Evaluation of childhood cataract characteristics at a tertiary referral center / Características de catarata na infância em um centro de referência terciário

ABSTRACT Purpose: To examine the epidemiological characteristics of children undergoing cataract surgery at a referral center in Sao Paulo State, Brazil, as well as the facts surrounding treatment delays. Methods: In this transversal observational study, 240 operated eyes from 178 children undergoing cataract surgery were reviewed. The following aspects were analyzed: epidemiological and clinical characteristics, parental observations, red reflex test, operated eye, and age at cataract diagnosis and surgery. Results: The mean ages at the first visit and cataract surgery were 48.9 months (SD=50.0 months) and 64.5 months (SD= 55.4 months), respectively. The most critical sign adverted by parents was leukocoria. The red reflex test was performed on two-thirds of the children, with abnormal results in 28.0%. A family history of cataracts was evident in 30 (20,9%) children (n=144). Previous ocular surgery was found in 37 (16,6%) of the eyes (n=223), anterior segment disorders in 20 (9,0%) eyes (n=221), strabismus in 21 (9,5%) of the eyes (n=220), and nystagmus in 38 (24,4%) of the children (n=156). Conclusions: One of the causes for the delay in admission may have been the failure to complete the red reflex. In terms of etiology, heredity was the most crucial component. The presence of strabismus and nystagmus in many of these children points to late diagnosis. The most significant impediments to adequate cataract treatment in children were the lack of referral programs and children's specialized ophthalmologic centers, in addition to the restricted number of support professionals trained in the field and pediatric ophthalmology specialists.

RESUMO Objetivos: Rever características epidemiológicas de crianças submetidas a cirurgia de catarata, em centro de referência no estado de São Paulo, Brasil, e fatos associados a atrasos no tratamento. Métodos: Um total de 240 olhos submetidos a cirurgia de catarata, em 178 crianças, foram revisados neste estudo transversal observacional. Os seguintes aspectos foram analisados: características clínicas e epidemiológicas, sinais apontados pelos pais, teste do reflexo vermelho, olho operado e idade no diagnóstico e na cirurgia. Resultados: A média de idades na primeira visita e cirurgia de catarata foi de 48.9 meses (DP=50,0 meses) e 64.5 meses (DP=55.4 meses), respectivamente. O sinal mais importante apontado pelos pais foi a leucocoria. O teste do reflexo vermelho foi realizado em dois terços das crianças com resultados anormais em 28%. Histórico familiar de catarata foi evidente em 30 (20,9%) crianças (n=144). Os achados mais prevalentes em termos de histórico de problemas oculares foram: cirurgias oculares prévias em 37 (16,6%) olhos (n= 223), alterações do segmento anterior em 20 (9,0%) olhos (n=221), estrabismo em 21 (9,5%) olhos (n=220) e nistagmo em 38 (24,4%) crianças (n=156). Conclusões: Uma das causas para o atraso na admissão pode ter sido a falha em realizar o teste do reflexo vermelho, apesar de não ter sido possível verificar se todas as crianças foram submetidas ao exame. A hereditariedade foi o fator mais importante quanto à causa da catarata nessas crianças. A presença de estrabismo e nistagmo mais uma vez aponta para o diagnóstico tardio. Ausência de programas de referência e centros oftalmológicos especializados em crianças, além do número restrito de profissionais de apoio treinados na área e especialistas em oftalmologia pediátrica, foram as barreiras mais importantes para o tratamento adequado da catarata em crianças.

Gene mutation analysis of 12 families with congenital cataract / 中华实验眼科杂志

Objective:To analyze the clinical manifestations of congenital cataract in 12 families and gene variants causing the disease.Methods:The method of pedigree investigation was adopted.Clinical data of 27 patients from 12 Chinese Han families with congenital cataract were collected, and genomic DNA was extracted from peripheral blood samples of patients and family members.Candidate variants were screened by next generation sequencing and were verified by Sanger sequencing.Population frequency of the variants were obtained through the Genome Arrgregation Database (gnomAD).Pathogenicity of variants was analyzed through the Human Gene Mutation Database (HGMD), Database of Single Nucleotide Polymorphism (dbSNP) and PubMed, and the mutation effect was interpreted by protein prediction softwares including SIFT, PolyPhen_2 and MutationTaster.The conservation analysis of amino acid sequences of variants was performed by GERP+ + software.Diagnosis was confirmed by clinical ophthalmic phenotype, medical history and mutation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.KS-2018-KY-36).Written informed consent was obtained from all subjects and their guardians.Results:Pathogenic genetic variants were found in all the 12 families, 9 of which had known pathogenic variants including MIP c.97C>T, GJA8 c.593G>A, CRYBA4 c.277T>C, CRYBB2 c.563G>A and c.436G>C, CRYGC c.470G>A, CRYGD c.70C>A, PAX2 c.70dupG as well as OCRL E5-E16dup, and 3 novel potential pathogenic variants including CRYGD c.422delG, ELP4 c.886C>A and CRYBB2 c.434G>C. CRYGD c.422delG could lead to the early termination of translation of protein products, which was pathogenic.The nucleotide and amino acid sites of ELP4 c.886C>A and CRYBB2 c.434G>C were highly conserved among species, and were predicted as harmful.The 12 families were consistent with co-segregation. Conclusions:CRYGD c.422delG, ELP4 c.886C>A and CRYBB2 c.434G>C may be novel pathogenic variants of congenital cataract.

Eyeball development assessment following monocular congenital cataract extraction in different age infants / 中华实验眼科杂志

Objective To investigate the changes of the axial length,corneal curvature and refractive power in infants with monocular congenital cataract.Methods A retrospective cohort study was carried out.The clinical data of 105 eyes of 105 cases with monocular congenital cataract who were received cataract extraction during January 2015 to December 2017 were collected in the First Affiliated Hospital of Zhengzhou University.According to the initial operation age,the infants were assigned to 3-6 month old group,7-12 month old group and 13-18 month old group.The patients were followed-up for 12 months.Axial length,corneal curvature and refractive power were recorded in 3,6 and 12 months after surgery.This study followed the Declaration of Helsinki,and written informed consent was obtained from each guardian prior to any medical examination.Results The increasing value of axial length in 3-6 month old group was larger than that in 7-12 month old group,and increasing value in 7-12 month old group was larger than that in 13-18 month old group (all at P＜0.001).The increasing value of axial length of operated eyes was larger than that of fellow eyes in both 3-6 month old group and 7-12 month old group during following-up,and so was in the 13-18 month old group at 6 months and 12 months after surgery (all at P＜0.001).The ocular axial length of operated eyes was significantly shorter than that of the fellow eyes in three groups before operation (t =-10.420,P＜0.001;t=-32.288,P＜0.001;t =-2.370,P =0.024),and at 12 months after operation,the axial length of operated eyes was longer than that of the fellow eyes in the 13-18 month old group (t =18.513,P＜0.001).No significant difference was found in the axial length between operated eyes and fellow eyes in both 3-6 month old group and 7-12month old group (P =0.051,0.062).The pre-operative corneal curvature was significantly larger than that of fellow eyes in both 3-6 month old group and 7-12 month old group (both at P＜0.01),and was not significantly different in 13-18 month old group (P =0.433).There were not significant differences in corneal curvature in the three groups at 12 months after surgery (all at P＞0.05).The change value of refractive power was gradually increased as aging at 12 months after surgery (all at P＜0.001).The surgical eye amplitude of change in refractive diopter was higher than healthy eye,with significant difference between them (P＜0.001).Conclusions The developing process of axial length and corneal curvature are interacted and coordinated in bilateral eyes in infants who received extraction surgery of monocular congenital cataract.It is better to remove the cataract as early as possible in infants.Refraction of bilateral eyes still has a trend to myopia,and the shifting amplitude of myopic power decreases with aging.

The role of a femtosecond laser in congenital cataract associated with aniridia / O papel do laser de femtosegundo na catarata congênita associada à aniridia

ABSTRACT A patient with bilateral aniridia and progressive congenital cataract was treated at the age of 7 years through phacoaspiration with femtosecond laser capsulotomy, in-the-bag intraocular lens implantation, and pars plana vitrectomy (combined with posterior capsulotomy). The diameter of the planned anterior capsulotomy was 4.7 mm; however, due to elevated tension in the young capsular bag, the capsulotomy diameter increased (to around 6 mm) shortly after release of the tension by the laser. In addition, the patient had a very flat and small cornea, causing the formation of air bubbles in the curved laser interface. This was addressed by filling the gap by using a viscoelastic. A very similar situation was observed in both eyes. Use of the femtosecond laser facilitated a successful outcome in a complex congenital cataract case with a safe capsulotomy that ensured in-the-bag intraocular lens placement.

RESUMO Paciente com aniridia bilateral e catarata congê­nita progressiva foi tratado com a idade de 7 anos através de facoemulsificação com capsulotomia anterior por laser de femtosegundo, implante de lente intra-ocular e vitrectomia via pars plana (combinada com capsulotomia posterior). O diâmetro da capsulotomia anterior prevista foi de 4,7mm, porém, devido à elevada tensão do saco capsular jovem, o diâmetro da capsulotomia aumentou (para cerca de 6mm) logo após a liberação da tensão pelo laser. Além disso, o paciente tinha uma córnea muito plana e pequena, causando a formação de bolhas de ar na interface do laser. Isso foi resolvido preenchendo a lacuna usando um viscoelástico. Uma situação muito semelhante foi observada em ambos os olhos. O uso do laser de femtosegundo facilitou um resultado bem-sucedido em um caso complexo de catarata congênita com uma capsulotomia anterior segura que garantiu a colocação da lente intra-ocular dentro do saco capsular.

Frequência da microftalmia associada à catarata congênita, sua frequência etiológica e o resultado visual pós-cirúrgico / Frequency and ethiological frequency of congenital cataract associated with microphthalmia and postoperative visual results

Resumo Objetivo: Determinar a frequência da microftalmia associada à catarata congênita e sua frequência etiológica. Comparar o resultado visual após a cirurgia da catarata congênita em olhos microftálmicos, com o resultado visual obtido em olhos não microftálmicos. Método: Estudo retrospectivo de 76 pacientes portadores de microftalmia e catarata congênita, selecionados após análise de 1050 prontuários dos pacientes atendidos no ambulatório de catarata congênita da UNIFESP. A microftalmia foi determinada pela ecobiometria ultrassonica. Exames oculares e complementares foram feitos para esclarecer a causa etiológica. O resultado visual pós- operatório do Grupo I (com microftalmia) foi confrontado com o resultado visual obtido no Grupo II (sem microftalmia). Resultados: O diâmetro ântero-posterior dos olhos microftálmicos variou de 13 à 21 mm. A frequência etiológica da catarata congênita associada aos olhos microftálmicos foi assim distribuída: doenças infecciosas (55,3%); seguidos de idiopáticas (26,3%), colobomas (7,9%), hereditárias (6,6%), persistência do vítreo primário hiperplásico (2,6%) e associada à síndrome de Lenz (1,3%) .A frequência da microftalmia foi de 7,23 %. 68,3% de olhos afácicos microftálmicos atingiram visão melhor e ou igual à 20/200. Conclusão: A frequência da microftalmia associada à catarata congênita foi de 7,23%. A maior frequência etiológica ocorreu nas doenças infecciosas (55,3%), Embora os olhos microftálmicos tenham tendência para piores resultados visuais quando comparados aos não microftálmicos, nesta pesquisa os olhos microftálmicos afácicos que atingiram visão melhor ou igual a 20/200 foram de 68,3%.

Abstract Objective: To determine the frequency of microphthalmia associated with congenital cataract and its etiological frequency. Compare the result of visual acuity in aphakic microphthalmus eyes, with the visual acuity result obtained in non microphthalmus eyes. Methods: Retrospective study of 76 patients with microphthalmia and congenital cataract, selected after analysis of 1050 medical records of patients seen in congenital cataract clinic of UNIFESP. All patients underwent complete ophthalmologic examination and microphthalmia determined by ultrasound biometry. Investigations were made to clarify the etiological cause. The postoperative visual outcome of Group I (with microphthalmia) was faced with the visual results obtained in Group II (control group without microphthalmia). Results: The anteroposterior diameter of microphthalmus eyes ranged from 13 to 21 mm. The etiological frequency of microphthalmia and congenital cataract was distributed as follows: infectious diseases (55.3%), idiopathic (26.3%), colobomas (7.9%), hereditary (6.6%), persistent hyperplastic vitreous (2.6%) and linked to the Lenz's syndrome (1.3%). The visual acuity in aphakic eyes that reached better view and or equal to 20/200 was 68.3%. Conclusion: The frequency of microphthalmia associated with congenital cataract was 7.23%. The etiological occurred more frequently in infectious disease (55.3%). The aphakics eyes with microphthalmia tend to have worse visual acuity results than the eyes without microphthalmia. If we consider the visual results same and above 20/200 as successful in this search, aphakic eyes with microphthalmia that hit these indices are 68.3%.

Timing and visual changes of secondary intraocular lens implantation in infants with congenital cataract / 中华实验眼科杂志

Background Bilateral congenital cataract is one of the vision-threating diseases during infant age.Intraocular lens (IOL) implantation is an ideal refraction correction method for children who have already received bilateral cataract extraction.However,the timing and effectiveness of secondary IOL implantation are still under debate.Objective This study was to analyze the visual changes and affecting factors before and after secondary IOL implantation and explore the operative timing.Methods The clinical data of 58 eyes of 29 patients who received bilateral cataract extraction-refractive correction and vision training-secondary IOL implantation in Peking University People's Hospital from January 2012 to December 2014 were retrospectively analyzed.All the patients received bilateral cataract extraction and posterior capsulotomy with anterior vitrectomy during their first year of life firstly,followed by the wearing of refractive spectacles or visual training,and secondary IOL implantation was simultaneously performed until ＞2 years old.Best corrected visual acurity (BCVA) (LogMAR) was examined at 1 week before and 3 months after secondary surgery under the mydriasis.Changes,distribution alternation of BCVA and the relationship of visual prognosis with preoperative visual acuity were evaluated.Results The average age at surgery of the patients was (3.26±2.07) months and that at secondary IOL implantation was (4.79± 1.38) years,with the operative interval of (4.28± 1.33) years.The BCVA before and after secondary IOL implantation was 0.790± 0.422 and 0.570±0.307 respectively,showing a significant difference between them (t =3.223,P＜0.001).The number of eyes with BCVA ≥ 0.5 after surgery was significantly more than that before surgery (x2=53.931,P＜0.001).A positive correlation in unilateral BCVA was seen between before and after secondary IOL implantation (R2 =0.232,F =17.037,P ＜ 0.001).Conclusions A systemic management of bilateral cataract extractionrefractive correction and vision training-secondary IOL implantation for congenital cataract is beneficial to BCVA improvement and amblyopia treatment,and it should be performed as early as possible on the premise of ensuring the safety of life.Secondary IOL implantation should be timely carried out for aphakic children with poor compliance and outcomes during vision training after congenital cataract extraction.

Congenital and developmental cataract: axial length and keratometry study in Brazilian children / Catarata congênita e do desenvolvimento: estudo do comprimento axial e da ceratometria em crianças brasileiras

ABSTRACT Purpose: To evaluate the ocular axial length (AL) and keratometry (K) in Brazilian children with congenital/developmental cataract, assess the differences and evolution of AL and K according to age, and establish functional models of AL and K as function of age. Methods: Children with congenital/developmental cataract aged 1.5 months old to 8 years old and no other ocular diseases were included. All eyes with unilateral cataract, the left eyes from children with bilateral cataracts, and healthy eyes from children with unilateral cataract were analyzed. After the administration of anesthesia, K was measured with a portable automatic keratometer, and AL was measured with a contact biometer. Cataract surgery was performed immediately after the measurements were taken. The data were statistically analyzed, and a linear regression with an age logarithm was used to model the relationship. Results: Forty-four eyes with cataract were included in this analysis, comprising 15 eyes with unilateral cataract and 29 left eyes from children with bilateral cataracts. The mean age was 27.3 months with a mean AL of 20.63 ± 2.11 mm and a mean K of 44.94 ± 2.44 D. The K value was significantly steeper and the AL value was significantly shorter in younger children (P< 0.001). No significant differences were found neither between eyes with unilateral and bilateral cataracts nor between eyes with unilateral cataract and their corresponding healthy eyes (P >0.05). Conclusion: The values of K and AL significantly change with age, especially during the first 6 months of life. A linear functional relationship between K and AL with the logarithm of age and between K and AL was established.

RESUMO Objetivo: Avaliar o comprimento axial (AL) e a ceratometria (K) de olhos de crianças brasileiras com catarata congênita/desenvolvimento, analisar diferenças e evoluções de acordo com a idade e estabelecer modelos funcionais de comprimento axial e ceratometria em função da idade e entre eles. Métodos: Crianças com catarata congênita/desenvolvimento com idade de 1,5 meses a 8 anos de idade e sem outras doenças oculares foram incluídas. Todos os olhos com catarata unilateral, o olho esquerdo de crianças com catarata bilateral e o olho sadio de crianças com catarata unilateral foram analisados. Após a administração de anestesia, a ceratometria foi obtida com um ceratômetro automático portátil e o comprimento axial medido com um biômetro de contato. Em seguida, a cirurgia de catarata foi realizada. Os dados foram analisados estatisticamente, a regressão linear com o logaritmo da idade foi utilizado para modelar os relacionamentos. Resultados: Todos os olhos com catarata unilateral (n=15) e um olho selecionados aleatoriamente a partir dos casos bilaterais (n=29) foram incluídos na análise (total= 44 olhos). A idade média foi de 27,3 meses, as médias do comprimento axial e da ceratometria foram respectivamente 20,63 ± 2,11 mm e 44,94 ± 2,44 dioptrias. A ceratometria foi significativamente mais curvo e comprimento axial significantemente mais curto em crianças mais jovens (P<0,001). Não foram encontradas diferenças significativas na comparação entre os olhos com cataratas unilaterais e bilaterais e comparando os olhos com catarata unilateral a correspondentes olhos saudáveis (P>0,05). Conclusão: Os valores de ceratometria e comprimento axial mudam significativamente com a idade, principalmente nos primeiros seis meses de vida. Foi estabelecida uma relação funcional linear entre comprimento axial e ceratometria com o logaritmo da idade e entre ceratometria e comprimento axial.

Intraocular lenses and clinical treatment in paediatric cataract

Pediatric cataract is the most common treatable cause of blindness in children. Prevalence, etiology and morphology vary with the socioeconomic development. The treatment goal is to reduce amblyopia, being difficult management especially in unilateral cases. The decision on aphakia or primary intraocular lens should be individualized as well as correction with contact lens or spectacles. The intraocular lens single-piece hydrophobic acrylic are the most implanted in children and the preferably is in the capsular bag. The Sanders-Retzlaff-Kraff theoretic (SRK/T) stressing that is described as more predictable, following Holladay I and SRK II and the recommendation is to under correction +6.0 or +8.0 dioptrias expecting the growth of the eye. The posterior capsule opacity is the most frequent complication and varies with the material choice of the lens. Glaucoma is the most serious postoperative complication and depends on the timing of the surgery, primary lens implantation and time of post surgical follow-up. The adherence to occlusion therapy with patching is critical to the visual prognosis and is determined by the child’s age and laterality of the cataract. There was significant improvement in the surgery and in IOLs, however the final visual prognosis is still not desirable.

A catarata pediátrica é a causa mais comum de cegueira tratável em crianças. Prevalência, etiologia e morfologia variam conforme o desenvolvimento sócioeconômico. O tratamento tem como objetivo diminuir a ambliopia, sendo de difícil manejo principalmente em casos unilaterais. A decisão sobre afacia ou implante primário de lente intraocular deve ser individualizado, assim como a correção com lente de contato ou óculos. As lentes intraoculares acrílicas hidrofóbicas de peça única são as mais implantadas em crianças com preferência de implante no saco capsular. A fórmula biométrica Sanders-Retzlaff-Krafftheoretic (SRK/T) é a mais precisa em pacientes pediátricos, seguida de Holladay I e SRK II, com recomendação de sob correção de +6 a +8.0 dioptrias, devido ao esperado crescimento rápido do globo ocular. A opacidade de cápsula posterior é a complicação mais frequente e varia com o material da lente a ser implantada e o glaucoma é a complicação pós-operatória mais grave e depende da idade da criança na cirurgia, implante primário de LIOs e da duração do acompanhamento pós-cirúrgico. A adesão ao tratamento oclusivo é fundamental para o prognóstico visual, sendo determinado de acordo com a idade da criança e a lateralidade da catarata. Mesmo com a melhora do tratamento cirúrgico e das lentes intraoculares o prognóstico visual final ainda não é o desejável.

A recurrent mutation of CRYGD gene in a northern Chinese family with autosomal dominant congenital nuclear cataract / 中华实验眼科杂志

Background Congenital cataract is a major cause for blindness of childhood.Genetic gene mutation accounts for almost 1/3 of congenital cataract patients.The most common inheritance type is autosomal dominant congenital cataract (ADCC).Over 100 mutations in 26 genes have been found to be associated with ADCC.Objective This study was to identify the disease-causing gene mutation in a family with ADCC.Methods This study was approved by Ethic Committee of Beijing Tongren Hospital and followed Declaration of Helsinki.A northern Chinese family with autosomal dominant congenital nuclear cataract was entrolled in Beijing Tongren Hospital in January 2011.Ocular examinations were performed and periphery blood specimens were collected from each family member under the informed consent.Genomic DNA was extracted.Twenty-one microsatellite markers around 17 ADCC genes were selected for linkage analysis,and two-point LOD score was calculated.CRYGC gene and CRYGD gene were amplified and screened for mutations using direct sequencing.ProtScale software was used to analyze the changes of hydrophobicity of the mutated protein.Co-segregation of the observed change with the disease phenotype was further detected by restriction fragment length polymorphism (RFLP).Results This family included 20 members of 4 generations,and 9 patients were examined in serial 4 passages,which conformed to autosomal dominant inheritance pattern.Clinical examination revealed binocular congenital nuclear cataract in the 9 patients.Maximum two-point LOD score was 4.68 at marker D2S325 (θ=0).A known T→C change at position 127 of cDNA sequence was found by mutations screening of CRYGD gene.ProtScale programs showed an obvious increase of the local hydrophobicity in the mutant protein.RFLP results indicated that this missense mutation co-segregated with affected members of the family,but was absent in unaffected members and 100 unrelated controls.Conclusions c.T127C mutation of CRYGD gene appears to be the molecular pathogenesis of this ADCC family.Aberrant structure of mutant CRYGD protein caused by hydrophobicity change may lead to opacification of lens.

Late diagnosis and surgical treatment of patients diagnosed with unilateral congenital cataract at Fundación Visión, in Asuncion, Paraguay / Diagnóstico tardio e tratamento cirúrgico de pacientes diagnosticados com catarata congênita unilateral na Fundación Visión, em Assunção, Paraguai

Purpose: Providing data on the late diagnosis and surgical treatment of patients who underwent surgery for total unilateral congenital cataract. Methods: Systematic retrospective review of the medical record of all patients between 0 and 16 years old with total unilateral congenital cataract who underwent surgery at Fundación Vision between January 2010 and July 2012. Results: Medical records of 37 patients (51 % females) were studied, age was 7.4 (± 4.9) years (average ± SD) and 62% lived on Departamento Central (the most populated region from Paraguay). A total of 97.3% patients underwent late surgical treatment and 86.5% received a late diagnosis. The average time elapsed between the diagnosis and the surgical treatment was one month, and 62.2% of the patients underwent surgery within six months from the diagnosis. Conclusion: This study evidences that most of the patients in our series had a late treatment as a result of a late diagnosis. Based on these results we recommend establishing strategies to improve the early detection and surgical treatment of the newborns. .

Objetivo: Fornecer dados sobre o diagnóstico tardio e o tratamento cirúrgico de pacientes submetidos à cirurgia de catarata congênita unilateral total. Métodos: Análise retrospectiva sistemática do prontuário de todos os pacientes entre 0 e 16 anos de idade com catarata congênita unilateral total, e que se submeteram à cirurgia na Fundación Visão, entre janeiro de 2010 e julho de 2012. Resultados: Prontuários de 37 pacientes (51% mulheres) foram estudados, a idade foi de 7,4 (± 4,9) anos (média ± SD) e 62% viviam no Departamento Central (a região mais populosa do Paraguai). Um total de 97,3% dos pacientes foi submetido ao tratamento cirúrgico tardio e 86,5% apresentaram um diagnóstico tardio. O tempo médio decorrido entre o diagnóstico e o tratamento cirúrgico foi de um mês, e 62,2% dos pacientes foram submetidos a cirurgia no prazo de seis meses a partir do diagnóstico. Conclusão: Este estudo evidencia que a maioria dos pacientes da nossa série teve um tratamento final tardio, como resultado de um diagnóstico tardio. Com base nesses resultados, recomendamos o estabelecimento de estratégias para melhorar a detecção precoce e o tratamento cirúrgico dos recém-nascidos. .

Current research in congenital cataract genes / 中华实验眼科杂志

Congenital cataract is the leading cause for low vision and blindness in infancy and childhood.One third of congenital cataract cases are associated with genetic mutation and hereditary,and the etiology of congenital cataract is heterogenous and its phenotype is variable.The known mutation genes include encoding structural lens protein,gap junction protein,membrane protein and lens-developing-related regulatory protein.Location and identification of mutation genes in congenital cataract patients are necessary for us to understand the molecular defects and pathophysiologic features of congenital cataract.With the development of molecular biology techniques,the study on the mechanism of congenital cataract has made great progress,which is helpful for us to further understand the heredity pattern as well as the influence of environment and nourishment to the metabolism of lens.The purpose of this review was to summarize the literature of current advance in the study on molecular genetic basis of congenital cataract.

Current research on molecular genetics of congenital cataract / 中华实验眼科杂志

Congenital cataract accounts for 10％ of childhood blindness worldwide and is the second leading cause of childhood blindness in China.30％-50％ of congenital cataract patients are caused by heritability,and majority of them is autosomal dominant traits.In addition,autosomal recessive and X-linked fashion also are found to lead to congenital cataract.Up to now,more than 20 disease-causing genes and 100 mutation locus have been mapped to different chromosomal locations in the human genome using genetic linkage methods.The cataract-associated genes were classified as four categories,including crystallin gene,membrane protein gene,transcription factor regulatory gene and others,and they induce different phenotypes of cataract by different molecular mechanisms.To understand the disease-causing genes and their mechanism is helpful for the genetic diagnosis and treatment of congenital cataract.The current researching progress in molecular genetics of cataract is summarized in this review.

Molecular mechanism of congenital cataract induced by heat shock transcription factor 4 gene mutation in lop11 mouse / 中华实验眼科杂志

Background Mutation of the heat shock transcription factor 4 (HSF4) gene causes autosomal recessive hereditary cataract in lens opacity locus 11 (lop1 1) mouse,but the molecular mechanism of the pathogenesis has not been determined.Objective This study was to investigate the molecular mechanism of congenital cataract induced by HSF4 gene mutation in lop1 1 mouse.Methods Twenty-four lop1 1 mice and 24 wild type C57BL/6 mice were used in this study.The animals were sacrificed and the lenses were obtained on postnatal days 1,7 and 12.Regular pathological examination was carried out to evaluate the morphological changes of the lens and count the number of lens epithelial cells (LECs) in the mice.The αB-Crystallin (CRYAB) content in the lenses was detected in postnatal day 1 mice by Western blot.The expression of the fibroblast growth factor (FGF) mRNA in the lenses was assayed by quantitative PCR (q-PCR).The data were compared between the lop1 1 mice and wild type C57BL/6 mice with independent sample t test.The use and care of the experimental animals complied with the ARVO statement.Results The morphology and array of LECs were uniform and regular in the wild type C57BL/6 mice,while proliferation of LECs and disorder of lens fibers were seen in the lop11 mice on postnatal day 1.On postnatal day 7,vacuolar degeneration of the lens appeared in 7-day-old lop11 mice.The numbers of LECs were (417±19),(467±16) and (489±21) in lop11 mice on the postnatal day 1,7 and 12,respectively,and those of wild type C57BL/6 mice were (378 ± 13),(391 ±9) and (395 ±7),respectively,showing statistically significant differences between them (1 day:t=6.696,P=0.000;7 days:t=6.578,P=0.000;14 days:t=7.240,P=0.000).The expression of CRYAB in the lenses was evidently weaker in the 1-day-old lop11 mice compared with wild type C57BL/6 mice.The relative folds of expression of FGF-1,FGF-4,FGF-7 mRNA in the lenses were significantly higher in the lop11 mice than those in the wild type C57BL/6 mice (2.04±0.13 vs.1.037±0.06;2.03±0.08 vs.0.97± 0.08;4.59±0.12 vs.1.0±0.04) (FGF-1 mRNA:t=14.000,P＜0.001;FGF-4 mRNA:t=15.510,P＜0.01;FGF-7 mRNA:t =29.41,P＜0.01).Conclusions HSF4 mutation leads to the abnormal development of the lens in lop1 1 mice by arresting the expression of αB-Crystallin protein and increasing the expression of the FGF gene.

Phenotype of congenital cataract accompanied with iris dysplasia / 中华实验眼科杂志

Background Certain relationship has been found between phenotype and genes mutation of congenital cataract.It is clear that different genetic mutations can cause the same complication in congenital cataract,meanwhile,different complications may be caused by the same gene mutation.However,their mechanism is still remained unclear.Objective This study was to observe the phenotype of congenital cataract accompanied with iris dysplasia.Methods Fifteen patients with congenital cataract accompanied with iris dysplasia were included in this study.The slit lamp,gonioscope and ophthalmoscope were used for the examination of the anterior ocular segment,the anterior chamber angle and fundus on all the patients.This study was approved by the Ethic Committee of Second People' s Hospital of Yunnan Province.Written informed consent was obtained from each patient or the custodian prior to any medical procedure.Results All the patients showed binocular involvement.Congenital nuclear cataract with whole coloboma of iris was seen in 7 cases,and 2 cases showed an entire cataract associated with incomplete coloboma of iris.Entire cataract with aniridia was diagnosed in 5 patients,and suture cataract complicated with aniridia was in 1 patient.Conclusions Some regular patterns can be implied between the morphological type of cataract and iris dysplasia,which may be helpful for further study of these diseases.

Application of double capsulorhexis combined with anterior vitrectomy in children with congenital cataract / 中国基层医药

Objective To study the effect of double capsulorhexis combined with anterior vitrectomy in children with congenital cataract.Methods 42 (71 eyes) (age from 3 months to 14 years) underwent posterior continuous circular capsulorhexis (PCCC) and anterior vitrectomy after cataract extraction, and intraocularlens (IOL) were implanted in some eyes.The median follow-up time was 24 months.Results Among the 61 eyes of 37 patients who could do the visual examination,39 eye shada corrected visual acutiy of 0.5 or better, 16 eyes had a corrected visual acutiy of 0.3 or better;6 eyes had a corrected visual acuity of 0.3 or below.The postoperative complications included uveitis in 9 eyes,cornealede main 8 eyes,posterior capsular opacity(PCO) in 5 eyes.Some severe complications such as off centre IOL,cystoid macularedema and retinal detachment did not occur.Conclusion The double capsulorhexis combined with anterior vitrectomy and IOL implanted into eye should be a safe and effective method to prohibit after cataract in children with congenital cataract.

The creation and study of an inherited congenital cataract model in rats / 眼科

We used the teratogen 5-hromodeoxy- uridine(BRDU)in the creation of a model of inherited congenital cataract in Wistar rats.The highest rate of impregnation(81%) of the rats was observed during the period oestrus.The frequency of occurrence and the density of the congenital cataract in the F1 generation varied with the dosage of BRDU,and the frequency of the cataract in the F2 generation was positively correla- ted with the dosage of the drug.The crea- tion of this inherited congenital cataract model may be useful in exploring the etio- logy of the cataract and its prevention and treatment.

Gene mapping of a congenital nuclear cataract in a Chinese family / 解放军医学杂志

Objective Mapping the responsible gene for congenital nuclear cataract in a family for five generations in Yantai City,Shandong Province,China.Methods Family history and clinical data were recorded.9 unaffected members and 13 affected members in this family were involved in the study.The genes of all the involved members were amplified by polymerase chain reaction(PCR).28 microsatellite polymorphism in the 15 reported disease loci were used as genetic markers.The PCR products from each DNA sample were separated on a 6% polyacrylamide gel and analyzed.Allele-sharing analysis was carried out for exclusion,and linkage analysis was calculated with the LINKAGE(Version 5.1)package.Direct sequencing was used for GJA3 gene.Results The clinical phenotype in this family was isolated congenital nuclear cataract,the pathogenic nutation of the phenotype of which has not been reported yet.For all the 28 markers around the 15 candidate loci,there was no allele-sharing between the affected family members.At the 0.00 recombination frequency,the LOD score was-∝ in 27 of the 28 microsatellite markers with exception of D11S898.No GJA3 gene mutation was found.It indicated that there was no linkage between these markers and the pathogenic gene in this family.Conclusion The responsible gene for the congenital nuclear cataract in this family is not located on the 15 reported loci,which further indicates the clinically and genetically heterogeneity of inherited cataract,and an important clue is provided for finding more cataract responsible genes.The pathogenic gene in this family should be identified through extensive scanning of genes.