Mário Teruo Sato

Long-term visual safety of voriconazole in adult patients with paracoccidioidomycosis.

BACKGROUND Voriconazole is an antifungal agent with in vitro activity and clinical efficacy against yeasts, molds, and dimorphic fungi (eg, Paracoccidioides brasiliensis). The safety profile of voriconazole includes transient visual adverse events (VAEs) that resolve while undergoing treatment or after its discontinuation. OBJECTIVE The goal of this study was to assess the long-term (ie, 6-12 months) visual safety of voriconazole in adult patients with paracoccidioidomycosis. METHODS Ophthalmic data were prospectively collected as part of a multicenter, open-label, comparative study. Patients aged ≥18 years with paracoccidioidomycosis were randomized in a 2:1 ratio to receive either voriconazole (200 mg BID orally, after the loading dose of 400 mg BID on day 1) or itraconazole (100 mg BID orally, with no loading dose). Patients were expected to receive treatment for a minimum of 6 months, or longer if needed as determined by the investigator (maximum duration, 1 year). Visual function tests and safety assessments were performed at baseline, week 12, week 24, end of treatment (EOT), and 8 weeks post-EOT. Ophthalmic examinations included visual acuity, color vision, contrast sensitivity, visual field, funduscopy, and slit lamp biomicroscopy. Treatment compliance was monitored via pill counts at each study visit. RESULTS Thirty-five patients (mean age, 48 years; 96.2% male; 83.0% white) were randomized to receive voriconazole and 18 to receive itraconazole. Fourteen voriconazole-treated patients received >6 months of treatment (median, 169 days). Efficacy and overall safety results have been published previously. Sixteen voriconazole-treated patients and 2 itraconazole-treated patients experienced drug-related VAEs; none was considered serious or severe or led to dose reductions or resulted in discontinuation. Overall, visual examination results were not clinically significantly different between patients treated with voriconazole or itraconazole. There was no apparent relationship between changes in visual function test results and the occurrence of VAEs in either treatment group. CONCLUSION Clinical assessment in this study found no evidence of an effect of voriconazole on long-term visual function in these adult patients with paracoccidioidomycosis.

Síndrome dos cabelos anágenos frouxos associada à distrofia macular: descrição de uma família

The article describes a family with loose anagen hair syndrome (LAHS) associated with macular dystrophy. Complete dermatological and ophthalmological exams, and hair examination under optical and electron microscopy were performed in eleven index cases. Two individuals demonstrated hair findings with LAHS without ocular problems. Within the four cases with ocular problems, two sisters presented with LAHS and pigmentary dispersion on the retina with macular coloboma. Two brothers presented with LAHS and pigmentary dispersion on the retina without macular coloboma. The findings suggest that this new association is a disorder among the ectodermal dysplasia.

Descrição de nova distrofia macular associada à síndrome dos cabelos anágenos frouxos

Purpose: To describe the ophthalmological, dermatological, light microscopy (LM) and scanning electron microscopy (SEM) findings of a new macular dystrophy associated with the loose anagen hair syndrome (LAHS). Methods: A family of seven patients, four of them affected, was examined. The patients underwent a complete ophthalmological examination, color test (Ishihara and Farnsworth D-15), ecography, angiography, laboratory and dermatological tests, sweat test, light microscopy and scanning electron microscopy of the hair. Results: In two affected sisters we found on eye fundoscopy pigmentary dispersions in the posterior pole of the retina, with macular staphyloma. In two brothers, the same pigmentary dispersions in the posterior pole was found, with more pigmentation and a yellow coloring in the macular area and without staphyloma. The light microscopy and scanning electron microscopy evaluation of the affected individuals confirmed loose anagen hair syndrome. In a not affected woman and man all examinations were normal, except the light microscopy and scanning electron microscopy that showed some similarities with the affected individuals. As for the way of inheritance, the pedigree is compatible with autosomal recessive inheritance with partial expression of the heterozygote. Conclusions: There is only one report in the international literature of loose anagen hair syndrome association with ocular coloboma. In this study we describe the findings of a new macular dystrophy associated with the loose anagen hair syndrome, a dystrophy whose fundoscopy findings are different between men and women. Since it is the first report in the literature, the described findings strongly suggest that this association can be part of a new nosological entity.

Discromatopsias congênitas e condução de veículos

Purpose: To determine the importance of the Ishihara test for the diagnosis of congenital dyschromatopsias and evaluate their incidence in a population of drivers, to assess the most common mistakes in the Color Box test and to study the relationship between dyschromatopsia, driving and traffic accidents. Methods: 523 drivers were examinated, in conformity with Contran resolution 734/89. The drivers were submitted to the color test with Ishihara plates, and those who had dyschromatopsia were submitted to the Color Box test (red, yellow and green), with LEDs as used in a traffic light. Results: An incidence of 5.5% (29 patients) of dyschromatopsias was observed. Of these patients, 3 were excluded from the study, 16 had severe disease and 10 had mild disease. In the latter group, 7 presented deuteranomaly and 3 protanomaly. Of those with deuteranomaly, 3 presented alterations in the Color Box test and 4 did not. Of those with protanomaly, 1 patient had abnormal results and 2 were normal. Of the patients with severe disease, 14 presented deuteranopia and 2 protanopia. All of them had an abnormal Color Box test. Conclusion: All patients with severe disease and half of those with moderate disease, made mistakes in the Color Box test. This study concludes that the Color Box test does not need to be performed in those patients who had the Ishihara Plate test done to diagnose congenital dyschromatopsias.

Different Cerebellar Ataxia Phenotypes Associated with Mutations of the PNPLA6 Gene in Brazilian Patients with Recessive Ataxias

Autosomal recessive cerebellar ataxias (ARCAs) represent a heterogeneous group of inherited disorders. The association of early-onset cerebellar ataxia with hypogonadotropic hypogonadism is related to two syndromes, known as Gordon Holmes syndrome (GHS—ataxia and pyramidal signs with hypogonadotropic hypogonadism) and Boucher-Neuhäuser syndrome (BNS—ataxia with chorioretinal dystrophy). Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations. We reported two Brazilian patients with sporadic, progressive cerebellar ataxia, associated with hypogonadotropic hypogonadism, in whom the GHS and BNS were confirmed by the demonstration of compound heterozygote mutations in the PNPLA6 gene. Genetic analysis of the patient 1 revealed compound heterozygous mutations, one allele in exon 34 and the other allele in exon 29. Genetic exam of the patient 2 also demonstrated compound heterozygous mutations. Three were novel mutations. The missense mutation c.3373G> A, found in the BNS patient, was previously related to Oliver-McFarlane syndrome. These different mutations in this gene suggest a complex phenotype associated disease spectrum.

Characterization of a novel form of progressive retinal atrophy in Whippet dogs: A clinical, electroretinographic, and breeding study

OBJECTIVE To describe a form of progressive retinal atrophy (PRA) in Whippets including clinical, electroretinographic, optical coherence tomographic changes and pedigree analysis. ANIMALS STUDIED Client-owned Whippet dogs (n = 51) living in Brazil. PROCEDURES All animals were submitted for routine ophthalmic screening for presumed inherited ocular disease, which included the following: visual tests, such as obstacle course tests, in scotopic and photopic conditions, cotton ball test, dazzle reflex, ocular fundus evaluation by indirect ophthalmoscopy followed by fundus photography. Additionally, electroretinography (ERG) and optical coherence tomography (OCT) were performed in 24 and four dogs, respectively. RESULTS Sixteen dogs were diagnosed with PRA. Vision deficits in dim light were detected in dogs examined at a young age associated with nystagmus. Funduscopic changes included the development of multifocal retinal bullae from 6 months of age. Retinal thinning became apparent later, at which time the bullae were no longer detected. OCT examination of selected young dogs revealed that the retinal bullae were due to separation between photoreceptors and the retinal pigment epithelium, and of dogs with more advanced disease confirmed the development of retinal thinning. Electroretinography in young dogs revealed a negative ERG due to a lack of b-wave in both scotopic and photopic recordings. With progression, the ERG became unrecordable. Pedigree analysis suggested an autosomal recessive mode of inheritance. CONCLUSION The retinal dystrophy reported here in Whippet dogs has a unique phenotype of an initial lack of ERG b-wave, development of retinal bullae then a progressive generalized retinal degeneration.

Distrofia retiniana com onda rápida escotópica (DRORE) associada à síndrome dos cabelos anágenos frouxos (SCAF). Parte II: Genética

OBJETIVOS: Propor complementacao da atual classificacao do eletrorretinograma (ERG) com a inclusao deste novo tipo de onda, discutir os possiveis mecanismos para a distrofia retiniana com onda rapida escotopica (DRORE) associada a sindrome dos cabelos anagenos frouxos (SCAF) e analise do heredograma da familia estudada. METODO: Foram descritos na parte I deste trabalho. RESULTADOS: A analise do heredograma da familia demonstrou tratar-se de heranca autossomica recessiva com expressao parcial no heterozigoto; outros resultados foram descritos na parte I deste trabalho. CONCLUSOES: Por se tratar do primeiro relato na literatura, os achados descritos sugerem fortemente que a distrofia retiniana com onda rapida escotopica associada a sindrome dos cabelos anagenos frouxos pode ser uma nova entidade nosologica. Neste trabalho propomos uma classificacao inedita de todas as distrofias maculares e degeneracoes retinianas associadas a disturbios capilares no grupo B das displasias ectodermicas.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration

PURPOSE To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. METHODS Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. RESULTS A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. CONCLUSIONS Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

THE EYE OF THE AZARA'S AGOUTI (DASYPROCTA AZARAE): MORPHOLOGICAL OBSERVATIONS AND SELECTED OPHTHALMIC DIAGNOSTIC TESTS

Abstract The purpose of this study was to carry out a descriptive investigation of the Azaras agouti (Dasyprocta azarae) eye and to establish reference values of select ophthalmic diagnostic tests and physiologic parameters. A total of 19 healthy agoutis were used. Select ophthalmic diagnostic tests were performed, including Schirmer tear test type I (STTI), analysis of the conjunctival bacterial microflora, corneal esthesiometry, and tonometry. B-mode ultrasonic biometry, fundus photography, optical coherence tomography, and gross and histologic analysis of two eyes were also performed. Reference range parameters found for the ocular diagnostic tests were esthesiometry, 4.50 ± 0.36 cm (0.7 ± 0.01 g/mm2); tonometry, 11.61 ± 0.44 mm Hg; palpebral fissure length, 1.70 ± 0.25 mm; STTI, 9.73 ± 0.47 mm/min; corneal thickness, 0.8 ± 0.003 mm; anterior chamber depth, 1.71 ± 0.07 mm; lens thickness, 5.03 ± 0.05 mm; vitreous chamber depth, 5.12 ± 0.01 mm; and globe axial length, 14.02 ± 0.01 mm. A paurangiotic, retinal, vascular pattern with a conspicuous pigment-laden optic disc was observed. The most frequent bacteria isolated were nonhemolytic Streptococcus sp. (36.84%), followed by Enterobacter harfinia (31.58%) and Escherichia coli (28.95%). No significant differences between genders or between left and right eyes were found for any of the results. Gross and histologic evaluation of two eyes confirmed the presence of melanocytic pigment granules between optic nerve fibers. The diagnostic values and the morphologic observations described here provide a reference to veterinarians to aid in the diagnosis of ocular disease.

Epidemiological profile of age-related macular degeneration patients in Federal University of Parana, Brazil

Objective: To evaluate the profile and severity of age-related macular degeneration (AMD) in ophthalmology ambulatory of Federal University of Parana in Curitiba, Parana, Brazil. Methods: This was a cross-sectional study with data collected among the 6155 outpatients ophthalmic appointments (november 2011 to november 2013). In this 6155 patients, a total of 346 patients had retinal diseases and were screened by two retinal specialists for signs of AMD. If present, they were submitted to a protocol including a new ophthalmic evaluation comprising visual acuity, tonometry, biomicroscopy, dilated fundus examination and optical coherence tomography (OCT). Results: A total of 6155 patients underwent ophthalmologic evaluation for several reasons. Three hundred and forty six patients had retinal diseases (incidence of 5.6%) and 68 of these (incidence of 19.6% in retinal patients) had AMD. The mean age of all patients was 53 years and in retinal patients was 60 years. In AMD patients mean age was 73 years. Ethnicity, body-mass index (BMI) and smoking habits were evaluated in the 68 patients diagnosed with AMD (34 exudative and 34 non-exudative) but none of those parameters were statistically significant comparing exudative and non-exudative forms. Conclusion: Most of the patients were European descendants. A higher proportion of advanced cases of AMD comparing with literature was found (50% of exudative form). Regarding ethnicity, iris color, smoking habit and BMI, there was no difference comparing exudative and non-exudative forms. These results may be compared to available AMD studies, since there is little information about AMD in Brazil.