Visual function in human ocular toxoplasmosis

AIM: To assess functional impairment in terms of visual acuity reduction and visual field defects in inactive ocular toxoplasmosis. METHODS: 61 patients with known ocular toxoplasmosis in a quiescent state were included in this prospective, cross-sectional study. A complete ophthalmic examination, retinal photodocumentation and standard automated perimetry (Octopus perimeter, program G2) were performed. Visual acuity was classified on the basis of the World Health Organization definition of visual impairment and blindness: normal (> or =20/25), mild (20/25 to 20/60), moderate (20/60 to 20/400) and severe (<20/400). Visual field damage was correspondingly graded as mild (mean defect <4 dB), moderate (mean defect 4-12 dB) or severe (mean defect >12 dB). RESULTS: 8 (13%) patients presented with bilateral ocular toxoplasmosis. Thus, a total of 69 eyes was evaluated. Visual field damage was encountered in 65 (94%) eyes, whereas only 28 (41%) eyes had reduced visual acuity, showing perimetric findings to be more sensitive in detecting chorioretinal damage (p<0.001). Correlation with the clinical localisation of chorioretinal scars was better for visual field (in 70% of the instances) than for visual acuity (33%). Moderate to severe functional impairment was registered in 65.2% for visual field, and in 27.5% for visual acuity. CONCLUSION: In its quiescent stage, ocular toxoplasmosis was associated with permanent visual field defects in >94% of the eyes studied. Hence, standard automated perimetry may better reflect the functional damage encountered by ocular toxoplasmosis than visual acuity.

Decreased visual function after patchy loss of retinal pigment epithelium induced by low-dose sodium iodate

PURPOSE: To correlate damage to the retinal pigment epithelium (RPE) with decreased visual function after the systemic administration of sodium iodate (NaIO(3)). METHODS: Damage was produced in mice by injection of 15, 25, or 35 mg/kg NaIO(3). Visual function was assessed with the cued water maze (WM) behavioral test and the optokinetic reflex (OKR) measurement at different times after injection. Autofluorescence in whole eye flatmounts was quantified, and hematoxylin and eosin staining of paraffin sections was performed to assess changes in the outer retina. RESULTS: After 15 mg/kg NaIO(3), cued WM test results were normal, whereas OKR measurements were significantly decreased at all times. Focal RPE loss began on day 21, but no significant damage to the outer nuclear layer was observed. After 25 mg/kg NaIO(3), the cued WM test was transitionally reduced and the OKR measurement again decreased at all times. Large areas of RPE loss occurred on day 14 with a reduced outer nuclear layer on the same day. With 35 mg/kg NaIO(3), the cued WM test was reduced beginning on day 14 with complete obliteration of the OKR beginning on day 3, large areas of RPE loss on the same day, and a reduced outer nuclear layer on day 7. CONCLUSIONS: Stable, patchy RPE loss was observed with a low concentration of NaIO(3). The OKR measurement showed changes in visual function earlier than the cued WM test and before histologic findings were observed.

Intrarenal resistance index for the assessment of early renal function impairment in patients with liver cirrhosis

BACKGROUND: Renovascular vasoconstriction in patients with hepatorenal syndrome can be quantified by the renal arterial resistance index (RI). We investigated the value of RI measurement in detection of renal function impairment in patients with different stages of chronic liver disease. METHODS: Subjects were divided into 4 groups containing 21 patients with liver cirrhosis and ascites, 25 patients with liver cirrhosis without ascites, 35 patients with fatty liver disease and 78 control subjects. All patients underwent abdominal ultrasound examination with renal RI measurement and correlation with laboratory results for renal function. RESULTS: RI was significantly higher in ascitic patients compared to non-ascitic patients (0.74 vs. 0.67, p<0.01) and in non-ascitic patients with liver cirrhosis than in control subjects (0.67 vs. 0.62, p<0.01). 48% (19/40) of patients with liver cirrhosis and normal serum creatinine concentration showed elevated RI levels. There were no significant differences in RI levels between patients with fatty liver disease and controls (0.63 vs. 0.62). CONCLUSIONS: Intrarenal RI measurement is a predictor of renal vasoconstriction and serves to detect early renal function impairment in cirrhotic patients. The diagnosis of elevated RI may be taken into account in the clinical management of these patients.

Specific attentional impairments and complex visual hallucinations in eye disease

OBJECTIVE: To test the prediction by the Perception and Attention Deficit (PAD) model of complex visual hallucinations that cognitive impairment, specifically in visual attention, is a key risk factor for complex hallucinations in eye disease. METHODS: Two studies of elderly patients with acquired eye disease investigated the relationship between complex visual hallucinations (CVH) and impairments in general cognition and verbal attention (Study 1) and between CVH, selective visual attention and visual object perception (Study 2). The North East Visual Hallucinations Inventory was used to classify CVH. RESULTS: In Study 1, there was no relationship between CVH (n=10/39) and performance on cognitive screening or verbal attention tasks. In Study 2, participants with CVH (n=11/31) showed poorer performance on a modified Stroop task (p<0.05), a novel imagery-based attentional task (p<0.05) and picture (p<0.05) but not silhouette naming (p=0.13) tasks. Performance on these tasks correctly classified 83% of the participants as hallucinators or non-hallucinators. CONCLUSIONS: The results suggest that, consistent with the PAD model, complex visual hallucinations in people with acquired eye disease are associated with visual attention impairment.

Long-term impact of treated congenital toxoplasmosis on quality of life and visual performance

Background: Long-term evolution of congenital toxoplasmosis is not documented. We assessed the outcome of treated congenital toxoplasmosis in a cohort of adult individuals who had undergone ante- and postnatal treatment to provide information for pediatricians and parents on the evolution of the disease. Methods: We conducted a questionnaire study on 126 adults with congenital toxoplasmosis (mean age: 22.2 years; age range: 18–31 years) monitored regularly until the time of inclusion. The main outcome measures were quality of life (Psychological General Well-Being Index) and visual function (VF14 questionnaire), and the outcomes were correlated with disease-specific factors. Results: Of the 102 patients (80.9%) who were finally included in the study, 12 (11.8%) presented neurologic effects and 60 (58.8%) manifested ocular lesions; in the latter category, 13 individuals (12.7%) had reduced visual function. The overall global quality-of-life score (74.7 ± 14.2) was close to the expected normal range for the general population (73.7 ± 15.3). Overall, visual function was only slightly impaired (M = 97.3; 95% confidence interval, 95.8–98.8). Although disease-independent critical life circumstances were associated with a reduced Psychological General Well-Being Index, this index was not influenced by any of the clinical characteristics of congenital toxoplasmosis. Neurologic pathologies, reduced visual acuity, foveal location of the retinal lesion, and squinting contributed to decreased visual function at follow-up. Conclusions: Our data reveal that treated congenital toxoplasmosis has little effect on the quality of life and visual function of the affected individuals. These encouraging findings may help to alleviate the anxiety of affected individuals and their parents.

Ocular manifestations in congenital toxoplasmosis

BACKGROUND: Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. The aim of this study was to determine the nature of the latter in treated cases of the disease and to assess their impact on visual function. METHODS: Four hundred and thirty consecutive children with serologically confirmed congenital toxoplasmosis were included in this study. Data were prospectively collected using standardized ophthalmological assessment forms. The presence of retinochoroiditis and of associated pathologies was ascertained, and their impact on visual function was assessed. RESULTS: After a median follow-up of 12 years [range 0.6-26 years], 130 children manifested retinochoroiditis. We detected 22 foci of retinochoroiditis at birth and 264 additional ones during the follow-up period. Of these, 48 (17%) were active when first diagnosed. Twenty-five of the 130 children (19%) had other associated ocular pathologies. Of these, 21 (16%) had a strabismus, which was due to macular lesions in 86% of the cases; 7 (5.4%) presented with unilateral microphthalmia, and 4 (3%) with cataracts. Most of these events were detected after the onset of retinochoroiditis. None of the children presented with ocular involvement in the absence of chorioretinal lesions. Macular lesions occurred more frequently in children with associated pathologies (p<0.0001), and associated pathologies were likewise more common in individuals with macular lesions (p=0.0003). Visual impairment occurred in 31/130 cases, and in all but 3 of these eyes it was due not to an associated pathology but to macular retinochoroiditis. CONCLUSIONS: At the end of the follow-up period, ocular involvement existed in 30% of the treated children with congenital toxoplasmosis. Associated eye pathologies were manifested less frequently than anticipated. They may occur later in life and are an indirect marker of the severity of congenital toxoplasmosis, but they do not have a direct impact on visual acuity. The overall functional prognosis of congenital toxoplasmosis is better than would be expected on the basis of literature findings, with only 2 of the 130 children suffering bilateral visual impairment.

Recovery of visual field and acuity after removal of epiretinal and inner limiting membranes

BACKGROUND: Visual acuity serves as only a rough gauge of macular function. The aim therefore was to ascertain whether central an assessment of the central visual field afforded a closer insight into visual function after removal of epiretinal membranes and Infracyanine-Green- or Trypan-Blue-assisted peeling of the inner limiting membrane. Patients and methods: Fourty-three patients undergoing pars-plana vitrectomy for the removal of epimacular membranes and dye-assisted peeling of the inner limiting membrane using either Infracyanine Green (n = 29; group 1) or Trypan Blue (n = 14; group 2) were monitored prospectively for 12 months. Preoperatively, and 1, 6 and 12 months postoperatively, distance and reading visual acuities were evaluated; the central visual field was assessed by automated static perimetry. RESULTS: Twelve months after surgery, distance and reading visual acuities had improved in both groups, but to a significant degree only in Trypan-Blue-treated eyes. The difference between the two groups was not significant. Likewise at this juncture, the mean size of the visual-field defect remained unchanged in Trypan-Blue-treated eyes (preoperative: 4.3 (SD 2.1) dB; 12 months: 4.0 (2.1) dB (p = 0.15)), but had increased in Infracyanine-Green-treated ones (from 5.3 (3.7) dB to 8.0 (5.2) dB (p = 0.027)). CONCLUSION: Unlike visual acuity, the central visual field had deteriorated in Infracyanine-Green-treated eyes but not in Trypan-Blue-treated eyes 12 months after surgery. Hence, as a predictor of functional outcome, testing of the central visual field may be a more sensitive gauge than visual acuity. Furthermore, Infracyanine Green may have a chronic and potentially clinically relevant effect on the macula which is not reflected in the visual acuity.

The Neuroscience of Visual Hallucinations

Each year, some two million people in the United Kingdom experience visual hallucinations. Infrequent, fleeting visual hallucinations, often around sleep, are a usual feature of life. In contrast, consistent, frequent, persistent hallucinations during waking are strongly associated with clinical disorders; in particular delirium, eye disease, psychosis, and dementia. Research interest in these disorders has driven a rapid expansion in investigatory techniques, new evidence, and explanatory models. In parallel, a move to generative models of normal visual function has resolved the theoretical tension between veridical and hallucinatory perceptions. From initial fragmented areas of investigation, the field has become increasingly coherent over the last decade. Controversies and gaps remain, but for the first time the shapes of possible unifying models are becoming clear, along with the techniques for testing these. This book provides a comprehensive survey of the neuroscience of visual hallucinations and the clinical techniques for testing these. It brings together the very latest evidence from cognitive neuropsychology, neuroimaging, neuropathology, and neuropharmacology, placing this within current models of visual perception. Leading researchers from a range of clinical and basic science areas describe visual hallucinations in their historical and scientific context, combining introductory information with up-to-date discoveries. They discuss results from the main investigatory techniques applied in a range of clinical disorders. The final section outlines future research directions investigating the potential for new understandings of veridical and hallucinatory perceptions, and for treatments of problematic hallucinations. Fully comprehensive, this is an essential reference for clinicians in the fields of the psychology and psychiatry of hallucinations, as well as for researchers in departments, research institutes and libraries. It has strong foundations in neuroscience, cognitive science, optometry, psychiatry, psychology, clinical medicine, and philosophy. With its lucid explanation and many illustrations, it is a clear resource for educators and advanced undergraduate and graduate students.

Risk factors for depressed mood amongst a community dwelling older age population in England: cross-sectional survey data from the PRO-AGE study.

BACKGROUND The Quality and Outcomes Framework in the United Kingdom (UK) National Health Service previously highlighted case finding of depression amongst patients with diabetes or coronary heart disease. However, depression in older people remains under-recognized. Comprehensive data for analyses of the association of depression in older age with other health and functional measures, and demographic factors from community populations within England, are lacking. METHODS Secondary analyses of cross-sectional baseline survey data from the England arm of a randomised controlled trial of health risk appraisal for older people in Europe; PRO-AGE study. Data from 1085 community-dwelling non-disabled people aged 65 years or more from three group practices in suburban London contributed to this study. Depressed mood was ascertained from the 5-item Mental Health Inventory Screening test. Exploratory multivariable logistic regression was used to identify the strongest associations of depressed mood with a previous diagnosis of a specified physical/mental health condition, health and functional measures, and demographic factors. RESULTS Depressed mood occurred in 14% (155/1085) of participants. A previous diagnoses of depression (OR 3.39; P < 0.001) and poor vision as determined from a Visual Function Questionnaire (OR 2.37; P = 0.001) were amongst the strongest factors associated with depressed mood that were independent of functional impairment, other co-morbidities, and demographic factors. A subgroup analyses on those without a previous diagnosis of depression also indicated that within this group, poor vision (OR 2.51; P = 0.002) was amongst the strongest independent factors associated with depressed mood. CONCLUSIONS Previous case-finding strategies in primary care focussed on heart disease and diabetes but health-related conditions other than coronary heart disease and diabetes are also associated with an increased risk for depression. Complex issues of multi-morbidity occur within aging populations. 'Risk' factors that appeared stronger than those, such as, diabetes and coronary heart disease that until recently prompted for screening in the UK due to the QOF, were identified, and independent of other morbidities associated with depressed mood. From the health and functional factors investigated, amongst the strongest factors associated with depressed mood was poor vision. Consideration to case finding for depressed mood among older people with visual impairment might be justified.

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

Stem cell-based therapeutic applications in retinal degenerative diseases

Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinal degeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus on stem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease.

Retinitis and optic neuritis in a child with chickenpox: case report and review of literature

In immunocompetent individuals, necrotizing retinopathy is a rare complication of chickenpox. Herein, we report on a 3-year-old immunocompetent boy who developed retinitis and optic neuritis 3 days after the onset of chickenpox and compare the findings to published cases. Since macula and optic nerve were affected, visual acuity remained poor. An early diagnosis and treatment of ocular manifestations in chickenpox is imperative for the preservation of a residual visual function and prevention of blinding secondary complications.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function.

Vitrectomy for juvenile uveitis: prognostic factors for the long-term functional outcome

PURPOSE: This study evaluated the long-term effect of pars plana vitrectomy (PPV) in children and adolescents with chronic uveitis on visual function, anatomical outcome, and the requirement of systemic treatment. Further, predictive preoperative factors associated with a beneficial visual outcome were assessed. METHODS: Retrospective review of 29 eyes of 23 consecutive paediatric and juvenile patients below 20 years of age with chronic uveitis who underwent a PPV for visually significant opacities in 25 eyes, vitreous haemorrhage in three eyes, and retinal detachment in one eye. The clinical diagnosis was chronic intermediate uveitis in 22 eyes and retinal vasculitis of different origin in seven eyes. RESULTS: LogMAR visual acuity improved from an average of 0.91 to 0.33 (P<0.001). Cystoid macular oedema (CME) was significantly reduced in eight of 10 eyes postoperatively (P=0.021). In the multiple regression analysis, a low preoperative logMAR visual acuity and the presence of a CME had a negative influence on the final logMAR visual acuity. Furthermore, the appearance of chronic uveitis relapses was significantly reduced from 15 eyes before to seven eyes after surgery (P=0.042). CONCLUSIONS: PPV has a beneficial effect on the course and the complications of chronic uveitis in paediatric and juvenile patients with respect to the anatomical and visual outcome. Preoperative logMAR visual acuity and clinically significant CME were the most accurate predictors for the functional outcome.

Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration

We characterized changes in the visual behavior of mice in which a loss of the retinal pigment epithelium (RPE) was experimentally induced with intravenous (i.v.) administration of sodium iodate (NaIO3). We compared and correlated these changes with alterations in neural retinal structure and function. RPE loss was induced in 4-6 week old male C57BL/6 mice with an i.v. injection of 1% NaIO3 at three concentrations: 35, 50, or 70 mg/kg. At 1, 3, 7, 14, 21, and 28 days (d) as well as 6 months post injection (PI) a behavioral test was performed in previously trained mice to evaluate visual function. Eye morphology was then assessed for changes in both the RPE and neural retina. NaIO3-induced RPE degeneration was both dose and PI time dependent. Our low dose showed no effects, while our high dose caused the most damage, as did longer PI times at our intermediate dose. Using the intermediate dose, no changes were detectable in either visual behavior or retinal morphology at 1 d PI. However, at 3 d PI visual behavior became abnormal and patchy RPE cell loss was observed. From 7 d PI onward, changes in retinal morphology and visual behavior became more severe. At 6 months PI, no recovery was seen in any of these measures in mice administered the intermediate dose. These results show that NaIO3 dosage and/or time PI can be varied to produce different, yet permanent deficits in retinal morphology and visual function. Thus, this approach should provide a unique system in which the onset and severity of RPE damage, and its consequences can be manipulated. As such, it should be useful in the assessment of rescue or mitigating effects of retinal or stem cell transplantation on visual function.