Photopsies: symptome souvent méconnu et apport de l'électrorétinographie [Photopsia: an often unrecognized symptom and sensitivity of electroretinography]

BACKGROUND: Photopsias are unformed luminous spontaneous visual hallucinations, often described as flickering or wiggling lights, sometimes like a glare. Phosphenes are more intense and of shorter duration whereas migraine fortifications have a specific time course and succession of events. Recognition of this symptom is often poor, hence patients are wrongly investigated. PURPOSE: To describe the clinical presentation and electroretinographic characteristics of patients with photopsias. METHODS: 4 patients were worked-up with clinical, psychophysical, angiographic and electroretinographic examinations. RESULTS: Despite normal fundus and angiographic examinations, full-field electroretinogram was diagnostic in all cases. Retinal dysfunction involved either inner or outer retina. Paraneoplastic, and probable autoimmune/inflammatory retinopathies were found in our cases. CONCLUSION: Photopsias are often secondary to sick retinal cells. In the presence of photopsias, investigations should be directed towards the retina and electroretinography is the gold standard. Recognition of the symptom should prevent useless and potentially harmful investigations for the patient.

Drainage of fluorescent liposomes from the vitreous to cervical lymph nodes via conjunctival lymphatics.

The use of liposomes as carriers for the delivery of biologically active molecules into the eye is of major interest. Indeed, encapsulation of biologically active molecules in liposomes may increase their bioavailability and may induce a sustained release, thus avoiding repeated intraocular injections and reducing side effects. We describe here the fate of rhodamine-conjugated liposomes (Rh-Lip) injected into the vitreous of normal Lewis rats. Twenty-four hours after intravitreal injection fluorescent liposomes were detected in the vitreous, the inner layer of the retina and to a lesser extent in the anterior segment of the eye. In addition, numerous Rh-Lip were also observed in the episclera and conjunctival stroma, in conjunctival lymphatic vessels and cervical lymph nodes (LN) draining the conjunctiva and the eye. In the LN, Rh-Lip were taken up by resident macrophages adjacent to CD4+ and CD8+ T cells. Thus, intravitreal injection of anti-inflammatory drugs loaded in liposomes could modulate the ocular immune microenvironment. In addition the passage of drugs into the cervical LN could alter the immune status of these LN and contribute to the regulation of intraocular inflammation. Our results suggest that this phenomenon should be taken into account to design new therapies based on intraocular drug administration.

Comparison of fundus autofluorescence images acquired by the confocal scanning laser ophthalmoscope (488 nm excitation) and the modified Topcon fundus camera (580 nm excitation).

To compare autofluorescence (AF) images obtained with the confocal scanning laser ophthalmoscope (using the Heidelberg retina angiograph; HRA) and the modified Topcon fundus camera, in a routine clinical setting. A prospective comparative study conducted at the Jules-Gonin Eye Hospital. Fifty-six patients from the medical retina clinic. All patients had complete ophthalmic slit-lamp and fundus examinations, colour and red-free fundus photography, AF imaging with both instruments, and fluorescein angiography. Cataract and fixation were graded clinically. AF patterns were analyzed for healthy and pathological features. Differences of image noise were analyzed by cataract grading and fixation. A total of 105 eyes were included. AF patterns discovered by the retina angiograph and the fundus camera images, respectively, were a dark optic disc in 72 % versus 15 %, a dark fovea in 92 % versus 4 %, sub- and intraretinal fluid visible as hyperautofluorescence on HRA images only, lipid exudates visible as hypoautofluorescence on HRA images only. The same autofluorescent pattern was found on both images for geographic atrophy, retinal pigment changes, drusen and haemorrhage. Image noise was significantly associated with the degree of cataract and/or poor fixation, favouring the fundus camera. Images acquired by the fundus camera before and after fluorescein angiography were identical. Fundus AF images differ according to the technical differences of the instruments used. Knowledge of these differences is important not only for correctly interpreting images, but also for selecting the most appropriate instrument for the clinical situation.

Eye screening for diabetics - prevents blindness

Diabetes is a common condition affecting around 69,000 people in Northern Ireland. One of the possible complications of diabetes is a condition called diabetic retinopathy, which can cause sight loss and blindness. Retinopathy causes damage to the tiny blood vessels (capillaries) that nourish the retina, the tissues in the back of the eye that deal with light. This can seriously affect vision.Research shows that if retinopathy is identified early, for example through retinal screening, and treated appropriately, blindness can be prevented in the majority of people with diabetes, both type 1 and type 2.Screening programmeIn Northern Ireland, a diabetic retinopathy screening programme (DRSP), run by the Public Health Agency, has been put in place to screen all eligible people with diabetes aged 12 years and over. Dr Bernadette Cullen, Consultant in Public Health Medicine, PHA, said: "Screening detects problems early and allows appropriate treatment to be offered. It is vital that everyone with diabetes attends diabetic retinopathy screening when it is offered. Early detection of potential problems offers a very real opportunity to intervene and, with appropriate treatment, can prevent blindness in the majority of those at risk."The screening testThe screening test involves photographs being taken of the back of each eye, using a special camera. The test is painless and takes about 15 minutes. If the person is over 50 years of age, they will need to have drops put in their eyes about 15 minutes before the test to dilate their pupils.The photographs are sent to the regional screening centre for analysis by trained graders. Results will show whether patients require further referral for assessment or treatment by hospital eye services (HES). If this is not required, screening will be offered again the following year.GPs are informed of all results and if the patient is under the care of a diabetologist, they too will be informed. Patients are informed of results by their GP and if they need an urgent referral, protocols are in place to ensure this happens.Many people with diabetes attend their optometrist (optician) on a regular basis to have a sight test for glasses. It is important they continue to do this - this test is free to people with diabetes. It is also vital that people with diabetes attend for diabetic retinopathy screening when invited, regardless of how or where their diabetes is treated, or whether they visit a hospital consultant/GP for their diabetic care.Patients are invited to screening via their GP practice. An information leaflet to help patients make an informed decision to attend for screening is also sent. This can be accessed via the PHA website: www.publichealth.hscni.net.

Meta-analysis based SVM classification enables accurate detection of Alzheimer's disease across different clinical centers using FDG-PET and MRI.

The application of support vector machine classification (SVM) to combined information from magnetic resonance imaging (MRI) and [F18]fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to improve detection and differentiation of Alzheimer's disease dementia (AD) and frontotemporal lobar degeneration. To validate this approach for the most frequent dementia syndrome AD, and to test its applicability to multicenter data, we randomly extracted FDG-PET and MRI data of 28 AD patients and 28 healthy control subjects from the database provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) and compared them to data of 21 patients with AD and 13 control subjects from our own Leipzig cohort. SVM classification using combined volume-of-interest information from FDG-PET and MRI based on comprehensive quantitative meta-analyses investigating dementia syndromes revealed a higher discrimination accuracy in comparison to single modality classification. For the ADNI dataset accuracy rates of up to 88% and for the Leipzig cohort of up to 100% were obtained. Classifiers trained on the ADNI data discriminated the Leipzig cohorts with an accuracy of 91%. In conclusion, our results suggest SVM classification based on quantitative meta-analyses of multicenter data as a valid method for individual AD diagnosis. Furthermore, combining imaging information from MRI and FDG-PET might substantially improve the accuracy of AD diagnosis.

Phenotype in Two Consanguineous Tunisian Families With non Syndromic Autosomic Recessive Retinitis Pigmentosa Caused by an USH2A Mutation

Purpose: To assess the clinical phenotype in two consanguineous Tunisian families with non syndromic autosomic recessive retinitis Pigmentosa (arRP) caused by an USH2A mutation.Methods: All accessible members of family A and B were included and underwent full ophthalmic examination with best corrected Snellen visual acuity, kinetic visual field testing, fundus photography, optical coherence tomography and full field electroretinography. Haplotype analyses were used to test linkage in the families to 20 arRP loci, including ABCA4, LRAT, USH2A, RP29, CERKL, CNGA1, CNGB1, CRB1, EYS, RP28, MERTK, NR2E3, PDE6A, PDE6B, RGR, RHO, RLBP1, TULP1. In addition, index patients were sent to AsperOphthalmics for arRP mutation screening.Results: Twenty three patients from the two families were ascertained for the study. Eight of the 23 members were clinically affected with arRP without hearing loss. Age range at baseline was 35 to 63 years (mean age was 46.5 years). For all affected members, night blindness appeared during the second decade. Visual acuity at baseline ranged from 20/50 to 20/32. Kinetic visual field was severely constricted. Fundus examination revealed typical RP changes with bone spicule-shaped pigment deposits in the mid periphery along with atrophy of the retina, narrowing of the vessels and waxy optic discs. Tomograms showed a thinning and even loss the outer nuclear layer of the fovea. ERG was unrecordable in scotopic conditions and the cone responses were markedly hypovolted. Haplotype analysis did not reveal any homozygosity. Screening at AsperOphthalmis showed a compound heterozygous [p.A1953G]+[p.I5126T] in family A and [p.G713R]+[p.W4149R] in family B.Conclusions: For these families, changes were typical of those that have been described in patients with moderate to severe forms of non syndromic recessive RP. Our findings support the need to consider possible involvement of USH2A not only in patients with Usher syndrome but also in patients with non syndromc arRP. Despite consanguinity, the presence of non-homozygous mutants illustrates the complexity of molecular analysis.

Incidence of presumed endophthalmitis after intravitreal injection performed in the operating room: a retrospective multicenter study.

PURPOSE: To evaluate the incidence of presumed endophthalmitis (EO) after intravitreal injection (IVI) of anti-vascular endothelial growth factor agents performed in the operating room. METHODS: Retrospective study at 2 Swiss eye hospitals between 2004 and 2012. Hospital records were used to identify patients treated with an IVI of an anti-vascular endothelial growth factor agent between 2004 and 2012 and those treated for EO, defined as any intraocular inflammation treated with intravitreal antibiotics. All IVIs were performed using standard sterile technique in a Swiss Class 1 operating room. No patient received preinjection topical antibiotics. Postinjection topical antibiotics were used only in one hospital. RESULTS: A total of 40,011 IVIs were performed at the 2 centers during the study period. Of the IVIs, ranibizumab was injected in 36,398 (91%), bevacizumab in 3,518 (9%), aflibercept in 89 (0.2%), and pegaptanib in 6 (<0.1%). Three cases of post-IVI presumed EO occurred, yielding a combined incidence of 0.0075% per injection (95% confidence interval: 0.0026-0.0220%) or 1 case per 13,337 IVIs. Two of the three cases of EO occurred in patients using post-IVI antibiotics. All three cases followed ranibizumab injection and were culture negative by anterior chamber tap or vitreous biopsy. CONCLUSION: The risk of EO after IVI performed under the sterile conditions of the operating room was very low.

Retinal dysfunction in combined methylmalonic aciduria and homocystinuria (Cblc) disease: a spectrum of disorders.

BACKGROUND: Cobalamin C methylmalonic aciduria with homocystinuria (cblC disease) is a rare hereditary inborn error of cobalamin metabolism, characterised by neurological, haematological and ophthalmological abnormalities. PATIENTS AND METHODS: Three consecutive patients with Cblc disease were examined. Investigations included slit lamp and fundus examination and full-field ERG. RESULTS: A maculopathy associated with both photopic and scotopic abnormal ERG was present in two cases and a salt and pepper retinopathy with abnormal photopic ERG was detected in the third patient. CONCLUSIONS: Despite early treatment and regular metabolic controls, all our patients exhibited both retinal and ERG abnormalities. There was no correlation between funduscopic appearance and the type of photoreceptor dysfunction. A literature review disclosed a retinopathy in 29 / 70 cases with cblC disease, with an abnormal ERG in 8 of the 12 tested cases, most with retinopathy. Retinal dysfunction in cblC disease may be more frequent than previously thought, and can involve cones only or both rods and cones. We recommend a formal ocular examination with full-field ERG in patients with Cblc disease.

Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta.

Cone-rod dystrophies are inherited dystrophies of the retina characterized by the accumulation of deposits mainly localized to the cone-rich macular region of the eye. Dystrophy can be limited to the retina or be part of a syndrome. Unlike nonsyndromic cone-rod dystrophies, syndromic cone-rod dystrophies are genetically heterogeneous with mutations in genes encoding structural, cell-adhesion, and transporter proteins. Using a genome-wide single-nucleotide polymorphism (SNP) haplotype analysis to fine map the locus and a gene-candidate approach, we identified homozygous mutations in the ancient conserved domain protein 4 gene (CNNM4) that either generate a truncated protein or occur in highly conserved regions of the protein. Given that CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis.

Ocular biocompatibility of a poly(ortho ester) characterized by autocatalyzed degradation.

The biocompatibility of autocatalyzed poly(ortho ester) (POE(70)LA(30)), a viscous, hydrophobic, bioerodible polymer, was investigated. POE(70)LA(30) was synthesized, sterilized by gamma irradiation, and injected in rabbit eyes at adequate volumes through subconjunctival, intracameral, intravitreal, and suprachoroidal routes. Clinical examinations were performed postoperatively at regular time points for 6 mo, and histopathologic analysis was carried out to confirm tissular biocompatibility. After subconjunctival injection, the polymer was well tolerated and persisted in the subconjunctival space for about 5 weeks. In the case of intracameral injections, polymer biocompatibility was good; the POE(70)LA(30) bubble was still present in the anterior chamber for up to 6 mo after injection. No major histopathologic anomalies were detected, with the exception of a localized Descemet membrane thickening. After intravitreal administration, POE(70)LA(30) biocompatibility was excellent, and no inflammatory reaction could be detected during the observation period. The polymer was degraded in approximately 3 mo. Suprachoroidal injections of POE(70)LA(30) were reproducible and well tolerated. POE(70)LA(30) triggered a slight elevation of the retina and choroid upon clinical observation. The polymer was detectable in the suprachoroidal space for about 6 mo. No inflammatory reaction and no major retinal anomalies could be detected by histology. In conclusion, POE(70)LA(30) appears to be a promising biomaterial for intraocular application, potentially providing sustained drug delivery over an extended period of time, with a good tolerance.

Acute retinal necrosis in primary herpes simplex virus type I infection.

Here we report the case of an immunocompetent 8-year-old child who developed acute retinal necrosis concomitant with a primary herpes simplex virus type I infection. Ocular inflammation changed along with the development of a specific antibody titer in the serum. This evidence suggests that the immune response of the host can significantly modulate the clinical aspect of the ocular infection.

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

Background: Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.Methods: We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis. Results: Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits. Conclusions: Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.

Treating ocular toxoplasmosis: current evidence

The current treatment of ocular toxoplasmosis is controversial. The mainstay of treatment has been pyrimethamine and sulphonamides with or without systemic corticosteroids, but the actual evidence that antibiotics have a beneficial effect in recurrent toxoplasmic retinochoroiditis is unsupported by randomised placebo controlled trials. Thus far there have only been three studies looking at the efficacy of antibiotic treatment, all of which were methodologically weak and two of which were perfomed more than 30 years ago. All studies reported adverse effects from treatment. There is an urgent need for further randomised, double blind, placebo controlled studies for lesions in all parts of the retina and to test the efficacy of adjunctive corticosteroid treatment.

Why prevent, diagnose and treat congenital toxoplasmosis?

Evidence that prevention, diagnosis and treatment of toxoplasmosis is beneficial developed as follows: anti-parasitic agents abrogate Toxoplasma gondiitachyzoite growth, preventing destruction of infected, cultured, mammalian cells and cure active infections in experimental animals, including primates. They treat active infections in persons who are immune-compromised, limit destruction of retina by replicating parasites and thereby treat ocular toxoplasmosis and treat active infection in the fetus and infant. Outcomes of untreated congenital toxoplasmosis include adverse ocular and neurologic sequelae described in different countries and decades. Better outcomes are associated with treatment of infected infants throughout their first year of life. Shorter intervals between diagnosis and treatment in utero improve outcomes. A French approach for diagnosis and treatment of congenital toxoplasmosis in the fetus and infant can prevent toxoplasmosis and limit adverse sequelae. In addition, new data demonstrate that this French approach results in favorable outcomes with some early gestation infections. A standardized approach to diagnosis and treatment during gestation has not yet been applied generally in the USA. Nonetheless, a small, similar experience confirms that this French approach is feasible, safe, and results in favorable outcomes in the National Collaborative Chicago-based Congenital Toxoplasmosis Study cohort. Prompt diagnosis, prevention and treatment reduce adverse sequelae of congenital toxoplasmosis.

Peripheral inflammation increases the damage in animal models of nigrostriatal dopaminergic neurodegeneration: possible implication in Parkinson's disease incidence.

Inflammatory processes described in Parkinson’s disease (PD) and its animal models appear to be important in the progression of the pathogenesis, or even a triggering factor. Here we review that peripheral inflammation enhances the degeneration of the nigrostriatal dopaminergic system induced by different insults; different peripheral inflammations have been used, such as IL-1β and the ulcerative colitis model, as well as insults to the dopaminergic system such as 6-hydroxydopamine or lipopolysaccharide. In all cases, an increased loss of dopaminergic neurons was described; inflammation in the substantia nigra increased, displaying a great activation of microglia along with an increase in the production of cytokines such as IL-1β and TNF-α. Increased permeability or disruption of the BBB, with overexpression of the ICAM-1 adhesion molecule and infiltration of circulating monocytes into the substantia nigra, is also involved, since the depletion of circulating monocytes prevents the effects of peripheral inflammation. Data are reviewed in relation to epidemiological studies of PD.