Ocular manifestations of liver disease: an important diagnostic aid.

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.

Antibody-Drug Conjugates and Ocular Toxicity.

Antibody-drug conjugates (ADCs) are a growing class of chemotherapeutic agents for the purpose of treating cancers that often have relapsed or failed first- and second-line treatments. ADCs are composed of extremely potent cytotoxins with a variety of side effects, one of the most significant being ocular toxicity. The available literature describes these toxicities as varying in severity and in incidence, although with disparate methods of evaluation and management. Some of the most common toxicities include microcyst-like epithelial keratopathy and dry eye. We discuss proposed mechanisms of ocular toxicity and describe the reports that mention these toxicities. We focus on ADCs with the most published literature and the most significant effects on ocular tissue. We propose areas for further investigation and possible ideas of future management. We provide a comprehensive look at the reports of ADCs in current literature to better inform clinicians on an expanding drug class.

Electrodiagnostic profile of conduction slowing in amyotrophic lateral sclerosis.

Objective: Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. Methods: First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. Results: CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. Conclusions: The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

Optic Neuritis After COVID-19 Vaccination: An Analysis of the Vaccine Adverse Event Reporting System.

BACKGROUND: To investigate the association of optic neuritis (ON) after the COVID-19 vaccines. METHODS: Cases of ON from Vaccine Adverse Event Reporting System (VAERS) were collected and divided into the prepandemic, COVID-19 pandemic, and COVID-19 vaccine periods. Reporting rates were calculated based on estimates of vaccines administered. Proportion tests and Pearson χ 2 test were used to determine significant differences in reporting rates of ON after vaccines within the 3 periods. Kruskal-Wallis testing with Bonferroni-corrected post hoc analysis and multivariable binary logistic regression was used to determine significant case factors such as age, sex, concurrent multiple sclerosis (MS) and vaccine manufacturer in predicting a worse outcome defined as permanent disability, emergency room (ER) or doctor visits, and hospitalizations. RESULTS: A significant increase in the reporting rate of ON after COVID-19 vaccination compared with influenza vaccination and all other vaccinations (18.6 vs 0.2 vs 0.4 per 10 million, P < 0.0001) was observed. However, the reporting rate was within the incidence range of ON in the general population. Using self-controlled and case-centered analyses, there was a significant difference in the reporting rate of ON after COVID-19 vaccination between the risk period and control period ( P < 0.0001). Multivariable binary regression with adjustment for confounding variables demonstrated that only male sex was significantly associated with permanent disability. CONCLUSIONS: Some cases of ON may be temporally associated with the COVID-19 vaccines; however, there is no significant increase in the reporting rate compared with the incidence. Limitations of this study include those inherent to any passive surveillance system. Controlled studies are needed to establish a clear causal relationship.

Neonatal Fc Receptor Inhibitor Therapeutics in Neuromuscular Disease.

ABSTRACT: The Neonatal Fc Receptor (FcRn) is integral to a wide variety of processes including IgG recycling, serum albumin turnover, and bacterial opsonization. Thus, targeting FcRn will increase antibody degradation including pathogenic IgGs. FcRn inhibition provides a novel therapeutic mechanism by which autoantibody titers are reduced resulting in clinical improvement and disease abatement. The FcRn targeting mechanism is similar to that of intravenous immunoglobulin (IVIg) in which saturated FcRn facilitates accelerated pathogenic IgG degradation. Recently, the FcRn inhibitor efgartigimod was approved for the treatment of myasthenia gravis. Subsequently, clinical trials of this agent have been conducted for numerous inflammatory conditions involving pathogenic autoantibodies. These disorders include the Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, and inflammatory myositis. Other disorders traditionally treated with IVIg may also benefit from FcRn inhibition in certain contexts. This manuscript discusses the mechanism of FcRn inhibition, preclinical data, and the results of clinical trials of this agent for a wide range of neuromuscular diseases.

Povidone-Iodine Adverse Effects and Alternatives for Ocular Procedures.

Purpose: Povidone-iodine (PVI), also known as Betadine, is a widely used antiseptic agent used in several fields of medicine. In ophthalmology, it is applied as a preoperative antiseptic to prevent infectious complications that can result from surgical procedures. PVI's safety and efficacy have been extensively studied and represented in the literature; however, the incidence of adverse effects has been reported in conjunction. The aim of this paper is to compile information regarding PVIs use, safety profile, adverse effects, and possible alternatives through a review of the existing literature. Methods: Literature was compiled utilizing the database PubMed and Google Scholar using specified keywords with a total of 86 reviewed articles, after excluding search results that did not meet the inclusion criteria. Results: While the allergic potential to PVI is a highly contested topic, there are several nonallergic adverse effects of PVI that should not be overlooked. These effects include chemical burn, cytotoxic effects, and general patient discomfort. In light of these adverse effects, alternatives to PVI may be considered. However, there has been little research identifying feasible alternatives in preoperative intraocular procedures. Alternatives including chlorhexidine, polyhexamethylene biguanide (polyhexanide), and octenidine were identified as potential substitutes for PVI. Conclusions: Further study is needed to provide robust evidence regarding the efficacy profiles of these alternatives in comparison with PVI and to demonstrate comparable tolerance to PVI in intraocular procedures.

Amantadine induced interface fluid formation after LASIK. A case report.

Purpose: To describe a case of bilateral interface fluid formation 2 years after laser-assisted in situ keratomileusis (LASIK) surgery caused by the side effect of amantadine. Observations: A 47-year-old male patient with a history of Parkinson's disease treated with amantadine who had uneventful LASIK surgery in both eyes 2 years ago, presented with a decline in vision over the past 6 weeks. Results: Best corrected vision was 20/200 and 20/400 in the right and left eye respectively. Intraocular pressures were measured within the normal range. Biomicroscopic exam showed bilateral corneal edema. Anterior segment optical coherence tomography (AS-OCT) revealed fluid accumulation within the LASIK flap interface in both corneas. The patient's corneal edema and fluid in the interface began to gradually resolve, and vision improved 2 weeks after discontinuing amantadine. Conclusions and Importance: Although there is no previous report, it is possible that amantadine may cause interface fluid formation in patients with LASIK surgery.

Streptococcus mitis/oralis Corneal Ulcer in a Patient with Severe Rheumatoid Arthritis: An Unusual Route.

Purpose: To report a case of Streptococcus mitis oralis (S. mitis/oralis) corneal ulcer in a patient with a possible preventable cause. Methods: Cultures were obtained from a 64-year-old woman with a 3.5 mm × 5 mm corneal ulcer with hypopyon in the left eye. Results: Culture reports demonstrated the growth of S. mitis/oralis, a commensal organism of the oral flora. Fortified vancomycin 5% eye drops were started, and the patient was counseled on the rarity of the bacteria as an etiology of corneal ulcers. On the return visit, the patient, who works in a doctor's office, volunteered information that the preservative free artificial tear vials that she used were difficult to open because of her hand deformity due to rheumatoid arthritis; thus, she had to bite the vials open. Conclusions: S. mitis/oralis is an organism commonly found in the mouth but is rarely found in the eye. We report a unique case of an immunocompromised patient with rheumatoid arthritis, severe dry eye, and a history of multiple episodes of keratolysis, who developed a corneal ulcer from a rare pathogen, with a plausible and preventable route of infection.

Expanding the phenotypic spectrum of Dejerine-Sottas syndrome caused by the trembler mutation.

Dejerine-Sottas syndrome (DSS) is the earlier onset, more severe form of Charcot-Marie-Tooth (CMT) disease with heterogenous neurologic manifestations in addition to the peripheral neuropathy depending not only on the underlying causative gene but also the specific mutation. The Trembler mutation is an uncommon missense mutation in the PMP22 gene, the most commonly mutated gene responsible for CMT. We report two cases of DSS in a mother and son with the Trembler mutation, with associated findings of hearing loss and cognitive impairment. The mother had developmental gait abnormalities and became wheelchair bound in adolescence. She displayed impairment on cognitive and audiologic testing. Her son had similar developmental gait abnormalities and became wheelchair bound at age 19. Cognitive function showed an earlier decline in the son as compared to his mother. This report extends the clinical spectrum of the Trembler mutation in humans to include associated hearing loss with cognitive impairment.