Structural evaluation in inherited retinal diseases

Varela, Malena Daich; Esener, Burak; Hashem, Shaima A; Guimarães, Thales Antonio Cabral de; Georgiou, Michalis; Michaelides, Michel

doi:10.1136/bjophthalmol-2021-319228

Cited by 25 publications

(15 citation statements)

References 132 publications

(157 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, 11 patients (7.9%) had normal vision and normal multimodal imaging (wide‐field imaging, macular SD‐OCT, UWF‐FAF). These patients included diagnosis of ischemia, 1 CSNB 13 and PAIR‐nPAIR 1 . Thirty‐nine patients (28.1%) had normal UWF‐FAF with foveal reduction of autofluorescence.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Electronegative electroretinogram in the modern multimodal imaging era

Sakti

Ali

Korsakova

et al. 2022

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

“…In this modern multimodal imaging era, spectral domain optical coherence tomography (SD‐OCT) and ultra wide‐field fundus autofluorescence (UWF‐FAF) have improved retinal assessment mainly enhancing structural evaluation 1 . Functional assessment of the visual system remains critical.…”

Section: Introductionmentioning

confidence: 99%

Electronegative electroretinogram in the modern multimodal imaging era

Sakti

Ali

Korsakova

et al. 2022

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

“…We also identified increased rate of decrease in area of macular ring in EYS , USH2A and RPGR compared to RHO ( Figure 6 ). Monitoring the rate in which the macular ring narrows down is common practice in generalised retinal dystrophies such as RP 5 . A more rapid encroachment of the macular ring in autosomal recessive ( USH2A , EYS ) and X-linked ( RPGR ) genes compared to the autosomal dominant RHO , is consistent with the latter having a slower disease progression compared to the others 43 .…”

Section: Discussionmentioning

confidence: 99%

“…Many IRDs are associated with structural changes within the retina, which can be detected with retinal imaging using different imaging modalities such as colour fundus, infrared-reflectance (IR), spectral-domain optical coherence tomography (SD-OCT), or fundus autofluorescence (FAF). FAF is of particular importance in the context of IRDs, as it allows the detection of patterns of fluorophores, often at the level of the photoreceptors and retinal pigment epithelium (RPE), which can be indicative of pathological changes such as loss of overlying photoreceptors 5,6 . Some of these FAF signal changes are highly characteristic of specific IRDs and can indicate features such as areas of RPE atrophy or lipofuscin deposits.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom

Woof,

de Guimarães,

Al-Khuzaei

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Purpose: To quantify relevant fundus autofluorescence (FAF) image features cross-sectionally and longitudinally in a large cohort of inherited retinal diseases (IRDs) patients. Design: Retrospective study of imaging data (55-degree blue-FAF on Heidelberg Spectralis) from patients. Participants: Patients with a clinical and molecularly confirmed diagnosis of IRD who have undergone FAF 55-degree imaging at Moorfields Eye Hospital (MEH) and the Royal Liverpool Hospital (RLH) between 2004 and 2019. Methods: Five FAF features of interest were defined: vessels, optic disc, perimacular ring of increased signal (ring), relative hypo-autofluorescence (hypo-AF) and hyper-autofluorescence (hyper-AF). Features were manually annotated by six graders in a subset of patients based on a defined grading protocol to produce segmentation masks to train an AI model, AIRDetect, which was then applied to the entire imaging dataset. Main Outcome Measures: Quantitative FAF imaging features including area in mm2 and vessel metrics, were analysed cross-sectionally by gene and age, and longitudinally to determine rate of progression. AIRDetect feature segmentation and detection were validated with Dice score and precision/recall, respectively. Results: A total of 45,749 FAF images from 3,606 IRD patients from MEH covering 170 genes were automatically segmented using AIRDetect. Model-grader Dice scores for disc, hypo-AF, hyper-AF, ring and vessels were respectively 0.86, 0.72, 0.69, 0.68 and 0.65. The five genes with the largest hypo-AF areas were CHM, ABCC6, ABCA4, RDH12, and RPE65, with mean per-patient areas of 41.5, 30.0, 21.9, 21.4, and 15.1 mm2. The five genes with the largest hyper-AF areas were BEST1, CDH23, RDH12, MYO7A, and NR2E3, with mean areas of 0.49, 0.45, 0.44, 0.39, and 0.34 mm2 respectively. The five genes with largest ring areas were CDH23, NR2E3, CRX, EYS and MYO7A, with mean areas of 3.63, 3.32, 2.84, 2.39, and 2.16 mm2. Vessel density was found to be highest in EFEMP1, BEST1, TIMP3, RS1, and PRPH2 (10.6%, 10.3%, 9.8%, 9.7%, 8.9%) and was lower in Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis genes. Longitudinal analysis of decreasing ring area in four RP genes (RPGR, USH2A, RHO, EYS) found EYS to be the fastest progressor at -0.18 mm2/year. Conclusions: We have conducted the first large-scale cross-sectional and longitudinal quantitative analysis of FAF features across a diverse range of IRDs using a novel AI approach.

show abstract

“…Eventually the RPE and photoreceptors undergo apoptosis, and this signal is lost (Spaide, 2003;Sparrow and Boulton, 2005;Ach et al, 2015), leading to hypoautofluorescence (Figure 1). IRDs often display typical patterns on FAF imaging that are helpful in diagnosis, but the progression of the hyperautofluorescent signal (leading disease front), and the hypoautofluorescent signal (trailing disease front) can also be used to assess the rate of disease progression (Cicinelli et al, 2020;Daich Varela et al, 2021).…”

Section: Structural Assessment In Inherited Retinal Diseases Treatment Trialsmentioning

confidence: 99%

Gene-Based Therapeutics for Inherited Retinal Diseases

et al. 2022

View full text Add to dashboard Cite

Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber’s congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.

show abstract

Structural evaluation in inherited retinal diseases

Cited by 25 publications

References 132 publications

Electronegative electroretinogram in the modern multimodal imaging era

Electronegative electroretinogram in the modern multimodal imaging era

Quantification of Fundus Autofluorescence Features in a Molecularly Characterized Cohort of More Than 3500 Inherited Retinal Disease Patients from the United Kingdom

Gene-Based Therapeutics for Inherited Retinal Diseases

Contact Info

Product

Resources

About