Ultra-wide–Field Fundus Autofluorescence for the Detection of Inherited Retinal Disease in Difficult-to-Examine Children

Abstract Stargardt disease is one of the most common forms of inherited retinal disease and leads to permanent vision loss. A diagnostic feature of the disease is retinal flecks, which appear hyperautofluorescent in fundus autofluorescence (FAF) imaging. The size and number of these flecks increase with disease progression. Manual segmentation of flecks allows monitoring of disease, but is time-consuming. Herein, we have developed and validated a deep learning approach for segmenting these Stargardt flecks (1750 training and 100 validation FAF patches from 37 eyes with Stargardt disease). Testing was done in 10 separate Stargardt FAF images and we observed a good overall agreement between manual and deep learning in both fleck count and fleck area. Longitudinal data were available in both eyes from 6 patients (average total follow-up time 4.2 years), with both manual and deep learning segmentation performed on all (n = 82) images. Both methods detected a similar upward trend in fleck number and area over time. In conclusion, we demonstrated the feasibility of utilizing deep learning to segment and quantify FAF lesions, laying the foundation for future studies using fleck parameters as a trial endpoint.

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Deep Learning-Based Classification of Inherited Retinal Diseases Using Fundus Autofluorescence

Journal of Clinical Medicine ◽

10.3390/jcm9103303 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3303

Author(s):

Alexandra Miere ◽

Thomas Le Meur ◽

Karen Bitton ◽

Carlotta Pallone ◽

Oudy Semoun ◽

...

Keyword(s):

Deep Learning ◽

Learning Algorithm ◽

Fundus Autofluorescence ◽

Area Under The Curve ◽

Retinal Disease ◽

Relevant Information ◽

Retinal Diseases ◽

Autofluorescence Imaging ◽

Comparable Group ◽

Inherited Retinal Disease

Background. In recent years, deep learning has been increasingly applied to a vast array of ophthalmological diseases. Inherited retinal diseases (IRD) are rare genetic conditions with a distinctive phenotype on fundus autofluorescence imaging (FAF). Our purpose was to automatically classify different IRDs by means of FAF images using a deep learning algorithm. Methods. In this study, FAF images of patients with retinitis pigmentosa (RP), Best disease (BD), Stargardt disease (STGD), as well as a healthy comparable group were used to train a multilayer deep convolutional neural network (CNN) to differentiate FAF images between each type of IRD and normal FAF. The CNN was trained and validated with 389 FAF images. Established augmentation techniques were used. An Adam optimizer was used for training. For subsequent testing, the built classifiers were then tested with 94 untrained FAF images. Results. For the inherited retinal disease classifiers, global accuracy was 0.95. The precision-recall area under the curve (PRC-AUC) averaged 0.988 for BD, 0.999 for RP, 0.996 for STGD, and 0.989 for healthy controls. Conclusions. This study describes the use of a deep learning-based algorithm to automatically detect and classify inherited retinal disease in FAF. Hereby, the created classifiers showed excellent results. With further developments, this model may be a diagnostic tool and may give relevant information for future therapeutic approaches.

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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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Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

International Journal of Molecular Sciences ◽

10.3390/ijms22052374 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2374

Author(s):

Laura Kuehlewein ◽

Ditta Zobor ◽

Katarina Stingl ◽

Melanie Kempf ◽

Fadi Nasser ◽

...

Keyword(s):

Visual Acuity ◽

Genetic Testing ◽

Retinitis Pigmentosa ◽

Fundus Autofluorescence ◽

Retinal Disease ◽

New Drugs ◽

Autofluorescence Imaging ◽

Full Field ◽

Tertiary Referral Center ◽

The Right

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.

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Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia

International Journal of Molecular Sciences ◽

10.3390/ijms22157842 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7842

Author(s):

Susanne Kohl ◽

Britta Baumann ◽

Francesca Dassie ◽

Anja K. Mayer ◽

Maria Solaki ◽

...

Keyword(s):

Segregation Analysis ◽

Molecular Genetic ◽

Retinal Disease ◽

Underlying Mechanism ◽

Recurrence Risk ◽

Molecular Genetic Analysis ◽

Recessive Mutation ◽

Chromosome 2 ◽

Inherited Retinal Disease ◽

Uniparental Isodisomy

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.

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A qualitative study among patients with an inherited retinal disease on the meaning of genomic unsolicited findings

Scientific Reports ◽

10.1038/s41598-021-95258-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marlies Saelaert ◽

Heidi Mertes ◽

Tania Moerenhout ◽

Caroline Van Cauwenbergh ◽

Bart P. Leroy ◽

...

Keyword(s):

Qualitative Study ◽

Interpretative Phenomenological Analysis ◽

Age Of Onset ◽

Genetic Diseases ◽

Retinal Disease ◽

Clinical Approach ◽

Inherited Retinal Disease ◽

Illness Experiences ◽

Meaning Structure ◽

Main Components

AbstractExome-based testing for genetic diseases can reveal unsolicited findings (UFs), i.e. predispositions for diseases that exceed the diagnostic question. Knowledge of patients’ interpretation of possible UFs and of motives for (not) wanting to know UFs is still limited. This lacking knowledge may impede effective counselling that meets patients’ needs. Therefore, this article examines the meaning of UFs from a patient perspective. A qualitative study was conducted and an interpretative phenomenological analysis was made of 14 interviews with patients with an inherited retinal disease. Patients assign a complex meaning to UFs, including three main components. The first component focuses on result-specific qualities, i.e. the characteristics of an UF (inclusive of actionability, penetrance, severity and age of onset) and the consequences of disclosure; the second component applies to a patient’s lived illness experiences and to the way these contrast with reflections on presymptomatic UFs; the third component addresses a patient’s family embedding and its effect on concerns about disease prognosis and genetic information’s family relevance. The complex meaning structure of UFs suggests the need for counselling procedures that transcend a strictly clinical approach. Counselling should be personalised and consider patients’ lived illness experiences and family context.

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Quantitative Color Fundus Autofluorescence in Patients with Diabetes Mellitus

Journal of Clinical Medicine ◽

10.3390/jcm10010048 ◽

2020 ◽

Vol 10 (1) ◽

pp. 48

Author(s):

Stela Vujosevic ◽

Caterina Toma ◽

Paolo Nucci ◽

Marco Brambilla ◽

Stefano De Cillà

Keyword(s):

Diabetes Mellitus ◽

Retinal Thickness ◽

Fundus Autofluorescence ◽

Retinal Disease ◽

Metabolic Evaluation ◽

Glycation End Products ◽

Custom Software ◽

Patients With Diabetes ◽

Immunohistochemical Studies ◽

Present Pilot Study

A new short wavelength confocal blue-light 450 nm-fundus autofluorescence (color-FAF) allows for visualization of minor fluorophores (e.g., advanced glycation end products, AGEs), besides lipofuscin. The aim of the present pilot study was to quantitatively evaluate color-FAF in patients with diabetes mellitus (DM) and to correlate these data with different stages of retinal disease severity. Optical coherence tomography and color-FAF images of 193 patients/eyes and 18 controls were analyzed using a custom software for quantification of the long (red) and short (green) wavelength components of the emission spectrum (REFC/GEFC). Measurements were performed in nine quadrants of the 6-mm ETDRS macular grid. Foveal GEFC and REFC intensities were higher in patients with DM compared to controls (p = 0.015 and p = 0.006 respectively) and in eyes with center involving diabetic macular edema (DME) compared to eyes without DME (p < 0.001). A positive correlation was found between GEFC and REFC intensities and central retinal thickness, r = 0.37 (p < 0.001) and r = 0.42 (p < 0.001), respectively. No differences were found in color-FAF among different DR severity groups. Quantitative color-FAF could become helpful for the metabolic evaluation of retina in patients with DM and in DME; however, further histologic and immunohistochemical studies on distribution of different retinal fluorophores in DM are needed to better understand its role.

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