Reduced macular thickness and macular vessel density in early-treated adult patients with PKU

Abstract

Purpose Macular structure is poorly evaluated in early-treated phenylketonuria (ETPKU). To evaluate potential changes, we aimed to examine retinas of PKU patients using optical coherence tomography (OCT) with additional OCT angiography (OCTA) and compare the results to healthy controls. Methods A total of 100 adults were recruited in this monocentric, case-control study: 50 patients with ETPKU (mean age: 30.66 ± 8.00 years) and 50 healthy controls (mean age: 30.45 ± 7.18 years). Macular thickness, vessel density and flow area of the right eye was assessed with spectral domain OCT angiography SD-OCT(A). Macular microstructural data between the ETPKU and control group was compared. In the ETPKU group, the relationship between visual functional parameters (best corrected visual acuity [VA], spherical equivalent [SE], contrast sensitivity [CS] and near stereoacuity) and microstructural alterations was examined. The dependency of OCT(A) values on serum phenylalanine (Phe) level was analysed. Results There was significant average parafoveal and perifoveal total retinal layer thinning in ETPKU patients compared to healthy controls ( p < 0.016 and p < 0.001, respectively), while the foveal region remained unchanged in the ETPKU group. Whole macular and parafoveal superficial capillary plexus density was significantly decreased in ETPKU compared to controls ( p < 0.001). There were no significant differences in the foveal avascular zone, nonflow area, macular superficial and deep capillary plexus between the groups. The temporal parafoveal inner retinal layer thickness was found to negatively correlate with individual Phe levels ( r = −0.35, p = 0.042). There was no difference in vascular density and retinal thickness in the subgroup analysis of patients with good therapy adherence compared to patients on a relaxed diet. Conclusions Durable elevation in Phe levels are only partially associated with macular retinal structural changes. However, therapy adherence might not influence these ophthalmological complications.

Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency

“…Based on these data one might hypothesize that retinal neuronal degeneration in adult ETPKU patients is triggered by increased and highly fluctuating Phe levels, whereas patients with good metabolic control do not show signs of retinal neuronal degeneration. Our observation of retinal neuronal degeneration in ETPKU is in line with the recent study of Serfozo et al demonstrating significant IRL thinning in ETPKU compared with HCs (39,40). However, this study described correlations to be found solely between the parafoveal IRL thickness and Phe levels within the last 10 years and therefore concluded no overall correlation between ganglion cell complex layer thickness and metabolic control (40).…”

“…Our observation of retinal neuronal degeneration in ETPKU is in line with the recent study of Serfozo et al demonstrating significant IRL thinning in ETPKU compared with HCs (39,40). However, this study described correlations to be found solely between the parafoveal IRL thickness and Phe levels within the last 10 years and therefore concluded no overall correlation between ganglion cell complex layer thickness and metabolic control (40). The discrepancies to our correlation analysis may arise from the OCT parameters analyzed and different OCT protocols used.…”

“…As expected from other similar indications (34,35), the changes in OCT parameters reported by us and the other ETPKU studies were small (38)(39)(40). Taking into account that PAH deficiency is a rare disease and various factors (e.g., phenotype, metabolic control, and age) might have an impact on retinal neuroaxonal degeneration, a potential bias could be caused by the study-specific characteristics.…”

“…Only recently, conflicting results of OCT studies on ETPKU cohorts have been described (37)(38)(39)(40). Hopf et al did not find any pathologies in the OCT measurements of the macula and optic nerve head in 10 pediatric and 9 adult PKU patients (37), whereas two other studies found evidence of retinal axonal degeneration in early treated pediatric (38) and adult PKU patients (39), as well as retinal neuronal degeneration in the early treated adult PKU patients (40).…”

Retinal thinning in phenylketonuria and Gaucher disease type 3

“…This study is one of the first, reporting OCT measurements in phenylketonuria and Gaucher disease type 3, besides the publications from Serfozo et al [16,26] and Tantawy et al [17]. Our main finding, GCC reduction, is in line with these two studies [16,17,26]. We additionally demonstrate that each of the individual components (NFL, GCL, and IPL) is reduced in thickness in phenylketonuria.…”