Neuro-ophthalmologic Disorders Research Articles

General Approach to Optic Neuropathies and Routine Examinations

Optic neuropathies are neuro-ophthalmological disorders characterized by decreased visual acuity, visual field defects and color vision changes as a result of damage to the optic nerve. The underlying causes, clinical features and treatments of optic neuropathies vary. Clarifying the etiology is very important in terms of visual prognosis and patient follow-up. Clinical history, examination findings, visual field, electrophysiological tests and imaging methods are used in diagnosis. In this article, the general characteristics, examination and ancillary diagnostic methods of optic neuropathies that develop due to different etiological reasons will be discussed

Holmes-Adie syndrome associated with BNT162b2 mRNA COVID-19 vaccine

Adie’s tonic pupil is a neuro-ophthalmologic disorder with dilation and poor light response. When deep tendon reflex loss accompanies the tonic pupil, it is called Adie syndrome or Holmes-Adie syndrome. The pupillary symptoms result from damage to the ciliary ganglion and the post-ganglionic parasympathetic nerves. Corona virus 2, which causes severe acute respiratory syndrome, has been named corona virus 19 (COVID-19) by the World Health Organization. It has been reported that the coronavirus infection has neurological manifestations including pupillary involvement.[1,2] The cases of two patients with Adie’s tonic pupil 10–15 days after they had BNT16b2b mRNA (Pfizer, BioNTech, Germany) vaccine were reported. One of them had Holmes-Adie syndrome.[3,4] In this case report, we aim to describe two patients who are a married couple with possible coronavirus BNT16b2b mRNA vaccine (Pfizer, BioNTech, Germany)-related Holmes-Adie syndrome.

Clinical Insights into Internuclear Ophthalmoplegia: A Case Report

Background: Internuclear ophthalmoplegia (INO) is a rare neuro-ophthalmological disorder characterized by impaired horizontal eye movement coordination due to lesion in the medial longitudinal fasciculus. INO commonly results from demyelinating diseases, vascular lesions, or structural brain abnormalities.
 Case presentation: A 60-year-old male patient presented with diplopia for the past 4 days. He had history of hypertension and diabetes mellitus and “mild” stroke for past years. Clinical examination revealed normal primary gaze, limited medial movement of the left eye, and diplopia in all gaze positions. Hess screen examination demonstrated underaction of the left medial rectus muscle and overaction of the right lateral rectus muscle. The laboratory results an elevated blood sugar level. Brain CT scan revealed multiple infarcts in the right parietal and cerebellar lobes and left parieto-occipital lobe, with evidence of brain atrophy. The patient was diagnosed with INO. Management involved addressing the underlying systemic diseases, namely diabetes and hypertension, in collaboration with internist and neurologist. The patient also received citicoline therapy and underwent regular follow-up. In the third-month follow-up, the patient demonstrated significant improvement, with reduction in diplopia and enhancement in left eye medial movement.
 Conclusion: This case report highlights the importance of considering INO in patients presenting with diplopia and a history of vascular risk factors. Timely diagnosis and comprehensive management with regular follow-up is crucial to monitor the progress and enhance the patient's quality of life.

A New Era in Ocular Therapeutics: Advanced Drug Delivery Systems for Uveitis and Neuro-Ophthalmologic Conditions.

The eye's intricate anatomical barriers pose significant challenges to the penetration, residence time, and bioavailability of topically applied medications, particularly in managing uveitis and neuro-ophthalmologic conditions. Addressing this issue, polymeric nano-based drug delivery systems (DDS) have surfaced as a promising solution. These systems enhance drug bioavailability in hard-to-reach target tissues, extend residence time within ocular tissues, and utilize biodegradable and nanosized polymers to reduce undesirable side effects. Thus, they have stimulated substantial interest in crafting innovative treatments for uveitis and neuro-ophthalmologic diseases. This review provides a comprehensive exploration of polymeric nano-based DDS used for managing these conditions. We discuss the present therapeutic hurdles posed by these diseases and explore the potential role of various biopolymers in broadening our treatment repertoire. Our study incorporates a detailed literature review of preclinical and clinical studies from 2017 to 2023. Owing to advancements in polymer science, ocular DDS has made rapid strides, showing tremendous potential to revolutionize the treatment of patients with uveitis and neuro-ophthalmologic disorders.

A CASE REPORT ON AYURVEDIC MANAGEMENT OF ACQUIRED OCULOMOTOR PALSY

Acquired oculomotor palsy is an ocular pathology resulting from damage to the third cranial nerve or its branches. Causes of this include head trauma, space-occupying lesions (neoplasms and aneurysms), and vascular lesions.The annual incidence was higher in older patients (aged greater than 60 years) compared to younger patients and in those with prominent or long-standing atherosclerotic risk factors, such as diabetes or hypertension. As per Ayurvedic classics, the diseases affecting neuro-ophthalmology can’t be correlated entirely with any disease entity. Some of the symptoms comes under Anyathovatam, Vataparyayam and Vatahatam. The neuro-ophthalmologic disorders are mainly due to the vitiation of Vata dosa, either Dathu kshaya or Avarana, so the treatment mainly focus to maintain the normalcy of Vata dosa and can be adopted according to the pathogenesis and involvement of other doshas.This case report discussed a 66 year old male patient consulted to the outpatient department, Govt. Ayurveda college, Thiruvananthapuram with unilateral complete ptosis, pain over right eye, right side of forehead and double vision since 2 weeks. The case was managed effectively with ayurvedic medications along with frequent Jalouka avacharana. After the treatment he got considerable relief; thus this study proves that ayurvedic management is effective to manage some of the neurological diseases.

An eye to the future: Acute and long-term neuro-ophthalmological and neurological complications of COVID-19.

COVID-19 has had a significant impact on the global population and has produced compelling evidence of non-pulmonary organ dysfunction, including the nervous system. It is vital that specialists in ophthalmology and neurology are informed of the potential complications of COVID-19 and gain a deeper understanding of how COVID-19 can cause diseases of the nervous system. In this review we detail four possible mechanisms by which COVID-19 infection may result in neurological or neuro-ophthalmological complications: (1) Toxic and metabolic effects of severe pulmonary COVID-19 disease on the neural axis including hypoxia and the systemic hyper-inflammatory state, (2) endothelial dysfunction, (3) dysimmune responses directed again the neuroaxis, and (4) direct neuro-invasion and injury by the virus itself. We explore the pathological evidence for each of these and how they may link to neuro-ophthalmological disorders. Finally, we explore the evidence for long-term neurological and neuro-ophthalmological complications of COVID-19, with a focus on neurodegeneration.

Unilateral Adie’s Tonic Pupil after Coronavirus Disease-19 (COVID-19): A Case Report

Introduction: Adie’s tonic pupil is a neuro ophthalmological disorder characterized by dilated pupil, which is unresponsive to light. It is caused by damage to postganglionic fibers of the parasympathetic innervation of the eye. Recent events of the coronavirus disease 2019 (COVID-19) pandemic had suggested that severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV-2) had neurotropic and neuroinvasive capabilities. Purpose: To report a rare case of unilateral Adie’s tonic pupil after COVID-19. Methods: A single case report study. Case Report: A 31-year-old woman presented with a glare on the right eye 3 months ago. No other symptom was reported. No prior history of using any eye drops and trauma. Further investigation revealed a history of asymptomatic SARS CoV-2 infection. Her best-corrected visual acuity of both eyes was 1.0, but we observed an impairment of accommodation on the right eye. A fixed dilated right pupil, 8 mm in diameter, was observed without any constriction on near reflex. Slit lamp and funduscopy examination were within normal limits on both eyes. Pilocarpine 0.1% test was positive on the right eye. Neurological examinations and brain imaging was within normal limits. The patient was diagnosed with Adie’s tonic pupil. She was treated with pilocarpine 0.1% once daily. After 2 months of follow up, her complaint of glare was diminished but no improvement of near acuity was seen on the right eye. Conclusions: This case report was one of the first few cases of Adie’s tonic pupil possibly associated with COVID-19.

Incidence and Pattern of Neuro-Ophthalmological Disorders Presenting to Vitreoretinal Clinics in Bhutan: A 3-Year National Study.

To inform national health policy, we quantified the pattern of neuro-ophthalmological disorders (NODs) presenting to the national vitreoretinal clinics in Bhutan. Retrospective cross-sectional study. We reviewed all new NODs patients over three years. Demographic data, presenting complaints, treatment history, systemic diseases, diagnostic procedures, and diagnoses were quantified. Logistic regression examined the odds of factors linked to more common NODs. Of 226 patients, the majority were males (54.0%), farmers (60.2%), and urbanites (55.8%). Loss of vision was the most common presenting complaint (57.9%), followed by head or orbital trauma (19.5%). The best corrected visual acuity (BCVA) of 216 eyes (47.8%) was ≤6/60. Hypertension was the most common systemic disease (16.4%), followed by diabetes (3.5%), and intracranial space-occupying lesions (3.5%). Neuroimaging (37.6%) was the most common diagnostic test performed, followed by visual field testings (VFTs) (22.9%). With a NOD incidence of 7.8% p.a. (226/2913), optic atrophy (OA) was diagnosed in 134 patients (59.3%). Other common NODs were optic neuritis (15.5%), papilloedema (9.3%), and traumatic optic neuropathy (8.4%). Female gender increased the odds for glaucomatous OA by 2.65× (p = 0.044), and age by 1.09× per year (p < 0.001). Being female increased the odds of optic neuritis by 2.57× (p = 0.03). Over half of the NODs were OA, which could be curable with timely treatment. Improved treatment of glaucoma and non-communicable diseases would reduce the risk of NODs-induced visual loss in Bhutan. The need for improved neuro-ophthalmological assessment and a coordinated multidisciplinary approach to NODs are the highest priorities.

Clinical and Demographic Characteristics of Patients with Neuro-ophthalmological Disorders Starting Later in Life

Objectives: To determine the demographic, etiological and clinical features as well as treatment modalities of patients with neuro-ophthalmological disorders starting at a later age. Materials and Methods: We retrospectively reviewed the clinical data related to the neuro-ophthalmology patients who presented at the age of ≥ 65 years at two tertiary eye care referral centers from 2004 to 2022. Results: Of the 2,127 patients who applied to the Neuro-Ophthalmology Department during this period, 162 (7.6%) were ≥ 65 years old at the time of diagnosis and their data were analyzed. The mean age at the onset of disease was 73.2 ± 6.7 (65–95) years, and mean follow-up time was 1.1±0.4 (1-3) years. Non-arteritic anterior ischemic optic neuropathy (NAAION) (n=85, 52.5%), isolated cranial nerve palsies (n=28, 17.3%), and cerebral vascular disorders (CVD) (n=14, 8.6%) were the most frequent diagnosis. The most common symptoms were as follows: sudden visual loss in 79 (48.8%), diplopia in 31 (19.1%), and blurred vision in 21 (13%) cases. The most common accompanying systemic disease was hypertension (HT) and diabetes mellitus (DM) in 31 (27.4%), followed by HT in 29 (25.7%) cases. There was no accompanying systemic disease in 49 (30.2%) patients. The diagnosis of NAAION and AAION resulted in poor visual outcomes, while CVD presented with homonymous hemianopsia. Conclusion: NAAION and CVD were the most common age-related neuro-ophthalmological disorders that cause visual acuity loss and a visual field defect at an advanced age. Identifying these disorders and managing the visual problems are essential to preserve the protection of the patient's quality of life.

Envisioning a New Era in the Diagnosis and Treatment of Neuro-Ophthalmologic Disorders

Envisioning a New Era in the Diagnosis and Treatment of Neuro-Ophthalmologic Disorders

Pineal cyst management: A single-institution experience spanning two decades.

Background: Pineal cysts (PCs) are benign lesions commonly found on intracranial imaging. Despite their high prevalence, there is no clear consensus on the most appropriate management of patients with PCs, especially those with symptomatic nonhydrocephalic cysts.Methods: A retrospective analysis was performed on 142 patients with PCs (103 surgical cases and 39 conservatively managed cases). Data were examined, including clinical presentation, imaging findings, ophthalmological status, natural course, postoperative outcomes, and complications.Results: Surgical group: the most common symptom was headache (92%), followed by signs of intracranial hypertension due to hydrocephalus (22%). New radiological feature of PCs was found in 11 patients. From 71 patients with long-term follow-up, headache completely resolved in 44 (62%) patients; marked improvement was observed in 20 (29%); in 7 (9%) – headache remained unchanged. The most common postoperative complication was neuro-ophthalmological disorders (23%), with a tendency for resolution in the long-term follow-up period. Neuro-ophthalmological symptoms at last follow-up included upward gaze palsy (6%) and skew deviation (5%), followed by convergence disorders (3%) and eyelid-retraction (2%). Natural course group: PC size remained stable in 34 (87%) patients during the follow-up period. The patient’s gender or age was not a significant predictor of cyst growth (P = 0.4, P = 0.56).Conclusion: The majority of patients with a newly diagnosed PC remain clinically and radiologically stable. Patients with nonhydrocephalic PCs and intractable headaches experience significant relief in headache symptoms, but are at risk of mild to moderate neuro-ophthalmological disorders. The natural course of PCs and factors promoting their growth still remains poorly defined.

Eye and Head Movement Recordings Using Smartphones for Telemedicine Applications: Measurements of Accuracy and Precision.

ObjectiveSmartphones have shown promise in the assessment of neuro-ophthalmologic and vestibular disorders. We have shown that the head impulse test results recorded using our application are comparable with measurements from clinical video-oculography (VOG) goggles. The smartphone uses ARKit's capability to acquire eye and head movement positions without the need of performing a calibration as in most eye-tracking devices. Here, we measure the accuracy and precision of the eye and head position recorded using our application.MethodsWe enrolled healthy volunteers and asked them to direct their eyes, their heads, or both to targets on a wall at known eccentricities while recording their head and eye movements with our smartphone application. We measured the accuracy as the error between the eye or head movement measurement and the location of each target and the precision as the standard deviation of the eye or head position for each of the target positions.ResultsThe accuracy of head recordings (15% error) was overall better than the accuracy of eye recordings (23% error). We also found that the accuracy for horizontal eye movements (17% error) was better than for vertical (27% error). Precision was also better for head movement (0.8 degrees) recordings than eye movement recordings (1.3 degrees) and variability tended to increase with eccentricity.ConclusionOur results provide basic metrics evaluating the utility of smartphone applications in the quantitative assessment of head and eye movements. While the new method may not replace the more accurate dedicated VOG devices, they provide a more accessible quantitative option. It may be advisable to include a calibration recording together with any planned clinical test to improve the accuracy.

Boosting visual perceptual learning by transcranial alternating current stimulation over the visual cortex at alpha frequency

BackgroundTranscranial alternating current stimulation (tACS) has been widely used to alter ongoing brain rhythms in a frequency-specific manner to modulate relevant cognitive functions, including visual functions. Therefore, it is a useful tool for exploring the causal role of neural oscillations in cognition. Visual functions can be improved substantially by training, which is called visual perceptual learning (VPL). However, whether and how tACS can modulate VPL is still unclear. ObjectiveThis work aims to explore how tACS modulates VPL and the role of neural oscillations in VPL. MethodsA between-subjects design was adopted. Subjects were assigned to six groups and undertook five daily training sessions to execute an orientation discrimination task. During training, five groups received occipital tACS stimulation at 6, 10, 20, 40, and sham 10 Hz respectively, and one group was stimulated at the sensorimotor regions by 10 Hz tACS. ResultsCompared with the sham stimulation, occipital tACS at 10 Hz, but not at other frequencies, accelerated perceptual learning and increased the performance improvement. However, these modulatory effects were absent when 10 Hz tACS was delivered to the sensorimotor areas. Moreover, the tACS-induced performance improvement lasted at least two months after the end of training. ConclusionTACS can facilitate orientation discrimination learning in a frequency- and location-specific manner. Our findings provide strong evidence for a pivotal role of alpha oscillations in boosting VPL and shed new light on the design of effective neuromodulation protocols that can facilitate rehabilitation for patients with neuro-ophthalmological disorders.

Retinal nerve fiber layer thickness evaluation in iron deficiency anemia patients using optical coherence tomography

Background Anemia is a widespread public health problem. Iron deficiency is the most common cause of anemia. Hemoglobin (Hb) concentration was supposed to affect the retinal nerve fiber layer thickness (RNFLT).Objective The aim of this study was to evaluate the influence of iron deficiency anemia (IDA) on the peripapillary RNFLT using optical coherence tomography (OCT).Patients and methods A total of 30 patients with IDA with Hb less than 12 g/dl were enrolled in the study. Optic disk and RNFL parameters obtained by Topcon OCT in these patients were compared with those of age-matched and sex-matched nonanemic 30 individuals. The anemia group was also divided according to the Hb concentration into three groups: mild, moderate, and severe.Results The average age of the IDA cases and the controls was 23.38±9.06 years (range=15–30 years), and 25.37±7.64 years (range=15–30 years), respectively (P=0.09). The average right eye RNFLT in IDA patients was 98.20±10.98 µm compared with 106.30±14.05 µm in the control group (P=0.001), while in the left eye, it was 98.87±12.24 µm in the IDA group, and 105.30±6.59 µm in the control group (P=0.015). The average nasal and inferior RNFLT of the IDA group were thinner than the control group in the right eye (P=0.003 and 0.045, respectively) and in the left eye (P=0.016 and 0.038, respectively). There was a positive association between average RNFLT and Hb concentration in the right eye (r=0.554) and in the left eye (r=0.561), which was statistically significant (P=0.001). In addition, there was a positive correlation between nasal and inferior RNFLT and Hb concentration in the right eye (P=0.002 and 0.001, respectively) and in the left eye (P=0.001 and 0.002, respectively). The degree of thinning was related to the severity of anemia as the RNFL thinning was significantly more in severe anemia cases than in mild and moderate ones.Conclusions The peripapillary RNFLT measured by OCT was significantly thinner in the IDA patients in the average, inferior, and nasal quadrants, with more thinning in the severe than in mild and moderate groups. This finding may have a significant effect, as these pseudoglaucomatous changes could be misdiagnosed as glaucoma or other neuro-ophthalmological disorders.

Intra-suprasellar Rathke's cleft cyst: a case report and literature review

Rathke´s cleft cysts are benign cystic lesions of the sellar and suprasellar region, forming out of remnant cells of the craniopharyngeal duct. Rarely diagnosed because they are often asymptomatic, sometimes they can be symptomatic by causing neuro-ophthalmological and/or endocrine disorders requiring surgical treatment. In this report we present a patient with a symptomatic Rathke´s cleft cysts in an intra-suprasellar location, and review of the literature.

Patients Prefer a Virtual Reality Approach Over a Similarly Performing Screen-Based Approach for Continuous Oculomotor-Based Screening of Glaucomatous and Neuro-Ophthalmological Visual Field Defects.

Standard automated perimetry (SAP) is the gold standard for evaluating the presence of visual field defects (VFDs). Nevertheless, it has requirements such as prolonged attention, stable fixation, and a need for a motor response that limit application in various patient groups. Therefore, a novel approach using eye movements (EMs) – as a complementary technique to SAP – was developed and tested in clinical settings by our group. However, the original method uses a screen-based eye-tracker which still requires participants to keep their chin and head stable. Virtual reality (VR) has shown much promise in ophthalmic diagnostics – especially in terms of freedom of head movement and precise control over experimental settings, besides being portable. In this study, we set out to see if patients can be screened for VFDs based on their EM in a VR-based framework and if they are comparable to the screen-based eyetracker. Moreover, we wanted to know if this framework can provide an effective and enjoyable user experience (UX) compared to our previous approach and the conventional SAP. Therefore, we first modified our method and implemented it on a VR head-mounted device with built-in eye tracking. Subsequently, 15 controls naïve to SAP, 15 patients with a neuro-ophthalmological disorder, and 15 glaucoma patients performed three tasks in a counterbalanced manner: (1) a visual tracking task on the VR headset while their EM was recorded, (2) the preceding tracking task but on a conventional screen-based eye tracker, and (3) SAP. We then quantified the spatio-temporal properties (STP) of the EM of each group using a cross-correlogram analysis. Finally, we evaluated the human–computer interaction (HCI) aspects of the participants in the three methods using a user-experience questionnaire. We find that: (1) the VR framework can distinguish the participants according to their oculomotor characteristics; (2) the STP of the VR framework are similar to those from the screen-based eye tracker; and (3) participants from all the groups found the VR-screening test to be the most attractive. Thus, we conclude that the EM-based approach implemented in VR can be a user-friendly and portable companion to complement existing perimetric techniques in ophthalmic clinics.

A case of Adie’s tonic pupil

Adie's tonic pupil, the round unilateral tonic pupil, is a neuro-ophthalmologic disorder with dilation and no light response. Although usually idiopathic, it may be associated with infection, inflammation, and postganglionic paraneoplastic nerve damage. It is called Holmes-Adie syndrome when deep tendon reflex loss accompanies Adie’s tonic pupil. The diagnosis is made by observing a miotic response after dilated pilocarpine instillation. Spontaneous recovery depends on etiological factors.

Peripheral Nervous System Manifestations Associated with COVID-19.

Purpose of ReviewThe present review discusses the peripheral nervous system (PNS) manifestations associated with coronavirus disease 2019 (COVID-19).Recent FindingsNerve pain and skeletal muscle injury, Guillain-Barré syndrome, cranial polyneuritis, neuromuscular junction disorders, neuro-ophthalmological disorders, neurosensory hearing loss, and dysautonomia have been reported as PNS manifestations in patients with COVID-19.SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19. COVID-19 has shown syndromic complexity. Not only does SARS-CoV-2 affect the central nervous system but also it involves the PNS. The PNS involvement may be due to dysregulation of the immune system attributable to COVID-19. Here we review the broad spectrum of PNS involvement of COVID-19.

Eye-Movement-Based Assessment of the Perceptual Consequences of Glaucomatous and Neuro-Ophthalmological Visual Field Defects.

PurposeAssessing the presence of visual field defects (VFD) through procedures such as perimetry is an essential aspect of the management and diagnosis of ocular disorders. However, even the latest perimetric methods have shortcomings—a high cognitive demand and requiring prolonged stable fixation and feedback through a button response. Consequently, an approach using eye movements (EM)—as a natural response—has been proposed as an alternate way to evaluate the presence of VFD. This approach has given good results for computer-simulated VFD. However, its use in patients is not well documented yet. Here we use this new approach to quantify the spatiotemporal properties (STP) of EM of various patients suffering from glaucoma and neuro-ophthalmological VFD and controls.MethodsIn total, 15 glaucoma patients, 37 patients with a neuro-ophthalmological disorder, and 21 controls performed a visual tracking task while their EM were being recorded. Subsequently, the STP of EM were quantified using a cross-correlogram analysis. Decision trees were used to identify the relevant STP and classify the populations.ResultsWe achieved a classification accuracy of 94.5% (TPR/sensitivity = 96%, TNR/specificity = 90%) between patients and controls. Individually, the algorithm achieved an accuracy of 86.3% (TPR for neuro-ophthalmology [97%], glaucoma [60%], and controls [86%]). The STP of EM were highly similar across two different control cohorts.ConclusionsIn an ocular tracking task, patients with VFD due to different underlying pathology make EM with distinctive STP. These properties are interpretable based on different clinical characteristics of patients and can be used for patient classification.Translational RelevanceOur EM-based screening tool may complement existing perimetric techniques in clinical practice.

Diagnostic imaging for Neuro-ophthalmologic disorders

Diagnostic imaging for Neuro-ophthalmologic disorders