Stem cell therapy in stargardt disease: a systematic review

This article aimed to review current literature on the safety and efficacy of stem cell therapy in Stargardt disease. A comprehensive literature search was performed, and two animal and eleven human clinical trials were retrieved. These studies utilized different kinds of stem cells, including human or mouse embryonic stem cells, mesenchymal stem cells, bone marrow mononuclear fraction, and autologous bone marrow-derived stem cells. In addition, different injection techniques including subretinal, intravitreal, and suprachoroidal space injections have been evaluated. Although stem cell therapy holds promise in improving visual function in patients with Stargardt disease, further investigation is needed to determine the long-term benefits, safety, and efficacy in determining the best delivery method and selecting the most appropriate stem cell type.

Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.

Choroidal Neovascularization in a Patient with Best Disease

PURPOSE: To report a case of choroidal neovascularization in a Best disease patient treated with intravitreal bevacizumab injection and followed up with optical coherence tomography angiography (OCTA). CASE SUMMARY: A 20-year-old female visited our clinic with decreased visual acuity of the left eye for 6 months. On optical coherence tomography (OCT), subretinal fluid and hyperreflective subretinal clumps were observed in the macula of the right eye. Subretinal hemorrhage and subretinal fluid were observed in the left eye. Choroidal neovascularization in the left eye was observed using OCTA, fluorescein angiography, and indocyanine green angiography. A full-field electroretinogram was normal in both eyes, but an electrooculogram revealed that the Arden ratio was 1.564 in the right eye and 1.081 in the left eye. Intravitreal bevacizumab injection was performed in the left eye. At 6 months after the intravitreal injection, the best-corrected visual acuity of the left eye had recovered to 20/20. OCT revealed that subretinal fluid reduced and choroidal neovascularization was stable. After 12 months, visual acuity of the left eye was maintained at 20/20, but OCTA revealed that choroidal neovascularization had increased. CONCLUSIONS: Choroidal neovascularization associated with Best disease can improve by intravitreal bevacizumab injection, and the changes in choroidal neovascularization can be followed using OCTA.

Phenotypic expression variability in Best Disease: a purpose of a series of cases / Variabilidade de expressão Fenotípica na Doença de Best: a propósito de uma série de casos

Abstract The objective of the following work is to document the phenotypic expression variability in Best Disease in first-degree relatives. The information was collected by assessing medical notes, interviewing the patient and obtaining photographic record of the diagnostic methods to which the patient was submitted. Data was analyzed along with a thorough review of the literature. A series of cases were reported in which the patient presenting the phenotypic characteristics of the disease has first degree relatives without ophthalmic findings during examination, but present an abnormal pattern on the electro-oculogram (EOG). Our article reveals the importance of electrophysiological exams in the diagnosis of Best vitelliform macular dystrophy, including the prevention of its clinical manifestation (autosomal dominant), providing concrete subsidies for genetic counseling.

Resumo O objetivo do presente trabalho é a documentação da variabilidade de expressão fenotípica da Doença de Best em parentes de primeiro grau. As informações foram obtidas por meio de revisão do prontuário, entrevista com o paciente e registro fotográfico dos métodos diagnósticos aos quais os pacientes foram submetidos. Dados foram analisados junto a uma extensa revisão da literatura. Relatamos uma série de casos, no qual o paciente que apresenta as alterações fenotípicas da doença tem familiares de primeiro grau sem alterações ao exame oftalmológico, porém os mesmos apresentam padrão anormal de eletro-oculograma (EOG). O nosso artigo revela a importância dos exames eletrofisiológicos no diagnóstico da distrofia macular viteliforme de Best, inclusive no que se refere à prevenção de sua manifestação clínica (autossômica dominante), fornecendo subsídios concretos para o aconselhamento genético.

Maculopatia viteliforme polimorfa exudativa aguda: um relato de caso / Acute exsudative polymorphous vitelliform maculopathy: a case report

Resumo A maculopatia viteliforme polimorfa exsudativa aguda é um distúrbio retiniano extremamente raro, que tem sido considerado como uma forma de retinopatia paraneoplásica, encontrada em pacientes com um tumor primário subjacente. Os sintomas de maculopatia viteliforme polimorfa exsudativa aguda incluem dor de cabeça precedente seguida de perda aguda da visão. O fundo de olho de um paciente com essa condição demonstra geralmente depósitos bilaterais, branco-amarelados na região macular. O relato de uma doença rara e que tem uma forte associação com neoplasia oculta é de extrema relevância, pois ajuda a conhecer melhor a sua historia natural, possíveis complicações e prognóstico.

Abstract Acute exudative polymorphous vitelliform maculopathy is an extremely rare retinal disorder, that has been considered as a form of paraneoplasic retinopathy, found in patients with a underlying primary tumor. Symptoms of acute exudative polymorphous vitelliform maculopathy include preceding headache followed by acute onset of vision loss. The fundus of a patient with this condition typically demonstrates bilateral, subretinal white-yellow deposits in the macular region. The report of a rare disease which has a strong association with underlying neoplasia is extremely relevant whereas it helps better comprehend its genuine history, possible complicacy and prognosis.

A Case of Adult-Onset Vitelliform Dystrophy Treated with Intravitreal Injection of Bevacizumab

PURPOSE: To report a patient diagnosed with adult-onset vitelliform dystrophy (AOVD) who received an intravitreal injection of bevacizumab in both eyes. CASE SUMMARY: A 47-year-old female presented with blurred vision and metamorphopsia in both eyes. On color fundus photograph, small, round, yellowish dots on the foveola and subreitnal fluid were observed. Optical coherence tomography (OCT) showed thick hyperreflective structures in the retinal pigment epithelium (RPE) layer with serous retinal detachment and subretinal fluid. Despite an intravitreal injection of bevacizumab on both eyes, anatomical improvement was not observed on fundus photography and OCT.

Adult foveomacular vitelliform dystrophy / Distrofia viteliforme foveomacular do adulto

Adult foveomacular vitelliform dystrophy is a rare pathology. Less than 1% of the reported cases display perifoveal capillary permeability. The three-year follow-up period of the case revealed a rare form, which had not yet been documented. The patient was a 40-year-old female with normal visual acuity, and a minor complaint of metamorphopsia on the left eye. Retinography showed a perifoveal yellowish subretinal area OS.Angiography showed perifoveal leakage OS. Follow up showed that, over 3 years, capillary incompetence disappeared and the yellow area underwent alterations, becoming atrophic OS. Angiography also showed hyperfluorescence (windows defect). Towards the end, it resembled the appearance of late stage of Best's Disease...

Distrofia viteliforme foveomacular do adulto é uma patologia rara. Menos de 1% dos casos relatados mostram permeabilidade capilar perifoveal. O acompanhamento de 3 anos deste paciente revelou uma forma rara, ainda pouco documentada. O paciente era uma mulher de 40 anos de idade com acuidade visual normal, mas com queixa de metamorfopsia leve no olho esquerdo. A retinografia mostrou uma área sub-retiniana amarelada, perifoveal, com hiperfluorescência na angiofluoresceinografia. O seguimento mostrou, em 3 anos, que a incompetência capilar desapareceu e que a área, antes amarelada, tornou-se atrófica, com hiperfluorescência na angiografia, lembrando o aspecto tardio da doença de Best...

Adult-onset foveomacular dystrophy

Objective@#To describe a case of adult-onset foveomacular vitelliform dystrophy (AOFVD).@*Method@#This is a case report.@*Results@#A 22-year-old female presented with painless blurring of vision and metamorphopsia 3 days prior to consultation. There were 2 similar episodes in the past that spontaneously resolved after 2 to 4 weeks. Visual acuity (VA) was 20/50 in the right eye (OD) and 20/40 in the left (OS), both best corrected to 20/25. Dilated-fundus examination revealed a discrete area of mixed hypoand hyperpigmentation 1 disc diameter over the fovea in OD and a solitary round hypopigmented lesion with a hyperpigmented border 3 to 4 disc diameters on the fovea in OS. Fluorescein angiography (FA) revealed an area of hyperfluorescence surrounded by a rim of hypoflourescence in OD and an area of blocked fluorescence with subtle hyperfluorescence superior to the lesion in OS, both of which did not increase in size and intensity toward the late phases. Optical coherence tomography (OCT) revealed neurosensory detachment in both eyes. Electrooculogram (EOG) was normal with Arden ratio of 0.91. VA returned to 20/25 in both eyes, and repeat fundus photography showed no change in the characteristics of the lesions.@*Conclusion@#Differential diagnosis of a hypopigmented macular lesion in the young with self-limited blurring of vision should include AOFVD. FA, OCT, and EOG can help distinguish AOFVD from Best’s disease or other similar macular conditions.

Best Disease With Old-age Onset Misdiagnosed as Chronic Central Serous Chorioretinopathy: A Case Report

PURPOSE: To report a case of Best's disease with old-age-onset with unusual clinical features. CASE SUMMARY: A 68-year-old woman with a six-month history of using oral steroids complained of decreased vision in both eyes. Fundus examination revealed a circular area of macular elevation measuring approximately 1.5 disc diameter size in both eyes. Optical coherence tomography (OCT) showed serous retinal detachment, but pigment epithelial detachment was seen only on fluorescein angiography and indocyanine green angiography. The patient received a diagnosis of chronic central chorioretinopathy with choroidal neovascularization. Photodynamic therapy (PDT) and intravitreal bevacizumab (IVB) injections were prescribed as treatment, but were ineffective. For a definitive diagnosis, we performed an electro-oculogram (EOG) and the result was abnormal with an Arden ratio below 1.5 in both eyes. A final diagnosis of Best's disease was established. Spectral domain OCT findings at the last visit showed a clearly visible RPE split and a low reflective space between the split RPE layers, as well as a high reflectivity corresponding to the subretinal material. CONCLUSIONS: We report a case of Best's disease with old-age onset with unusual clinical features and abnormal EOG findings. Spectral domain OCT was helpful in evaluating the disease. Treatment with PDT and IVB was not effective.

Optical Coherence Tomography Findings in Best Disease

PURPOSE: To report the optical coherence tomography (OCT) findings of three cases in various stages of juvenile-onset vitelliform macular dystrophy (Best disease). CASE SUMMARY: Medical records of six eyes from three patients diagnosed with Best disease were reviewed retrospectively. We evaluated the clinical features of the fundus, the electro-oculogram, and the optical coherence tomography (OCT) results. In the fundi of the three patients with Best disease, the characteristic stages of vitelliform, pseudohypopyon, and scrambled egg appearance were identified. Optical coherence tomography findings in the eyes of the patients with Best disease showed two types of outer retina-choroid complex (ORCC) changes, including splitting with intervening hyporeflective areas and elevation over hyporeflective area. CONCLUSIONS: The OCT findings showed variable patterns according to the progression of Best disease. In the pseudohypopyon stage, both neurosensory detachment and retinal pigment epithelial detachment appearance were identified. The exact location of the resulting lesions seems to depend on the relative impediment of fluid movement caused by the mutation of bestrophin.

Angiographic Findings in Patients with Vitelliform Macular Dystrophy

PURPOSE: To evaluated the fluorescein and indocyanine green angiographic findings (FAG and ICGA) of each stage in vitelliform macular dystrophy. METHODS: In this study (3 patients, 6 eyes), the stage of macula lesion was classified as follows: stage A (vitelliform), stage B (pseudohypopyon), stage C (scrambled egg), stage D (early cicatricial), and stage E (advanced cicatricial). RESULTS: At stage A, the lesion was hypofluorescent in the early phase and was hyperfluorescent in the late phase of both FAG and ICGA. At stage B, FAG showed hyperfluorescent in the upper portion and hypofluorescent in the lower portion of the lesion. ICGA showed hypofluorescent in the upper portion. However, ICGA showed hypofluorescent in the early and hyperfluorescent in the late phase in the lower portion. At stage C, the lesion was hypofluorescent in the early phase and hyperfluorescent in the late phase of both FAG and ICGA. At stage D, FAG showed hyperfluorescent and ICGA showed hypofluorescent. At stage E, FAG showed central hypofluorescent lesions and a hyperfluorescent ring. While ICGA showed typically hypofluorescent. CONCLUSIONS: The FAG and ICGA findings showed variable patterns according to the evolution of the lesion.

The Study of Normal Visual Fields Using Goldmann Module in OCTOPUS 101 Automated Perimetery in Koreans

PURPOSE: Kinetic automated perimetric tests were performed with OCTOPUS 101 perimeter using Goldmann module. Normal isopter positions in the peripheral visual field were visualized by the average position +/- 2 standard deviations. METHODS: We examined 102 eyes of 51 normal healthy Koreans who had no family history of glaucoma, no specific ophthalmologic disease, best corrected visual acuity more than 1.0 and normal intraocular pressure less than 21 mmHg with OCTOPUS 101 perimeter using Goldmann module in 5 isopters (I1e, I2e, I3e, I4e, II4e) at 8 meridians (0degree, 45degrees, 90degrees, 135degrees, 180degrees, 225degrees, 270degrees, 315degrees). RESULTS: The visual field was oval shape, and widest at the inferotemporal area, followed by temporal, and inferior. CONCLUSIONS: The normal position of 4 isopters can be used as a reference index for the peripheral visual field test.

Foveomacular Vitelliform Dystrophy, Adult Type

Vitelliform macular dystrophy, adult type, is a type of pattern dystrophies of the pigment epithelium characterized by autosomal daminant inheritance, mid-life onset and small, round or oval, yellow deposits located at the level of the pigment epithelium. The authors report a case of this dystrophy which showed small yellow round lesion measuring 1/4-1/3 D.D. within the macula, normal electroretinogram, subnormal electrooculogram light-peak/dark-traugh ratio. typical irregular ring-like transmitted fluorescence surrounding the central non-fluorescent Iesion and leakage from perifoveal capillaries on fluorescent angiogram.

A case of Best's Vitelliform Macular Dystrophy

The authors experienced the Best's Vitelliform macular dystrophy in 77 year-old female. Ophthamoscopically, there was about 1.4 D.D. sized, slightly elevated, homogeneous yellowish egg-yolk like macular lesion with well defined brown pigmented margin in the left eye. Fellow eye had senile cataract and no fundus abnormalities except for mild inferior temporal branch retinal vein occlusion. Fluorescein angiography showed blockage of fluorescence in the vitelliform lesion and revealed no leakages or hyperfluolescences on perimacular area. Bilaterally, ERG showed normal findings. EOG revealed abnormally low light pead/Dark trough ratio.

Pseudohypopyon in Vitelliform Macular Dystrophy

We examined a 28-year-old male patient with pseudohypopyon in vitelliform macular dystrophy. The ocular fundi showed round cystoid lesions in the macula with clear fluid superiorly and yellow material inferiorly. Fluorescein angiography showed hyperfluorescent defects in the retinal pigment epithelium of the superior half of the lesion and blocked fluorescence in the area of the yellow material in feriorly. The electroretinography was normal and the electro-oculographic findings were abnormal.

Hereditary Macular Degeneration which Involved A Brother and Sister of One Family

Hereditary macular degeneration is characterized by bilateral degenerative changes in the macular area without a simultaneous degeneration in the central nervous system. This hereditary macular degeneration was first described by Rayner Battern in 1897. Since then, not only this degeneration but also many other types of hereditary macular degeneration have been described. In 1940, Behr classified macular degeneration into six types: Infantile, Juvenile, Adolescent, Adult, Presenile, Senile types. In 1973, Hughes classified this degeneration, by electro-and psychophysiologic evidence, as; 1) Progressive cone degeneration mainly affecting the photoreceptors; 2) Stargardt's disease or fundus flavimacultus type II; 3) Best's disease or vitelliform degeneration probably affecting primarily the basal portion of the pigment epithelium cells; 4) Doyne's or hereditary drusen affecting Bruch's membrane; and 5) Central choroid sclerosis affecting the choriocapillaries. Upon reviewing the literatures relating to this disease, two case reports have been included here of hereditary macular degeneration without apparent cause which involved a brother and sister of one family.