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

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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Abstract

PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints 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 ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), 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 (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. 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 endpoint in future human treatment trials for CRB1-associated retinal dystrophies.

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

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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., Ingeborgh van den Born, L., 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{9cecbad31b2841af83ba8d641365ac0e,

title = "CRB1-associated retinal dystrophies: a prospective natural history study in anticipation of future clinical trials",

abstract = "PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints 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 ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), 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 (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. 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 endpoint in future human treatment trials for CRB1-associated retinal dystrophies.",

author = "Xuan-Thanh-An Nguyen 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 {Ingeborgh van den Born}, L and Hoyng, {Carel B} and Thiadens, {Alberta A H J} and Bergen, {Arthur A} and Boon, {Camiel J F}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier Inc.",

year = "2022",

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 USA",

}

Nguyen, X-T-A, 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, Ingeborgh van den Born, L, 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 - Ingeborgh van den Born, L

AU - Hoyng, Carel B

AU - Thiadens, Alberta A H J

AU - Bergen, Arthur A

AU - Boon, Camiel J F

PY - 2022

Y1 - 2022

N2 - PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints 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 ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), 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 (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. 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 endpoint in future human treatment trials for CRB1-associated retinal dystrophies.

AB - PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints 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 ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), 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 (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. 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 endpoint in future human treatment trials for CRB1-associated retinal dystrophies.

U2 - 10.1016/j.ajo.2021.07.021

DO - 10.1016/j.ajo.2021.07.021

M3 - Article

C2 - 34320374

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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