Ocular Dysfunction Research Articles

Burning the candle at both ends: Intraretinal signaling of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors located in the ganglion cell layer. They project to brain regions involved in predominately non-image-forming functions including entrainment of circadian rhythms, control of the pupil light reflex, and modulation of mood and behavior. In addition to possessing intrinsic photosensitivity via the photopigment melanopsin, these cells receive inputs originating in rods and cones. While most research in the last two decades has focused on the downstream influence of ipRGC signaling, recent studies have shown that ipRGCs also act retrogradely within the retina itself as intraretinal signaling neurons. In this article, we review studies examining intraretinal and, in addition, intraocular signaling pathways of ipRGCs. Through these pathways, ipRGCs regulate inner and outer retinal circuitry through both chemical and electrical synapses, modulate the outputs of ganglion cells (both ipRGCs and non-ipRGCs), and influence arrangement of the correct retinal circuitry and vasculature during development. These data suggest that ipRGC function plays a significant role in the processing of image-forming vision at its earliest stage, positioning these photoreceptors to exert a vital role in perceptual vision. This research will have important implications for lighting design to optimize the best chromatic lighting environments for humans, both in adults and potentially even during fetal and postnatal development. Further studies into these unique ipRGC signaling pathways could also lead to a better understanding of the development of ocular dysfunctions such as myopia.

The Potential Role of Regulated Cell Death in Dry Eye Diseases and Ocular Surface Dysfunction.

The research on new treatments for dry eye diseases (DED) has exponentially grown over the past decades. The increased prevalence of dry eye conditions, particularly in the younger population, has received much attention. Therefore, it is of utmost importance to identify novel therapeutical targets. Regulated cell death (RCD) is an essential process to control the biological homeostasis of tissues and organisms. The identification of different mechanisms of RCD stimulated the research on their involvement in different human pathologies. Whereas apoptosis has been widely studied in DED and included in the DED vicious cycle, the role of RCD still needs to be completely elucidated. In this review, we will explore the potential roles of different types of RCD in DED and ocular surface dysfunction. Starting from the evidence of oxidative stress and inflammation in dry eye pathology, we will analyse the potential therapeutic applications of the following principal RCD mechanisms: ferroptosis, necroptosis, and pyroptosis.

Microfluidic contact lenses for ocular diagnostics and drug delivery

AbstractThe human eye and tear provide essential physiological information for the detection of ocular dysfunctions and therapy monitoring. The measurements of biomarkers in tear composition are critical for disease diagnosis and early interventions. Hence, significant efforts are dedicated to the development of functional contact lenses that can quantify tear analytes and ocular physiological condition. The combination of microfluidics and contact lens technologies offer real‐time monitoring of ocular physiology and timely detection of eye disorders through wireless components. This review discusses the fundamentals of microfluidic contact lenses and their diverse applications in ophthalmic diagnostics and drug delivery. It also elucidates the strategies for the commercialization of microfluidic contact lenses to create clinical and point‐of‐care products.

Evaluation of tear film Osmolarity in glaucomatous and ocular hypertensive patients under topical therapies: A real life experience of a glaucoma unit

AbstractPurpose: The aim of the study was to evaluate the presence of alterations in the tear film osmolarity and in other parameters that can define the OSD in POAG/OH patients treated with different topical therapies in order to better define the role of osmolarimetry in the clinical management of patients in a real life setting.Methods: This is a cross‐sectional, observational study. All patients with POAG/OH treated with topical medications and 20 subjects age and sex matched as a control group, were consecutively and prospectively enrolled. The following exams were performed: tear film osmolarity assessed using Tearlab®, tear break‐up time (TBUT), corneal staining score (Oxford scale), ocular symptom assessment using Ocular Surface Disease Index (OSDI) questionnaire. These data were compared between POAG/OH patients and control group and correlations were analysed between tear film osmolarity and other DED parameters.Results: 50 POAG/OH patients (25 M/25F; mean age 69 ± 17y) and 20 controls, matched for age and sex, were enrolled. The mean treatment duration was 2.5 ± 1.2 years. Benzalkonium chloride (BAK) was used in 92% of cases. The mean osmolarity value (mOsms/L) in POAG/OH patients was 306 ± 12 versus 296 ± 12 in control group (p < 0.05). TBUT (sec) was 5 ± 2 versus 9 ± 2 (p < 0.05). OSDI ranged from 0 to 96 and the mean value was 18 ± 19 in the study group vs 16 ± 14 in controls (NS). No significant difference was found in corneal staining between the two groups. In POAG/OH eyes tear film osmolarity values were ≤308 in 17/50 (34%) patients and in control group were 4/20 (20%). TBUT<8 s in 41/50(82%) vs 5/20 (25%). OSDI was <12 in 50% of cases vs 55% of controls, ranging from 13 to 32 in 36% versus 30% and from 33 to 100 in 14% versus 20%; corneal staining >1 in 12% versus 10%. Tear osmolarity was significantly correlated to TBUT (r = 0.11; p = 0.05).Conclusions: The differences between OSM and TBUT are statistically significant between the two groups. OSDI score difference is not significant, but the self‐administered questionnaire has inherent limitations. Tear film osmolarimetry has the advantage of providing a quantitative, operator‐independent indication of possible ocular surface dysfunction and it may be useful in the real life practice of a glaucoma unit in identifying the most vulnerable patients who might benefit from a switch to BAK‐free preparations.

Resveratrol increases tear production and ocular pain after corneal abrasion in male, but not female, rats using a photorefractive keratectomy model.

Photorefractive keratectomy (PRK) is an alternative to LASIK and can cause intense acute pain that is often not relieved by standard treatments. To assess potential therapeutics for this type of acute pain, appropriate preclinical models are needed. We describe a preclinical corneal abrasion rat model that simulates the initial stages of PRK surgery and demonstrates similar pain and tear dysfunction as seen clinically. We used both behavioral and homeostatic assays to determine the therapeutic potential of resveratrol on pain and tear production. Studies were conducted in male and female Sprague-Dawley rats. Heptanol was applied to one eye and the superficial corneal epithelium was removed, mimicking the abrasion used in PRK. Spontaneous pain was assessed with orbital tightening (OT) scores for 7 days. Topical resveratrol increased OT scores sex-specifically in abraded males, but not females, at 72h and 1 week after abrasion. Resveratrol increased tear production in abraded males, with no effect in abraded females. There was no correlation between OT score at 1 week and tear production measurements, demonstrating no relationship between spontaneous ocular pain and tear dysfunction in this model. These findings demonstrate the usefulness of our corneal abrasion preclinical PRK model for the assessment of ocular pain therapeutics and indicate that topical resveratrol may not be useful for managing PRK-induced pain.

Serum MicroRNAs Profiling in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the retina which ultimately results in the irreversible loss of central vision. AMD is one of the foremost causes of blindness in people over the age of 50. Although the precise pathogenesis of AMD has not yet been elucidated, AMD results from a complex interaction between genetic predisposition and environmental provoking factors. These factors might lead to ocular homeostasis dysfunction resulting in inflammation, oxidative stress, and in some cases neovascularization. MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs and are approximately 22 nucleotides long. miRNAs play a central role in several pathophysiological processes such as immune and inflammatory responses, pathological angiogenesis, and the response to oxidative stress, all of which have been suggested to be associated with AMD pathogenesis and progression. Here we discuss methods to isolate miRNAs using serum specimens from AMD patients and miRNA profiling for the better understanding of the pathogenesis and progression of AMD.

Impact of Viewing Conditions and Vision Anomalies on Accuracy and Dynamics of Noncycloplegic Autorefraction.

This study was conducted to analyze the influence of binocular vision and accommodation anomalies on refraction dynamics. Our results may help to design more accurate autorefractors and to better understand the difficulties in prescribing an optical correction or adaptation to a correction. This study aimed to verify whether viewing conditions (open- or closed-field) or vision anomalies, such as ocular surface diseases, accommodative dysfunctions, and binocular vision anomalies, influence (1) the differences between subjective refraction and autorefraction and (2) the characteristics of the short-term refractive state variation. The subjective refraction of 64 subjects aged 23 to 60 years was measured during a comprehensive optometric examination, and the Ocular Surface Disease Index questionnaire was collected. Twenty successive measurements of automated refraction of each eye were obtained using a conventional autorefractor Nidek ARK-510A and an open-field autorefractor Shin-Nippon NVision-K 5001. Conventional notation of refractive error (sphere, cylinder, axis) was transformed to h-vectors, presented in scatterplots, and analyzed statistically. The three-way analysis of variance tests showed that there is no influence of accommodation dysfunctions (P = .22 for ARK-510A), binocular vision anomalies (P = .97 for ARK-510A), and ocular surface diseases (P = .20 for ARK-510A) on differences between autorefraction and subjective refraction. The binocular vision anomalies affected the results from open-field autorefractor, whereas the accommodation impacted closed-field refraction measurements. Changes in short-term refractive state variation occurred in sphere power, indicating accommodative state changes; however, 30 subjects demonstrated at least one outlier and/or polymodality of refractive state distributions. The study showed that the presence of accommodative dysfunctions or binocular vision anomalies might increase the range of short-term refractive state variation. The impact of vision anomalies differs between viewing conditions. The polymodal distribution of refractive state variation and the presence of outliers imply that automatic modes used typically in autorefractors with three to five readings may not accurately represent the refractive state of the eye.

Viral Infection and Antiviral Treatments in Ocular Pathologies.

Ocular viral infections are common and widespread globally. These infectious diseases are a major cause of acute red eyes and vision loss. The eye and its nearby tissues can be infected by several viral agents, causing infections with a short course and limited ocular implications or a long clinical progression and serious consequences for the function and structure of the ocular region. Several surveillance studies underline the increased emergence of drug resistance among pathogenic viral strains, limiting treatment options for these infections. Currently, in the event of resistant infections, topical or systemic corticosteroids are useful in the management of associated immune reactions in the eye, which contribute to ocular dysfunction. Many cases of viral eye infections are misdiagnosed as being of bacterial origin. In these cases, therapy begins late and is not targeted at the actual cause of the infection, often leading to severe ocular compromises, such as corneal infiltrates, conjunctival scarring, and reduced visual acuity. The present study aims at a better understanding of the viral pathogens that cause eye infections, along with the treatment options available.

Astrocytic dysfunction induced by ABCA1 deficiency causes optic neuropathy.

Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that Abca1 loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice. ABCA1 was highly expressed in retinal astrocytes in mice. Thus, we generated macroglia-specific Abca1-deficient mice (Glia-KO) and found that aged Glia-KO mice had RGC degeneration and ocular dysfunction without affected intraocular pressure, a conventional risk factor for glaucoma. Single-cell RNA sequencing revealed that Abca1 deficiency in aged Glia-KO mice caused astrocyte-triggered inflammation and increased the susceptibility of certain RGC clusters to excitotoxicity. Together, astrocytes play a pivotal role in eye diseases, and loss of ABCA1 in astrocytes causes glaucoma-like neuropathy.

A Retrospective Cohort Study of 5-Year Aesthetic Outcomes: Fronto-orbital Distraction Osteogenesis Versus Fronto-orbital Advancement & Remodeling

INTRODUCTION: Unicoronal craniosynostosis (UCS) phenotypically presents with ipsilateral frontal and parietal bone flattening, supraorbital rim elevation and recession, temporal retrusion, palpebral fissure widening, and vertical orbital dystopia – known as the ‘harlequin deformity.’ Fronto-orbital advancement and remodeling (FOAR) is currently the most common surgical approach for UCS, although outcomes suggest high rates of ocular dysfunction, failure to achieve long-term aesthetic normalcy, and relapse over time. Fronto-orbital distraction osteogenesis (DO) is an alternative treatment for UCS, with literature suggesting improved anterior cranial base deviation, decreased perioperative morbidity, and lower rates of ocular dysmotility. This study compared long-term objective photogrammetric aesthetic and postoperative outcomes of patients with UCS treated with DO and FOAR. METHODS: Patients presenting with non-syndromic UCS between 2007 and 2021 undergoing DO were compared to a matched cohort of patients undergoing FOAR. Clinical photographs and ImageJ were used to quantify palpebral fissure height and width, pupil-to-brow distance (PTB), and margin-reflex distance (MRD1) in pixels. The formula symmetry ratio = - [|(1 - (s/n)| × 100] was used to compare synostosed (s) and nonsynostosed (n) sides, where a symmetry ratio value of ‘0’ indicated perfect symmetry, and lower (more negative) symmetry ratio values indicated increased asymmetry. Positive differences in pre- and post-operative symmetry ratios indicate improved symmetry. The difference in canthal tilt angles was calculated with canthal tilit angle = |(s - n)|. Whitaker classification was assigned in a blinded fashion by two attending craniofacial surgeons. Statistical analysis was performed with unpaired t-tests. RESULTS: Forty patients (ten males) were included. The average age at surgery for FOAR and DO groups was 9.4 vs. 6.5 months (p < 0.001) and average length of follow up was 6.0 vs. 5.1 years (p = 0.456), respectively. Photogrammetric analysis and unpaired t-tests demonstrated significantly improved postoperative symmetry in the DO cohort for palpebral width [FOAR: -2.24, DO: 3.07 (p = 0.020)], MRD1 [FOAR: -9.92, DO: 12.87, (p = 0.045)], and canthal tilt [FOAR: 0.97°, DO: 6.54°, (p = 0.010)]. Analysis did not reveal significant symmetry ratio improvement in palpebral height (p = 0.157) and PTB (p = 0.202) between DO and FOAR cohorts. Unpaired t-tests revealed no significant difference in Whitaker Classification scores between FOAR and DO cohorts, with average scores of 1.97 ± 0.56 and 1.78 ± 0.54, respectively (p = 0.394). CONCLUSION: Photogrammetric analysis of the periorbital region in UCS patients five years after surgery reveals significant improvement in those treated with both FOAR and DO, with DO patients demonstrating superior results in palpebral width and canthal tilt symmetry. However, patients treated with DO achieved similar Whitaker Classification compared to their FOAR counterparts. It will be important to continue to follow these cohorts to craniofacial maturity prior to making any definitive conclusions.

A RARE CASE OF WERNICKE'S ENCEPHALOPATHY INDUCED BY HYPEREMESIS GRAVIDARUM: A DIAGNOSTIC DILEMMA

A RARE CASE OF WERNICKE'S ENCEPHALOPATHY INDUCED BY HYPEREMESIS GRAVIDARUM: A DIAGNOSTIC DILEMMA

Immunobiologicals and ocular surface disease.

Immunobiologicals have surfaced to become a new cornerstone of treatment for a wide spectrum of inflammatory disorders with an immune basis. The targets have ranged from autoimmune conditions to transplantation, and now more into atopic inflammatory disorders with primary targets of asthma and atopic dermatitis. The clinical information garnered from these studies have provided an initial snapshot on the potential adverse effects of the immunobiologicals on the ocular surface as well as providing a potential opening of their use in the treatment of various chronic ocular surface and intraocular inflammatory disorders that have previously been relegated to limited therapeutic options primarily to the broad anti-inflammatory use of glucocorticosteroids. The use of immunobiologicals provides a more directed therapeutic approach to many of the ocular inflammatory disorders, as we continue to appreciate more of their underlying immunopathophysiology of ocular surface disorder,s including ocular allergy and tear film dysfunction.

From your kidneys to your eyes: lessons from computational kidney models

Purpose: The purpose of this review is to describe computational models that have been developed for studying kidney function and howthese models may be adapted to study the eyes. Methods: We derive equations for modeling solute andwater transport across epithelial cell membranes in the kidney. These equations describe mass conservation, as well membrane transport via cotransporters, exchangers, and primary active transport. Results: Wedescribe howcomputational models of renal transport have been applied to investigate kidney function in physiological and pathophysiological conditions. Conclusion: The computational models herein described for the kidney may be adapted to study ocular functions and dysfunction.

Can Nutrition Play a Role in Ameliorating Digital Eye Strain?

Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.

Computational Insights into the Sequence-Activity Relationships of the NGF(1-14) Peptide by Molecular Dynamics Simulations.

The Nerve Growth Factor (NGF) belongs to the neurothrophins protein family involved in the survival of neurons in the nervous system. The interaction of NGF with its high-affinity receptor TrkA mediates different cellular pathways related to Alzheimer’s disease, pain, ocular dysfunction, and cancer. Therefore, targeting NGF-TrkA interaction represents a valuable strategy for the development of new therapeutic agents. In recent years, experimental studies have revealed that peptides belonging to the N-terminal domain of NGF are able to partly mimic the biological activity of the whole protein paving the way towards the development of small peptides that can selectively target specific signaling pathways. Hence, understanding the molecular basis of the interaction between the N-terminal segment of NGF and TrkA is fundamental for the rational design of new peptides mimicking the NGF N-terminal domain. In this study, molecular dynamics simulation, binding free energy calculations and per-residue energy decomposition analysis were combined in order to explore the molecular recognition pattern between the experimentally active NGF(1–14) peptide and TrkA. The results highlighted the importance of His4, Arg9 and Glu11 as crucial residues for the stabilization of NGF(1–14)-TrkA interaction, thus suggesting useful insights for the structure-based design of new therapeutic peptides able to modulate NGF-TrkA interaction.

Proteases and Their Potential Role as Biomarkers and Drug Targets in Dry Eye Disease and Ocular Surface Dysfunction

Dry eye disease (DED) is a multifactorial disorder that leads to ocular discomfort, visual disturbance, and tear film instability. DED is accompanied by an increase in tear osmolarity and ocular surface inflammation. The diagnosis and treatment of DED still present significant challenges. Therefore, novel biomarkers and treatments are of great interest. Proteases are present in different tissues on the ocular surface. In a healthy eye, proteases are highly regulated. However, dysregulation occurs in various pathologies, including DED. With this review, we provide an overview of the implications of different families of proteases in the development and severity of DED, along with studies involving protease inhibitors as potential therapeutic tools. Even though further research is needed, this review aims to give suggestions for identifying novel biomarkers and developing new protease inhibitors.

Induction of Ocular Surface Inflammation and Collection of Involved Tissues.

Ocular surface diseases include a range of disorders that disturb the functions and structures of the cornea, conjunctiva, and the associated ocular surface gland network. Meibomian glands (MG) secrete lipids that create a covering layer that prevents the evaporation of the aqueous part of the tear film. Neutrophils and extracellular DNA traps populate MG and the ocular surface in a mouse model of allergic eye disease. Aggregated neutrophil extracellular traps (aggNETs) formulate a mesh-like matrix composed of extracellular chromatin that occludes MG outlets and conditions MG dysfunction. Here, a method for inducing ocular surface inflammation and MG dysfunction is presented. The procedures for collecting organs related to the ocular surface, such as the cornea, conjunctiva, and eyelids, are described in detail. Using established techniques for processing each organ, the major morphological and histopathological features of MG dysfunction are also shown. Ocular exudates offer the opportunity to assess the inflammatory state of the ocular surface. These procedures enable the investigation of topical and systemic anti-inflammatory interventions at the preclinical level.

Fluorescence Sensing Technologies for Ophthalmic Diagnosis.

Personalized and point-of-care (POC) diagnoses are critical for ocular physiology and disease diagnosis. Real-time monitoring and continuous sampling abilities of tear fluid and user-friendliness have become the key characteristics for the applied ophthalmic techniques. Fluorescence technologies, as one of the most popular methods that can fulfill the requirements of clinical ophthalmic applications for optical sensing, have been raised and applied for tear sensing and diagnostic platforms in recent decades. Wearable sensors in this case have been increasingly developed for ocular diagnosis. Contact lenses, as one of the commercialized and popular tools for ocular dysfunction, have been developed as a platform for fluorescence sensing in tears diagnostics and real-time monitoring. Numbers of biochemical analytes have been examined through developed fluorescent contact lens sensors, including pH values, electrolytes, glucose, and enzymes. These sensors have been proven for monitoring ocular conditions, enhancing and detecting medical treatments, and tracking efficiency of related ophthalmic surgeries at POC settings. This review summarizes the applied ophthalmic fluorescence sensing technologies in tears for ocular diagnosis and monitoring. In addition, the cooperation of fabricated fluorescent sensor with mobile phone readout devices for diagnosing ocular diseases with specific biomarkers continuously is also discussed. Further perspectives for the developments and applications of fluorescent ocular sensing and diagnosing technologies are also provided.

An epidemiologic analysis of the association between eyelid disorders and ocular motility disorders in pediatric age

Aim of the study was to assess: (a) the prevalence and type of strabismus, ptosis and eyelid dynamic disorders features, (b) the prevalence of refractive errors, amblyopia and, (c) their association with ocular/systemic syndromes in a cohort of patients. This is a retrospective observational multicenter cohort study. Patients with coexisting ocular motility disorders, comitant and incomitant strabismus, ptosis and dynamic eyelid disorders who have never undergone surgery were enrolled throughout a 3-years a study period. 137 out of 19,089 patients were enrolled, of which 97 with uniocular and 40 with binocular disease. Isolated congenital ptosis was observed in 84 patients. A polymalformative syndrome was present in almost one third of cases, whilst among strabismus type, esotropia was slightly more prevalent. Most patients were hypermetropic. In monocular disease, myopia mainly affected older patients, who were characterized by a worse ptosis margin reflex distance and levator function, and significantly higher astigmatism. Amblyopia occurred in 67.4% of the study sub-population. Of note, in monocular disease this was mild in 25.8%, moderate in 24.2% and severe in 11.3% of cases, whilst in binocular disease it was mild in 25%, moderate in 41.7% and severe in 16.7%. All patients with coexisting eyelid and ocular motility dysfunctions in pediatric age need ophthalmologic and systemic evaluation to accurately assess amblyopia, refractive errors and systemic/ocular disorders.

Video-oculographic biomarkers for evaluating vertical ocular dysfunction in progressive supranuclear palsy

IntroductionProgressive supranuclear palsy (PSP) patients show reduced amplitude and velocity of vertical saccades, but saccadic abnormalities have also been reported in Parkinson's disease (PD). We investigated amplitude and velocity of vertical saccades in PSP and PD patients, to establish the best video-oculographic (VOG) parameters for PSP diagnosis. MethodsFifty-one PSP patients, 113 PD patients and 40 controls were enrolled. The diagnosis was performed on a clinico-radiological basis (MR Parkinsonism index [MRPI] and MRPI 2.0). We used VOG to assess the diagnostic performances of saccadic amplitude, peak velocity, and their product (AxV) in upward or downward direction and in vertical gaze (upward and downward averaged) in distinguishing PSP from PD patients. The vestibulo-ocular reflex, necessary to establish the supranuclear nature of ocular dysfunction, was evaluated clinically. ResultsPSP patients showed significantly reduced amplitude and peak velocity of ocular saccades in upward and downward directions compared to PD and healthy subjects. In PD patients, upward gaze amplitude was lower than in controls. In vertical gaze, the peak velocity showed 99.1% specificity and 54.7% sensitivity for PSP classification. The AxV product showed high specificity (94.7%) and sensitivity (84.3%) and yielded higher accuracy (91.5%) than velocity and amplitude used alone in distinguishing PSP from PD. ConclusionOur study demonstrates that the peak velocity of vertical saccades was a very low sensitive parameter and cannot be used alone for PSP diagnosis. A new index combining amplitude and peak velocity in vertical gaze seems the most suitable video-oculographic biomarker for differentiating PSP from PD and controls.