Novel Insight into Morphological Features and Vascular Profile of Selected Macular Dystrophies Using Swept-Source Optical Coherence Tomography and Optical Coherence Tomography Angiography

Our perception of macular dystrophies has evolved overtime from collective grouping into hereditary disorders of unclear etiology and no effective treatment to avid search for the underlying pathogenic mechanism that would provide base for future therapy. A causal conjunction between abnormalities in the photoreceptors layer and the RPE—Bruch’s membrane complex and abnormal profile of the retinal vascular plexuses and the choriocapillaris—stands out as a plausible theory of pathogenesis. The recently introduced swept-source optical coherence tomography (SS-OCT) technology incorporates long-wavelength (1050-nm) scanning light, less susceptibility to sensitivity roll-off, and ultrahigh-speed image acquisition. These features enabled in vivo noninvasive visualization of different strata of the outer retina and the choriocapillaris with unprecedented finesse. Furthermore, the SS-OCT technology incorporated a blood flow detection algorithm; OCTARA that in tandem with the deeper penetration and superior axial resolution of SS-OCT enabled detailed assessment of the retinal capillary plexuses and the choriocapillaris in terms of structure and density. This novel technology could help explore yet undiscovered frontiers in the pathophysiology of macular dystrophies and guide future therapeutic approaches. This chapter includes a review of literature along with the authors’ experience in imaging selected macular dystrophies using SS-OCT and SS-OCT angiography (SS-OCTA)

정상 안저를 보이는 한국인의 황반이상증에 대한 임상적 및 유전적 특징

학위논문 (석사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 박규형.Purpose: To investigate the clinical and genetic characteristics of Korean macular dystrophy patients with normal fundus appearances. Methods: Twenty-one patients with macular dystrophies with normal fundus appearances were evaluated. Exome sequencing targeting 204 candidate genes of inherited retinal diseases and direct Sanger sequencing were performed. Examinations including best-corrected visual acuities (BCVA) and retinal morphologic abnormalities analyzed by spectral-domain optical coherence tomography (SD-OCT), electroretinogram (ERG), and multifocal ERG were performed. Results: The median age at the initial examination (n=21) and the final visit (n=13) were 19 years with a range of 5 to 71 years, and 19 years with a range of 13 to 49 years. Genetic mutations in macular dystrophies with normal fundus appearances had RP1L1, CNGA3, GNAT1, GNAT2, GUCY2D, CACNA1F, and PROM1. There were significant negative correlations between the BCVA and external limiting membrane-retinal pigment epithelium thickness (ERT) at the initial examination and final visit, and BCVA and central retinal thickness (CRT) at the initial examination. Retinal structural features based on OCT findings were documented as foveal bulge and notable changes in ellipsoid zone (EZ) and interdigitation zone (IZ). Conclusions: In this study, unique pathogenic genetic mutations along with retinal morphologic changes were identified and correlated to the visual function in Korean macular dystrophy patients with normal fundus appearances. Further studies with larger number of macular dystrophy subjects should be investigated.목적 : 정상 안저를 보이는 한국인 황반이상증 환자의 임상적 및 유전적 특징을 조사한다. 방법 : 정상 안저를 보이는 21명의 한국인 황반이상증 환자를 대상으로 유전성 망막질환과 관련된 204개의 후보 유전자를 목표로 하는 exome sequencing과 direct Sanger sequencing을 시행하였다. 임상적인 데이터로는 최대교정시력과 안저검사, 빛간섭단층촬영, 망막전위도검사, 다초첨 망막전위도검사를 시행하였다. 결과 : 21명의 초기검사에서 나이 중간값은 19세에 5세부터 71세까지의 범위였고, 그 중 13명의 환자가 정기검사를 시행받았으며 마지막 검사에서 나이 중간값은 19세에 13세부터 49세까지의 범위였다. 정상 안저 소견을 보이는 황반이상증의 유전적인 변이는 RP1L1, CNGA3, GNAT1, GNAT2, GUCY2D, CACNA1F와 PROM1 유전자가 도출되었다. 임상적으로 초기검사에서 최대교정시력과 중심망막두께 및 외경계막-망막상피세포층 두께는 음성적인 연관성이 있었고, 마지막 검사에서도 최대교정시력과 외경계막-망막상피세포층 두께 또한 음성적인 연관성이 있었다. 빛간섭단층촬영으로 분석한 망막의 구조적인 변화에서는 황반의 변화 및 ellipsoid zone과 interdigitation zone의 변화가 관찰되었다. 결론 : 정상 안저를 보이는 한국인의 황반이상증에서는 특징적인 유전자 변이와 동반된 망막의 구조적인 변화가 관찰되었고, 이는 시력과 연관성이 있었다. 많은 수의 환자를 대상으로 한 추가적인 연구가 필요하겠다.Introduction 7 Materials and Methods 10 Results 15 Discussion 17 Table 22 Figure 26 Reference 31Maste

Phenotype characterization in macular dystrophies: The role of multifocal electroretinography and high-resolution optical coherence tomography

The multifocal electroretinogram (mfERG) and the high-resolution optical coherence tomography (OCT) were used as an objective measure and characterization of retinal function and morphology of hereditary and acquired macular dystrophies. MfERG and OCT permit phenotypisation even in early, partially sub-clinical diseases. MfERG changes, in particular delayed latencies, were sensitive measures in long time follow up investigations. Differences in localization and topographical extent of retinal deposits and structural changes were demonstrated by high-resolution Fourier-domain OCT.Das multifokale Elektroretinogramm (mfERG)und die hoch-auflösende optische Kohärenz Tomographie (OCT) wurden zur objektiven Messung und Darstellung retinaler Funktion und Morphologie bei hereditärer oder erworbener Makuladystrophien angewendet. Eine Phenotypisierung war mittels mfERG und OCT in frühen, teils sublinischen Stadien möglich. MfERG Veränderungen, insbesonder Latenzverzögerungen, zeigten sich als sensitiver Parameter bei Langzeitbeobachtungen. Die Lokalisation und die topographische Ausdehnung von Netzhautablagerungen bei verschiedenen Makuladystrophien wurde durch die hochauflösende Fourier-domain OCT dargestellt

Topographic mapping of retinal function with the SLO-mfERG under simultaneous control of fixation in Best's disease

Purpose: To introduce the scanning laser ophthalmoscope-evoked mfERG (SLO-mfERG) as a new method to measure focal retinal function. Methods: Sixty-two healthy individuals and 12 patients with Best's disease were examined. mfERGs were recorded using a scanning laser ophthalmoscope as a stimulator and trigger device (He-Neon 632.8 nm) as well as a fundus-monitoring system (infrared 730 nm). Results: Amplitudes in the central concentric area were found to be significantly lower in patients with Best's disease than in healthy controls, while no significant differences were found for the more peripheral areas. Conclusion: SLO-mfERG is a reliable new technique for topographic mapping of retinal function under simultaneous control of fixation

Development of refractive errors - what can we learn from inherited retinal dystrophies?

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: _Study population:_ 302 patients with IRD from two ophthalmogenetic centers in the Netherlands. _Reference population:_ population-based Rotterdam Study-III and ERF Study (N=5,550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell related dystrophies were associated with the highest risk of SE high myopia 239.7; OR mild hyperopia 263.2, both P<0.0001; SE -6.86 D [SD 6.38]); followed by cone dominated dystrophies (OR high myopia 19.5, P<0.0001; OR high hyperopia 10.7, P=0.033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P<0.0001; OR high hyperopia 9.7, P=0.001; SE -2.27 D [SD 4.65]); and RPE related dystrophies (OR low myopia 2.7; P=0.001; OR high hyperopia 5.8; P=0.025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia; in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse, and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development

Adult Onset Best Vitelliform Macular Dystrophy: A Case Report

Introduction: Best disease or vitelliform macular dystrophy is a rare autosomal dominant disorder with bilateral presentation characterized by subretinal accumulation of yellowish material in the macular area. Macular findings range from a small yellow spot, multiple vitelliform or atrophic lesions to a chorio-retinal scar. Case report: A 35 years male presented to our outpatient department with chief complaint of blurring of vision of both eyes for the past three months. His visual acuity was 6/12 in both right and left eyes. On slit-lamp bio-examination anterior segments of both eyes were normal. On fundus examination, both eyes revealed a single, circular, yellow-opaque egg yolk-like macular lesion with no other abnormalities. Optical coherence tomography of both eyes revealed deposits of homogenous hyper- reflective material beneath retinal pigment epithelium at fovea. Fundus fluorescence angiography showed blocked fluorescence at the site of vitelliform lesion of both eyes. Conclusion: Best vitelliform macular dystrophy is a rare genetic disorder with incomplete penetrance. Optical coherence tomography and fundus fluorescence angiography support the diagnosis

Optical Coherence Tomographic Finding in a Case of Macular Coloboma

PURPOSE: To report the optical coherence tomography (OCT) findings in a patient with unilateral macular coloboma. METHODS: A 12-year-old male was presented with macular coloboma in the left eye. The optical coherence tomography was performed with fluorescein angiography (FA). RESULTS: The OCT revealed the crater-like depression in the macula, demonstrating atrophic neurosensory retina, and an absence of retinal pigment epithelium and choroid in the lesion. FA showed hypofluorescence corresponding to the size of the lesion in both early and late frames without leakage of dye at any stage. CONCLUSIONS: The OCT can be beneficial to confirm the diagnosis of macular coloboma