This review delineates the ocular motor disturbances across a spectrum of neurodegenerative disorders, including Alzheimer's Disease (AD) and related disorders (ADRD), Parkinson's Disease (PD), atypical parkinsonism, and others, leveraging advancements in eye-tracking technology for enhanced diagnostic precision. We delve into the different classes of eye movements, their clinical assessment, and specific abnormalities manifesting in these diseases, highlighting the nuanced differences and shared patterns. For instance, AD and ADRD are characterized by increased saccadic latencies and instability in fixation, while PD features saccadic hypometria and mild smooth pursuit impairments. Atypical parkinsonism, notably Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), presents with distinct ocular motor signatures such as vertical supranuclear gaze palsy and saccadic apraxia, respectively. Our review underscores the diagnostic value of eye movement analysis in differentiating between these disorders and also posits the existence of underlying common pathological mechanisms. We discuss how eye movements have potential as biomarkers for neurodegenerative diseases but also some of the existing limitations.

A putative mechanism of neurodegeneration in multiple sclerosis (MS) is trans-synaptic degeneration (TSD), whereby injury to a neuron leads to degeneration of synaptically connected neurons. The visual system is commonly involved in MS and provides an ideal model to study TSD given its well-defined structure. TSD may occur in an anterograde direction (optic neuropathy causing degeneration in the posterior visual pathway including the optic radiations and occipital gray matter) and/or retrograde direction (posterior visual pathway lesions causing retinal degeneration). In the current review, we discuss evidence supporting the presence of anterograde and retrograde TSD in the visual system in MS.

Glaucoma is a neurodegenerative disorder characterized with optic nerve injury and the loss of retinal ganglion cells (RGCs). Ferroptosis has been proved to be associated with the degradation of RGCs. The aim of this study is to elucidate the relationship between ferroptosis and glaucoma pathogenesis, and unveil the underlying mechanism. Methyl thiazolyl tetrazolium (MTT) assay was used to evaluate the proliferation of RGCs. The accumulation of cellular iron was measured by Iron assay kit, and the level of reactive oxygen species (ROS) was detected by fluorescence probe. The mitochondrial morphology and autophagosomes were analysed by using transmission electron microscopy (TEM). The contents of glutathione (GSH) and malondialdehyde (MDA) were tested by a GSH assay kit and an MDA detection kit, respectively. The expression of autophagy-related proteins was detected by Western blotting. A serious cell damage, aberrant iron homeostasis, and oxidative stress was shown in RGC-5 after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and gamma-Glutamyl transpeptidase 1 (GGT1) knockdown, but these effects were significantly alleviated by overexpression of GGT1 or ferroptosis inhibitors. The TEM and immunofluorescent results indicated that mitochondria impairment and autophagosome accumulation in OGD/R-treated cells was improved after GGT1 overexpression, while the phenomenon in GGT1-silenced cells was aggravated. Furthermore, we found that GGT1 can interact with glutamate cysteine ligase catalytic subunit (GCLC) to inhibit autophagy and ferroptosis in RGC-5 cells. GGT1 represses autophagy in RGC-5 cells by targeting GCLC, which further restrains the development of ferroptosis in cells.

Whereas excitation and inhibition of neurons are well understood, it is clear that neuromodulatory influences on neurons and their synapses play a major role in shaping neural activity in the brain. Memory and learning, emotional and other complex behaviors, as well as cognitive disorders have all been related to neuromodulatory mechanisms. A number of neuroactive substances including monoamines such as dopamine and neuropeptides have been shown to act as neuromodulators, but other substances thought to play very different roles in the body and brain act as neuromodulators, such as retinoic acid. We still understandlittle about how neuromodulatory substances exert their effects, and the present review focuses on how two such substances, dopamine and retinoic acid, exert their effects. The emphasis is on the underlying neuromodulatory mechanisms down to the molecular level that allow the second order bipolar cells and the output neurons of the retina, the ganglion cells, to respond to differentenvironmental (ie lighting) conditions. The modulation described affects a simple circuit in the outer retina, involves several neuroactive substances and is surprisingly complex and not fully understood.

Cerebrospinal fluid disorders have a wide-ranging impact on vision, headache, cognition and a person's quality of life. Due to advances in technology and accessibility, intracranial pressure measurement and monitoring, usually managed by neurosurgeons, are being employed more widely in clinical practice. These developments are of direct importance for Ophthalmologists and Neurologists because the ability to readily measure intracranial pressure can aide management decisions. The aim of this review is to present the emerging evidence for intracranial pressure measurement methods and interpretation that is relevant to Neuro-ophthalmologists.

Horner's syndrome (HS) is caused by a damage to theoculosympathetic pathway. HS may be congenital, but it is usually acquired and may reveal a life-threatening condition. According to the anatomic location of the underlying pathologic process, HS is classified as central, pre- or postganglionic, when the lesion affects the first, second or third-order neuron, respectively. Pharmacological testing, if available, can be used to differentiate HS from «pseudo-HS » in patients with mild symptoms. Given the financial burden that imaging of the entire oculosympathetic pathway represents, a targeted imaging approach is advised. Although in the majority of cases, clinical examination may predict etiology, in other cases pharmacological testing can help in the localization process. We searched PubMed data base for papers published before December 2022 that concerned Horner's syndrome, its neuro-ophthalmological manifestations and diagnosis. In this article, we describe the main neuro-ophthalmological manifestations of the three types of HS, the most common etiologies, and a targeted diagnostic strategy in each type.

Parkinson's disease (PD) affects approximately 10 million individuals worldwide. Visual impairments are a common feature of PD. Patients report difficulties with visual scanning, impaired depth perception and spatial navigation, and blurry and double vision. Examination of PD patients reveals abnormal fixational saccades, strabismus, impaired convergence, and abnormal visually-guided saccades. This review aims to describe objective features of abnormal eye movements in PD and to discuss the structures and pathways through which these abnormalities may manifest.

We improve pupillary responses and diagnostic performance of flicker pupil perimetry through alterations in global and local color contrast and luminance contrast in adult patients suffering from visual field defects due to cerebral visual impairment (CVI). Two experiments were conducted on patients with CVI (Experiment 1: 19 subjects, age M and SD 57.9 ± 14.0; Experiment 2: 16 subjects, age M and SD 57.3 ± 14.7) suffering from absolute homonymous visual field (VF) defects. We altered global color contrast (stimuli consisted of white, yellow, cyan and yellow-equiluminant-to-cyan colored wedges) in Experiment 1, and we manipulated luminance and local color contrast with bright and dark yellow and multicolor wedges in a 2-by-2 design in Experiment 2. Stimuli consecutively flickered across 44 stimulus locations within the inner 60 degrees of the VF and were offset to a contrasting (opponency colored) dark background. Pupil perimetry results were compared to standard automated perimetry (SAP) to assess diagnostic accuracy. A bright stimulus with global color contrast using yellow (p=0.009) or white (p=0.006) evoked strongest pupillary responses as opposed to stimuli containing local color contrast and lower brightness. Diagnostic accuracy, however, was similar across global color contrast conditions in Experiment 1 (p=0.27) and decreased when local color contrast and less luminance contrast was introduced in Experiment 2 (p=0.02). The bright yellow condition resulted in highest performance (AUC M =0.85±0.10, Mdn=0.85). Pupillary responses and pupil perimetry's diagnostic accuracy both benefit from high luminance contrast and global but not local color contrast.

To investigate the impact of attention orientation in young myopic adults with astigmatism. The effect of attention on foveal meridional performance and anisotropy was measured in corrected myopes with various levels of astigmatism (with-the-rule astigmatism ≤ -0.75D, Axis: 180 ± 20) using orientation-based attention. Attention was manipulated by instructing subjects to attend to either the horizontal or the vertical line of a central pre-stimulus (a pulsed cross) along separate blocks of trials. For each attention condition, meridional acuity and reaction times were measured via an annulus Gabor target situated remotely from the cross and presented at random horizontally and vertically in a two-alternative forced-choice employing two interleaved staircase procedures (one-up/one-down). Attention modulations were estimated by the difference in performance between horizontal and vertical attention. Foveal meridional performance and anisotropy were strongly affected by the orientation of attention, which appeared critical for the enhancement of reaction times and resolution. Under congruent orienting of attention, foveal meridional anisotropy was correlated with the amount of defocus for both reaction time and resolution, demonstrating greater vertical performance than horizontal performance as myopia increased. Compatible with an attentional compensation of blur through optimal orienting of attention, vertical attention enhanced reaction times compared to horizontal attention and was accompanied by an increase in overall acuity when myopia increased. Increased astigmatism was associated with smaller attention effects and asymmetry, suggesting potential deficits in the compensation of blur in astigmatic eyes. Collectively, attention to orientation plays a significant role in horizontal-vertical foveal meridional anisotropy and can modulate the asymmetry of foveal perception imposed by the optics of the eye in episodes of uncorrected vision. Further work is necessary to understand how attention and refractive errors interact during visual development. These results may have practical implications for methods to enhance vision with attention training in myopic astigmats.

Pineal germinomas can be very complex in terms of presentation, diagnosis, and management. This review attempts to simplify this complexity in an organized manner, addressing the anatomic relationships that provide the basis for the uniqueness of pineal germinoma. Ocular findings and signs and symptoms of elevated intracranial pressure are the keys to suspecting the diagnosis and obtaining the necessary imaging and cerebrospinal fluid studies. Other symptoms can suggest spread beyond the pineal region. Surgery may only be needed to obtain tissue for a definitive diagnosis, as germinoma is highly responsive to chemotherapy and focused radiation therapy. Hydrocephalus, usually related to tumor obstruction of the cerebral aqueduct, may also need to be addressed. Outcome for pineal germinoma is usually excellent, but relapse can occur and may require additional intervention. These issues are detailed in this review.