[The visual snow phenomenon.] / Le phénomène de neige visuelle.

INTRODUCTION: Visual snow is a symptom described by some patients and poorly recognized by ophthalmologists. It consists in the permanent perception of a textured or a snowy vision, sometimes associated with palinopsia, exaggerated perception of the blue field entoptic phenomenon and photophobia. We report a group of patients suffering from visual snow in order to precise its characteristics and discuss its pathophysiology. MATERIALS AND METHODS: Prospective study of patients diagnosed between September 2010 and December 2012 with a visual snow phenomenon. For each patient, a formal ophthalmologic examination, an Amsler grid test, an automated visual field (central 20°), a color vision test (15 Hue), a full field, a pattern and a multifocal electroretinogram as well as flash and pattern visual evoked potentials (Métrovision©) were performed. A brain imaging was not systematically performed. RESULTS: Twelve patients aged 9-48old were included (six men and six women, 85 % of students). Several signs were variably associated with the visual snow phenomenon: palinopsia (50 %), constant blue field entoptic phenomenon (40 %), photophobia (30 %), migraine (30 %); in 20 % of cases, an initial toxic intake was found (20 %). DISCUSSION: This study highlights the reproducibility of typical symptoms described by patients reporting the visual snow phenomenon. This feature strongly supports the organic origin of the phenomenon. The pathophysiology of this phenomenon, however, remains unclear; the hypothesis of a lower threshold for perception of entoptic images cannot entirely account for the reported symptoms.

[Critical review of the new recommendations on screening for hydroxychloroquine retinopathy]. / Lecture critique des nouvelles recommandations américaines sur le suivi ophtalmologique des patients traités par hydroxychloroquine (Plaquénil®).

New recommendations for screening of hydroxychloroquine retinopathy, updating those of 2002, have been recently published by the American Academy of Ophthalmology. These recommendations have been necessary because of new knowledge about the prevalence of toxicity and because of improved screening tools. Amsler grid testing, color vision testing, fluorescein angiography, full-field electroretinogram, and electro-oculogram are no longer recommended. It is now recommended to perform fundus examinations with 10-2 automated fields, and whenever possible, at least one objective test including multifocal electroretinogram, fundus autofluorescence or spectral domain optical coherence tomography (SD-OCT). A baseline examination is advised as a reference and then, annual screening should be initiated no later than 5 years after starting hydroxychloroquine therapy.

[Ophthalmological monitoring protocol for patients treated with long-term antimalarials or vigabatrin]. / Protocole de surveillance ophtalmologique des patients traités par antipaludéens de synthèse ou par vigabatrin au long cours.

Treatment with the antimalarials chloroquine or hydroxychloroquine rarely causes retinopathy. Chloroquine and hydroxychloroquine toxicity are untreatable and can progress to legal blindness. Since 1957, there has been a consensus on the need to monitor patients on long-term chloroquine or hydroxychloroquine therapy. Currently, the procedure for follow-up includes collection of patient information, complete ophthalmological exam with automated central perimetry, and retinal electrophysiology. Screening should take place before treatment or no more than 6 months after initiation of antimalarial therapy. During treatment, monitoring relative to the baseline should be at a frequency determined by whether there are risk factors for development of toxicity, such as a cumulative dose greater than 1.8 kg, a daily dose greater than 6.5mg of hydroxychloroquine/kg/day, concurrent or past ophthalmological diseases, hepatic or renal insufficiency, age older than 65 years, and chloroquine intake. Retinopathy can occur in the absence of risk factors. The risk/benefit ratio favors therapy despite the time and expense of screening. Vigabatrin (VGB) is an effective drug for treatment of epilepsy and has been used in the treatment of West syndrome and epilepsy resistant to other drugs. VGB treatment improves quality of life, but it can induce characteristic bilateral nasal visual field defects and changes in retinal electrophysiology. Currently, the recommended procedure is to screen these patients before treatment, if possible, with a complete ophthalmological exam including perimetry and retinal electrophysiology every 6 months. It may be necessary to rely on retinal electrophysiology since some patients may not be able to undergo perimetry. The risk/benefit ratio sill clearly favors VGB treatment. Patients whose seizure incidence is reduced and have only minimal visual changes could continue VGB with strict monitoring. The others must discontinue VGB.

Ocular motility and Wilson's disease: a study on 34 patients.

BACKGROUND: Wilson's disease is an autosomal recessive genetic disorder resulting from an abnormality of copper metabolism. The excessive accumulation of copper in the brain induces an extrapyramidal syndrome. Oculomotor abnormalities occur in most extrapyramidal disorders but have rarely been studied in Wilson's disease. OBJECTIVE: To evaluate the ocular motility manifestations of Wilson's disease. METHODS: A prospective study of 34 patients affected by Wilson's disease who were recruited and their ocular motility recorded by electro-oculography (EOG). RESULTS: Vertical smooth pursuit was abnormal in 29 patients (85%). Vertical optokinetic nystagmus and horizontal smooth pursuit were impaired in 41% and 41% of patients, respectively. No MRI abnormality was found in the lenticular nuclei of seven patients who manifested ocular motility abnormalities. CONCLUSION: Vertical eye movements, in particular vertical pursuits, are impaired in Wilson's disease, more often than vertical optokinetic nystagmus and vertical saccades. EOG abnormalities can be found in patients who do not yet exhibit anatomical lesions on MRI.

[Severe chloroquine- and hydroxychloroquine-induced retinopathy]. / Intoxication rétinienne sévère aux anti-paludéens de synthèse.

INTRODUCTION: Antimalarial drug-induced retinopathy was first described in the 1950s. Irreversible retinal damage still occurs 50 years later, despite knowledge of the phenomenon. This raises several questions: How aware are physicians of this problem and do they inform their patients? What efficient prevention strategies should be advocated and what are the legal aspects? We present four cases of severe chloroquine- and hydroxychloroquine-induced retinopathy to try to understand what led to these situations. CASE REPORTS: The fist case, a male patient born in 1956, had chloroquine therapy for lupus initiated in 1987, at a dose ranging from 3 to 6 mg/kg per day. In 1992, no toxicity was clinically or electrophysiologically noted. In 1997, macular abnormalities were diagnosed; chloroquine treatment was nevertheless continued. In 2002, the electroretinogram and central visual field examinations were abnormal. Chloroquine treatment was discontinued. In 2005, abnormalities of full-field and multifocal electroretinograms, electro-oculogram, color vision, and visual field confirmed the maculopathy. The second case, a female patient, born in 1956, had chloroquine therapy for rheumatoid arthritis beginning in 1993, at a dose of 5 mg/kg per day. In 1999, 2000, and 2001, electroretinograms were reported as normal. Clinical maculopathy occurred in 2003 and treatment was continued. In January 2004, the central visual field was found abnormal; treatment was discontinued in July 2004. The third case, a female patient born in 1931, had chloroquine therapy for malaria prevention initiated in 1975, at a dose of 1.7 mg/kg per day. No exams were performed after 1983. In 2001, she complained of a left unilateral vision loss. Bilateral maculopathy was clinically found, and confirmed by full-field and multifocal electroretinograms. The fourth case, a female patient born in 1944, had hydroxychloroquine therapy for lupus initiated in 1982 at a dose of 6.9 mg/kg per day. In 2000 and 2002, full-field electroretinograms were reported as normal despite low amplitudes. In 2004, clinical examination was normal, whereas electroretinogram, electro-oculogram, color vision, and central visual field examinations proved severe damage; the treatment was discontinued. DISCUSSION: Retinal damage in these cases was caused by several factors. Treatment was not stopped despite clinically obvious maculopathy in cases 1 and 2. In case 3, no ophthalmologic examinations were performed between 1983 and 2001. In case 4, despite a high cumulative dose, therapy was not discontinued, as also seen in cases 1 and 2, in which ophthalmologic monitoring was not increased. Higher doses than the maximal recommended daily dose occurred in cases 1, 2, and 4. CONCLUSION: Antimalarial drug therapy still requires intensive monitoring to avoid severe retinal damage that can lead to legal blindness. Appropriate examinations should be performed regularly in order to decide whether to taper or stop when damage is still mild, preclinical, or reversible.

Kearns Sayre syndrome: an unusual form of mitochondrial diabetes.

Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by the emergence before age 20 of progressive external ophthalmoplegia, pigmentary retinopathy, together with other heterogeneous clinical manifestations, including cardiac conduction defects, muscle abnormalities and endocrinopathies. KSS is associated with large heteroplasmic deletions in mitochondrial DNA. We report the case of a 43-year-old woman, with diabetes mellitus as a first manifestation at age 19. Later, she exhibited bilateral ptosis and external ophthalmoplegia with progressive worsening. DNA analysis identified a large mitochondrial DNA (mtDNA) deletion, which confirmed the diagnosis of KSS. By reporting this case with diabetes mellitus as first manifestation, we aim at emphasizing problems of diagnosis in these subtypes of mitochondrial diabetes.

[Ophthalmologic prevention of chloroquine and hydroxychloroquine induced retinopathy]. / Prévention ophtalmologique de l'intoxication rétinienne induite par les antipaludéens de synthèse.

INTRODUCTION: Antimalarial drugs induce severe retinal toxicity. The aims of this study were to evaluate the strategy of screening clinical and preclinical intoxication due to antimalarial agents in two centres of reference and to describe the results of ophthalmologic examination. PATIENTS AND METHODS: Patients referred for ophthalmologic evaluation in connection with antimalarial agents therapy in the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts from October 1999 to December 2000 and in the Hôpital Lariboisière from January 1995 to December 1998 were investigated. A retrospective review of results of ophthalmologic examination, electroretinogram, electro-oculogram, colour vision test and central visual field was conducted to assess retinal intoxication. RESULTS: Among 705 patients recruited in the Centre des Quinze-Vingts, 10 out of 133 who were never treated had an electrophysiological contra-indication to the treatment. Among the 572 other patients, 31 presented with preclinical intoxication (5.4 p. 100) and 8 other patients presented with clinical intoxication. Among 925 patients recruited in the Hôpital Lariboisière, 37 presented with preclinical intoxication (4 p. 100) and four patients presented with clinical intoxication. DISCUSSION: The antimalarial drugs clinical intoxication is rare but nevertheless real. Screening for preclinical intoxication can prevent the evolution toward irreversible retinal intoxication. Diagnosis of preclinical intoxication is established through the confrontation of results of different tests and their evolution. The multifocal electroretinogram remains to be evaluated. CONCLUSION: Ophthalmologic monitoring including funduscopy, should be recommended at least once a year. Visual field seems to become interesting in the screening. Electroretinogram and electro-oculogram remain useful quantitative and obvious tests. A prospective study to assess the optimal way to prevent retinal intoxication is mandatory.

[Electroretinogram "b" wave varies with the posology of the antimalarial treatment]. / Influence de la variation de la posologie d'hydroxychloroquine (Plaquénil) sur l'électrorétinogramme.

INTRODUCTION: The electroretinogram (ERG) is currently, together with the central visual field test, color vision test and electroculogram (EOG), an examination dedicated to prevent retinopathy due to hydroxychloroquine (HCQ) or chloroquine (CQ) intoxication. MATERIAL AND METHODS: Thirty-two patients on treatment with HCQ were studied. Each patient had underwent a complete clinical ophthalmological examination and a set of paraclinical examinations including at least an ERG. All the patients were requested to decrease or stop their HCQ treatment. Following this change, a second ERG was recorded for each patient. The ERGs before and after stopping HCQ treatment were compared. We noted a statistically significant increase in the amplitude of "b" wave of the ERG, following after decrease or discontinuation of HCQ treatment. DISCUSSION AND CONCLUSION: This study has demonstrated the ERG "b" wave sensitivity due to the variation of HCQ consumption. The amplitude and the culmination time of the ERG "b" wave are important parameters to monitor during long term treatment with HCQ. A decrease of the "b" wave amplitude, coupled with an increase of its culmination time in a patient on long term HCQ treatment showing for the same daily dose, shall be a sign of alert, imposing the performance of additional visual functional tests and leading a decrease or a discontinuation of the treatment with HCQ. The ERG is an objective examination, which needs almost no participation from the patient. Its usefulness has been demonstrated, for the prevention of retinopathy due to hydroxychloroquine or chloroquine intoxication in condition that successive ERGs of the same patient are precisely compared.

[Analysis of 925 patients on long-term hydroxychloroquine or chloroquine treatment: results of ophthalmological screening]. / Surveillance ophtalmologique des patients sous APS au long cours: analyse d'une population de 925 patients.

PURPOSE: The aim of this 4-Year study was to analyze the population referred to our laboratory for the visual follow-up of hydroxychloroquine or chloroquine treatment. MATERIAL AND METHODS: We received 925 patients: 78% female, 22% male. For each patient, a 13-item criteria was filled out and regular exams were performed. The pathologies were divided in to 4 groups: rheumatoid polyarthritis (P), lupus (L), sarcoidosis (S), others (O). RESULTS: The pathologies were distributed as follows: 48% "P", 29% "L", 3% "S", 1% "P + L", 19% "O". Of these patients, 19% had less than 1 Year of treatment, 73% 1-10 Years and 8% more than 10 Years. The screening exposed no retinal intoxications but 3% presented pre-clinical intoxication (PCI) and 80% were allowed to continue their treatment. The most important statistical results were: 1) a significant relation between the PCI and the duration of the treatment (p<0.001); 2) a non-significant relation between the PCI and the daily dose (p=0.417); and 3) a significant relation between PCI and the cumulative dose (p=0.003). CONCLUSION: The results shows the advantage of the ERG in screening to prevent anti-malarial retinal toxicity. This study confirms that the cumulative dose seems to be more important than the daily dose, but we agree with the international consensus to respect a daily dose under 6.5 mg/kg/d. The results also demonstrated that, with this large and diversified population, there is a need for prospective and multi-centric studies. With the above results, international standards should be established in order to obtain the most efficient screening for each category of patient.

[Retinopathy caused by interferon alpha associated with ribavirin therapy and the importance of the electro-oculogram: a case report]. / Rétinopathie à l'interféron-alpha associé à la ribavirine: atteinte de l'électro-oculogramme. A propos d'un cas.

AIM: Ophthalmological complications with interferon alpha (INF-alpha) have been described since 1992: toxic retinopathy with cotton-wool spots, retinal hemorrhages, visual evoked potential (VEP) modifications and visual field abnormalities. MATERIAL AND METHOD: In 2002, a 44-year-old woman was referred complaining of visual problems. In 1986, she had been diagnosed with chronic hepatitis C and underwent INF-alpha therapy for 6 months with no ophthalmological symptoms. In 2001, she began a second course of INF-alpha therapy along with ribavirin. After 5 months, in February 2002, she developed hypothyroidism induced by INF, received levothyroxine and her treatment for the hepatitis C was stopped. One month later, in March, she complained of visual difficulties in dim light. Clinical ophthalmological examination and Goldmann visual field testing, electroretinogram (ERG) and visual evoked potentials (VEP) were normal but the electro-oculogram (EOG) showed that the light-peak-to-dark-trough ratios were very low: 148% in the right eye, 156% in the left eye. The fluorescein angiography was normal. The patient was followed up 4 months later, in June 2002 (after 5 months without INF-alpha therapy), showing a slight improvement of the EOG and no visual symptoms. Two other follow-up examinations were done in September 2002 and January 2003: the slight improvement persisted but the EOGs remain below the normal range values. DISCUSSION AND CONCLUSION: A review of the literature brought out that an EOG is not usually done in the monitoring of patients taking INF-alpha, but we decided to do this examination because of her symptoms, the first case to our knowledge in a patient taking INF-alpha. This case report underlines the necessity of an EOG on patients with INF-alpha therapy. Until now, the pathogenesis of this retinal toxicity has been poorly understood. These results show that the retinal pigmented epithelium is probably implicated at an early stage in this retinal toxicity.

[Up-dated ophthalmological screening and follow-up management for long-term antimalarial treatment]. / Surveillance ophtalmologique de la prise des antipaludéens de synthèse au long cours: mise au point et conduite à tenir à partir de 2003.

The early detection of macular toxicity linked to long-term antimalarial treatment requires regular ophthalmological screening based on patients'classification based on their results compared to successive controls. Patients are classified as "low risk" with screening every 18 months if all of the following criteria are met: age under 65 years, no associated renal, hepatic or retinal disease, treatment for less than 5 years, dose less than or equal to 6,5mg/kg/d for hydroxychloroquine and 3mg/kg/d for chloroquine (for a lean patient's weight); "at risk, without fundus findings" with screening every 12 months if one of the following criteria is met: age over 65 years (at the start of or during treatment), antimalarial treatment for more than 5 years, daily dose higher than recommended, presence of renal and/or hepatic disease; "at risk, with fundus findings" with screening every 6 months if a retinal dysfunction has been detected and even if treatment is established or followed. Screening consists of an in-depth clinical examination and at least two complementary tests of macular function: color vision (desaturated-Panel-D15 test) and/or static macular perimetry (central 10 degrees) and/or macular electroretinography (pattern ERG/multifocal ERG). If any changes or anomalies are found between two successive check-ups, the state of the retina can be assessed by angiography and global retinal function by full-field-ERG and electro-oculogram (EOG). The progression from one check-up to the next decides whether a course of treatment will be followed.

[Anatomy, physiology, and functional exploration of the optic nerve]. / Anatomie, physiologie et explorations fonctionnelles du nerf optique.

Disturbances of the optic nerve make up a large part of neuro-ophthalmology. They consist in large part of glaucoma and toxic inflammation of the optic nerve (retro-bulbar optic neuropathy). Progress in the understanding of the function of ganglion cells, in particular the discovery of the M and P pathways, comprise a considerable advance in the comprehension of the optic system as a whole. Progress in techniques of studying the visual field, the ERG pattern and imaging of the pupil have an influence on the diagnosis, the follow-up and the initiation of new therapeutic strategies in glaucoma and disorders of the SEP.

[Functional visual explorations of Bardet-Biedl syndrome. A study of three cases]. / Exploration fonctionnelle visuelle dans le syndrome de Bardet-Biedl. A propos de 3 cas.

Laurence-Moon syndrome, which is very rare, and Bardet-Biedl syndrome, which is more frequent are now well-recognized as two distinct entities in pediatric neurology. Bardet-Biedl syndrome includes a number of common clinical signs it shares with Laurence-Moon syndrome but also with other syndromes, particularly Alströme syndrome. These signs are retinitis pigmentosa, mental retardation, obesity, and hypogonadism. Ophthalmological and electrophysiological examinations are essential for confirmation and correct diagnosis of Bardet-Biedl syndrome. We present three case histories. Our third case illustrates the possibility of below normal yet discernable electroretinogram amplitudes which do not infirm the diagnosis of Bardet-Biedl syndrome.

[Static contrast sensitivity in idiopathic Parkinson disease]. / Sensibilité au contraste statique dans la maladie de Parkinson idiopathique.

During Parkinson's disease static contrast sensitivity (C.S.) abnormalities are linked to an impairment of the sensitive visual function. C.S. was tested in twelve parkinsonians and 12 controls without neurological and/or ophthalmological pathology, using a Colored Stripes Electronic Generator (GEPCO). Results for parkinsons showed a general deficiency over the spectrum of spatial frequencies, which was statistically significant and particularly pronounced for intermediate frequencies. This study was repeated for three patients: it showed threshold deterioration for two of them, correlated by evolution in the disease, and an improvement for the third patient after introduction of dopatherapy. C.S. is subjected to dopaminergic control. Among parkinsonians. C.S. deterioration may result in an operating failure of both the visual cortex and retina, and is improved by dopatherapy. The Static Gepco contrast sensitivity test is easy to reproduce and can be used easily to monitor the sensory visual defect in parkinsonian patients under treatment.

The dark choroid in systemic argyrosis.

Argyrosis is a cutaneous discoloration caused by silver. Ocular involvement, including conjunctival and corneal discoloration, has been previously reported. To our knowledge, a retinal involvement was never reported and no data is available about fluorescein angiography patterns of patients with argyrosis. Fluorescein angiography was performed in six consecutive patients with iatrogenic systemic argyrosis. A dark choroid was observed in each case. Red light monochromatic pictures disclosed a leopard spot pattern on the fundus, which was more clearly revealed in one patient by infrared light pictures. These findings suggest that the silver deposit in Bruch's membrane may be responsible for the obscuration of choroidal fluorescence during dye transit and for the visualization of choriocapillary units in pictures using long-wavelength light. The dark choroid is not only present in central retinal dystrophies, but may be observed in other conditions, such as systemic argyrosis.

[Retinal protection using glasses filtering short wave lengths in patients with hereditary degenerative diseases. First electrophysiologic results]. / Protection rétinienne par des verres filtrant les courtes longueurs d'ondes chez des patients atteints de maladies hérédo-dégénératives. Premiers résultats électrophysiologiques.

The electrophysiological action of the ORMA RT glasses filtering the short and middle wavelengths are exposed through the first results of this work by retinitis pigmentosa patients. In 90% of the tested patients A.E.R.G. and V.E.P. are improved.