Intra-familial Similarity of Wide-Field Fundus Autofluorescence in Inherited Retinal Dystrophy

Aim: To evaluate the variation of peripheral alterations in different retinal diseases over a period of >3 years by using wide-field fundus autofluorescence (FAF) scanning laser ophthalmoscopy (SLO). Methods: A total of 26 eyes from 13 patients (median age 66 years, range 19-80) with age-related macular degeneration and other retinal degenerations were examined. In 2009, the Optos P200CAF prototype and from 2012 onwards, the Optos 200Tx (Optos plc, Scotland) were used for wide-field FAF SLO (excitation 532 nm). Results: The area involvement in outer retinal pathological alterations, such as atrophy and mottling of the retinal pigment epithelium far beyond the vascular arcades, was readily and better visualized within one image frame using wide-field FAF as compared to pseudocolor SLO of the same device. Over time, progression of existing and the development of de novo peripheral lesions were recorded with a concomitant enlargement of central lesions. In two cases (unilateral paravenous pigmented choroidal atrophy and suspected phenocopy of retinal dystrophy), no longitudinal changes of the topographic distribution of peripheral FAF intensities were noted. Conclusions: Wide-field FAF SLO allows the mapping of dynamic changes at the outer retina far beyond the vascular arcades. While its ability to detect and monitor these changes appears to be better than that of pseudocolor imaging, wide-field FAF SLO may not only be helpful to assess more widespread retinal dysfunction, but may also be useful for longitudinal assessments in natural history studies and interventional clinical trials.

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Multimodal Imaging Characteristics of ADRP in a Family with p.Thr58Arg Substituted RHO Mutation

Case Reports in Genetics ◽

10.1155/2020/8860863 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Misty Ruppert ◽

John Pyun ◽

K. V. Chalam ◽

David Sierpina

Keyword(s):

Retinitis Pigmentosa ◽

Multimodal Imaging ◽

Fundus Autofluorescence ◽

Visual Fields ◽

Retinal Dystrophy ◽

Young Patients ◽

Photoreceptor Cells ◽

Wide Field ◽

Photoreceptor Layer ◽

Imaging Characteristics

Background. Autosomal dominant retinitis pigmentosa (adRP) is a rare cause of progressive visual impairment in young patients and is frequently a result of RHO gene mutations. p.Thr58Arg rhodopsin mutation leads to misfolding of rhodopsin, subsequent accumulation in the endoplasmic reticulum, and leads to consecutive atrophy of photoreceptor cells through apoptosis. Materials and Methods. We describe multimodal imaging findings in a 58-year-old female with adRP due to a c.173 C > G, p.Thr58Arg rhodopsin mutation (confirmed on genotyping), including ultra-wide-field fundus autofluorescence (UWF-FAF), color scanning laser ophthalmoscopy, structural optical coherence tomography (OCT), OCT-angiography (OCT-A), electroretinography (ERG), and visual field testing (HVF). Additionally, we compare the patient’s phenotypic findings to those of her offspring, who was also affected by adRP. Results. The 58-year-old female and her son with symptoms of nyctalopia and decreased vision showed macular pigmentary changes in a bull’s-eye pattern along with bone spicules in periphery with retinal atrophy. Genotyping confirmed p.Thr58Arg rhodopsin mutation. Wide area of dystrophic retina was noted on UWF-FAF, along with corresponding atrophy of photoreceptor layer on OCT. OCTA revealed complete nonperfusion of the superficial capillary plexus in areas of retinal dystrophy. ERG revealed increased latency and decreased amplitudes; HVF revealed constriction of visual fields consistent with retinal findings. Conclusions. Multimodal imaging is extremely helpful in delineating the extent of retinal dystrophy and comparable to ERG for monitoring of progress in retinitis pigmentosa. Photoreceptor layer thickness (measured with OCT) strongly correlated with ERG and can be used as a secondary surrogate for monitoring the disease progress.

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Correlation between fundus autofluorescence and visual function in patients with cone-rod dystrophy

Scientific Reports ◽

10.1038/s41598-021-81597-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Satoru Kanda ◽

Takumi Hara ◽

Ryosuke Fujino ◽

Keiko Azuma ◽

Hirotsugu Soga ◽

...

Keyword(s):

Visual Field ◽

Significant Relationship ◽

Fundus Autofluorescence ◽

Univariate Analysis ◽

Retrospective Chart Review ◽

Mean Deviation ◽

Wide Field ◽

The Mean ◽

The Relationship ◽

Field Imaging

AbstractThis study aimed to investigate the relationship between autofluorescence (AF) signal measured with ultra-wide field imaging and visual functions in patients with cone-rod dystrophy (CORD). A retrospective chart review was performed for CORD patients. We performed the visual field test and fundus autofluorescence (FAF) measurement and visualized retinal structures with optical coherence tomography (OCT) on the same day. Using binarised FAF images, we identified a low FAF area ratio (LFAR: low FAF/30°). Relationships between age and logMAR visual acuity (VA), central retinal thickness (CRT), central choroidal thickness (CCT), mean deviation (MD) value, and LFAR were investigated. Thirty-seven eyes of 21 CORD patients (8 men and 13 women) were enrolled. The mean patient age was 49.8 years. LogMAR VA and MD were 0.52 ± 0.47 and − 17.91 ± 10.59 dB, respectively. There was a significant relationship between logMAR VA and MD (p = 0.001). LogMAR VA significantly correlated with CRT (p = 0.006) but not with other parameters. Conversely, univariate analysis suggested a significant relationship between MD and LFAR (p = 0.001). In the multivariate analysis, LFAR was significantly associated with MD (p = 0.002). In conclusion, it is useful to measure the low FAF area in patients with CORD. The AF measurement reflects the visual field deterioration but not VA in CORD.

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Na-K-activated adenosinetriphosphatase in retinae of rats with and without inherited retinal dystrophy

Vision Research ◽

10.1016/0042-6989(70)90124-0 ◽

1970 ◽

Vol 10 (5) ◽

pp. 435-438 ◽

Cited By ~ 10

Author(s):

F.J.M. Daemen ◽

J.J.H.H.M. de Pont ◽

F. Lion ◽

S.L. Bonting

Keyword(s):

Retinal Dystrophy ◽

Inherited Retinal Dystrophy

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Wide-Field Fundus Autofluorescence Imaging of Retinitis Pigmentosa

Ophthalmology ◽

10.1016/j.ophtha.2013.01.050 ◽

2013 ◽

Vol 120 (9) ◽

pp. 1827-1834 ◽

Cited By ~ 43

Author(s):

Akio Oishi ◽

Ken Ogino ◽

Yukiko Makiyama ◽

Satoko Nakagawa ◽

Masafumi Kurimoto ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Fundus Autofluorescence ◽

Wide Field ◽

Autofluorescence Imaging

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Gene therapy for RPE65 -mediated inherited retinal dystrophy completes phase 3

The Lancet ◽

10.1016/s0140-6736(17)31622-7 ◽

2017 ◽

Vol 390 (10097) ◽

pp. 823-824 ◽

Cited By ~ 6

Author(s):

Helena Lee ◽

Andrew Lotery

Keyword(s):

Gene Therapy ◽

Retinal Dystrophy ◽

Phase 3 ◽

Inherited Retinal Dystrophy

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Innate and Autoimmunity in the Pathogenesis of Inherited Retinal Dystrophy

Cells ◽

10.3390/cells9030630 ◽

2020 ◽

Vol 9 (3) ◽

pp. 630 ◽

Cited By ~ 2

Author(s):

T. J. Hollingsworth ◽

Alecia K. Gross

Keyword(s):

Disease Progression ◽

Age Of Onset ◽

Retinal Dystrophy ◽

Inherited Retinal Dystrophies ◽

Retinal Dystrophies ◽

Major Player ◽

Inherited Retinal Dystrophy ◽

Rate Of Progression ◽

Immunohistochemical Methods ◽

Onset Rate

Inherited retinal dystrophies (RDs) are heterogenous in many aspects including genes involved, age of onset, rate of progression, and treatments. While RDs are caused by a plethora of different mutations, all result in the same outcome of blindness. While treatments, both gene therapy-based and drug-based, have been developed to slow or halt disease progression and prevent further blindness, only a small handful of the forms of RDs have treatments available, which are primarily for recessively inherited forms. Using immunohistochemical methods coupled with electroretinography, optical coherence tomography, and fluorescein angiography, we show that in rhodopsin mutant mice, the involvement of both the innate and the autoimmune systems could be a strong contributing factor in disease progression and pathogenesis. Herein, we show that monocytic phagocytosis and inflammatory cytokine release along with protein citrullination, a major player in forms of autoimmunity, work to enhance the progression of RD associated with a rhodopsin mutation.

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NICE recommends gene therapy for inherited retinal dystrophy

BMJ ◽

10.1136/bmj.l5394 ◽

2019 ◽

pp. l5394

Author(s):

Elisabeth Mahase

Keyword(s):

Gene Therapy ◽

Retinal Dystrophy ◽

Inherited Retinal Dystrophy

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Phenotypic variability of SLC7A14 mutations in patients with inherited retinal dystrophy

Ophthalmic Genetics ◽

10.1080/13816810.2019.1586964 ◽

2019 ◽

Vol 40 (2) ◽

pp. 118-123 ◽

Cited By ~ 1

Author(s):

Li-Yun Guo ◽

Sui-Lian Zheng ◽

Jun Li ◽

Qin Zhu ◽

Wen-Hua Duan ◽

...

Keyword(s):

Phenotypic Variability ◽

Retinal Dystrophy ◽

Inherited Retinal Dystrophy

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Novel mutations in the 3-box motif of the BACK domain of KLHL7 associated with nonsyndromic autosomal dominant retinitis pigmentosa

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-019-1275-2 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Jin Kyun Oh ◽

Jose Ronaldo Lima de Carvalho ◽

Young Joo Sun ◽

Sara Ragi ◽

Jing Yang ◽

...

Keyword(s):

Retinitis Pigmentosa ◽

Autosomal Dominant ◽

Fundus Autofluorescence ◽

Retinal Dystrophy ◽

Protein Modeling ◽

Fundus Photography ◽

Imaging Biomarkers ◽

Loss Of Function ◽

Gene Panel Testing ◽

Sd Oct

Abstract Background Mutations in the Kelch-like protein 7 (KLHL7) represent a recently described and, to date, poorly characterized etiology of inherited retinal dystrophy. Dominant mutations in KLHL7 are a cause of isolated, non-syndromic retinitis pigmentosa (RP). In contrast, recessive loss-of-function mutations are known to cause Crisponi or Bohring-Opitz like cold induced sweating syndrome-3 (BOS-3). In this study, the phenotype and progression of five unrelated patients with KLHL7 mediated autosomal dominant RP (adRP) are characterized. Clinical evaluation of these patients involved a complete ophthalmic exam, full-field electroretinography (ffERG), and imaging, including fundus photography, spectral domain optical coherence tomography (SD-OCT), short wavelength fundus autofluorescence (SW-AF), and near-infrared fundus autofluorescence (NIR-AF). Molecular diagnoses were performed using whole-exome sequencing or gene panel testing. Disease progression was monitored in three patients with available data for a mean follow up time of 4.5 ± 2.9 years. Protein modeling was performed for all variants found in this study in addition to those documented in the literature for recessive loss-of-function alleles causing Crisponi or Bohring-Opitz like cold-induced sweating syndrome. Results Genetic testing in three patients identified two novel variants within the 3-box motif of the BACK domain: c.472 T > C:p.(Cys158Arg) and c.433A > T:p.(Asn145Tyr). Clinical imaging demonstrated hyperautofluorescent ring formation on both SW-AF and NIR-AF in three patients, with diffuse peripheral and peripapillary atrophy seen in all but one case. SD-OCT demonstrated a phenotypic spectrum, from parafoveal atrophy of the outer retina with foveal sparing to widespread retinal thinning and loss of photoreceptors. Incidence of cystoid macular edema was high with four of five patients affected. Protein modeling of dominant alleles versus recessive loss-of-function alleles showed dominant alleles localized to the BTB and BACK domains while recessive alleles were found in the Kelch domain. Conclusions We report the phenotype in five patients with KLHL7 mediated adRP, two novel coding variants, and imaging biomarkers using SW-AF and NIR-AF. These findings may influence future gene-based therapies for adRP and pave the way for mechanistic studies that elucidate the pathogenesis of KLHL7-mediated RP.

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