Top PDF Causes of visual loss in uveitis

Background/Aim. Epidemiological studies of blindness in a working age population require a precise definition of the true connection of uveitis and visual damage. Since most patients with more severe types of uveitis are hospitalized in tertiary referral uveitis service, our aim was to determine whether age, sex and age of onset of uveitis, as well as dura- tion of visual loss and its causes influence the degree of vis- ual damage in patients with different types of uveitis. Methods. The data were collected from medical records of 237 patients at the Department for Uveitis of the Institute for Eye Diseases in Belgrade over a three-year period (March 2005 to March 2008). Results. Visual acuity reduc- tion (≤ 0.3) was found in 161/237 (67.9%) patients, 85 of whom had visual acuity of ≤ 0.1 later. Working age patients (up to 60 years of age) most often suffered from uveitis (173/237; 73%). The highest noumber of patients with vis- ual loss was in the group suffering from panuveitis (77/94; 81.91%). The age of onset of uveitis and sex have no statis- tically significant influence on visual loss. The most com- mon causes of visual loss (34/161; 21.1%) were cystoid macular oedema (CMO) (43/161; 26.7%), cataract (28/161; 17.39%) and combination of CMO and cataract. Conclu- sion. The risk factors for severe visual loss (≤ 0.1) are pa- nuveitis, bilateral inflammation, prolonged visual reduction and a significant number of relapses. The main causes of visual loss in 65.2% of our patients were CMO and cataract.

mice were then crossed with mice expressing the Cre-recombinase under the control of the Nestin promoter (nes-Cre;Dmxl2 wt/wt ) [29], to obtain mice bearing a Dmxl2 allele from which exon 7 was deleted in nestin-expressing cells (nes-Cre;Dmxl2 –/wt ) (Figure S3). Adult nes-Cre;Dmxl2 –/wt mice displayed no obvious morpholog- ical defects. Hypothalamic Dmxl2 mRNA levels were 50% lower in nes-Cre;Dmxl2 –/wt than in Dmxl2 lox/wt mice (Figure S3). Female nes-Cre;Dmxl2 –/wt mice weighed less than WT mice (Figure 4A), Figure 2. Rbcn-3a is expressed in exocytosis vesicles in the external layer of the median eminence. (A) ISH with a mouse Dmxl2 antisense probe (AS) and a sense probe (S). (B) Immunolabeling with an antibody against Rbcn-3a revealed high levels of Dmxl2/Rbcn-3a expression in the dentate gyrus, the CA1 and CA3 regions of the hippocampus, and the cortex (black arrowheads). Scale bars, 200 mm. (C and D) Rbcn-3a was found to be strongly expressed in the external layer of the ME (C) and the OVLT (D). Scale bars, 100 mm. (E) Confocal analysis with an antibody against Rbcn-3a showed punctate staining in the median eminence and staining of the long processes extending from the cell bodies lining the third ventricle. (F and G) Rbcn-3a immunoreactivity was observed in small clear vesicles and LDCVs at the extremities of the axons in the ME (white arrow). Scale bar, 0.2 mm.

The diagnosis was established based on complete ophthalmological consultations consisting of the clinical history of the patient (history of present disease, past pathological history) and eye exam (measurement of visual acuity, ectoscopy, biomicroscopy of the anterior and posterior segments, ophthalmoscopy), until the subsequent request for complementary, general and/or eye exams, according to the need, for confirmation of the diagnosis. The patients who didn’t bring the complementary exams and did not continue the assessment were excluded, as well as the patients with uveitis triggered shortly after surgery or trauma, so we don’t know for sure the amount of patients with possible uveitis excluded from the study, because some abandoned the hospital follow up before the diagnostic hypothesis had been proven. Uveitis with signs and symptoms of activity during consultation and follow up were included in the statistics. They were considered to be active when they presented cells and flare in the anterior chamber, fine or coarse keratic precipitates (KPs), fibrin on the corneal endothelium, hypopyon, iris nodules, anterior or posterior synechiae, vitreous cells, snowballs, snowbanks, inflammatory lesions in the retina or choroid, vasculitis associated to symptoms such as pain, red eye, photophobia, decreased visual acuity, floaters, perikeratic or limbic hyperemia. A uveitis expert assessed the pre-selected medical records to make sure about the diagnostic hypothesis.

The disease can be classified into 2 stages: non- proliferative and proliferative. In nonproliferative DR, the earliest visible signs are microaneurysms and reti- nal hemorrhages. Progressive capillary nonperfusion is accompanied by the development of cotton-wool spots, venous beading, and intraretinal microvascular abnor- malities. Proliferative DR is characterized by the growth of new blood vessels on the surface of the retina or the op- tic disc. These abnormal vessels may bleed, resulting in vitreous hemorrhage, subsequent fibrosis, and tractional retinal detachment. Diabetic macular edema (DME), which can occur at any stage of DR, is characterized by increased vascular permeability and the deposition of hard exudates at the central retina. Primary interventions, such as intensive glycemic and blood pressure control, can reduce the incidence of DR, while secondary inter- ventions, such as laser photocoagulation, may prevent further progression of DR and vision loss (Mohamed et al. 2007).

Six weeks after the incident, fundoscopic examination in the left eye showed large cupping, atrophic and pale optic disc. All the major retinal arterioles showed attenuation, especially on the inferotemporal branch, which were confirmed by the angiogram. There were some coarse granular changes of the pigmented background. The foveal avascular zone was enlarged and all the arterioles around it ended abruptly (Figure 3). Ocular treatment was ineffective since the patient was not responsive to standard treatments. In addition, the visual prognosis was extremely poor in his left eye.

We identified in Krz several conserved aminoacids (Val94, Leu440/IsoLeu441/Leu443 and Ser427; see Figure S1) whose human counterparts are implicated in the targeting of GPCR to clathrin-coated pits without affecting receptor signalling (Val94) [33–34], in the binding of b-arrestin to clathrin (Leu440/ IsoLeu441/Leu443) [34–35], or that reduce its ability to promote internalization of the b2-adrenergic receptor (Ser427) [36–37]. To explore whether the function of these residues is conserved in Krz, we made several constructs with mutant forms of Krz fused to the Flag tag (UAS-krz V94D -Flag, UAS-krz S427D -Flag, and UAS-krz Leu - Flag). As a control construct we used wild type Krz fused to Flag (UAS-krz WT -Flag). The expression of Krz-Flag in the dorsal compartment eliminates Smo from the cell membranes of dorsal cells (Figure 6A). In contrast, neither the over-expression of Krz V94D -Flag nor of Krz Leu -Flag affects the localization of Smo (Figure 6B and 6D). These results show that Val94 and the Leu440/IsoLeu441/Leu443 domain are conserved regions essen- tial to the function of Krz, and suggest that Krz binds to Smo and internalizes it via clathrin-coated vesicles. The over-expression of Krz S427D -Flag causes the same reduction in Smo levels as the wild type form (Figure 6C), suggesting that modulation at Ser427 is not functional in Drosophila. Over-expression experiments using the wild-type and the mutant Flag-Krz forms in myc-Smo S2 cells were consistent with the in vivo data (Figure 6E). Co-immunopre- cipitation studies showed that all mutant Krz forms interact with Smo (Figure 6F). Interestingly, Krz V94D and Krz Leu mutants co- immunoprecipitated higher levels of Smo (3 and 4 times over wild type Krz, respectively), consistent with an altered Smo internal- ization and degradation in such conditions. Overall, these results suggest that Krz promotes Smo internalization via clathrin vesicles, and that this step is relevant for its enhancing effect on Smo degradation.

Particles of polyethylene and other debris are dis- pensed through the joint fluid. Fluid flows according to pressure gradients, and any area of bone accessed by joint fluid is a potential site for deposition of wear de- bris. Schmalzried, Jasty and Harris described “the ef- fective joint space” where debris and fluids migrate around the components of the prostheses and cause bone lysis out of the joint space. This concept explains the development of osteolysis at the tip of a well-fixed femoral component, or over the dome of an acetabular component with holes in the metal backing 2,3 .

In this study, we used in vivo multiphoton imaging of yellow cameleon 3.6 (YC3.6), a ratiometric FRET based calcium indicator encoded and delivered by an adeno-associated virus (YC3.6AAV2) [27,29] to visualize intracellular calcium concentration in the brain of living adult mice that over-express human mutant P301L tau (rTg4510). At 8-9 months of age, these mice are beginning to lose neurons and to accumulate neurofibrillary tangles in the neocortex [30,31]. Further, P301L tau expressing neurons at this age have been shown to have either “atrophic” or “intact” morphologies with atrophic neurons demonstrating dendritic spine loss and loss of dendritic branches [32], indicating that this is a time when synapse loss is actively occurring. Here we demonstrate that 8-9 month old rTg4510 mice exhibit significant loss of dendritic spines but maintain baseline calcium levels in dendrites and dendritic spines despite accumulation of tau pathology. These data indicate that pathological changes in tau cause synapse loss in a calcium-independent manner, suggesting that pathological changes in tau may be downstream of both Aβ and calcium dysregulation in synapse loss in AD.

of the wild-type human LRRK2 protein does not always achieve the same mutant effect, as demonstrated in rat studies [17], raising a question on how much can be inferred from such ‘gain-of- function’ analysis of mutant alleles in understanding the normal function of LRRK2. When measuring the kinase activity of LRRK2 mutations using moesin as substrate [18], the most frequent mutation, G2019S, is the only one showing stimulated kinase activity. Hence, the mechanism by which LRRK2 mutation induces PD is more complex than previously imagined and is not only due to an increase in LRRK2 kinase activity. Analysis of loss- of-function mutations in Drosophila (dLRRK2) revealed conflicting findings; and it was not clear whether the disruption of dLRRK’s function caused parkinsonism-like neurodegeneration and loco- motive defects in this model system [19,20]. So far, there are no reports on the function of WD40 or other domains in vertebrate models, such as the mouse or rat and the decreased kinase model for LRRK2 is very limited.

Ocular inflammation is one of the leading causes of blindness and loss of vision. Human uveitis is a complex and heterogeneous group of diseases characterized by inflammation of intraocular tissues. The eye may be the only organ involved, or uveitis may be part of a systemic disease. A significant number of cases are of unknown etiology and are labeled idiopathic. Animal models have been developed to the study of the physiopathogenesis of autoimmune uveitis due to the difficulty in obtaining human eye inflamed tissues for experiments. Most of those models are induced by injection of specific photoreceptors proteins (e.g., S-antigen, interpho- toreceptor retinoid-binding protein, rhodopsin, recoverin, phosducin). Non-retinal antigens, including melanin-associated proteins and myelin basic protein, are also good inducers of uveitis in animals. Understanding the basic mechanisms and pathogenesis of autoimmune ocular diseases are essential for the development of new treatment approaches and therapeutic agents. The present review describes the main experimental models of autoimmune ocular inflammatory diseases.

microglobulin was below 0.3 mg/L. Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare immunological disorder occuring in less than 2% of cases of uveitis. Diagnosis requires the pres- ence of both tubulointerstitial nephritis and uveitis. The most common signs and symptoms of uveitis include photophobia, eye pain and redness, eyelid edema and progressive loss of vision.

of low-density barium, but there are no results showing that these transit prolongations occur in old people as in young people. Although there was a superposition between the results of pharyngeal transit and clearance between the two age groups, the means of each one are different, raising the possibility that an increase in transit duration with the increase of barium density may happen in some younger subjects but not in older subjects. The aging process causes a progressive loss of pharyngeal and supraglottic sensitivity (1) , and loss of the swallowing relex (7, 23) , which

CASE฀REPORT:฀We฀describe฀a฀17-year-old฀male฀with฀ progressive฀ bilateral฀ visual฀ loss.฀ Two฀ maternal฀ uncles฀ had฀ had฀ similar฀ patterns฀ of฀ visual฀ loss.฀ The฀patient฀had฀a฀history฀of฀smoking฀and฀alcohol฀ abuse.฀ Neuro-ophthalmological฀ examination฀ revealed฀visual฀acuity฀of฀20/800฀in฀both฀eyes,฀ with฀decreased฀direct฀and฀consensual฀pupillary฀ light฀reflexes.฀Fundus฀examination฀demonstrated฀ pale฀optic฀discs.฀The฀visual฀evoked฀potential฀test฀ showed฀signs฀of฀conduction฀disturbances฀in฀both฀ optic฀ nerves฀ and฀ campimetric฀ study฀ showed฀ complete฀ visual฀ loss฀ in฀ all฀ fields฀ of฀ both฀ eyes.฀ A฀ diagnosis฀ of฀ bilateral฀ optic฀ neuropathy฀ with฀ a฀ clinical฀ suspicion฀ of฀ Leber’s฀ hereditary฀ optic฀ neuropathy฀ was฀ made.฀ A฀ blood฀ sample฀ was฀ submitted฀ to฀ genetic฀ analysis฀ in฀ relation฀ to฀ the฀ principal฀mutations฀of฀this฀disorder,฀and฀homo- plasmic฀mutation฀in฀11778฀was฀detected,฀thereby฀ confirming฀ the฀ diagnosis฀ of฀ Leber’s฀ hereditary฀ optic฀neuropathy.

Case report: A male patient, 39 years old, 71 kg, 1.72 m, ASA I, admitted to undergo fusion and discectomy at L4---L5 and L5---S1. Venoclysis, cardioscopy, oximetry, NIBP; induction with remifentanil, propofol and rocuronium; intubation with ETT (8.0 mm) followed by capnography and urinary catheterization for diuresis. Maintenance with full target-controlled intravenous anesthesia. During fixation and laminectomy, the patient developed severe bleeding and hypo- volemic shock. After 30 min, hemostasis and hemodynamic stability was achieved with infusion of norepinephrine, volume expansion, and blood products. In the ICU, the patient developed mental confusion, weakness in the limbs, and bilateral visual loss. It was not possible to iden- tify clinical, laboratory or image findings of organic lesion. He evolved with episodes of anxiety, emotional lability, and language impairment; the hypothesis of conversion syndrome with visual component was raised after psychiatric evaluation. The patient had complete resolution of symptoms after visual education and introduction of low doses of antipsychotic, antidepres- sant, and benzodiazepine. Other symptoms also regressed, and the patient was discharged 12 days after surgery. After 60 days, the patient had no more symptoms.

The Mozart mouse was identified in a mouse ENU mutagenesis program in which G3 offspring of ENU-mutagenised mice were screened for recessively inherited hearing loss. To identify the causative mutation in the Mozart mouse, genome-wide microsat- ellite marker analysis on DNA from 20 affected F2 mice was completed. The results showed linkage to D17Mit113 on chromosome 17 with a LOD score of 4.5. Fine mapping of 69 affected mice using amplifluor SNP assays narrowed the candidate region to a 2.1Mb interval between rs13482843 and rs13482851. The coding regions of all 8 known protein coding genes within this region were sequenced and the only change found was in the Synj2 gene. The causative mutation in Mozart is a T to A nucleotide change at nucleotide 1641 (c.1641T.A) in the Synj2 mRNA (Ensembl transcript ENSMUST00000061091). This results in a p.Asn538Lys (N538K) substitution (UniProtKB/Swiss-Prot data- base Q9D2G5) in the highly conserved catalytic 5-phosphatase domain of the enzyme (Fig. 1A and 1B). Previous studies have predicted that this Asn orientates a catalytic Asp by forming a hydrogen bond and mutation of this residue results in a complete loss in the ability of INPP5A to hydrolyze Ins(1,4,5)P 3 [21,22]. To

minance is more common in studies from developing countries. In studies from India was observed a male predominance higher than 60%, but the reasons for this are unclear and may involve exposure patterns in agricultural societies or differences in the propensity to seek medical care. In the other hand, uveitis disorders affect men and women differently, and to analyze gender discrepancies are un- doubtedly complex (11,17-21) .

Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies’ population and interventions.

Long-term follow-up noted recurrence of visual loss, final visual acuity, color plates, ophthalmoscopic appear- ance of the optic nerves, interval medical history and neu- rological examination to detect any symptom or sign of central nervous system involvement which could herald the development of MS. Cerebrospinal fluid (CSF) exami- nation, whenever available was analyzed in relation to number and types of cells, glucose and protein concen- tration, and protein electrophoresis. As the presence of oligoclonal bands in the CSF was not searched by isoelec- tric focusing electrophoresis it was not considered in the present study. Most patients did not have a brain MRI as this test was not available to them at the time of onset of the optic neuritis. When it was performed the presence of T2-weighted hyperintense areas in the optic nerves or brain white matter was noted.

Patients’ medical records were reviewed in order to collect data such as uveitis and other ocular complications (glaucoma, cataract, visual loss, eye surgery), arthritis and enthesitis and their respective sites of involvement, gastrointestinal (inflammatory bowel disease), cutaneous (psoriasis, erythema nodosum, pyoderma gangrenosum), or cardiovascular (aortitis, arrhythmias, valve insufficiency) involvement, and the type of treatment used by the patients.

he main reasons for loss to follow-up among our cohort were the lack of understanding of patients about the need for clinical care (71%) and health care access diiculties (14%). Sundus et al. 23 , investigated the causes for loss to follow-up of hepatitis patients at a liver center of a tertiary care hospital in Pakistan, a developing country, and found that 85% of patients did not adhere to follow-up for not understanding the importance of clinical follow-up, thus highlighting the importance of medical advice about this chronic infection and its implications so that patients receive the diagnosis and adhere to follow-up treatment. Health care access diiculties have been extensively described as a signiicant barrier to HCV treatment, which requires a specialized medical team and speciic laboratory and pharmaceutical structure 10,16,20 .