Exploring microperimetry and autofluorescence endpoints for monitoring disease progression in PRPF31-associated retinopathy

ABSTRACT

Background

Mutations in the splicing factor pre-messenger RNA processing factor 31 (PRPF31) gene cause autosomal dominant retinitis pigmentosa 11 (RP11) through a haplo-insufficiency mechanism. We describe the phenotype and progression of microperimetry and autofluorescence endpoints in an Indigenous Australian RP11 family.

Patients and Methods

Ophthalmic examination, optical coherence tomography, fundus autofluorescence and microperimetry were performed at baseline and every 6–12 months. Baseline and annual change in best-corrected visual acuity (BCVA), microperimetry mean sensitivity (MS) and number of scotoma loci, residual ellipsoid zone (EZ) span and hyperautofluorescent ring (HAR) area were reported. Next-generation and Sanger sequencing were performed in available members.

Results

12 affected members from three generations were examined. Mean (SD, range) age at onset of symptoms was 11 (4.5, 4–19) years. MS declined steadily from the third decade and EZ span and HAR area declined rapidly during the second decade. Serial microperimetry showed negligible change in MS over 2–3 years. However, mean EZ span, near-infrared and short-wavelength HAR area reduction was 203 (6.4%) µm/year, 1.8 (8.7%) mm²/year and 1.1 (8.6%) mm²/year, respectively. Genetic testing was performed on 11 affected and 10 asymptomatic members and PRPF31 c.1205 C > A (p.Ser402Ter) mutation was detected in all affected and two asymptomatic members (non-penetrant carriers).

Conclusions

Our findings suggest that in the studied cohort, the optimal window for therapeutic intervention is the second decade of life and residual EZ span and HAR area can be considered as efficacy outcome measures. Further studies on larger samples with different PRPF31 mutations and longer follow-up duration are recommended.

KEYWORDS:

• Retinitis pigmentosa
• PRPF31
• RP11
• non-penetrance
• Indigenous Australian

Acknowledgments

The AIRDR gratefully acknowledges the assistance from Ling Hoffman and Isabella Urwin of the Department of Medical Technology and Physics, Sir Charles Gairdner Hospital. We also acknowledge the support from Amanda Scurry and Jayme Glynn of Lions Eye Institute in organizing appointment and the transport for the long journeys these patients had to travel for their clinical assessments. We also thank Mr Shang-Chih Chen from the Ocular Tissue Engineering Laboratory for extracting DNA from the biobank for genetic analysis.

Declaration of interest

FKC: Consultant for PYC Therapeutics, Novartis and Allergan. Other authors have no financial disclosure.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the Australian National Health and Medical Research Council [GNT116360 (DAM, FKC), GNT1188694 (SM, SF, FKC), GNT1054712 (FKC) and MRF1142962 (FKC)], McCusker Foundation (JC), Miocevich Retina Fellowship (MA, SA), Australian Government International Research Training Program Scholarship (DR), and Retina Australia (JAT, TL, JNDR, TLM). The sponsor or funding organization had no role in the design or conduct of this research.