An electrophysiological biomarker for the classification of cataract-reversal patients: A case-control study

Abstract

Background Untreated congenital blindness through cataracts leads to lasting visual brain system changes, including substantial alterations of extrastriate visual areas. Consequently, late-treated individuals (> 5 months of age) with dense congenital bilateral cataracts (CC) exhibit poorer visual function recovery compared to individuals with bilateral developmental cataracts (DC). Reliable methods to differentiate between patients with congenital and developmental cataracts are often lacking, impeding efficient rehabilitation management and introducing confounds in clinical and basic research on recovery prognosis and optimal timing of surgery. A persistent reduction of the P1 wave of visual event-related potentials (VERPs), associated with extrastriate visual cortical activity, has been reported in CC but not in DC individuals. Using two experiments, this study developed and validated P1-based biomarkers for diagnosing a history of congenital blindness in cataract-reversal individuals. Methods Congenital and developmental cataract-reversal individuals as well as typically sighted matched controls took part in a first experiment used for exploring an electrophysiological biomarker ( N CC = 13, N DC = 13, N Control = 26). Circular stimuli containing gratings were presented in one of the visual field quadrants while visual event-related potentials (VERPs) were recorded. Two biomarkers were derived from the P1 wave of the VERP: (1) The mean of the normalized P1 amplitude at posterior electrodes, and (2) a classifier obtained from a linear support vector machine (SVM). A second experiment with partially new CC/DC individuals and their matched controls ( N CC = 14, N DC = 15, N Control = 29) was consecutively used to validate the classification based on both biomarkers. Performance of the classifiers were evaluated using receiver operating characteristic (ROC) curve analyses. All cataract-reversal individuals were tested after at least one year of vision recovery. Findings The normalized P1 amplitude over posterior electrodes allowed a successful classification of the CC from the DC individuals and typically sighted controls (area under ROC curve, AUC = 0.803 and 0.929 for the normalized P1 amplitude and the SVM-based biomarker, respectively). The validation for both biomarkers in experiment 2 again resulted in a high classification success (AUC = 0.800 and 0.883, respectively for the normalized P1 amplitude and the SVM-based biomarker). In the most conservative scenario involving classification of CC from DC individuals in a group of only cataract-reversal individuals, excluding typically sighted controls, the SVM-based biomarker was found to be superior to the mean P1 amplitude based biomarke...

Gaze following requires early visual experience

“…Thus, only patients with a minimal spatial resolution, who could reliably perceive the eye position cue took part in our study. Naturally, this population typically had better visual acuity than in other studies of late-treated patients ( 21 , 31 , 34 , 38 ). However, despite this, our late-treated patients were unable to automatically follow the eye gaze of others.…”

Active Vision in Sight Recovery Individuals with a History of Long-Lasting Congenital Blindness

“…Retrospective classification of CC and DC participants comes with some degree of uncertainty. However, the use of the classification criteria as implemented in the present study have recently been confirmed by an electrophysiological biomarker ( Sourav et al, 2020 ).…”

“…Of the 10 participants, 5 had a documented history of strabismus (2 esotropia/3 exotropia), 7 had implanted intraocular lenses, and the remaining 3 used corrective Retrospective classification of CC and DC participants comes with some degree of uncertainty. However, the use of the classification criteria as implemented in the present study have recently been confirmed by an electrophysiological biomarker (Sourav et al, 2020).…”

“…By contrast, real-world visual exploration is not just driven by low-level information such as luminance contrast, but additionally uses high-level features, and integrates top-down influences such as goals and prior knowledge retrieved from memory ( Tatler et al, 2011 ; König et al, 2016 ; Veale et al, 2017 ). Since previous research has documented better recovery of low-level than high-level visual processing in CC individuals ( McKyton et al, 2015 ; Sourav et al, 2020 ; Pitchaimuthu et al, 2021 ), we expected that visual exploration of natural images would be mostly guided by low-level visual features. Contrary to this hypothesis, CC individuals relied on high-level information, and used both low-level and high-level information in a manner similar to that of SC and DC control groups.…”

Learning to see after early and extended blindness: A scoping review

“…Despite our targeted approach, even within included studies confirmation of congenital onset remained somewhat speculative. This may change in the future, as objective measures associated with congenital onset of blindness are being developed (Sourav et al, 2020 ).…”