Structural evaluation in inherited retinal diseases

Abstract

Ophthalmic genetics is a field that has been rapidly evolving over the last decade, mainly due to the flourishing of translational medicine for inherited retinal diseases (IRD). In this review, we will address the different methods by which retinal structure can be objectively and accurately assessed in IRD. We review standard-of-care imaging for these patients: colour fundus photography, fundus autofluorescence imaging and optical coherence tomography (OCT), as well as higher-resolution and/or newer technologies including OCT angiography, adaptive optics imaging, fundus imaging using a range of wavelengths, magnetic resonance imaging, laser speckle flowgraphy and retinal oximetry, illustrating their utility using paradigm genotypes with on-going therapeutic efforts/trials.

Electronegative electroretinogram in the modern multimodal imaging era

“…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.…”

“…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.…”

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

“…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 .…”

“…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.…”

Gene-Based Therapeutics for Inherited Retinal Diseases

“…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).…”