by
Victor Kovac;
Elsa G Shapiro;
Kyle D Rudser;
Bryon A Mueller;
Julie B Eisengart;
Kathleen A Delaney;
Alia Ahmed;
Kelly E King;
Brianna D Yund;
Morton J Cowan;
Julian Raiman;
Eva G Mamak;
PaulR Harmatz;
Suma P Shankar;
Nadia Ali;
Stephanie R Cagle;
Jeffrey R Wozniak;
Kelvin O Lim;
Paul J Orchard;
Chester B Whitley;
Igor Nestrasil
Objective: To assess our hypothesis that brain macrostructure is different in individuals with mucopolysaccharidosis type I (MPS I) and healthy controls (HC), we conducted a comprehensive multicenter study using a uniform quantitative magnetic resonance imaging (qMRI) protocol, with analyses that account for the effects of disease phenotype, age, and cognition. Methods: Brain MRIs in 23 individuals with attenuated (MPS IA) and 38 with severe MPS I (MPS IH), aged 4–25 years, enrolled under the study protocol NCT01870375, were compared to 98 healthy controls. Results: Cortical and subcortical gray matter, white matter, corpus callosum, ventricular and choroid plexus volumes in MPS I significantly differed from HC. Thicker cortex, lower white matter and corpus callosum volumes were already present at the youngest MPS I participants aged 4–5 years. Age-related differences were observed in both MPS I groups, but most markedly in MPS IH, particularly in cortical gray matter metrics. IQ scores were inversely associated with ventricular volume in both MPS I groups and were positively associated with cortical thickness only in MPS IA. Conclusions: Quantitatively-derived MRI measures distinguished MPS I participants from HC as well as severe from attenuated forms. Age-related neurodevelopmental trajectories in both MPS I forms differed from HC. The extent to which brain structure is altered by disease, potentially spared by treatment, and how it relates to neurocognitive dysfunction needs further exploration.
PURPOSE OF REVIEW: The purpose of this study is to review commonly encountered adverse ocular effects of illicit drug use. RECENT FINDINGS: Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called 'designer', drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. SUMMARY: In this review, we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them.
Acute retinal necrosis is a viral syndrome characterized by a panuveitis with necrotizing retinitis that may be complicated by retinal detachment, vaso-occlusion, optic neuropathy, and other causes of decreased visual acuity. Polymerase chain reaction testing provides a rapid and sensitive method of identifying the viral etiology of acute retinal necrosis, which is most commonly caused by herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus. Prompt diagnosis and treatment is paramount to prevent further vision loss. We review the management of acute retinal necrosis including systemic, local intravitreal, and combination antiviral medications. We also discuss the appropriate and inappropriate use of corticosteroids, laser retinopexy, surgical therapy, and other adjunctive measures.
Mitochondrial diseases frequently manifest neuro-ophthalmologic symptoms and signs. Because of the predilection of mitochondrial disorders to involve the optic nerves, extraocular muscles, retina, and even the retrochiasmal visual pathways, the ophthalmologist is often the first physician to be consulted. Disorders caused by mitochondrial dysfunction can result from abnormalities in either the mitochondrial DNA or in nuclear genes which encode mitochondrial proteins. Inheritance of these mutations will follow patterns specific to their somatic or mitochondrial genetics. Genotype-phenotype correlations are inconstant, and considerable overlap may occur among these syndromes. The diagnostic approach to the patient with suspected mitochondrial disease entails a detailed personal and family history, careful ophthalmic, neurologic, and systemic examination, directed investigations, and attention to potentially life-threatening sequelae. Although curative treatments for mitochondrial disorders are currently lacking, exciting research advances are being made, particularly in the area of gene therapy. Leber hereditary optic neuropathy, with its window of opportunity for timely intervention and its accessibility to directed therapy, offers a unique model to study future therapeutic interventions. Most patients and their relatives benefit from informed genetic counseling.
Background: Horizontal strabismus due to a weak rectus muscle can be treated with an augmented Hummelsheim procedure, in which both vertical rectus muscle tendons are split, resected by 4 mm, and reattached to the sclera adjacent to the weak rectus muscle. Compared with vertical rectus transposition, the procedure spares two ciliary vessels and does not require placement of augmentation sutures. In this study, we evaluated binocular alignment and ocular motility in patients with abducens nerve palsy treated with an augmented Hummelsheim procedure. Methods: The medical records of consecutive patients with complete abducens nerve palsy who underwent the augmented Hummelsheim procedure, usually combined with medial rectus muscle recession, were retrospectively reviewed. Binocular alignment, ocular motility, and complications were analyzed. Results: Ten patients (age range, 12-57 years) met inclusion criteria for the study, of whom 9 of 10 had simultaneous medial rectus recession. Follow-up ranged from 1 week to 24 months. The augmented Hummelsheim procedure improved esotropia from 43Δ ± 5 Δ preoperatively to 6Δ ± 7 Δ postoperatively (P < 0.0001) and reduced abduction deficits from -4 to -3 (P < 0.0001). One patient with coexisting oculomotor nerve palsy developed consecutive exotropia; 2 had induced vertical deviations. There were no cases of anterior segment ischemia. Conclusions: The augmented Hummelsheim procedure combined with medial rectus muscle recession reduced mean primary position esotropia and improved abduction in patients with complete abducens nerve palsy.
by
Jessica Shantha;
Dominick Canady;
Caleb Hartley;
Amy Cassedy;
Chris Miller;
Sheila T Angeles-Han;
Lloyd CM Harrison-Williams;
Matthew J Vandy;
Natalie Weil;
Gilberte Bastien;
Steven Yeh
Background: Ebola virus disease (EVD) outbreaks in West Africa (2013-2016) and the Democratic Republic of Congo (2018-2020) have resulted in thousands of EVD survivors who remain at-risk for survivor sequelae. While EVD survivorship has been broadly reported in adult populations, pediatric EVD survivors are under-represented. In this cross-sectional study, we investigated the prevalence of eye disease, health-related quality-of-life, vision-related quality-of-life, and the burden of mental illness among pediatric EVD survivors in Sierra Leone. Methods: Twenty-three pediatric EVD survivors and 58 EVD close contacts were enrolled. Participants underwent a comprehensive ophthalmic examination and completed the following surveys: Pediatric Quality of Life Inventory Version 4.0, Effect of Youngsters Eyesight on Quality-of-Life, and the Revised Child Anxiety and Depression Scale. Findings: A higher prevalence of uveitis was observed in EVD survivor eyes (10·8%) cohort compared to close contacts eyes (1·7%, p=0·03). Overall, 47·8% of EVD survivor eyes and 31·9% of close contact eyes presented with an eye disease at the time of our study (p=0·25). Individuals diagnosed with an ocular complication had poorer vision-related quality-of-life (p=0·02). Interpretation: Both health related quality-of-life and vision-related quality-of-life were poor among EVD survivors and close contacts. The high prevalence of eye disease associated with reduced vision health, suggests that cross-disciplinary approaches are needed to address the unmet needs of EVD survivors. Funding: National Institutes of Health R01 EY029594, K23 EY030158; National Eye Institute; Research to Prevent Blindness (Emory Eye Center); Marcus Foundation Combating Childhood Illness; Emory Global Health Institute; Stanley M. Truhlsen Family Foundation.
by
Stefanie Kunst;
Tanja Wolloscheck;
Debra K. Kelleher;
Uwe Wolfrum;
S. Anna Sargsyan;
P Michael Iuvone;
Kenkichi Baba;
Gianluca Tosini;
Rainer Spessert
Purpose. The neurohormones melatonin and dopamine mediate clock-dependent/circadian regulation of inner retinal neurons and photoreceptor cells and in this way promote their functional adaptation to time of day and their survival. To fulfill this function they act on melatonin receptor type 1 (MT1 receptors) and dopamine D4 receptors (D4 receptors), respectively. The aim of the present study was to screen transcriptional regulators important for retinal physiology and/or pathology (Dbp, Egr-1, Fos, Nr1d1, Nr2e3, Nrial. Pgc-1α. Rorβ) for circadian regulation and dependence on melatonin signaling/MT1 receptors or dopamine signaling/D4 receptors. Methods. This was done by gene profiling using quantitative polymerase chain reaction in mice deficient in MT1 or D4 receptors. Results. The data obtained determined Pgc-1α and Nr4a1 as transcriptional targets of circadian melatonin and dopamine signaling. respectively. Conclusions. The results suggest that Pgc-1α and Nr4a1 represent candidate genes for linking circadian neurohormone release with functional adaptation and healthiness of retina and photoreceptor cells.
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a drug reaction featuring high fever, eosinophilia, skin rashes, and multi-organ involvement that may be fatal. Ocular manifestations, including cicatrizing conjunctivitis, corneal infiltration, and anterior uveitis, are rarely reported[1]–[6] but may cause serious complications if untreated. Therefore, it is important to diagnose DRESS syndrome in patients with ocular features promptly with appropriate treatment. This article reports a case diagnosed with DRESS syndrome associated with pseudomembranous conjunctivitis secondary to carfilzomib.
A 52-year-old man visited our ophthalmology department complaining of ocular pain, foreign body sensation, and blurred vision in both eyes that had begun two days prior. Ocular symptoms were manifested with a fever over 38°C. Two days after the ocular manifestation, a skin rash started to spread over his whole body (Figure 1). Laboratory findings showed eosinophilia (eosinophils of 12.5%) and elevated liver enzyme levels [aspartate transaminase (AST) 41 IU/L, alkaline phosphatase (ALP) 165 IU/L, and gamma-glutamyl transferase (GGT) 332 IU/L]. Two years prior, he was diagnosed with multiple myeloma and was treated with peripheral blood stem cell transplantation. Recently, the patient suffered a relapse of multiple myeloma and began chemotherapy with carfilzomib three weeks before visiting our clinic. The written informed consent was obtained from the patient to publish a caser report. All research and data collection adhered to the tenets of the Declaration of Helsinki.
by
David T. Selewski;
Ashton Chen;
Ibrahim F. Shatat;
Priya Pais;
Larry Greenbaum;
Pavel Geier;
Raoul Nelson;
Stefan G. Kiessling;
Patrick Brophy;
Alejandro Quiroga;
Michael E. Seifert;
Caroline E. Straatmann;
John Mahan;
Maria Ferris;
Jonathan Troost;
Debbie Gipson
Background
Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20–100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation.
Methods
Multicenter longitudinal study of children (2–18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later.
Results
Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D<20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D<20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p<0.01) in children supplemented with vitamin D.
Conclusions
In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2–4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.
PURPOSE. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects. METHODS. Using a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch’s membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or “pathological,” conditions. We considered choroidal expansion (c. 35 μL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position. RESULTS. Supra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a “blunt” choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively. CONCLUSIONS. Acute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.