Promises and pitfalls of evaluating photoreceptor-based retinal disease with adaptive optics scanning light ophthalmoscopy (AOSLO)

Wynne, Niamh; Carroll, Joseph; Duncan, Jacque L.

doi:10.1016/j.preteyeres.2020.100920

Cited by 48 publications

(24 citation statements)

References 320 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) (13). AOSLO enables noninvasive, imaging of the human retina at single-cell resolution (14). Cones and rods can be distinguished by cellular morphology in patients by AOSLO imaging of their retinas in planes orthogonal to the polarized photoreceptor cell bodies (15).…”

Section: Significancementioning

confidence: 99%

ATF6 is essential for human cone photoreceptor development

Kroeger

Grandjean

Chiang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) stress and Unfolded Protein Response (UPR) signaling promote the pathology of many human diseases. Loss-of-function variants of the UPR regulator Activating Transcription Factor 6 (ATF6) cause severe congenital vision loss diseases such as achromatopsia by unclear pathomechanisms. To investigate this, we generated retinal organoids from achromatopsia patient induced pluripotent stem cells carrying ATF6 disease variants and from gene-edited ATF6 null hESCs. We found that achromatopsia patient and ATF6 null retinal organoids failed to form cone structures concomitant with loss of cone phototransduction gene expression, while rod photoreceptors developed normally. Adaptive optics retinal imaging of achromatopsia patients carrying ATF6 variants also showed absence of cone inner/outer segment structures but preserved rod structures, mirroring the defect in cone formation observed in our retinal organoids. These results establish that ATF6 is essential for human cone development. Interestingly, we find that a selective small molecule ATF6 signaling agonist restores the transcriptional activity of some ATF6 disease-causing variants and stimulates cone growth and gene expression in patient retinal organoids carrying these variants. These findings support that pharmacologic targeting of the ATF6 pathway can promote human cone development and should be further explored for blinding retinal diseases.

show abstract

Section: Significancementioning

confidence: 99%

ATF6 is essential for human cone photoreceptor development

Kroeger

Grandjean

Chiang

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“… 14 , 15 Additionally, AOSLO has been used to demonstrate that visual acuity is not highly correlated with peak cone density, suggesting post-receptor disruptions. 16 Although AOSLO has been used in dozens of other conditions, 17 applications to ACHM and albinism provide some of the clearest demonstrations of the contribution of AOSLO to the elucidation of disease pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure

Litts

Woertz

Wynne

et al. 2021

Trans. Vis. Sci. Tech.

Self Cite

View full text Add to dashboard Cite

Adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in patients with achromatopsia (ACHM) and albinism is not always successful. Here, we tested whether optical coherence tomography (OCT) measures of foveal structure differed between patients for whom AOSLO images were either quantifiable or unquantifiable. Methods:The study included 166 subjects (84 with ACHM; 82 with albinism) with previously acquired OCT scans, AOSLO images, and best-corrected visual acuity (BCVA, if available). Foveal OCT scans were assessed for outer retinal structure, outer nuclear layer thickness, and hypoplasia. AOSLO images were graded as quantifiable if a peak cone density could be measured and/or usable if the location of peak density could be identified and the parafoveal mosaic was quantifiable.Results: Forty-nine percent of subjects with ACHM and 57% of subjects with albinism had quantifiable AOSLO images. Older age and better BCVA were found in subjects with quantifiable AOSLO images for both ACHM (P = 0.0214 and P = 0.0276, respectively) and albinism (P = 0.0073 and P < 0.0004, respectively). There was a significant trend between ellipsoid zone appearance and ability to quantify AOSLO (P = 0.0028). In albinism, OCT metrics of cone structure did not differ between groups.Conclusions: Previously reported AOSLO-based cone density measures in ACHM may not necessarily reflect the degree of remnant cone structure in these patients.Translational Relevance: Until AOSLO is successful in all patients with ACHM and albinism, the possibility of the reported data from a particular cohort not being representative of the entire population remains an important issue to consider when interpreting results from AOSLO studies.

show abstract

“…While several AO systems, such as the Imagine Eyes rtx1 and Physical Sciences compact AO retinal imager (CAORI), are commercially available, broad adoption of the technology is limited because of system complexity, the need for long imaging and post-processing times, and lack of standardized processing and analysis algorithms. 225 Sensorless AO systems have been demonstrated in research prototypes and eliminate the need for physical wavefront sensors, which significantly reduces system complexity. [226][227][228][229][230] These technologies have been recently integrated into handheld probes for AO imaging in supine and pediatric patients, which may further motivate broad clinical adoption.…”

Section: Oct-slomentioning

confidence: 99%

Advances in multimodal imaging in ophthalmology

2021

View full text Add to dashboard Cite

Multimodality ophthalmic imaging systems aim to enhance the contrast, resolution, and functionality of existing technologies to improve disease diagnostics and therapeutic guidance. These systems include advanced acquisition and post-processing methods using optical coherence tomography (OCT), combined scanning laser ophthalmoscopy and OCT systems, adaptive optics, surgical guidance, and photoacoustic technologies. Here, we provide an overview of these ophthalmic imaging systems and their clinical and basic science applications.

show abstract

Promises and pitfalls of evaluating photoreceptor-based retinal disease with adaptive optics scanning light ophthalmoscopy (AOSLO)

Cited by 48 publications

References 320 publications

ATF6 is essential for human cone photoreceptor development

ATF6 is essential for human cone photoreceptor development

Examining Whether AOSLO-Based Foveal Cone Metrics in Achromatopsia and Albinism Are Representative of Foveal Cone Structure

Advances in multimodal imaging in ophthalmology

Contact Info

Product

Resources

About