Reduced Electroretinogram Responses in Morphologically Normal Retina in Patients with Primary Hyperoxaluria Type 1

Efrat Naaman; Netta Malul; Shadi Safuri; Nitai Bar; Shirley Pollack; Daniella Magen; Rina Leibu; Ido Perlman; Shiri Zayit-Soudry

doi:10.1016/j.xops.2022.100268

Reduced Electroretinogram Responses in Morphologically Normal Retina in Patients with Primary Hyperoxaluria Type 1

Ophthalmol Sci. 2023 Jan 2;3(2):100268. doi: 10.1016/j.xops.2022.100268. eCollection 2023 Jun.

Authors

Efrat Naaman¹, Netta Malul², Shadi Safuri¹, Nitai Bar³, Shirley Pollack^{2

4}, Daniella Magen^{2

4}, Rina Leibu¹, Ido Perlman^{2

5}, Shiri Zayit-Soudry^{1

2}

Affiliations

¹ Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel.
² Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³ Department of Radiology, Rambam Health Care Campus, Haifa, Israel.
⁴ Pediatric Nephrology Institute, Ruth Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
⁵ Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Abstract

Purpose: To describe ocular findings in individuals with primary hyperoxaluria type 1 (PH1), focusing on the correlations between retinal anatomy and retinal function. To characterize the retinal alterations that occur at different disease stages by evaluating individuals with diverse degrees of renal impairment associated with PH1.

Design: A cross-sectional study.

Participants: Patients diagnosed with PH1 based on clinical criteria and genetic testing, treated in the Pediatric Nephrology Unit of the Ruth Children's Hospital, Rambam Health Care Campus, Haifa, Israel between 2013 and 2021.

Methods: The ophthalmological assessment included a slit-lamp biomicroscopy of the anterior and posterior segment or indirect ophthalmoscopy. Electroretinography was employed for assessment of the retinal function, and retinal imaging included spectral-domain OCT and fundus autofluorescence. A systematic evaluation of the disease stage was based on clinical criteria including physical examination, purposeful imaging (X-ray, echocardiography, and US abdomen), and laboratory tests as needed.

Main outcome measures: Anatomical and functional assessment of the retina in patients with PH1, and the relationship between retinal dysfunction and kidney impairment.

Results: A total of 16 eyes were examined in the study of 8 children ranging in age from 4 to 19 years. Four eyes (25%) showed normal structural and functional retinal findings, 8 eyes (50%) presented functional impairment in the absence of pathological structural findings, and 4 eyes (25%) had advanced retinal damage that manifested as significant morphological and functional impairment. There was no direct relationship between the severity of the renal disease and the severity of the retinal phenotype.

Conclusions: Subjects with PH1 present varying severity levels of the retinal phenotype, with possible discrepancy between the clinical retinal morphology and the retinal function noted on electroretinography. These findings raise questions about the molecular basis of the retinal manifestations in PH1. The presence of functional impairment in the absence of evident crystal deposition in the retina suggests that, in addition to oxalate crystal accumulation, other biomolecular processes may play a role in the development of retinopathy.

Keywords: CKD, chronic kidney disease; ERG, electroretinography; ESRD, end-stage renal disease; Electroretinogram; Hyperoxaluria; Inherited retinal disease; Metabolite self-assembly; PH1, primary hyperoxaluria type 1; RPE, retinal pigment epithelium; Retinal disease.