Genetic counseling and prevetion of blindness : perception and conduct of brazilian ophtalmologists and patients with visual impairement

Orientadores: Antonio Sergio Ramalho, Luis Alberto MagnaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: O presente trabalho tem por objetivos verificar a percepção de oftalmologistas brasileiros em relação à contribuição da Genética em sua atuação médica rotineira e a conduta frente a portadores de doenças hereditárias; investigar o nível de conhecimento e a conduta desses pacientes a respeito de sua condição e verificar a contribuição do aconselhamento genético na vida destes pacientes. Duzentos oftalmologistas que atuam na região de Campinas, SP, Brasil (universidades e/ou clínicas particulares) foram convidados a participar, por via postal, de uma entrevista sobre os seus conhecimentos, práticas e opiniões no campo da genética. A casuística de pacientes foi constituída por 53 portadores de deficiência visual importante (acuidade visual com a melhor correção menor que 0,3), de provável etiologia genética, entrevistados em um hospital universitário no período de 18 meses. O conteúdo da entrevista consistiu de perguntas sobre seus conhecimentos, opiniões, condutas e a situação ocular relativos à sua condição, utilizando-se de questionários de múltipla escolha, que permitiram a análise estatística, com comparação de proporções e testes de associação. Examinou-se também uma amostra-controle, constituída por 142 irmãos normais de pacientes, para comparação de alguns indicadores de integração social, principalmente o estabelecimento de parcerias conjugais estáveis e reprodução. Dentre os 73 profissionais que responderam o questionário (36%), foram constatadas altas taxas (49% a 88%) de respostas positivas sobre os seus conhecimentos básicos de genética, porém baixas taxas (10% a 33%) de utilização desses conhecimentos na rotina clínica. Apenas 45% dos indivíduos com oftalmopatias hereditárias receberam aconselhamento genético, geralmente fornecido pelo próprio oftalmologista. O encaminhamento a serviço de genética foi observado em 25% dos casos. O aconselhamento genético foi uma das variáveis que, juntamente com o sexo feminino e o maior nível educacional, mostraram-se associadas a mudanças no planejamento familiar. Embora os pacientes tenham revelado maior dificuldade no estabelecimento de vínculos reprodutivos estáveis, eles tiveram filhos na mesma proporção que os seus irmãos sem a deficiência visual, o que reforça a importância do aconselhamento genético. O potencial terapêutico e preventivo do aconselhamento genético não está sendo explorado adequadamente na prevenção da cegueira. A genética merece ser discutida de forma menos teórica e mais pragmática, não somente entre os oftalmologistas, mas entre os médicos e a população em geral, sobre a aplicação do potencial da genética em benefício dos pacientes, por meio de um aconselhamento genético abrangente, direcionado para a comunidadeAbstract: This study verified the perception and behavior of Brazilian ophthalmologists in relation to hereditary eye diseases and the contribuition of Genetics in their routine practice; and verified the perception and behavior of patients with severe visual impairment and the contribuition of genetic counseling in their lives. Invitations were posted to 200 ophthalmologists, who practice in the area of Campinas, SP, Brazil, to participate in an interview concerning their knowlegde, behavior and opinions in the field of Genetics. Patients sample was composed of 53 individuals with severe visual impairment (visual acuity of less than 0.3 in the better eye with the best correction) caused by genetic factors. The interviews were held in a university hospital over a period of 18 months. The multiple-choice questionnaire applied permitted statistical analysis, for proportion comparisons and associative tests. A control sample composed of 142 normal patients siblings was also examined to compare some social integration indicators - mainly the establishment of stable couples and reproduction. Of the 73 professionals who answered the questionnaire (36%), the percentage of affirmative responses regarding basic genetic knowledge was high (49% to 88%) but the application of this knowledge to regular clinical routine was poor (10% to 33%). Only 45% of the individuals with hereditary ophthalmopathies received genetic counseling, which was usually offered by the ophthalmologist. Referrals to the genetic service consisted of 25% of the cases. The variable genetic couseling, together with others such as female sex and those having a higher educational level, significantly influenced alterations in family planning. Although they had poor access to the establishment of stable conjugal unions, they had children in the same proportion as their normal siblings. This fact underscores the importance of genetic counseling. The therapeutic and preventive potential of genetic counseling in the prevention of blindness is not adequately used. Discussions on genetics held with Brazilian ophthalmologists and the community about the use of this potential, for the benefit of patients, through genetic counseling, should be more pragmatic and less theoreticalMestradoOftalmologiaMestre em Ciências Médica

Age-related macular degeneration : study of the risk factors in a Brazilian population

Orientadores: Antonia Paula Marques de Faria, Luis Alberto MagnaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: A degeneração macular relacionada à idade (DMRI) é uma das principais causas de cegueira no mundo desenvolvido, acometendo indivíduos com mais de 65 anos. É uma condição multifatorial degenerativa e progressiva, ocasionando perda da visão central de um ou ambos os olhos e afetando a independência do idoso. Vários fatores de risco estão associados com essa condição incluindo fatores oculares, genéticos, demográficos, nutricionais, médicos e ambientais, mas não há estudo sistemático dos mesmos na população brasileira. Seria oportuno conhecê-los, considerando estabelecer eventuais estratégias para prevenção e diagnóstico precoce, pois apesar dos notáveis avanços na terapêutica da DMRI, o impacto socioeconômico dessa condição e de suas complicações tenderá a aumentar com o envelhecimento da população. Objetivos: Identificar os fatores de risco associados ao desenvolvimento e progressão da DMRI em uma população brasileira. Métodos: Realizado estudo transversal com grupo controle envolvendo 236 participantes com idade >50 anos incluindo 141 indivíduos afetados e 95 controles sem DMRI, todos pacientes assistidos no serviço de Oftalmologia do Hospital de Clínicas da Unicamp. Todos os participantes foram submetidos a exame oftalmológico completo incluindo fundoscopia, retinografia e angiografia e responderam a um questionário contendo perguntas sobre fatores demográficos, antecedentes médicos e oculares, história familial de DMRI, estilo de vida, hábitos de tabagismo e etilismo. Resultados: Dos 141 portadores de DMRI, 99 (71%) indivíduos apresentavam DMRI da forma avançada em pelo menos um dos olhos (57% DMRI neovascular e 13% atrofia geográfica) e 42 (30%) da forma inicial da doença (DMRI seca leve ou moderada). Os indivíduos afetados apresentaram acuidade visual (média de 20/200) significativamente menor do que os controles (média de 20/40) e mais de 50% dos pacientes com DMRI eram portadores de cegueira ou visão subnormal, (RR 9,89; 95%CI 3,79-25,81). Houve diferença significativa em relação aos fatores como: idade (RR 1.51; 95% CI: 0,88-2,58), história familial de DMRI (RR 6,58; 95% CI: 1,94-22,31), presença de doença cardiovascular (DCV) (RR 2,39; 95% CI: 1,08-5,28), altos níveis de colesterol plasmático (RR 1,49; 95% CI: 0,84-2,65) e sedentarismo (RR 1,39; 95% CI: 0,82-2,37). Não houve diferença significativa em relação ao sexo, IMC, catarata e/ou cirurgia de catarata, cor da pele, cor da íris, exposição solar, uso de antioxidantes, hipertensão arterial sistêmica, diabetes, tabagismo e etilismo na comparação entre pacientes e controles. Quanto ao tipo de DMRI, foi observada associação significativa em relação à presença de doença cardiovascular e a DMRI avançada (RR 2,29; 95% CI: 0,81-6,44). O nível de colesterol nos portadores de DMRI inicial foi mais alto que os de DMRI avançada (RR 1,67; 95% CI: 1,09-4,80). A correlação de 0,351 foi obtida na análise discriminante (stepwise), onde os fatores antecedentes familiais, idade, sedentarismo e dislipidemia foram considerados. Conclusão: Verificou-se na amostra estudada que os principais fatores de risco para DMRI são: idade, história familial de DMRI, doença cardiovascular, dislipidemia e sedentarismo. Entre estes fatores, indivíduos com DCV apresentaram risco aumentado para o desenvolvimento da forma avançada da DMRI e a hipercolesterolemia foi predominante naqueles com DMRI inicial. Como a DCV e a DMRI na forma avançada aparentemente apresentam vários fatores de risco em comum, foi feita recomendação final de que poderiam ser prevenidas conjuntamente por meio de programas de promoção da saúde do idoso envolvendo combate a fatores como hipertensão arterial, diabetes, obesidade (alto IMC), tabagismo, etilismo e maus hábitos alimentares, embora isoladamente não fossem estatisticamente significativos no presente estudo. Também foi destacado o papel da hereditariedade desta condição e a perspectiva de que membros das famílias de portadores sejam informados sobre risco de recorrência e medidas preventivasAbstract: Background: Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness among individuals 65 years of age or older in developed countries. It is a degenerative and complex condition causing lost of central vision that impacts the independence of the elderly. A number of major risk factors for AMD have been identified worldwide, including genetic, demographic, nutritional, lifestyle, medical, environmental, and ocular factors, but there are no systematic studies on Brazilian population until now. The knowledge of these factors will lead to the elaboration of early diagnostic and preventive strategies taking into account that despite remarkable developments in therapy, the socio-economic burden of the disease is likely to increase worldwide as the population ages. Purpose: To identify risk factors associated with the onset and progression of age-related macular degeneration in a Brazilian population aiming the assessment of possible preventive measures based in the profile of these patients. Methods: A cross-sectional study with control group was performed in 236 participants aged 50 years or older including 141 affected individuals and 95 controls without disease, all current patients from the Department of Ophthalmology-Otorhinolaryngology of Clinical Hospital, Faculty of Medical Sciences-Unicamp. Ocular examinations were performed including color stereoscopic fundus photographs and data including demographic factors, ocular and medical history, family history of AMD, lifestyle, smoking and drinking habits was obtained by questionnaire from all participants. Results: Of the 141 AMD cases, 99 (71%) had late AMD in at least one eye (57% neovascular AMD and 13% geographic atrophy) and 42 (30%) had early AMD. The visual acuity of the AMD patients (mean of 20/200) was substantially lower than controls (mean of 20/40). More than 50% of AMD cases had visual impairment among (RR 9.89; 95%CI: 3.79-25.81). Age (RR 1.51; 95% CI: 0.88-2.58), positive family history of AMD (RR 6.58; 95% CI: 1.94-22.31); presence of cardiovascular disease (CVD) (RR 2.39; 95% CI: 1.08-5.28), low physical activity level (RR 1.39; 95% CI: 0.82-2.37) and high serum cholesterol (RR, 1.49; 95% CI: 0.84-2.65) were associated to increased risk for AMD. There was no significant association with sex, IMC, cataract/cataract surgery, skin color, iris color, sunlight exposure, antioxidants intake, history of hypertension, diabetes, smoking status and alcohol consumption between the groups of AMD patients and controls. Comparing data between affected individuals, there was a significant association with history of CVD and incidence of late AMD (RR 2.29; 95% CI 0.81-6.44). There were higher levels of serum cholesterol among subjects with early AMD than those with late AMD (RR 1.67; 95% CI: 1.09-4.80). A correlation of 0.351 was obtained in discriminant analysis (stepwise), where factors such as family history, age, low physical activity and high serum cholesterol were considered. Conclusions: This findings show that the main risk factors associated to AMD in this population are: age, family history, cardiovascular disease (CVD), high level of cholesterol and low physical activity. Among these factors, patients with history of CVD were associated with increased risk to advanced AMD and higher levels of plasma cholesterol were found among individuals with early AMD. As CVD and late AMD apparently share multiple risk factors, final recommendation was made that both conditions could be prevented jointly through programmes of health promotion for the elderly. The targets include combat of hypertension, diabetes, obesity (high BMI), smoking, alcoholism and bad eating habits, although in isolation were not statistically significant in this study. The role of heredity in this condition was also highlighted as well as the prospect of family members of affected individuals to be informed about risk of recurrence and preventive measuresDoutoradoOftalmologiaDoutor em Ciências Médica

Ophthalmic Aspects Of Gapo Syndrome: Case Report And Review.

This paper reports on a 36-year-old woman with GAPO syndrome, a rare autosomal recessive condition characterized by growth retardation (G), alopecia (A), pseudoanodontia (P), and optic atrophy (O). Her parents are consanguineous and one of her sisters is also affected. Since the first description by Anderson and Pindborg in 1947, 27 individuals have been reported with this diagnosis. They were from at least 19 different families (four of them from Brazil, including the present one), suggesting a founder effect. The phenotype of this condition, initially considered as the result of an ectodermal dysplasia, could be attributed to the accumulation of extracellular connective tissue matrix and its progressive character must be pointed out. The clinical findings, especially ophthalmological features that include bilateral glaucoma, are reviewed and discussed.26143-

Genetics And Prevention Of Blindness.

To verify the perception of Brazilian ophthalmologists regarding the role played by Genetics in their routine medical activity and their conduct when dealing with patients, with hereditary diseases who need genetic counseling. A cross-sectional survey was conducted by means of invitations to participate in an interview on this subject. The questionnaires were sent to 200 ophthalmologists who work in the area of Campinas, SP, Brazil. Among the 73 professionals who answered the questionnaire (36%), there was a high rate of positive answers (49-88%) concerning their knowledge of genetics and a low rate (10-33%) of use of this knowledge in their clinical practice. The frequency of genetic ophthalmopathies in clinical practice was relevant in the opinion of 68% of the interviewees; 92% indicated a relevant relationship between genetically determined ocular disorders and the prevention of blindness through detection, early treatment and genetic counseling. More extensive genetic knowledge was considered indispensable to 84% of the professionals, but 16% answered that it was irrelevant. Although these ophthalmologists have basic notions of genetics (88,0%) and are aware of its importance in the prevention of blindness, a great majority of Brazilian ophthalmologists have not acquired adequate knowledge of genetics and, in practice, rarely use its therapeutic and preventive potential.69481-

Genética e prevenção da cegueira

PURPOSE: To verify the perception of Brazilian ophthalmologists regarding the role played by Genetics in their routine medical activity and their conduct when dealing with patients, with hereditary diseases who need genetic counseling. METHODS: A cross-sectional survey was conducted by means of invitations to participate in an interview on this subject. The questionnaires were sent to 200 ophthalmologists who work in the area of Campinas, SP, Brazil. RESULTS: Among the 73 professionals who answered the questionnaire (36%), there was a high rate of positive answers (49-88%) concerning their knowledge of genetics and a low rate (10-33%) of use of this knowledge in their clinical practice. The frequency of genetic ophthalmopathies in clinical practice was relevant in the opinion of 68% of the interviewees; 92% indicated a relevant relationship between genetically determined ocular disorders and the prevention of blindness through detection, early treatment and genetic counseling. More extensive genetic knowledge was considered indispensable to 84% of the professionals, but 16% answered that it was irrelevant. CONCLUSIONS: Although these ophthalmologists have basic notions of genetics (88,0%) and are aware of its importance in the prevention of blindness, a great majority of Brazilian ophthalmologists have not acquired adequate knowledge of genetics and, in practice, rarely use its therapeutic and preventive potential.OBJETIVO: Verificar a percepção de oftalmologistas brasileiros em relação à contribuição da Genética em sua atuação médica rotineira, bem como a sua conduta em face de portadores de doenças hereditárias que necessitem de aconselhamento genético MÉTODOS: Estudo transversal, em que duzentos oftalmologistas que atuam na região de Campinas, SP, Brasil (universidades e/ou clínicas particulares) foram convidados a participar de uma entrevista sobre o assunto. RESULTADOS: Aqueles que aceitaram o convite (36%), enviaram um questionário respondido, via correio (n=73). A importância das oftalmopatias genéticas em relação a sua freqüência na clínica prática foi relevante na opinião de 68% dos entrevistados e 92% manifestaram sua opinião como sendo muito importante a relação das oftalmopatias genéticas e a prevenção à cegueira, por meio da detecção e tratamento precoces e aconselhamento genético. Quanto à opinião dos entrevistados sobre melhorar seus conhecimentos em genética, 84% consideraram imprescindível, porém 16% responderam que é irrelevante. CONCLUSÕES: De um modo geral, embora os oftalmologistas entrevistados tenham adquirido noções básicas de Genética (88%) e estão conscientes de sua importância na prevenção da cegueira, os conhecimentos de genética da grande maioria dos oftalmologistas brasileiros são incompletos e, na prática, quase que inexplorados em seu potencial terapêutico e preventivo.48148

Ocular findings in Brazilian identical twins with Cohen syndrome: case report Achados oftalmológicos em gêmeos idênticos brasileiros com síndrome de Cohen: relato de caso

A case of identical male twins with Cohen syndrome who present multiple ophthalmic findings is reported. The patients were identical 16 year-old twin boys who showed down slanting eyelids, mild ptosis, high-grade myopia, small cortical lens opacities, posterior subcapsular cataracts, myotic and corectopic pupils with poor dilation due to focal iris atrophy and retinochoroidal dystrophy. Ophthalmologists must be aware of the ocular and systemic findings of Cohen syndrome in the evaluation of young patients with mental retardation and visual impairment.<br>Relata-se caso de gêmeos idênticos com síndrome de Cohen que apresentam múltiplos achados oftalmológicos. Os pacientes eram gêmeos idênticos, do sexo masculino, que apresentavam pálpebras em forma de onda, ptose moderada, alta miopia, opacidades cristalinianas corticais discretas, catarata subcapsular posterior, pupilas mióticas e corectópicas com pobre dilatação devido à atrofia focal de íris, além de distrofia retinocoroidiana. Os oftalmologistas devem estar atentos quanto aos achados oftalmológicos e sistêmicos da síndrome de Cohen na avaliação de pacientes jovens com retardo mental e baixa visão

Ocular Findings In Brazilian Identical Twins With Cohen Syndrome: Case Report.

A case of identical male twins with Cohen syndrome who present multiple ophthalmic findings is reported. The patients were identical 16 year-old twin boys who showed down slanting eyelids, mild ptosis, high-grade myopia, small cortical lens opacities, posterior subcapsular cataracts, myotic and corectopic pupils with poor dilation due to focal iris atrophy and retinochoroidal dystrophy. Ophthalmologists must be aware of the ocular and systemic findings of Cohen syndrome in the evaluation of young patients with mental retardation and visual impairment.72815-

Association Of Loc387715/arms2 (rs10490924) Gene Polymorphism With Age-related Macular Degeneration In The Brazilian Population.

Abstract Background: An association between LOC387715/ARMS2 (rs10490924) gene polymorphism and AMD has been reported. The aim of this study was to evaluate whether this polymorphism is associated with AMD in a Brazilian cohort. Materials and Methods: In total, 126 unrelated AMD patients (mean age 74.17 ± 7.64) were compared with 86 healthy controls (mean age 71.82 ± 7.12). Study subjects were classified according to the International ARM Epidemiological Study Group definition for early and late-stage AMD. LOC387715/ARMS2 rs10490924 polymorphism was evaluated through polymerase chain reaction and direct sequencing. Results: The T allele frequency was significantly higher in AMD patients than in controls (39.6% compared to 20.3%). The odds ratio (OR) for AMD was 2.05 (95% CI 1.13-3.71) for heterozygotes (TG) and 8.32 (95% CI 2.30-45.99) for homozygotes (TT). Conclusions: These results suggest that there is a contribution of the rs10490924 SNP of the LOC387715/ARMS2 gene to AMD susceptibility in this sample of the Brazilian population.1-

Association of LOC387715/ARMS2 (RS10490924) gene polymorphism with age-related macular degeneration in the brazilian population

An association between LOC387715/ARMS2 (rs10490924) gene polymorphism and AMD has been reported. The aim of this study was to evaluate whether this polymorphism is associated with AMD in a Brazilian cohort. In total, 126 unrelated AMD patients (mean age 74.17 +/- 7.64) were compared with 86 healthy controls (mean age 71.82 +/- 7.12). Study subjects were classified according to the International ARM Epidemiological Study Group definition for early and late-stage AMD. LOC387715/ARMS2 rs10490924 polymorphism was evaluated through polymerase chain reaction and direct sequencing. The T allele frequency was significantly higher in AMD patients than in controls (39.6% compared to 20.3%). The odds ratio (OR) for AMD was 2.05 (95% CI 1.13-3.71) for heterozygotes (TG) and 8.32 (95% CI 2.30-45.99) for homozygotes (TT). These results suggest that there is a contribution of the rs10490924 SNP of the LOC387715/ARMS2 gene to AMD susceptibility in this sample of the Brazilian population363224228CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ472645/200