Vitelliform Macular Dystrophy Research Articles

Nanomedicine-based Curcumin Approach Improved ROS Damage in Best Dystrophy-specific Induced Pluripotent Stem Cells

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.

Optical coherence tomography angiography in best vitelliform macular dystrophy

PurposeTo report best vitelliform macular dystrophy (BVMD) with an intriguing pattern of vascular flow on optical coherence tomography angiography (OCTA). MethodsFour eyes of two patients with BVMD were evaluated. Complete ophthalmic examination including best corrected visual acuity (BCVA), spectral domain optical coherence tomography (SD-OCT), and OCTA were performed. Diagnosis was confirmed by electroretinography (ERG) and electrooculography (EOG) testing. ResultsAll eyes had the electrophysiologic confirmation of the BVMD. The first patient was 35 years old with BCVA of 20/20 and pseudohypopyon stage macular lesion in right eye (RE) and BCVA of 20/32 and vitelliruptive stage macular lesion in the left eye (LE). The second patient was 18 years old with BCVA of 20/25 and macular lesion in vitelliform stage in the RE and BCVA of 20/60 and choroidal neovascularization (CNV) in the LE. In all eyes, a distinct foveal avascular zone (FAZ) was not detectable in OCTA, with a bridging vessel in the FAZ. A dense subretinal capillary network compatible with CNV in the LE of second patient was observed. ConclusionIn our cases, we found bridging vessel in the FAZ, and it may be due to the effects of bestrophin on the calcium content and vascular endothelial growth factor (VEGF) secretion of the retinal pigment epithelium (RPE) cells.

Multimodal Imaging in Best Vitelliform Macular Dystrophy.

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.

Establishment of an induced pluripotent stem cell line (FDEENTi002-A) from a patient with Best's disease carrying c.888C > A mutation in BEST1 gene

Best's disease (BD) is an inherited retinal degenerative disease caused by mutations in BEST1 gene. A human induced pluripotent stem cell (iPSC) line has been generated with integration-free Sendai virus method from peripheral blood mononuclear cells (PBMCs) of a BD patient carrying c.888C > A mutation in BEST1 gene. This cell line may serve as a model for the study of pathogenesis of BD.

Optical coherence tomography angiography findings in a case of adult‐onset vitelliform dystrophy

Adult‐onset vitelliform dystrophy (AOVD) is characterised by progressive vision loss due to sub‐macular deposition of drusenoid material, with an onset between 30–50-years of age.1974 In this case,...

Test performance of optical coherence tomography angiography in detecting retinal diseases: a systematic review and meta-analysis.

To investigate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in detecting vascular characteristics of chorio-retinal disease. Evidence acquisition: We searched Web of Science, Scopus, and Medline by the citation of references and complemented these electronic searches by checking the list of references of included and review articles. Screening, selection, assessment, and extraction was performed in parallel by two authors. Evidence synthesis: Systematic review and exploratory meta-analysis. The ten studies that contributed to the meta-analysis enrolled 440 eyes and allowed constructing ten two-by-two tables. The tables reported on detection of choroidal neovascularization (CNV) in eyes suffering from either age-related macular degeneration (4), central serous chorioretinopathy (2), myopia (2), foveomacular vitelliform dystrophy (1), or a mixed cohort suffering from multiple retinal diseases (1). Of the ten studies, six used a cohort and four a case-control design. We found a pooled sensitivity of 0.90 (95% confidence intervals (CIs): 0.82-0.95) and a pooled specificity of 0.97 (95% CI: 0.89-0.99). Corresponding positive and negative likelihood ratios were 32.3 (95% CI: 7.4-141.6) and 0.10 (95% CI: 0.06-0.20), respectively. No pooling was possible for retinal vascular parameters of diabetic retinopathy, polypoidal choroidal vasculopathy, or detection of CNV activity. The results of highly biased and heterogeneous studies assessing the diagnostic performance of OCTA highlight the need for further analyses of methodologically sound and sufficiently sized clinical evaluations.

Optical Coherence Tomography of Adult-Onset Foveomacular Vitelliform Dystrophy Concomitant with Diabetic Cystoid Macular Edema

Optical Coherence Tomography of Adult-Onset Foveomacular Vitelliform Dystrophy Concomitant with Diabetic Cystoid Macular Edema

Chromatic pupilloperimetry for objective diagnosis of Best vitelliform macular dystrophy.

PurposeTo determine the pupil response of Best vitelliform macular dystrophy (BVMD) patients for focal blue and red light stimuli presented at 76 test points in a 16.2° visual field (VF) using a chromatic pupilloperimeter.MethodsAn observational study was conducted in 16 participants: 7 BVMD patients with a heterozygous BEST1 mutation and 9 similar-aged controls. All participants were tested for best-corrected visual acuity, chromatic pupilloperimetry and Humphrey perimetry. Percentage of pupil contraction (PPC), maximal pupil contraction velocity (MCV) and latency of MCV (LMCV) were determined.ResultsThe mean PPC and MCV recorded in BVMD patients in response to red stimuli were lower by >2 standard errors (SEs) from the mean of controls in 47% and 43% of VF test points, respectively. The mean PPC and MCV recorded in the patients in response to blue stimuli were lower by >2 SEs from the mean of controls in 36% and 24% of VF test points, respectively. The patients’ mean and median MCV recorded in response to red light correlated with their Humphrey mean deviation score (r=−0.714, P=0.071 and r=−0.821, P=0.023, respectively) and visual acuity (r=0.709, P=0.074 and r=0.655, P=0.111, respectively). A substantially shorter mean LMCV was recorded in BVMD patients compared to controls in 54% and 93% of VF test points in response to red and blue light, respectively. Receiver operating characteristic analysis for LMCV in response to red light identified a test point at the center of the VF with high diagnostic accuracy (area under the curve of 0.94).ConclusionChromatic pupilloperimetry may potentially be used for objective noninvasive assessment of rod and cone cell function in different locations of the retina in BVMD patients.

IMAGING OF VITELLIFORM MACULAR LESIONS USING POLARIZATION-SENSITIVE OPTICAL COHERENCE TOMOGRAPHY.

To examine the involvement of the retinal pigment epithelium (RPE) in the presence of vitelliform macular lesions (VML) in Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy, and adult-onset vitelliform macular degeneration using polarization-sensitive optical coherence tomography (PS-OCT). A total of 35 eyes of 18 patients were imaged using a PS-OCT system and blue light fundus autofluorescence imaging. Pathogenic mutations in the BEST1 gene, 3 of which were new, were detected in all patients with BVMD and autosomal recessive bestrophinopathy. Polarization-sensitive optical coherence tomography showed a characteristic pattern in all three diseases with nondepolarizing material in the subretinal space consistent with the yellowish VML seen on funduscopy with a visible RPE line below it. A focal RPE thickening was seen in 26 eyes under or at the edge of the VML. Retinal pigment epithelium thickness outside the VML was normal or mildly thinned in patients with BVMD and adult-onset vitelliform macular degeneration but was diffusely thinned or atrophic in patients with autosomal recessive bestrophinopathy. Patients with autosomal recessive bestrophinopathy showed sub-RPE fibrosis alongside the subretinal VML. Polarization-sensitive optical coherence tomography was more reliable in assessing the localization and the integrity of the RPE than spectral domain OCT alone. On spectral domain OCT, identification of the RPE was not possible in 19.4% of eyes. Polarization-sensitive optical coherence tomography allowed for definite identification of the location of VML in respect to the RPE in all eyes, since it provides a tissue-specific contrast. Polarization-sensitive optical coherence tomography confirms in vivo the subretinal location of VML and is useful in the assessment of RPE integrity.

Suppression of Choroidal Neovascularization by AAV-Based Dual-Acting Antiangiogenic Gene Therapy

Vascular endothelial growth factor A (VEGFA) is involved in the pathogenesis of vasoproliferative retinal diseases, such as exudative age-related macular degeneration (AMD). The objective of this study was to investigate whether dual-acting therapy based on the simultaneous expression of anti-VEGFA microRNAs (miRNAs) and the secreted, antiangiogenic protein pigment endothelial-derived factor (PEDF) delivered by adeno-associated virus (AAV) vectors provides improved protection against choroidal neovascularization (CNV). To investigate this, a multigenic AAV vector allowing retina pigment epithelium (RPE)-specific expression of anti-VEGFA miRNAs and PEDF was engineered. Robust expression of PEDF, driven by the RPE-specific vitelliform macular dystrophy 2 promoter, was observed in human cells and in mouse retina. A significant reduction in CNV was observed in a laser-induced CNV mouse model 57 days post-injection of the AAV5 particles conveying either anti-VEGFA miRNA and PEDF dual therapy or anti-VEGFA miRNA monotherapy. Overall, CNV reduction was most prominent in animals receiving dual-acting therapy. In both cases, the reduction in CNV was accompanied by a significant attenuation of VEGFA. In conclusion, the presented data reveal that gene therapy targeting VEGFA via multigenic AAV vectors displays combined efficacy, suggesting that dual-acting therapy is an important tool in future eye gene therapy for the treatment of neovascular ocular diseases, including AMD.

Best vitelliform macular dystrophy in a large Brazilian family

BackgroundTo describe the clinical and multimodal imaging findings of a Brazilian family with Best vitelliform macular dystrophy.MethodsA retrospective chart review of a Brazilian family was conducted and complementary fundus images (color photography, autofluorescence, fluorescein angiography and optical coherence tomography) were analyzed.ResultsSeven patients had typical macular lesions at different stages of Best vitelliform macular dystrophy. Electrooculography was performed in two of them and showed abnormal Arden ratio. The pedigree strongly suggests an autosomal dominant inheritance. Low visual acuity was mainly associated with advanced age, retinal pigment epithelium atrophy, and photoreceptors damage. However, yellow subretinal deposits were evidenced in patients with better visual acuity.ConclusionWe present the largest case series of a Brazilian family with Best vitelliform macular dystrophy. Multimodal imaging analysis is important to determine retinal abnormalities. Retinal pigment epithelium atrophy and loss of photoreceptors outer segments seem to be a late but important finding related to severe visual acuity impairment.

Current research status of optical coherence tomography angiography in hereditary retinochoroidal degeneration

OCT angiography (OCTA) is a fast, noninvasive and quantifiable new technique, which is especially suitable for long-term follow-up in patients with hereditary retinochoroidal degeneration, such as retinitis pigmentosa, Best vitelliform macular dystrophy, adult onset foveomacular vitelliform dystrophy, doyne honeycomb retinal dystrophy, choroideremia and Stargardt disease. During the follow-up, clinicians can find the subtle signs that explain disease development from the blood flow imaging, quantitatively describe the vascular density, timely detect and treat choroidal neovascularization. It is significant to explore the etiology and monitor the course of these diseases. With the development of more treatments for these diseases, OCTA parameters can also be used as indicators to evaluate and compare different therapeutic effects. In the future, more quantitative indicators of OCTA will be applied to evaluate the course of hereditary retinochoroidal degeneration, and provide valuable basis for early diagnosis and treatment. Key words: Tomography, optical coherence; Retinal diseases/diagnosis; Choroid diseases/ diagnosis; Eye Diseases, Hereditary; Review

The Y227N mutation affects bestrophin-1 protein stability and impairs sperm function in a mouse model of Best vitelliform macular dystrophy.

ABSTRACTHuman bestrophin-1 (BEST1) is an integral membrane protein known to function as a Ca2+-activated and volume-regulated chloride channel. The majority of disease-associated mutations in BEST1 constitute missense mutations and were shown in vitro to lead to a reduction in mutant protein half-life causing Best disease (BD), a rare autosomal dominant macular dystrophy. To further delineate BEST1-associated pathology in vivo and to provide an animal model useful to explore experimental treatment efficacies, we have generated a knock-in mouse line (Best1Y227N). Heterozygous and homozygous mutants revealed no significant ocular abnormalities up to 2 years of age. In contrast, knock-in animals demonstrated a severe phenotype in the male reproductive tract. In heterozygous Best1Y227N males, Best1 protein was significantly reduced in testis and almost absent in homozygous mutant mice, although mRNA transcription of wild-type and knock-in allele is present and similar in quantity. Degradation of mutant Best1 protein in testis was associated with adverse effects on sperm motility and the capability to fertilize eggs. Based on these results, we conclude that mice carrying the Best1 Y227N mutation reveal a reproducible pathologic phenotype and thus provide a valuable in vivo tool to evaluate efficacy of drug therapies aimed at restoring Best1 protein stability and function.

INTRARETINAL HYPERREFLECTIVE FOCI IN BEST VITELLIFORM MACULAR DYSTROPHY.

To report on the presence of hyperreflective foci (HF) on spectral domain optical coherence tomography in patients with Best vitelliform macular dystrophy (BVMD), and to describe the relationship between HF and stages of the disease. Consecutive patients diagnosed with BVMD were enrolled in a prospective cross-sectional study. All patients and control subjects underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. identification of HF in BVMD. Secondary outcome: assessment of the HF in each stage and correlation with best-corrected visual acuity. Overall, 75 eyes of 39 patients were included in the study (Stage 1: 13%, Stage 2: 43%, Stage 3: 15%, Stage 4: 21%, and Stage 5: 8%). On spectral domain optical coherence tomography assessment, intraretinal HF were present in 83% of all eyes, in 91% of eyes affected by clinical BVMD (Stages 2-5) and in 100% of patients in Stages 4 and 5. In 46% of clinically diseased eyes, HF were localized in the fovea and in correspondence with the BVMD lesions at the level of the outer nuclear layer and outer plexiform layer. Hyperreflective foci were present in 16% of control eyes. Mean number of HF in eyes affected by clinical BVMD stood at 7.67 ± 7.35. These were predominantly small HF (6.23 ± 6.14, P < 0.001) localized in the outer nuclear layer (5.19 ± 5.38, P = 0.001) and presented largely in the extrafoveal, rather than the foveal area (5.21 ± 5.57 vs 2.46 ± 2.73, P = 0.001). Analysis of HF distribution revealed that the control group and Stage 1 eyes had the fewest HF; Stage 4 displayed a significant increase in the number of HF compared with Stages 2 and 3; Stage 5 also showed an increased number of HF, although this difference was statistically significant only with Stage 3 eyes. The best-corrected visual acuity was negatively related to the number of HF, with best-corrected visual acuity deteriorating as the number of HF increased in Stages 2 to 5 (P < 0.001). This study describes the presence of HF in BVMD using spectral domain optical coherence tomography. Our data suggest that HF identification is correlated with the progression of the disease and could represent a useful biomarker of BVMD.

Clinical and Mutation Analysis of Patients with Best Vitelliform Macular Dystrophy or Autosomal Recessive Bestrophinopathy in Chinese Population.

Mutations in the gene BEST1 usually cause bestrophinopathies, such as the rare progressive diseases Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). This study aimed to investigate the clinical characteristics of patients with BVMD or ARB carrying BEST1 mutations. A total of 12 probands including 9 patients with a clinical diagnosis of BVMD and 3 patients with a clinical diagnosis of ARB were recruited for genetics analysis. All patients underwent detailed ophthalmic examination. All coding exons of the BEST1 gene were screened by PCR-based DNA sequencing. Programs of PolyPhen-2, SIFT, and MutationTaster were used to analyze the potential pathogenicity of the mutations in BEST1. In the 9 unrelated patients with BVMD, one heterozygous BEST1 mutation was revealed in 8 patients and two compound heterozygous mutations in 1 patient. In the 3 unrelated patients with ARB, two compound heterozygous mutations were revealed in 2 patients and three compound heterozygous mutations in 1 patient. Molecular analyses identified a total of 15 mutations, including 3 novel mutations (c.424A>G p.S142G, c.436G>A p.A146T, and c.155T>C p.L52P). Antivascular endothelial growth factor (VEGF) drugs were given to two affected eyes, especially those also exhibiting choroidal neovascularization (CNV), and no serious adverse events occurred. Our study indicates that there is wide genotypic and phenotypic variability in patients with BVMD or ARB in China. The screening of BEST1 gene is significant for the precise diagnosis of BVMD and ARB.

THE EXPANDING CLINICAL SPECTRUM OF CHOROIDAL EXCAVATION IN MACULAR DYSTROPHIES.

To assess the prevalence and the clinical course of focal choroidal excavation (FCE) in patients affected by macular dystrophies. Prospective case series. All the patients underwent a complete ophthalmologic examination, including best-corrected visual acuity and spectral domain optical coherence tomography. The presence of choroidal neovascularization (CNV) was assessed on the basis of the leakage detected on fluorescein angiography. A total of 162 eyes from 81 patients with macular dystrophy were included in the study. FCE was diagnosed in seven eyes (4.3% of the eyes), including four eyes with Best vitelliform dystrophy, two eyes with pattern dystrophy associated with pseudoxanthoma elasticum, and one case of Stargardt disease. In eyes with FCE and macular dystrophy, the mean best-corrected visual acuity was 0.4 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at baseline and was stable to 0.41 ± 0.1 logarithm of the minimum angle of resolution (approximately corresponding to 20/50 Snellen equivalent) at the final visit. In four of these seven eyes, FCE was associated with a subfoveal CNV. The CNV was managed with one intravitreal anti-vascular endothelial growth factor injection, achieving the complete anatomical stabilization of the CNV and recovery of the best-corrected visual acuity. Focal choroidal excavation can be infrequently encountered in patients with macular dystrophies. The presence of CNV may complicate FCE in these patients, and anti-vascular endothelial growth factor seems to be an effective treatment with no progression of FCE over time.

Fibrotic pillar leads to focal choroidal excavation in Best vitelliform dystrophy.

To study focal choroidal excavations in patients with Best vitelliform dystrophy using optical coherence tomography and their topographical relation with fibrotic pillars. This is a retrospective cross-sectional study of consecutive patients diagnosed with Best vitelliform dystrophy at a tertiary eye care center. Records of patients with Best vitelliform dystrophy were reviewed for best-corrected visual acuity, color fundus photographs, shortwave autofluorescence, optical coherence tomography, and electrooculogram with special emphasis on the presence of focal choroidal excavation (FCE) and fibrotic pillar. Main outcome measure was to study the fibrotic pillar in relation to the FCE. Thirty-eight eyes of 19 patients with mean age of 34.6years were enrolled in the study. FCE was seen in eight eyes of six patients. Two patients had bilateral FCE and all the FCEs were located in the area of vitelliform lesion. Six out of eight eyes with FCE were in vitelliruptive stage of disease; one was in pseudohypopyon stage and one in atrophic stage. A fibrotic pillar was seen lying directly above the FCE in seven eyes. In one eye, hyper-reflective material not amounting to fibrotic pillar was seen lying above the FCE. A focal choroidal excavation in the setting of Best vitelliform dystrophy is seen predominantly in the vitelliruptive stage of the disease. Fibrotic pillars appear to play a role in the formation of these FCEs.

Next generation sequencing identifies novel disease-associated BEST1 mutations in Bestrophinopathy patients

Bestinopathies are a spectrum of retinal disorders associated with mutations in BEST1 including autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD). We applied whole-exome sequencing on four unrelated Indian families comprising eight affected and twelve unaffected individuals. We identified five mutations in BEST1, including p.Tyr131Cys in family A, p.Arg150Pro in family B, p.Arg47His and p.Val216Ile in family C and p.Thr91Ile in family D. Among these, p.Tyr131Cys, p.Arg150Pro and p.Val216Ile have not been previously reported. Further, the inheritance pattern of BEST1 mutations in the families confirmed the diagnosis of ARB in probands in families A, B and C, while the inheritance of heterozygous BEST1 mutation in family D (p.Thr91Ile) was suggestive of BVMD. Interestingly, the ARB families A and B carry homozygous mutations while family C was a compound heterozygote with a mutation in an alternate BEST1 transcript isoform, highlighting a role for alternate BEST1 transcripts in bestrophinopathy. In the BVMD family D, the heterozygous BEST1 mutation found in the proband was also found in the asymptomatic parent, suggesting an incomplete penetrance and/or the presence of additional genetic modifiers. Our report expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES IN DIFFERENT STAGES OF BEST VITELLIFORM MACULAR DYSTROPHY.

To provide a systematic classification of findings regarding the different stages of vitelliform macular dystrophy on spectral domain optical coherence tomography (SD-OCT). Ninety-four eyes of 47 patients were recruited in a prospective cross-sectional study. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity using Early Treatment Diabetic Retinopathy Study (ETDRS) charts, biomicroscopy, and SD-OCT. The findings assessed included vitelliform material, neurosensory detachment, status of external limiting membrane, ellipsoid zone and retinal pigment epithelium, choroidal excavation, foveal cavitation, choroidal neovascularization, vitreomacular traction, and macular hole. The primary outcome measure was the identification of SD-OCT findings in each vitelliform macular dystrophy stage. Secondary outcomes included the correlations between SD-OCT features and visual acuity changes. The outer retinal layers (external limiting membrane, ellipsoid zone, and retinal pigment epithelium) were found to be more commonly disrupted in Stages 2 to 4 (range: 86%-100%), whereas their absence was more typical of Stage 5 (71%-86%). Vitelliform material was found in 100% of Stages 2 and 3, 93% of Stage 4, and interestingly in 43% of Stage 5. Eyes characterized by vitelliform material showed a greater correlation with higher best-corrected visual acuity than eyes without it (0.35 logarithm of the minimum angle of resolution vs. 0.80 ± 0.36 logarithm of the minimum angle of resolution, approximately 20/45 and 20/125 Snellen equivalent, respectively) (t = 3.726, P < 0.05). Moreover, its absence was associated with a best-corrected visual acuity of 0.5 logarithm of the minimum angle of resolution or worse (approximately 20/63 Snellen equivalent; P < 0.05). Subretinal fluid was more common in Stages 3 and 4 (72.7% and 75%, respectively) than Stages 2 and 5 (P = 0.004). Eyes with subretinal fluid were significantly associated with a visual acuity of 0.2 logarithm of the minimum angle of resolution or worse (approximately 20/32 Snellen equivalent; P = 0.04). Spectral domain optical coherence tomography assessment primarily indicates an outer retinal layer disruption in Stages 2 to 4, along with the presence of vitelliform material extending into the more advanced clinical stages too. Eyes characterized by the persistence of vitelliform material show better best-corrected visual acuity. Future investigations based on a longitudinal follow-up are warranted to correlate SD-OCT modifications with functional responses to identify SD-OCT indicators for prognostic and therapeutic purposes.

Generation of induced pluripotent stem cells from a patient with Best Dystrophy carrying 11q12.3 (BEST1 (VMD2)) mutation

Best disease (BD), also termed Best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and central visual loss. In this report, we generated an induced pluripotent stem cell (iPSC) line, TVGH-iPSC-012-04, from the peripheral blood mononuclear cells of a female patient with BD by using the Sendai virus delivery system. The resulting iPSCs retained the disease-causing DNA mutation, expressed pluripotent markers and could differentiate into three germ layers. We believe that BD patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.