Baseline Microperimetry and OCT in the RUSH2A Study: Structure-Function Association and Correlation With Disease Severity

Eleonora M Lad; Jacque L Duncan; Wendi Liang; Maureen G Maguire; Allison R Ayala; Isabelle Audo; David G Birch; Joseph Carroll; Janet K Cheetham; Todd A Durham; Abigail T Fahim; Jessica Loo; Zengtian Deng; Dibyendu Mukherjee; Elise Heon; Robert B Hufnagel; Bin Guan; Alessandro Iannaccone; Glenn J Jaffe; Christine N Kay; Michel Michaelides; Mark E Pennesi; Ajoy Vincent; Christina Y Weng; Sina Farsiu; Foundation Fighting Blindness Consortium Investigator Group

doi:10.1016/j.ajo.2022.08.013

Baseline Microperimetry and OCT in the RUSH2A Study: Structure-Function Association and Correlation With Disease Severity

Am J Ophthalmol. 2022 Dec:244:98-116. doi: 10.1016/j.ajo.2022.08.013. Epub 2022 Aug 22.

Authors

Eleonora M Lad¹, Jacque L Duncan², Wendi Liang³, Maureen G Maguire³, Allison R Ayala⁴, Isabelle Audo⁵, David G Birch⁶, Joseph Carroll⁷, Janet K Cheetham⁸, Todd A Durham⁸, Abigail T Fahim⁹, Jessica Loo¹⁰, Zengtian Deng¹⁰, Dibyendu Mukherjee¹⁰, Elise Heon¹¹, Robert B Hufnagel¹², Bin Guan¹², Alessandro Iannaccone¹, Glenn J Jaffe¹, Christine N Kay¹³, Michel Michaelides¹⁴, Mark E Pennesi¹⁵, Ajoy Vincent¹¹, Christina Y Weng¹⁶, Sina Farsiu¹⁷; Foundation Fighting Blindness Consortium Investigator Group

Affiliations

¹ From the Department of Ophthalmology, Duke University Medical Center Durham, North Carolina, USA.
² Department of Ophthalmology, University of California, San Francisco, California, USA.
³ Jaeb Center for Health Research, Tampa, Florida, USA.
⁴ Jaeb Center for Health Research, Tampa, Florida, USA. Electronic address: ffbcorrespauth@jaeb.org.
⁵ Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423, Paris, France.
⁶ Retina Foundation of the Southwest, Dallas, Texas, USA.
⁷ Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁸ Foundation Fighting Blindness, Columbia, Maryland, USA.
⁹ Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, USA.
¹⁰ Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
¹¹ University of Toronto and Hospital for Sick Children, Toronto, Ontario, Canada.
¹² National Eye Institute, Bethesda, Maryland, USA.
¹³ Vitreoretinal Associates, Gainesville, Florida, USA.
¹⁴ Moorfields Eye Hospital and UCL Institute of Ophthalmology (M.M.), London, United Kingdom.
¹⁵ Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
¹⁶ Baylor College of Medicine, Houston, Texas.
¹⁷ From the Department of Ophthalmology, Duke University Medical Center Durham, North Carolina, USA; Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.

Abstract

Purpose: To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, including best corrected visual acuity (BCVA) and central subfield thickness (CST) within the central 1 mm, were assessed using Spearman correlation coefficients.

Main outcome measures: Mean sensitivity on MP; EZ area and CST on OCT.

Results: All participants (N = 127) had OCT, while MP was obtained at selected sites (N = 93). Participants with Usher syndrome type 2 (USH2, N = 80) and nonsyndromic autosomal recessive Retinitis Pigmentosa (ARRP, N = 47) had the following similar measurements: EZ area (median (interquartile range [IQR]): 1.4 (0.4, 3.1) mm² vs 2.3 (0.7, 5.7) mm²) and CST (median (IQR): 247 (223, 280) µm vs 261 (246, 288), and mean sensitivity (median (IQR): 3.5 (2.1, 8.4) dB vs 5.1 (2.9, 9.0) dB). Longer disease duration was associated with smaller EZ area (P < 0.001) and lower mean sensitivity (P = 0.01). Better BCVA, larger EZ area, and larger CST were correlated with greater mean sensitivity (r > 0.3 and P < 0.01). Better BCVA and larger CST were associated with larger EZ area (r > 0.6 and P < 0.001).

Conclusions: Longer disease duration correlated with more severe retinal structure and function abnormalities, and there were associations between MP and OCT metrics. Monitoring changes in retinal structure-function relationships during disease progression will provide important insights into disease mechanism in USH2A-related retinal degeneration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Retinal Degeneration*
Severity of Illness Index
Tomography, Optical Coherence / methods
Usher Syndromes* / diagnosis
Usher Syndromes* / genetics
Visual Acuity
Visual Field Tests

Supplementary concepts

Usher syndrome, type 2A

Abstract

Publication types

MeSH terms

Supplementary concepts

Grants and funding