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J-L Dufier

Publications and source records attributed to J-L Dufier.

9 recordsLinked to original sources

[Severe chloroquine- and hydroxychloroquine-induced retinopathy].

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.

Aged↗

[Leber congenital amaurosis: comprehensive survey of genetic heterogeneity. A clinical definition update].

Leber congenital amaurosis (LCA) is the earliest and most severe form of all inherited retinal dystrophies, responsible for congenital blindness. Disease-associated mutations have been hitherto reported in seven genes. These genes are all expressed preferentially in the photoreceptor cells or the retinal pigment epithelium, but they are involved in strikingly different physiologic pathways, resulting in an unforeseeable pathophysiologic variety. This broad genetic and physiologic heterogeneity, which could greatly increase in the coming years, hinders molecular diagnosis in LCA patients. Genotyping is, however, required to establish genetically defined subgroups of patients ready for therapy. Here we report a comprehensive mutational analysis of all the known genes in 179 unrelated LCA patients, including 52 familial and 127 sporadic (27/127 consanguineous) cases. Mutations were identified in 47.5% of patients. GUCY2D accounted for by far the largest part of the LCA cases in our series (21.2%), followed by CRB1 (10%), RPE65 (6.1%), RPGRIP1 (4.5%), AIPL1 (3.4%), TULP1 (1.7%) and CRX (0.6%). The clinical history of all patients with mutations was carefully revisited in the search for phenotype variations. Genotype-phenotype correlations were found that made it possible to divide patients into two main groups. The first one includes patients whose symptoms fit the traditional definition of LCA, i.e., congenital or very early cone-rod dystrophy, while the second group gathers patients affected with severe yet progressive rod-cone dystrophy. In addition, objective ophthalmologic data subdivided each group into two subtypes. Based on these findings, we have drawn decisional flowcharts directing the molecular analysis of LCA genes in a given case. These flowcharts will hopefully lighten the onerous task of genotyping new patients, but only if the most precise clinical history since birth is available.

Animals↗

[Hereditary macular dystrophies].

Hereditary macular dystrophies are degenerative diseases of the central area of the retina associating primary anomalies of the retinal pigment epithelium and sensory retina. These conditions, whose hallmark is a loss of visual acuity, are a major cause of blindness and affect patients at all ages. Macular dystrophies group diseases that are heterogenous at the genetic level, as well as at the clinical, histological and physiopathological levels. Monogenic macular dystrophies are rare autosomal dominant conditions, with the exception of Stargardt disease in its typical form, which is not only relatively frequent but is also inherited as an autosomal recessive trait. During the last few years, the molecular bases of these conditions have begun to be elucidated with the identification of several responsible genes. For some macular dystrophies, this new information has confirmed pre-existing hypotheses on their pathophysiology, but for others, the discovery of the disease gene has added further complexity to the disease process. Two contradictory concepts were particularly highlighted by these genetic studies. Several phenotypes previously described as different clinical entities were brought together by the identification of mutations in the same gene, and converselyome conditions that were clinically assigned the same name, often heterogeneous at the clinical level, appeared genetically and physiopathologically heterogeneous. In addition, it is worth noting that the monogenic macular dystrophy genes were often regarded as potential factors for susceptibility to age-related macular degenerations. However, to date, only ABCA4 mutations have been associated with a minority of this frequent multifactorial condition. The aim of this article is to give a progress report on the monogenic macular dystrophy genes and to review current knowledge concerning the pathophysiology of these conditions.

Humans↗

[Computer-assisted diagnosis and therapy for glaucoma].

Boolean algebra, or combinatory analysis and their related computer routines, can provide invaluable help in resolving classic diagnostic problems. However complex each case may be, the diagnosis is always made from a finite set of data, and the fundamental problem is thus how to exploit this data. Invention no longer has a place in ascertaining a diagnosis. Traditional ways of reasoning are numerous, personal, and fragile, but fortunately redundant. They may give rise to four types of error: omission or mistake (an error of judgment), either during the semiotic or the dialectic stages. Whereas the physiological capacity of the human brain and memory only enables it to make a limited number of hypotheses concerning certain aspects of glaucoma, computer programs can take the total number of hypotheses into account, i.e., 3000. For every input the program explores each of the 3,000 items, thus eliminating the four types of error. The probabilistic nature of data, which compromises the confidence one can have in conclusions resulting from such complex reasoning, is treated by the adjusted probabilities. The use of such diagnostic aids, whose thesaurus is updated regularly, is reserved for ophthalmologists, the only authority capable of assessing the pertinence of the computer responses. Consequently, the specialist can rest assured that the patient has benefited from the most comprehensive and updated knowledge in medical science.

Glaucoma↗

[Managing of retinopathy of prematurity in a tertiary center].

INTRODUCTION: Retinopathy of prematurity is a complication of prematurity whose risk factors are well known. Its prognosis remains fearsome and its treatment is difficult. PATIENTS AND METHODS: Fifty-four children were managed (108 eyes analyzed) for retinopathy of prematurity in the Ophthalmology Ward of Necker-Enfants-Malades Hospital between 1996 and 2002. A retrospective review of those cases was performed to describe their clinical features, their treatment and their outcome. RESULTS: Mean gestational age was 26.75 weeks after the mother's last period (24-32.5 weeks) and mean birth weight was 842 g (530-2260 g). Stage zero occurred in ten eyes, stage 1 in two eyes, stage 2 in seven eyes, stage 3 in 42 eyes, stage 4 in ten eyes, stage 5 in 24 eyes, and after-effects stage in 13 eyes. Initial treatment (combined treatments possible) was abstention in 45 eyes, cryotherapy in 16 eyes, laser photocoagulation in 43 eyes, surgical treatment of 13 eyes (scleral buckling or vitrectomy). Cryotherapy was effective in 71.5% of cases, photocoagulation was effective in 77%, and scleral buckling was effective in 25%. Vitrectomy failed in the five eyes treated. Outcome was complicated by legal blindness in 33 eyes. DISCUSSION AND CONCLUSION: The cases of retinopathy of prematurity that we manage are often severe, stage 3 or above, which explains the outcome of the patients. The 7-year experience reported herein shows how difficult it is to manage this condition, though the need for its detection, diagnosis criteria, and therapeutical indications are well known. Because younger and smaller premature newborns are successfully managed by pediatricians, retinopathy of prematurity is far from having vanished and its morbidity is considerable.

Adolescent↗

[Ocular injuries and childbirth].

INTRODUCTION: Severe ocular traumatisms related to childbirth are rare and often subordinate to maneuvers with instruments. The aim of this study was to report on the different severe ocular injuries that might occur during childbirth and their possible consequences. There can be several of these ocular injuries. PATIENTS AND METHODS: Since 1984, we have examined 11 cases of this type of traumatism. For each case, the childbirth circumstances, the affected side, the different injuries observed such as ocular, orbital, cranial and even cerebral lesions, and the results of the ophthalmological follow-up examinations were recorded. RESULTS: In most cases, lesions resulted from forceps traumatisms, and the injuries were corneal (vertical tears in the Descemet's membrane), retinal (hemorrhages), and orbital (e.g., the optical nerve and oculomotor nerve). CONCLUSION: These injuries, sometimes severe, must benefit from early and complete examination, possibly with general anesthesia, and long-term follow-up. Furthermore, a radiographic and clinical neurological examination is recommended to prevent any cerebral complication.

Birth Injuries↗