best vitelliform macular dystrophy (BVMD).To characterize outer retinal structure in BVMD using spectral-domain optical coherence tomography (SD-OCT) and AOSLO.Prospective, observational case series. Four symptomatic members of a family with BVMD with known BEST1 mutation were recruited at the Advanced Ocular Imaging Program research lab at the Medical College of Wisconsin Eye Institute, Milwaukee.Thickness of 2 outer retinal layers corresponding to photoreceptor inner and outer segments was measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in 2 subjects.Photoreceptor structure.Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size were consistent with Henle fibers.AND RELEVANCE: The AOSLO findings indicate that substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation.
| S-EPMC3968428 | biostudies-literature
Project description:Adult-onset vitelliform macular dystrophy (AVMD) is a common and benign macular degeneration which can be caused by BEST1 mutation. Here, we investigated the clinical characteristics associated with a newly identified BEST1 mutation, p.Ile38Ser and confirmed the associated physiological functional defects. The 51-year-old patient presented bilateral small subretinal yellow deposits. Consistent with AVMD, the corresponding lesions showed hyperautofluorescence, late staining in fluorescein angiography, and subretinal hyper-reflective materials in spectral-domain optical coherence tomography. Genetic analysis demonstrated that the patient presented with a heterozygous p.Ile38Ser BEST1 mutation. Surface biotinylation and patch clamp experiments were performed in transfected HEK293T cells. Although, the identified BEST1 mutant maintains normal membrane expression, p.Ile38Ser mutant showed significantly smaller currents than wild type (WT). However, it showed larger currents than other BEST1 mutants, p.Trp93Cys, causing autosomal dominant best vitelliform macular dystrophy (BVMD), and p.Ala195Val, causing autosomal recessive bestrophinopathy (ARB). The cells expressing both WT and each BEST1 mutant showed that the functional defect of p.Ile38ser was milder than that of p.Trp93Cys, whereas combination of p.Ala195Val with WT showed good current. We identified and described the phenotype and in vitro functions of a novel BEST1 mutation causing AVMD. AVMD induced by p.Ile38Ser BEST1 mutation is a mild form of BVMD.
| S-EPMC5567297 | biostudies-literature
Project description:PurposeTo characterize outer retina structure in best vitelliform macular dystrophy (BVMD) and to determine the effect of macular lesions on overlying and adjacent photoreceptors.MethodsFive individuals with BVMD were followed prospectively with spectral domain optical coherence tomography and confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). The AOSLO cone photoreceptor mosaic images were obtained within and around retinal lesions. Cone density was measured inside and outside lesions. In 2 subjects, densities were compared with published measurements acquired ∼2.5 years before. One subject was imaged 3 times over a 5-month period.ResultsThe AOSLO imaging demonstrated that photoreceptor morphology within BVMD retinal lesions was highly variable depending on the disease stage, with photoreceptor structure present even in advanced disease. The AOSLO imaging was repeatable even in severe disease over short-time and long-time intervals. Photoreceptor density was normal in retinal areas immediately adjacent to lesions and stable over ∼2.5 years. Mobile disk-like structures possibly representing subretinal macrophages were also observed.ConclusionCombined confocal and nonconfocal split-detector AOSLO imaging reveals substantial variability within clinical lesions in all stages of BVMD. Longitudinal cellular photoreceptor imaging could prove a powerful tool for understanding disease progression and monitoring emerging therapeutic treatment response in inherited degenerations such as BVMD.
| S-EPMC5362286 | biostudies-literature
Project description:PurposeTo analyze fixation location and stability in best vitelliform macular dystrophy (BVMD) and test their association with best-corrected visual acuity (BCVA).DesignObservational, cross-sectional study.ParticipantsThirty patients (55 eyes) affected by genetically confirmed BVMD were followed up at the Retinal Heredodystrophies Unit of IRCCS San Raffaele Scientific Institute, Milan.MethodsPatients underwent testing with macular integrity assessment (MAIA) microperimeter. Fixation location was measured as distance in degrees (°) between preferred retinal locus (PRL) and estimated fovea location (EFL); fixation was defined as eccentric when the distance between PRL and EFL exceeded 2°. Fixation stability was graded as stable, relatively unstable, or unstable and expressed as bivariate contour ellipse area (BCEA, °2).Main outcome measuresFixation location and stability.ResultsThe median distance of the PRL from the anatomic fovea was 0.7°, and fixation location was eccentric in 27% of eyes. Fixation was graded as stable in 64% of eyes, relatively unstable in 13%, and unstable in 24%, with a median 95% BCEA of 6.2°2. The atrophic/fibrotic stage was associated with worse fixation parameters (all P < 0.01). Both PRL eccentricity and fixation stability were linearly associated with BCVA: every 1° increase in PRL eccentricity was associated with a 0.07 logarithm of the minimum angle of resolution (logMAR) worse BCVA (P < 0.0001) while every 1°2 increase in 95% BCEA was associated with a 0.01 logMAR worse BCVA (P < 0.001). No significant intereye correlation was found for PRL eccentricity and fixation stability, as well as no association between the patient's age and fixation parameters.ConclusionsWe demonstrated that most eyes affected by BVMD retain a central stable fixation and provided evidence that both fixation eccentricity and stability are strongly associated with visual acuity in BVMD. These parameters may serve as secondary end points for future clinical trials.Financial disclosuresProprietary or commercial disclosure may be found after the references.
| S-EPMC10251068 | biostudies-literature
Project description:PurposeThis study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD).DesignProspective cross-sectional study.MethodsThis study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated.ResultsThe total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P < 0.0001) by a 1.6:1 ratio (r2 = 0.90). CCVD within regions of matched degeneration (85.6% ± 2.7%; P < 0.0001), isolated IS/OS junction loss (93.6% ± 1.0%; P = 0.0011), and isolated RPE atrophy (94.1% ± 1.1%; P = 0.0065) were all significantly lower than normal (99.0% ± 0.17%). There was a trend for CCVD within intact areas (97.6% ± 0.38%) to decline as the area diminished (r = 0.68).ConclusionsPhotoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.
| S-EPMC6548611 | biostudies-literature