Clinical Stages of Occult Macular Dystrophy Based on Optical Coherence Tomographic Findings

Abstract

PURPOSE. To determine the course of occult macular dystrophy (OMD, Miyake's disease) and to propose stages of OMD based on the optical coherence tomographic (OCT) findings. METHODS. Sixty-one patients from 33 families with OMD who carried one of the proven variants of the RP1L1 gene were studied at seven centers in Japan. Ophthalmological examinations including the best-corrected visual acuity (BVCA) and OCT were performed. RESULTS. The median age at the last visit was 50 years with a range of 10 to 88 years, and the median age at the symptom onset was 30 years with a range of 3 to 60 years. There were significant negative correlations between the duration of OMD and BCVA, the central retinal thickness (CRT) and the thickness between external limiting membrane and retinal pigment epithelium (ERT). The BCVA gradually decreased for 10 years after symptom onset and was stable thereafter. Kaplan-Meier survival curves of the BCVA and retinal thickness showed that all of the patients had retained a vision of 1.0 logMAR, and over 80% of the patients had retained 50% thickness of the normal CRT and ERT for at least 60 years after symptom onset. The stages of OMD based on the visual symptoms and OCT findings are proposed. CONCLUSIONS. The photoreceptors do not become completely atrophic even at the late stage, which may account for the good retinal pigment epithelium (RPE) structure and normalappearing fundus. The proposed stages facilitate the investigation of the pathogenicity of OMD and provide information to determine the effectiveness of therapeutic procedures.

Clinical and genetic characteristics of 10 Japanese patients with PROM1‐associated retinal disorder: A report of the phenotype spectrum and a literature review in the Japanese population

“…In addition, the duration of disease was 47 years in Patient 10, but this patient still had a similar level of vision compared to a patient with 8 years of disease (Patient 6). These findings suggest that age of onset and duration of disease are not clearly related to the severity of visual acuity in PROM1 ‐RD, unlike other macular dystrophies (Fujinami, Sergouniotis, Davidson, Wright, et al, 2013; Fujinami, Sergouniotis, Davidson, Mackay, et al, 2013; Fujinami et al, 2014, 2015, 2019; Nakamura et al, 2019). These are probably because of the frequent presence of foveal sparing (bull's eye maculopathy) in PROM1 ‐RD.…”

“…For example, relatively similar phenotypes of CORD, COD, STGD, and MD share causative genes such as ABCA4 , BEST1 , PRPH2 , RPGR , CRX , GUCY2D , RS1 , POC1B , PROM1 , CNGA3 , CNGB3 , GUCA1A , KCNV2 , and RIMS1 (Ba‐Abbad, Robson, MacPhee, Webster, & Michaelides, 2019; Bouzia et al, 2020; Fujinami‐Yokokawa et al, 2020; Fujinami, Lois, Davidson, et al, 2013; Fujinami, Lois, Mukherjee, et al, 2013; Fujinami et al, 2015; Georgiou et al, 2020; Gill et al, 2019; Hirji et al, 2018; Hunt, Buch, & Michaelides, 2010; Kameya et al, 2019; Kominami et al, 2018; Kondo et al, 2019; Liu et al, 2020; Mawatari et al, 2019; Michaelides et al, 2010; Mizobuchi et al, 2019; Nakanishi et al, 2016; Oishi et al, 2016; Rahman et al, 2020; Sisodiya et al, 2007; Strauss et al, 2016, 2018; Tanna et al, 2017; Tee et al, 2016, 2019). There are genes that are associated with different phenotypes of CORD/COD/MD and RP; EYS , CRX , PRPH2, GUCY2D , and RP1L1 (Ba‐Abbad et al, 2019; Bouzia et al, 2020; Davidson et al, 2013; Fujinami‐Yokokawa et al, 2019, 2020; Fujinami et al, 2019; Hull et al, 2014; Katagiri et al, 2018; Koyanagi et al, 2019; Liu et al, 2020; Nakamura et al, 2019; Oishi et al, 2014, 2016; L. Yang et al, 2020). Moreover, different inheritances such as autosomal dominant (AD) and autosomal recessive (AR) are associated with differences in phenotypes (Bouzia et al, 2020; Fujinami‐Yokokawa et al, 2020; Gill et al, 2019; Hull et al, 2014; Liu et al, 2020; Rahman et al, 2020).…”

“…et al, 2019;Liu et al, 2020;Mawatari et al, 2019;Michaelides et al, 2010;Mizobuchi et al, 2019;Nakanishi et al, 2016;Oishi et al, 2016;Rahman et al, 2020;Sisodiya et al, 2007;Strauss et al, 2016Strauss et al, , 2018Tanna et al, 2017;Tee et al, 2016Tee et al, , 2019. There are genes that are associated with different phenotypes of CORD/COD/MD and RP; EYS, CRX, PRPH2, GUCY2D, and RP1L1 (Ba-Abbad et al, 2019;Bouzia et al, 2020;Davidson et al, 2013;Fujinami-Yokokawa et al, 2019Hull et al, 2014;Katagiri et al, 2018;Koyanagi et al, 2019;Liu et al, 2020;Nakamura et al, 2019;Oishi et al, 2014Oishi et al, , 2016L. Yang et al, 2020).…”

Spatial Functional Characteristics of East Asian Patients With Occult Macular Dystrophy (Miyake Disease); EAOMD Report No. 2

“…SDOCT provides valuable in vivo information about the microstructure of photoreceptors in OMD. 6,7,13,[16][17][18][19][20][21][22][23][24][25][26] There are 2 microstructural subtypes of occult macular dysfunction syndrome: a classical type with both blurred ellipsoid zone (EZ) and absence of the interdigitation zone (IZ) and a nonclassical type lacking these 2 features. 4,7 Most patients with Miyake disease show classical SDOCT findings.…”

RP2‐associated retinal disorder in a Japanese cohort: Report of novel variants and a literature review, identifying a genotype–phenotype association

“…Patients with a clinical diagnosis of IRD and available whole‐exome sequencing (WES) genetic data were studied between 2008 and 2018. A total of 1,294 subjects from 730 families for whom genotype–phenotype association studies were completed, were surveyed, including 47 families with XLRP and 141 families with sporadic RP (Fujinami et al, 2016; Fujinami et al, 2019; Fujinami‐Yokokawa et al, 2019; Fujinami‐Yokokawa et al, 2020; Kameya et al, 2019; Katagiri et al, 2020; Kondo et al, 2019; Maeda‐Katahira et al, 2019; Mawatari et al, 2019; Mizobuchi et al, 2019; Nakamura et al, 2019; Nakanishi et al, 2016; Pontikos et al, 2020; Xiao Liu et al, 2020; Yang et al, 2020).…”