Drug- and Toxin-Induced Opsoclonus - a Systematized Review, including a Case Report on Amantadine-Induced Opsoclonus in Multiple System Atrophy.

Background: Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus. Methods: Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies. Results: The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus. Conclusion: Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.

Susac Syndrome: A Case Series.

BACKGROUND: Susac syndrome (SS) is an autoimmune disorder that involves the eyes, the brain, and the ears. It is a rare cause of recurrent branch retinal artery occlusion. The purpose of this study was to report cases of SS, highlighting the clinical presentations, therapeutic options, and their outcome. PATIENTS AND METHODS: Retrospective case series of patients seen at our institution for SS between 2005 and 2020. Demographics, clinical characteristics, treatment, and outcome were studied. RESULTS: Four patients (3 females, mean age 29 years old) were included in the study. According to the recently revised diagnostic criteria, three patients had definite and one patient had probable SS (distinctive ophthalmological and brain involvement without ear involvement). Initial visual acuity (VA) was normal in all eyes, but two patients had unilateral visual field impairment. Gass plaques (defined as yellow-white plaques found in the arteriolar wall away from arterial bifurcations) were observed on fundus examination in all patients. Fluorescein angiography revealed arteriolar wall hyperfluorescence and branch retinal arterial occlusions (BRAOs) in the absence of other signs of intraocular inflammation in all patients. Initial treatment consisted of a high-dose corticosteroid (intravenous or oral) with additional immunosuppressive therapy (azathioprine, intravenous immunoglobulins, mycophenolate mofetil, and/or cyclophosphamide). Residual symptoms were present in all patients and included scotoma (n = 2) and hearing loss (n = 3). CONCLUSION: SS is a rare disease with characteristic ophthalmological manifestation. The majority of patients present a crude form of the triad, and retinal findings may be the first initial manifestation. Ophthalmologists should consider the possibility of an SS in all young patients presenting with BRAOs.

Case Report: Multimodal Imaging of Toxic Retinopathies Related to Human Immunodeficiency Virus Antiretroviral Therapies: Maculopathy vs. Peripheral Retinopathy. Report of Two Cases and Review of the Literature.

Purpose: We report two patients with toxic retinopathy from either ritonavir or didanosine and reviewed the literature on the topics. We provide an overview of the retinal toxicity of these two antiretroviral drugs in human immunodeficiency virus-positive patients. Methods: First, we performed a retrospective study of the medical charts of two patients examined by us, one with ritonavir maculopathy and one with didanosine peripheral retinopathy. Secondly, we searched the world literature for similar cases through PubMed and Google Scholar, using the terms "HIV," "AIDS," "ritonavir," "didanosine," "maculopathy," "retinopathy," "visual loss," and "toxicity" to retrieve the appropriate literature on the subject. Results: Patient 1: A 49-year-old woman complained of progressive central visual loss over the past 12 months. History disclosed ongoing ritonavir therapy for the past 11 years. Ritonavir maculopathy was diagnosed, and visual loss increased relentlessly despite cessation of treatment. Patient 2: A 55-year-old man complained of slowly progressive peripheral visual field constriction for the past 5 years. History disclosed didanosine therapy for 13 years, however, stopped 4 years before the onset of visual symptoms. No alteration of therapy was offered to patient 2 as didanosine therapy was interrupted 9 years previously. Since 2011, 11 cases of ritonavir maculopathy have been reported in the literature. Relentless worsening of vision was reported in 3/7 patients despite cessation of ritonavir therapy. Didonasine peripheral retinopathy was first described in 1992, and a total of 24 patients have been reported since. Relentlessly progressive peripheral retinopathy was diagnosed despite the previous cessation of therapy in 14 patients. Conclusion: Ritonavir causes a slowly progressive atrophic maculopathy, and didanosine toxicity results in a relentlessly progressing peripheral atrophic retinopathy. The relentless progression of both toxic retinopathies reflects permanent alterations of the retinal metabolism by these medications. Both ritonavir and didanosine toxic retinopathies are rare events, but their clinical presentation is highly specific.

The Spectrum of Maculopathy in Mitochondrial DNA A3243G Mutation: A Case Series of Six Patients.

BACKGROUND: The mitochondrial DNA (mtDNA) A3243G point mutation encompasses a heterogenous group of disorders including mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), and, rarely, chronic progressive external ophthalmoplegia (CPEO). Regardless of the clinical phenotype, a specific retinopathy has been associated with the presence of this mitochondrial DNA mutation. We present six female patients exhibiting retinopathy of the A3243G point mutation at various stages. HISTORY AND SIGNS: Six female patients (37 - 70 years old) with the A3243G point mutation (four MELAS, one MIDD, and one CPEO) exhibited a maculopathy. Visual acuity ranged from 1/60 to 10/10. Visual field abnormalities varied from minimal decreased sensitivity to absolute central scotomas. They all exhibited, at various degrees, a characteristic pattern of perimacular and peripapillary retinal pigment epithelium (RPE) alterations, with mottled dys-autofluorescence and RPE atrophy and deposits on OCT. THERAPY AND OUTCOME: The level of visual impairment depended on the foveal involvement and the extension of RPE atrophy. The severity of the maculopathy was not related to age. In the only long-term follow-up (15 years), evolution was slowly progressive. CONCLUSIONS: A single mtDNA point mutation at locus 3243 can result in a variety of clinical presentations (MELAS, MIDD, or CPEO). Ocular involvement may manifest as a perimacular/peripapillary RPE atrophy/deposit, which can variably impact central visual function (from asymptomatic to legal blindness). The discovery of such a maculopathy should prompt the ophthalmologist to complete the personal and family history, namely, asking for the presence of diabetes mellitus and/or deafness.

Homonymous visual field defects in patients with multiple sclerosis: results of computerised perimetry and optical coherence tomography.

AIMS OF THE STUDY: Visual dysfunction is frequent in multiple sclerosis, usually resulting from retrobulbar optic neuritis or papillitis. Less frequently, demyelinating lesions can affect the retrochiasmal pathways. There are few reports of homonymous visual field defects (HVFD) in multiple sclerosis and little is known about their evolution. The purpose of this study was to better define both the clinical profile and the evolution of HVFD in patients with multiple sclerosis. METHODS: We performed a retrospective study of all multiple sclerosis patients who presented HVFD and were examined by automated static perimetry. A subset of patients benefited from macular assessment with optical coherence tomography (OCT). We also reviewed the worldwide literature on the subject. RESULTS: Twenty patients were retrieved from the neuro-ophthalmology database of the Hôpital Ophtalmique Jules-Gonin. There were 11 women and 9 men, and their average age was 35 ± 11 years. The relapsing-remitting form of multiple sclerosis was most common (18/20; 90%), the primary progressive form (1/20; 5%) and the secondary progressive form (1/20; 5%) were rare. HVFD were the presenting symptom of multiple sclerosis in seven patients (35%). The recovery was complete in 12/20 patients (60%), and the median time to recovery was 10 weeks (2-13 weeks). An incomplete recovery was found in 5/20 subjects (25%) and no recovery occurred in 3/20 subjects (15%). Magnetic resonance imaging disclosed a definite lesion explaining the HVFD in 7/11 patients: five within the optic radiations (71.4%), one within the optic tract (14.3%) and one within the lateral geniculate nucleus (14.3%). Our results were comparable to those compiled from our literature search (29 publications, totalling 70 cases). A recurrent episode of HVFD occurred in three patients (15%). OCT was performed in 10/20 patients. Retinal ganglion cell layer thickness was assessed and revealed a homonymous thinning in three patients, diffuse unilateral or bilateral thinning (resulting from previous episodes of optic neuritis) in six patients, and normal retinal ganglion cell layer thickness in one patient. CONCLUSION: HVFD in multiple sclerosis are found mostly in young patients with relapsing-remitting multiple sclerosis, which is consistent with the epidemiology of multiple sclerosis. HVFD can be the first manifestation of multiple sclerosis and have a relatively good prognosis. Like optic neuritis, HVFD can recur. The incidence of HVFD in multiple sclerosis is unknown, as it is probably underdiagnosed. Systematic automated static perimetry and OCT could help to determine the true incidence of HVFD in multiple sclerosis.  .

Normal Visual Recovery after Optic Neuritis Despite Significant Loss of Retinal Ganglion Cells in Patients with Multiple Sclerosis.

BACKGROUND: Optic neuritis (ON) is a frequent manifestation of demyelinating attack in multiple sclerosis (MS). Initial visual loss can vary from minimal to complete. Visual improvement occurs in about 95% of patients, some of them recovering to normal [visual acuity (VA), color vision, visual field (VF)]. We analyzed retinal ganglion cell layer (RGCL) thickness in MS patients who recovered their normal vision after ON to determine whether a relative preservation of RGCL existed in these patients. MATERIALS AND METHODS: We conducted a retrospective study of all patients with MS and ON examined by one of us (F. X. B.) between 2013 and 2018. Inclusion criteria were strictly unilateral ON, full recovery of vision, computerized visual field, and OCT examinations. Full recovery of vision was defined as VA ≥ 10/10, Ishihara ≥ 11/13, and VF mean defect (MD) ≤ 2.6 dB. Evaluation of RGCL was obtained with spectral domain optical coherence tomography (SD-OCT). The normal fellow eye of all patients served as the control group. Relative thinning of RGCL, expressed as percentage, was calculated by comparing results from the affected eye to the fellow eye of the same patient. RESULTS: Twenty-one patients (21 affected eyes - Group 1, 21 normal fellow eyes - Group 2) satisfying the inclusion criteria were retrieved from our database. All patients exhibited the relapsing-remitting form of MS. There were 16 women and 5 men. Mean age was 39.3 years old. There were no statistically significant differences between Group 1 and Group 2 for either VA (p = 0.3934) or Ishihara (p = 0.140), but a significant difference was found for VF MD (p = 0.0405). A markedly significant difference for RGCL thickness (p = 0.0001) was found, without any correlation with the degree of visual recovery. A subgroup of patients (n = 14) was examined at the time of initial visual loss. We correlated their results of visual function to the final RGCL thickness, and a correlation was found between either the initial VA loss or the initial VF loss and the final loss of RGCL (R2 = 0.4075 and R2 = 0.00739, respectively). CONCLUSIONS: In our study, all patients with ON lost a significant amount of RGCL despite a full recovery of vision, as defined by our criteria. The percentage of RGCL loss varied from 5 - 27% and could not be correlated with any final visual indices. However, a correlation was found with the degree of initial visual loss. Despite sometimes marked RGCL loss after ON, patients with MS can recover normal visual function, according to standard clinical tests.

The Heimann-Bielschowsky Phenomenon: A Retrospective Case Series and Literature Review.

BACKGROUND: The Heimann-Bielschowsky phenomenon (HBP) is an unusual form of monocular vertical pendular nystagmus and is usually asymptomatic. It always occurs in an eye with longstanding, profound visual loss. Reports of HBP are few and HBP is probably underdiagnosed. Recognition of HBP could prevent unnecessary and potentially harmful investigations. The purpose of this study was to report a series of patients with HBP and to summarise the international literature on the subject in order to better define the clinical presentation of HBP. PATIENTS AND METHODS: The study was approved by the local ethics committee. Medical records of patients diagnosed with HBP and examined by one of us (F. X. B.) were retrieved. Eye movements were quantified, either from video or eye tracking recordings, in all patients. The international literature on HBP was reviewed using the keywords "Heimann-Bielschowsky" or "monocular nystagmus". RESULTS: From 2007 to 2017, we retrieved seven patients with HBP. In the literature, we found only 8 publications, accounting for 66 cases. In both our cases and those from the literature, VA was worse in the eye with HBP and was usually ≤ 20/200. Visual loss was either congenital or acquired and resulted from a variety of aetiologies. The eye movement was strictly monocular, pendular, mostly vertical, but sometimes oblique. Characteristically, its frequency was irregular but low (0.2 to 2.6 Hz in our cases, 0.05 to 5 Hz in the literature) and its amplitude very variable (1 to 9° and 1.5 to 50°, respectively). Extraocular movements were always preserved. CONCLUSIONS: HBP is a benign monocular eye movement disorder that is always secondary to severe visual loss. Being asymptomatic, HBP is still under-recognised and easily overlooked. Furthermore, both amplitude and frequency of HBP may be small and irregular. Recognition of HBP is mandatory in order to prevent costly, unnecessary, and potentially hazardous investigations, and caution is advised, as cataract surgery might be responsible for postoperative oscillopsia.

Visual Outcomes of Fractionated Radiotherapy in Optic Nerve Sheath Meningioma: A Retrospective Study.

BACKGROUND: Optic nerve sheath meningioma (ONSM) is a rare benign tumour of the optic nerve sheath that can lead to blindness if untreated. Radiotherapy is commonly accepted as being the treatment of choice. We conducted a retrospective monocentric study to assess the effect of radiotherapy on visual outcomes and tumour control in patients with ONSM. PATIENTS AND METHODS: The charts of all patients affected by ONSM between 1994 and 2016 were reviewed retrospectively. Inclusion criteria were: having been followed by our department, initial visual acuity (VA) better than no light perception, and stereotactic fractionated radiotherapy. VA (Snellen), colour vision (Ishihara), and visual field mean defect (in dB), as well as ONSM size (on MRI) were compared before and after radiotherapy. Visual function was considered improved if two or more criteria improved, stabilised if none or only one criterion changed, and worsened if two or more criteria worsened. The Wilcoxon signed-rank test was used to assess the effect of radiotherapy (significant if p value < 0.05). RESULTS: VA improved or stabilised in 13/16 patients (81.25%), with median VA improving from 0.1 logMAR (8/10) to 0 logMAR (10/10) (p value = 0.0134). Colour vision improved or stabilised in 11/15 patients (73.33%), with median results improving from 5/13 to 12/13 (p value = 0.3212). The visual field mean defect improved in 13/15 patients (86.66%), and the median mean defect (MD) improved from 10 dB to 4 dB (p value = 0.0106). The size of the ONSM diminished or stabilised in 100% of our patients. No adverse events of radiotherapy were either reported or detected. CONCLUSION: Fractionated radiotherapy is a safe procedure and may improve visual function in patients with ONSM.

Acetazolamide Reduces Retinal Inner Nuclear Layer Thickness in Microcystic Macular Edema Secondary to Optic Neuropathy.

Optic neuropathy (ON) is commonly complicated by microcystic macular edema (MME), that is, small vertical cystoid spaces in the inner nuclear layer (INL) of the macula. We performed a retrospective consecutive case series of 14 eyes from 11 patients with ON and MME that were treated with oral acetazolamide, acting on cellular water transport. Contralateral eyes without MME were used as controls. Segmentation of images obtained with OCT was used to determine changes of individual retinal layer thickness during treatment. Retinal INL thickness consistently decreased in all eyes after 2-3 weeks of treatment. Recurrence of MME was observed after treatment cessation. No significant change of retinal thickness was found in contralateral unaffected eyes. Visual function did not change with treatment. Acetazolamide significantly improved the MME in eyes with ON. However, visual function did not. Acetazolamide is a treatment option for MME associated with ON but without an impact on the visual function.

Cross-sectional study assessing the addition of contrast sensitivity to visual acuity when testing for fitness to drive.

OBJECTIVES: The aim of this study is to quantify the importance of loss of contrast sensitivity (CS) and its relationship to loss of visual acuity (VA), driving restrictions and daytime, on-road driving evaluations in drivers aged 70+. DESIGN: A predictive cross-sectional study. SETTING: Volunteer participants to a drivers' refresher course for adults aged 70+ delivered by the Swiss Automobile Club in western Switzerland from 2011 to 2013. PARTICIPANTS: 162 drivers, male and female, aged 70 years or older. CLINICAL PREDICTORS: We used a vision screener to estimate VA and the The Mars Letter Contrast Sensitivity Test to test CS. OUTCOMES: We asked drivers to report whether they found five driving restrictions useful for their condition; restrict driving to known roads, avoid driving on highways, avoid driving in the dark, avoid driving in dense traffic and avoid driving in fog. All participants also underwent a standardised on-road evaluation carried out by a driving instructor. RESULTS: Moderate to severe loss of CS for at least one eye was frequent (21.0% (95% CI 15.0% to 28.1%)) and often isolated from a loss of VA (11/162 cases had a VA ≥0.8 decimal and a CS of ≤1.5 log(CS); 6.8% (95% CI 3.4% to 11.8%)). Drivers were more likely (R2=0.116, P=0.004) to report a belief that self-imposed driving restrictions would be useful if they had reduced CS in at least one eye. Daytime evaluation of driving performance seems limited in its ability to correctly identify difficulties related to CS loss (VA: R2=0.004, P=0.454; CS: R2=0.006, P=0.332). CONCLUSION: CS loss is common for older drivers. Screening CS and referring for cataract surgery even in the absence of VA loss could help maintain mobility. Reduced CS and moderate reduction of VA were both poor predictors of daytime on-road driving performances in this research study.