Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies

Danial Roshandel; Jennifer A. Thompson; Rachael C. Heath Jeffery; Danuta M. Sampson; Enid Chelva; Terri L. Mc Laren; Tina M. Lamey; John N. De Roach; Shane R. Durkin; Fred K. Chen

doi:10.1167/tvst.10.2.38

Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies

Danial Roshandel, Jennifer A. Thompson, Rachael C. Heath Jeffery, Danuta M. Sampson, Enid Chelva, Terri L. Mc Laren, Tina M. Lamey, John N. De Roach, Shane R. Durkin, Fred K. Chen

Centre for Ophthalmology and Visual Science (affiliated with the Lions Eye Institute)

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies.

Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing.

Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9).

Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points.

Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

Original language	English
Article number	38
Pages (from-to)	1-17
Number of pages	17
Journal	Translational Vision Science and Technology
Volume	10
Issue number	2
DOIs	https://doi.org/10.1167/tvst.10.2.38
Publication status	Published - Feb 2021

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10.1167/tvst.10.2.38Licence: CC BY-NC-ND

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Roshandel, D., Thompson, J. A., Heath Jeffery, R. C., Sampson, D. M., Chelva, E., Mc Laren, T. L., Lamey, T. M., De Roach, J. N., Durkin, S. R., & Chen, F. K. (2021). Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies. Translational Vision Science and Technology, 10(2), 1-17. Article 38. https://doi.org/10.1167/tvst.10.2.38

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title = "Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies",

abstract = "Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies.Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing.Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9).Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points.Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.",

keywords = "Eye Proteins/genetics, Humans, Membrane Proteins/genetics, Nerve Tissue Proteins/genetics, Phenotype, Retina, Retinitis Pigmentosa/diagnosis, Visual Field Tests",

author = "Danial Roshandel and Thompson, {Jennifer A.} and {Heath Jeffery}, {Rachael C.} and Sampson, {Danuta M.} and Enid Chelva and {Mc Laren}, {Terri L.} and Lamey, {Tina M.} and {De Roach}, {John N.} and Durkin, {Shane R.} and Chen, {Fred K.}",

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language = "English",

volume = "10",

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journal = "Translational Vision Science and Technology",

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publisher = "Association for Research in Vision and Ophthalmology (ARVO)",

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Roshandel, D, Thompson, JA, Heath Jeffery, RC, Sampson, DM, Chelva, E, Mc Laren, TL, Lamey, TM, De Roach, JN, Durkin, SR & Chen, FK 2021, 'Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies', Translational Vision Science and Technology, vol. 10, no. 2, 38, pp. 1-17. https://doi.org/10.1167/tvst.10.2.38

TY - JOUR

T1 - Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies

AU - Roshandel, Danial

AU - Thompson, Jennifer A.

AU - Heath Jeffery, Rachael C.

AU - Sampson, Danuta M.

AU - Chelva, Enid

AU - Mc Laren, Terri L.

AU - Lamey, Tina M.

AU - De Roach, John N.

AU - Durkin, Shane R.

AU - Chen, Fred K.

PY - 2021/2

Y1 - 2021/2

N2 - Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies.Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing.Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9).Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points.Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

AB - Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies.Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing.Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9).Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points.Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

KW - Eye Proteins/genetics

KW - Humans

KW - Membrane Proteins/genetics

KW - Nerve Tissue Proteins/genetics

KW - Phenotype

KW - Retina

KW - Retinitis Pigmentosa/diagnosis

KW - Visual Field Tests

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U2 - 10.1167/tvst.10.2.38

DO - 10.1167/tvst.10.2.38

M3 - Article

C2 - 34003923

AN - SCOPUS:85102420403

SN - 2164-2591

VL - 10

SP - 1

EP - 17

JO - Translational Vision Science and Technology

JF - Translational Vision Science and Technology

IS - 2

M1 - 38

ER -

Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies

Abstract

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MRFF - Developing Personalised Treatment for Retinal Degeneration

Monitoring disease progression in retinitis pigmentosa

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Multimodal retinal imaging and microperimetry reveal a novel phenotype and potential trial end points in CRB1-associated retinopathies

Abstract

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Projects

MRFF - Developing Personalised Treatment for Retinal Degeneration

Research output

Monitoring disease progression in retinitis pigmentosa

Cite this