CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials

Xuan Thanh An Nguyen; Mays Talib; Mary J. van Schooneveld; Jan Wijnholds; Maria M. van Genderen; Nicoline E. Schalij-Delfos; Caroline C.W. Klaver; Herman E. Talsma; Marta Fiocco; Ralph J. Florijn; Jacoline B. ten Brink; Frans P.M. Cremers; Magda A. Meester-Smoor; L. Ingeborgh van den Born; Carel B. Hoyng; Alberta A.H.J. Thiadens; Arthur A. Bergen; Camiel J.F. Boon

doi:10.1016/j.ajo.2021.07.021

CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials

Xuan Thanh An Nguyen
, Mays Talib
, Mary J. van Schooneveld
, Jan Wijnholds
, Maria M. van Genderen
, Nicoline E. Schalij-Delfos
, Caroline C.W. Klaver
, Herman E. Talsma
, Marta Fiocco
, Ralph J. Florijn
, Jacoline B. ten Brink
, Frans P.M. Cremers
, Magda A. Meester-Smoor
, L. Ingeborgh van den Born
, Carel B. Hoyng
, Alberta A.H.J. Thiadens
, Arthur A. Bergen
, Camiel J.F. Boon

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

35 Citations (Scopus)

Abstract

PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.

DESIGN: Single-center, prospective case series.

METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.

RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.

CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

Original language	English
Pages (from-to)	37-48
Number of pages	12
Journal	American Journal of Ophthalmology
Volume	234
DOIs	https://doi.org/10.1016/j.ajo.2021.07.021
Publication status	Published - Feb 2022
Externally published	Yes

Keywords

Electroretinography
Eye Proteins/genetics
Humans
Membrane Proteins/genetics
Nerve Tissue Proteins/genetics
Retina
Retinal Dystrophies/diagnosis
Retinitis Pigmentosa/diagnosis
Tomography, Optical Coherence/methods
Visual Field Tests
Visual Fields

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10.1016/j.ajo.2021.07.021

Cite this

Nguyen, X. T. A., Talib, M., van Schooneveld, M. J., Wijnholds, J., van Genderen, M. M., Schalij-Delfos, N. E., Klaver, C. C. W., Talsma, H. E., Fiocco, M., Florijn, R. J., ten Brink, J. B., Cremers, F. P. M., Meester-Smoor, M. A., van den Born, L. I., Hoyng, C. B., Thiadens, A. A. H. J., Bergen, A. A., & Boon, C. J. F. (2022). CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials. American Journal of Ophthalmology, 234, 37-48. https://doi.org/10.1016/j.ajo.2021.07.021

@article{b3d8c744954a4e89b96b19d840f4534f,

title = "CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials",

abstract = "PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.DESIGN: Single-center, prospective case series.METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86\%]), cone-rod dystrophy (2 [9\%]), or isolated macular dystrophy (1 [5\%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.",

keywords = "Electroretinography, Eye Proteins/genetics, Humans, Membrane Proteins/genetics, Nerve Tissue Proteins/genetics, Retina, Retinal Dystrophies/diagnosis, Retinitis Pigmentosa/diagnosis, Tomography, Optical Coherence/methods, Visual Field Tests, Visual Fields",

author = "Nguyen, \{Xuan Thanh An\} and Mays Talib and \{van Schooneveld\}, \{Mary J.\} and Jan Wijnholds and \{van Genderen\}, \{Maria M.\} and Schalij-Delfos, \{Nicoline E.\} and Klaver, \{Caroline C.W.\} and Talsma, \{Herman E.\} and Marta Fiocco and Florijn, \{Ralph J.\} and \{ten Brink\}, \{Jacoline B.\} and Cremers, \{Frans P.M.\} and Meester-Smoor, \{Magda A.\} and \{van den Born\}, \{L. Ingeborgh\} and Hoyng, \{Carel B.\} and Thiadens, \{Alberta A.H.J.\} and Bergen, \{Arthur A.\} and Boon, \{Camiel J.F.\}",

year = "2022",

month = feb,

doi = "10.1016/j.ajo.2021.07.021",

language = "English",

volume = "234",

pages = "37--48",

journal = "American Journal of Ophthalmology",

issn = "0002-9394",

publisher = "Elsevier Inc.",

}

Nguyen, XTA, Talib, M, van Schooneveld, MJ, Wijnholds, J, van Genderen, MM, Schalij-Delfos, NE, Klaver, CCW, Talsma, HE, Fiocco, M, Florijn, RJ, ten Brink, JB, Cremers, FPM, Meester-Smoor, MA, van den Born, LI, Hoyng, CB, Thiadens, AAHJ, Bergen, AA & Boon, CJF 2022, 'CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials', American Journal of Ophthalmology, vol. 234, pp. 37-48. https://doi.org/10.1016/j.ajo.2021.07.021

TY - JOUR

T1 - CRB1-Associated Retinal Dystrophies

T2 - A Prospective Natural History Study in Anticipation of Future Clinical Trials

AU - Nguyen, Xuan Thanh An

AU - Talib, Mays

AU - van Schooneveld, Mary J.

AU - Wijnholds, Jan

AU - van Genderen, Maria M.

AU - Schalij-Delfos, Nicoline E.

AU - Klaver, Caroline C.W.

AU - Talsma, Herman E.

AU - Fiocco, Marta

AU - Florijn, Ralph J.

AU - ten Brink, Jacoline B.

AU - Cremers, Frans P.M.

AU - Meester-Smoor, Magda A.

AU - van den Born, L. Ingeborgh

AU - Hoyng, Carel B.

AU - Thiadens, Alberta A.H.J.

AU - Bergen, Arthur A.

AU - Boon, Camiel J.F.

PY - 2022/2

Y1 - 2022/2

N2 - PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.DESIGN: Single-center, prospective case series.METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

AB - PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.DESIGN: Single-center, prospective case series.METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.RESULTS: Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

KW - Electroretinography

KW - Eye Proteins/genetics

KW - Humans

KW - Membrane Proteins/genetics

KW - Nerve Tissue Proteins/genetics

KW - Retina

KW - Retinal Dystrophies/diagnosis

KW - Retinitis Pigmentosa/diagnosis

KW - Tomography, Optical Coherence/methods

KW - Visual Field Tests

KW - Visual Fields

UR - https://www.scopus.com/pages/publications/85118889813

UR - https://www.mendeley.com/catalogue/52a54462-5222-33b2-a86d-c9b5bb66ee78/

U2 - 10.1016/j.ajo.2021.07.021

DO - 10.1016/j.ajo.2021.07.021

M3 - Article

C2 - 34320374

AN - SCOPUS:85118889813

SN - 0002-9394

VL - 234

SP - 37

EP - 48

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

ER -

CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials

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Keywords

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