Optokinetic nystagmus (OKN) is a repetitive eye movement characterized by an alternating slow and fast phase evoked by a visual stimulus on the retina. A commonly used method to induce OKN is by using a full-field visual pattern rotating around a vertical or horizontal axis aligned with the subject’s head. Frequently used visual patterns in research consist of evenly spaced vertical black and white bars displayed on a drum. The OKN, the smooth pursuit (SP) and the vestibulo-ocular reflex (VOR) are responsible for achieving eye stabilization on the Earth-fixed visual scene (1). The VOR enhances visual stability by coordinating eye movements with head movements to maintain a stable gaze during head rotations (2). The SP is an eye movement in which the eyes track a single moving visual stimulus. Since the SP and OKN are connected, the optokinetic system is best studied through the optokinetic after-nystagmus (OKAN) (3). First described by Ohm in 1921 (4), this neural phenomenon can be recognized as a gradual decrease of the nystagmus after visual stimulation is terminated abruptly. The decrease typically follows an inverse exponential decay characterized by a single time constant (TC). The responsible mechanism for the production of OKAN is thought to be the velocity storage mechanism (VSM), a neural network responsible for multisensory integration (5). The VSM charges when the optokinetic stimulus is observed by the participants. When the visual stimulation is abruptly removed, the VSM slowly discharges and the OKAN occurs as a neurophysiological effect. The general characteristics of OKAN were initially investigated in healthy rhesus monkeys, and later on, the effects of labyrinthectomy in rhesus monkeys on OKAN were explored (5, 6). They found that OKAN TC significantly decreased after unilateral labyrinthectomy. The OKAN TC toward the lesioned side was significantly shorter compared to the OKAN TC toward the healthy side. Moreover, the OKAN TC completely disappeared in bilateral vestibulopathy (7).

The OKAN findings in animals seemed promising for diagnosing vestibular disorders, raising the question as to whether these findings could be applied to humans. Although Cohen et al. (5) found the maximum slow phase eye velocity to be 2–3 times higher in monkeys compared to humans, and Fletcher et al. (8) found the amplitude of the OKAN to be much smaller in humans, these findings did not stop researchers from exploring further the diagnostic possibilities of OKAN in humans. In 1976, Zee et al. (9) examined OKAN in humans to study a cohort of patients suffering from bilateral vestibular loss after meningitis. The findings demonstrated that patients with labyrinthine loss were incapable of generating adequate OKAN velocities when compared to normal patients. The aim of this article is to evaluate the clinical relevance of an abnormal OKAN in medical practice. The systematic overview will examine the available literature on OKAN TC in human vestibular disorders. The meta-analysis aims to assess the between-group mean difference in OKAN TC between individuals with and without vestibular disorders.

To our knowledge, this systematic review provides the most up-to-date and comprehensive evidence of the use of OKAN in vestibular disorders, summarizing estimates from seven original studies. The OKAN TC in patients with peripheral unilateral vestibulopathy was found to be asymmetrical compared to the symmetrical OKAN TC in healthy patients according to both Brantberg and Magnusson (15, 16), and Hain et al. (20). Additionally, the former authors found that the asymmetry in OKAN TC seemed to normalize in patients that recovered from vestibular neuritis. This observation indicates that OKAN TC can be a helpful measure in tracking recovery or improvements in individuals with vestibular neuritis. In bilateral vestibulopathy, Hain et al. (19), Zasorin et al. (17), and Dellepiane et al. (21) found that OKAN TC was symmetrically significantly reduced compared to the OKAN TC in healthy subjects. Lastly, Jell et al. (18) showed that despite caloric tests had returned to normal values, simultaneous measurements of OKAN still exhibited persistent asymmetry in patients suffering from multiple vestibular pathologies. These findings suggest that OKAN measurements might provide additional insights into vestibular function beyond what is captured by traditional caloric tests.

The overall analysis showed a significant difference in the OKAN TC between people with vestibular deficits and those without. In addition, the prediction interval indicates, with 95% certainty, the OKAN TC of patients will be different from that of controls in future studies. This means the observed difference is quite reliable and likely to be consistent in similar studies down the line.

In summary, OKAN TC is found to be asymmetric in unilateral vestibulopathies, reduced bilaterally in bilateral vestibulopathies, symmetric in healthy patients and appears to lose asymmetry in recovering pathologies. Therefore, OKAN TC could be a tool in monitoring the recovery process of patients, which is an added value for several reasons. This can help healthcare professionals to track changes in functionality and give patients a tool that records their recovery progress. However, further research is warranted to integrate OKAN into clinical settings effectively.

In the past, the use of OKAN has been studied in well-known vestibular pathologies such as vestibular neuritis. With the emergence of new technologies such as cVEMP and vHIT, the use of OKAN has become largely redundant. Nevertheless, while these tests focus mainly on the SCC and the otoliths, OKAN measurements can offer crucial insights into the visuo-vestibular pathway. Recent research suggests that visual dependency, dizziness triggered by seeing movements, moving images or busy patterns, can be objectively assessed through OKAN (24). It is hypothesized that the velocity storage mechanism (VSM), the central system responsible for multisensory integration, is impacted in individuals with visual dependence. Therefore, the VSM discharges more slowly after the removal of visual stimulation, leading to an extended duration of OKAN in individuals with visual dependence (25–28). This prompts the question as to whether OKAN could potentially serve in more recently discovered diagnoses like persistent postural-perceptual dizziness (PPPD) and vestibular migraine—conditions characterized by visual dependency for which objective diagnostic tests are currently lacking (29). Further research is necessary to define the diagnostic use of OKAN TC in PPPD.

Importantly, the meta-analysis uncovered insights not apparent in individual studies. When analyzing our data, the 60-s stimulus duration exhibited a significantly higher average OKAN TC compared to the studies using an 87-s stimulus duration. Combining prior research with our own, a 60-s stimulus duration seems to be the preferred choice for determining OKAN TC (30). However, important questions remain unclarified. For instance, the ideal stimulus velocity that would gain the most accurate outcome is unknown. Furthermore, we are unsure about how many seconds after the stimulus has terminated, we must measure OKAN to not let the OKN interfere with the SP. Unfortunately, too little research has been done to provide sufficiently informed answers to those questions. Nevertheless, these are aspects to consider while executing future research on OKAN.

It is noteworthy that only seven articles were included in this review. This is likely due to the strict inclusion criteria, e.g., only English-language articles were included. This could possibly contribute to the research finding of only a small number of publications on a topic that has been extensively researched in the past. Furthermore, several articles included in this meta-analysis are relatively outdated. However, the quality assessment and risk of bias demonstrate that the studies are generally well-constructed. In addition, findings from more recent studies do not differ from the oldest ones. Although the results seem promising, the use of OKAN is currently used in study set-up but not in clinical practice. An obvious explanation is because generating OKAN has traditionally posed challenges by the spatial requirements and complex experimental set-ups. For example, OKAN is only elicited by large field stimuli and the darkness after stimulus should be completely dark. However, with ongoing technological advancements, there is potential for improving the feasibility of OKAN measurements in clinical practice. The landscape of medical technology is undergoing a transformative shift toward innovative technology such as Virtual and Augmented Reality, and Artificial Intelligence. These technologies hold the potential to regain interest in the approach of OKAN measurement and its diagnostics use.

The risk of selection bias exists since restrictions during inclusion were applied. For example, articles that were not included in this study examined OKAN findings in central pathologies such as multiple sclerosis and concussion. This decision was made to ensure comprehensible conclusions. Since OKAN is a very specific topic, a limited number of papers were included in the meta-analyses. However, the reduction in OKAN TC is a consistent finding across almost all investigated studies. We conclude that a 60 s stimulus duration is the most ideal choice for gaining the highest mean OKAN TC realizing that cofounders were not included in statistical analysis. Our future research will focus on this item.

This meta-analysis suggests that OKAN TC is a useful examination for vestibular deficits. The identified preference for a 60-s stimulus duration, in line with previous research, can be a guide for practical application of OKAN assessments in clinical settings. OKAN is not currently used for vestibular function measurement due to its large and complex set-up, but it could be useful in conditions where the visuo-vestibular pathway is impaired.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

MR: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing – original draft, Writing – review & editing. LS: Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing. JB: Conceptualization, Writing – original draft, Writing – review & editing. WC: Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing. VT: Conceptualization, Writing – original draft, Writing – review & editing, Supervision, Validation.