Cellular imaging of inherited retinal diseases using adaptive optics

Abstract

Adaptive optics (AO) is an insightful tool that has been increasingly applied to existing imaging systems for viewing the retina at a cellular level. By correcting for individual optical aberrations, AO offers an improvement in transverse resolution from 10-15 μm to~2 μm, enabling assessment of individual retinal cell types. One of the settings in which its utility has been recognised is that of the inherited retinal diseases (IRDs), the genetic and clinical heterogeneity of which warrants better cellular characterisation. In this review, we provide a summary of the basic principles of AO, its integration into multiple retinal imaging modalities and its clinical applications, focusing primarily on IRDs. Furthermore, we present a comprehensive summary of AO-based cellular findings in IRDs according to their associated disease-causing genes.

Novel Heterozygous Deletion in Retinol Dehydrogenase 12 (RDH12) Causes Familial Autosomal Dominant Retinitis Pigmentosa

“…Here, we describe two unrelated families with a novel autosomal dominant variant in RDH12, displaying a RP phenotype (Gill et al, 2019). In patients with autosomal recessive RDH12 variants, Aleman et al (2018) described a rapidly progressing condition leaving only residual islands intact by the second decade of life with very poor visual acuity.…”

Recent advances in imaging technologies for assessment of retinal diseases

“…This is achieved using highly deformable mirrors, which can change shape by tiny electronic motor actuators on their rear surface. (44,46) Applying this technology in an automated, real time fashion to existing cSLO and fundus cameras, has allowed imaging of the retina on a cellular level. (46) In recent years, the integration of AO with multiple ophthalmic imaging techniques such as optical coherence tomography (OCT) has increased both contrast and resolution with great success.…”

Is subretinal AAV gene replacement still the only viable treatment option for choroideremia?

“…Accordingly, structural changes typical of photoreceptor stress secondary to RPE disease have been observed in the form of outer retinal tubulations [ 7 , 8 ]. Adaptive optics imaging in choroideremia indicates that a degree of photoreceptor structural abnormality is present within the islands of surviving RPE [ 9 ] and cone photoreceptors may be able to survive a short distance beyond the edge of RPE degeneration [ 10 ]. However, it remains unclear to what extent these stressed or structurally abnormal photoreceptors are amenable to therapeutic rescue.…”