Abstract
Purpose :
The primary hyperoxalurias (PH; PH1-3) are three rare inherited disorders of the glyoxylate metabolism characterized by endogenous overproduction of oxalate. As oxalate cannot be metabolized by humans, PH may affect various organs, most notably the kidneys, bones, heart, and eyes. Vision loss and severe oxalate deposition are commonly seen in infantile PH1, whereas non-infantile PH1 usually present with no or mild retinal alterations. If patients with PH2 and PH3 develop retinal disease has not been investigated so far. This is, however, important in light of emerging therapeutic options. Here, the ocular phenotype in patients with PH2 and PH3 and its relation to systemic disease is investigated.
Methods :
A renal, molecular and ophthalmic examination including multimodal retinal imaging (OCT, fundus autofluorescence imaging, fundus photography) was performed of each patient.
Results :
Thirteen patients (4 with PH2; 9 with PH3) from 11 families were included. Median age at first renal symptoms and diagnosis was 1.5 and 4.5 years in PH2 patients; and 3 and 7 years in PH3 patients. Median age at time of ophthalmic examination was 11 years and median BCVA was 20/20. A 30-years-old patient with PH2 had drusen-like deposits in both eyes that were interpreted as crystallized oxalate. On OCT imaging, these deposits appeared as focal hyperreflective subretinal lesions. At the time of the ophthalmic examination, he was on dialysis and his oxalate level was markedly elevated. The remaining 12 patients showed no retinal oxalate deposits. Out of those 12, only the oldest PH2 patient (59-years-old) had elevated oxalate levels and end-stage kidney failure (ESKF), whereas all other PH2 and PH3 patients had had normal or near-normal plasma oxalate levels.
Conclusions :
Retinal disease manifestation in PH2 and PH3 clearly differs from patients with infantile PH1. Age of ESKF-onset might be an important predictor for retinal alterations in PH. A later decline in kidney function associated with increased plasma oxalate levels could also increase the risk of systemic oxalosis with subretinal oxalate deposition. At this mild end of the phenotypic spectrum, additional genetic and/or environmental modifiers might result in variable susceptibility.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.