Retinal Findings in Two Patients With Tumefactive Multiple Sclerosis.

Tumefactive multiple sclerosis (TMS) often presents a diagnostic challenge because it can mimic neoplastic, infectious, or ischemic disease. We describe 2 patients with TMS with retinal findings of venous sheathing and bone spicule pigmentation. Mechanisms for such findings are discussed.

Idiopathic Intracranial Hypertension Progressing to Venous Sinus Thrombosis, Subarachnoid Hemorrhage, and Stroke.

Idiopathic intracranial hypertension (IIH) is a syndrome characterized by increased intracranial pressure (ICP), the absence of structural lesions on neuroimaging, and normal cerebrospinal fluid composition. Cerebral venous sinus thrombosis (CVST) is a common cause of increased ICP and can be differentiated from IIH with magnetic resonance venography. We describe a young woman with typical IIH who underwent lumbar puncture and was treated with a short course of high-dose corticosteroids followed by acetazolamide. She subsequently developed CVST, subarachnoid hemorrhage, and stroke. Risk factors that may have resulted in CVST are discussed.

Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial.

Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥ 50% reduction in palpable spleen length and/or a ≥ 50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66.7%) experienced ≥ 50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80.0%, 72.7%, and 72.2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment.

The genome of the model beetle and pest Tribolium castaneum.

Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.

A patient with albinism and retinitis pigmentosa, a case report.

Purpose: To present a case of molecularly confirmed oculocutaneous albinism (OCA) and retinitis pigmentosa (RP). Observations: A 46-year-old male with a lifelong established diagnosis of OCA and baseline best corrected visual acuity (BCVA) of 20/200, presented for worsening visual acuity over the last few years. BCVA was light perception and hand motion at face for the right and left eye, respectively. Fundus exam showed hypopigmented fundi with visible choroidal vessels and blunted foveal reflexes in both eyes. Optical coherence tomography showed foveal hypoplasia and outer retinal degenerative changes not typical of OCA. Fundus autofluorescence (FAF) imaging showed focal areas of decreased signal at the fovea, similar to areas of atrophy in an age matched patient with PDE6A-RP. Genetic testing identified a homozygous disease-causing variant in TYR c.1467dup, p. (Ala490Cysfs*20) causing OCA, and a homozygous pathogenic variant c.304C > A, p. (Arg102Ser) in PDE6A causing autosomal recessive RP. Conclusions and importance: This is the first report of a patient with OCA and RP. The lack of pigmentary changes can make the diagnosis of RP challenging in patients with albinism. FAF can show features suggestive of RP and genetic testing can establish the diagnosis. The findings described herein may help physicians diagnose an extremely rare phenotype.

Posterior Segment Manifestations of Syphilis and Correlation With Serologic Markers of Infection.

BACKGROUND AND OBJECTIVE: Retrospective analysis correlating serologic titers of ocular syphilis with posterior segment manifestations. PATIENTS AND METHODS: This study consisted of 40 patients (80 eyes imaged, 68 affected) with positive rapid plasma reagin (RPR) and Treponema Pallidum immunoglobulin G. We collected demographic and presentation data including HIV status, absolute CD4 count, RPR, cerebrospinal fluid-venereal disease research laboratory (CSF-VDRL) test, and retinal zone. We categorized imaging into syphilitic outer retinopathy (SOR), acute syphilitic posterior placoid chorioretinopathy, retinitis/chorioretinitis (RC), and papillitis. Multivariate analysis correlated HIV status, RPR, and VDRL titers with posterior segment findings and zone. RESULTS: Mean age of 42.8 ± 10.7 years, with 70% male patients. Presenting visual acuity (logMAR) 0.66 ± 0.74 did not correlate with RPR, nor was it associated with papillitis, RC, or acute syphilitic posterior placoid chorioretinopathy. Higher RPR (≥ 1:128) positively associated with SOR (P = 0.031) and zone 1 (odds ratio [OR], 1.62; P = 0.02), but negatively associated with zone 2 (OR 0.35; P = 0.005). HIV positivity increased RC odds (OR, 4.45; P = 0.047). CONCLUSION: Higher RPR correlated with SOR and zone 1, whereas HIV positivity correlated with RC. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Bilateral optic neuritis due to malaria.

Malaria is a mosquito-borne infectious disease caused by protists of the genus Plasmodium. Malaria is widespread in tropical regions around the equator, including much of sub-Saharan Africa, Asia, and the Americas, and uncommonly seen in the developed world. Although a variety of ocular manifestations have been linked to malaria, optic neuritis is rare. We report a patient who developed bilateral optic neuritis after he was treated successfully for acute falciparum malaria.

Demographic and clinical characteristics of age-related distance esotropia.

BACKGROUND: Age-related distance esotropia (ARDE), is an acquired, small, comitant esodeviation that is greater at distance than at near. It occurs in older adult patients without a history of neurological event or prior strabismus. It has been observed more frequently in White adults than in other racial groups. The purpose of this study was to assess the demographic and clinical characteristics of patients with ARDE presenting at a tertiary neuro-ophthalmology clinic. METHODS: In this retrospective study, ICD-9/10 (ICD-9 378.85 and ICD-10 H51.8) codes were used to identify all patients with ARDE from 2005 to 2020 seen in a single tertiary neuro-ophthalmology clinic. ARDE was defined as esotropia greater at distance than near with associated clinical signs of adnexal tissue laxity. Patients with history or findings compatible with other etiologies of strabismus, such as thyroid eye disease, neuromuscular disorders, sensory deviations, sudden onset of diplopia, and high myopia, as well as those with prior strabismus surgery, were excluded. RESULTS: A total of 89 patients (59 females [66%]) met inclusion criteria. Mean patient age was 76.6 years. All patients were White except for a single patient of African descent. Mean follow-up time was 25.2 months. Mean esodeviation at distance on presentation was 6.6Δ. Of the 87 patients electing nonsurgical treatment, 80 achieved remission of diplopia symptoms with prism therapy alone. Of the 89 patients, 59 had no neuroimaging. CONCLUSIONS: ARDE in our neuro-ophthalmology clinic population was diagnosed almost exclusively in older White adults. Prism therapy was effective for a majority of our patients.

Documented Reperfusion of the Retina on Fluorescein Angiography after Administration of Intravenous Prostaglandin E1 for Central Retinal Artery Occlusion: A Case Report.

Central retinal artery occlusion (CRAO) can result in devastating permanent vision loss. Presently, there is no evidence-based treatment for CRAO that is widely accepted. In the literature, multiple studies propose intravenous (IV) prostaglandin E1 (IV PGE1) as a potential treatment option for patients with CRAO. We illustrate 2 cases of CRAO successfully treated with IV PGE1. In both cases, our patients with vascular risk factors were diagnosed with CRAO of the left eye. They were started on twice daily IV 40 µg PGE1 in 100 mL normal saline, with each dose administered over 3 h. In the first case, we documented reperfusion of the retina on fluorescein angiography after administration of IV PGE1. In the second case, our patient improved from no light perception visual acuity (VA) to count fingers VA within 48 h of treatment with IV PGE1. Our study highlights the vasodilatory effect of IV PGE1. Due to its mechanism of action and safety profile, it should be considered a potential treatment option for CRAO. Further randomized controlled trials are necessary to determine the overall therapeutic effect of IV PGE1 for CRAO.

Temporal Alterations of Sphingolipids in Optic Nerves After Indirect Traumatic Optic Neuropathy.

Purpose: To identify optic nerve (ON) lipid alterations associated with sonication-induced traumatic optic neuropathy (TON). Design: Experimental study. Subjects: A mouse model of indirect TON was generated using sound energy concentrated focally at the entrance of the optic canal using a laboratory sonifier with a microtip probe. Methods: Analyses of datasets generated from high-performance liquid chromatography-electrospray tandem mass spectrometry of ONs dissected from the head of the ON to the optic chiasm at 1 day, 7 days, and 14 days postsonication compared with that in nonsonicated controls. Main Outcome Measures: Lipid abundance alterations in postsonicated ONs were evaluated using 1-way analysis of variance (false discovery rate-adjusted significant P value < 0.01), lipid-related gene sets, biochemical properties, and receiver operating characteristic to identify lipids associated with optic neuropathy. Results: There were 28 lipid species with significantly different abundances across the control and postsonication groups. The 2 most significantly upregulated lipids included a sphingomyelin (SM) species, SM(d40:7), and a hexosylceramide (CerG1) species, CerG1(d18:1/24:2). Hexosylceramide (d18:1/24:2) was noted to have a stepwise increasing trend from day 1 to day 14 after sonication-induced optic neuropathy. Investigation of biophysical properties showed notable enrichment of lipids with high and above-average transition temperatures at day 14 after sonication. Lipid-related gene set analysis revealed enrichment in sphingolipid and glycosphingolipid metabolic processes. The best classifier to differentiate day 14 postsonication from controls, based on area under the receiver operating characteristic curve, was CerG1(d18:1/24:2) (area under the receiver operating characteristic curve: 1). Conclusions: Temporal alterations in sphingolipid metabolism and biochemical properties were observed in the ON of mice after sonication-induced optic neuropathy, with notable elevations in sphingomyelin and hexosylceramide species. Hexosylceramide (d18:1/24:2) may be associated with damage after indirect trauma, indicating that lipid membrane abnormalities may be a mediator of pathology due to trauma.

Clinical and Mechanistic Review of Amiodarone-Associated Optic Neuropathy.

Amiodarone-associated optic neuropathy (AAON) is a complex clinical diagnosis, requiring distinction from non-arteritic ischemic optic neuropathy (NAION) due to a shared at-risk patient population. Diagnosis of AAON is complicated by a varied clinical presentation and incomplete pathophysiologic mechanisms. This article reviews pertinent literature for describing and clinically delineating AAON from NAION, as well as newly reported protective mechanisms of insulin-like growth factor 1 (IGF-1) and PI3K/Akt against amiodarone-induced oxidative and apoptotic injury in retinal ganglion and pigment epithelial cells. These studies offer a basis for exploring mechanisms of amiodarone toxicity in the optic nerve.

Toxoplasma Neuroretinitis.

Neuroretinitis is an inflammatory condition with rapid unilateral vision loss, optic disc edema, and macular star formation. While neuroretinitis is commonly due to infectious causes such as Bartonella henselae, neuroretinitis due to toxoplasmosis is uncommon. A 29-year-old male presents to our neuro-ophthalmology clinic on December 7, 2021, at the University of Arkansas for Medical Sciences with symptoms of left eye pain and blurred vision. Subsequent workup led to the diagnosis and treatment of toxoplasma neuroretinitis. The fundus exam eventually demonstrated a notable macular star. Treatment was well tolerated, and the patient regained total visual acuity in the affected eye. Toxoplasma neuroretinitis is known for a characteristic appearance of optic disc edema prior to appearance of stellate maculopathy with vitreous inflammation and peripheral chorioretinal scars. Although loss of vision due to toxoplasmosis is rare, it should be included as part of the differential diagnosis with pertinent history.