Heterocromia de íris: uma revisão das condições que podem afetar a pigmentação iridiana / Heterochromia: a review of conditions that may affect iris pigmentation

RESUMO A íris é responsável pela cor dos olhos. Ela ainda realiza o controle da quantidade de luz que penetra no olho pela pupila. Variações nos genes de cada indivíduo, além da quantidade e da qualidade de melanina na íris, determinam a cor dos olhos. A heterocromia é caracterizada por diferenças na coloração da íris de um mesmo indivíduo, sendo, na maioria das vezes, benigna. Existem basicamente três tipos de heterocromia de íris: central, setorial e completa. A heterocromia de íris pode ter como causa alterações genéticas e congênitas, relacionadas ou não a síndromes específicas, como a de Sturge-Weber, a de Waardenburg, a de Parry-Romberg e a de Horner congênita. Há também causas adquiridas, como doenças ou lesões, trauma ocular e corpos estranhos intraoculares, uso de certas medicações tópicas, siderose ocular, irites ou uveítes como a síndrome uveítica de Fuchs, dentre outras. Diante de um paciente com heterocromia de íris, deve-se entender o contexto e o curso clínico desse sinal, pois pode se tratar de uma alteração de pigmentação benigna ou existir uma doença base em curso, que requer terapêutica específica. Este artigo de revisão de literatura visa abordar as principais etiologias relacionadas à heterocromia de íris, além de discorrer sobre a anatomia e a fisiologia da coloração iridiana e sobre a fisiopatologia de suas possíveis alterações.

ABSTRACT The iris is responsible for eye color and controls the amount of light that enters the eye through the pupil. Variation in each individual's genes, besides the quantity and quality of melanin in the iris, determine eye color. Heterochromia is characterized by different colors of irises in the same individual, and it is benign in most cases. There are basically three types of heterochromia: central, partial and complete. Heterochromia can be caused by genetic and congenital alterations, which may or may not be related to specific conditions, such as Sturge-Weber syndrome, Waardenburg syndrome, Parry-Romberg syndrome and congenital Horner syndrome. It may be associated to acquired causes like diseases or injuries, such as eye trauma and intraocular foreign bodies, use of some topical medications, ocular siderosis, iritis or uveitis, such as Fuchs´ uveitis, among others. When assessing a patient with heterochromia, one must understand the context and clinical course of this signal, since it may be a benign pigmentation disorder or there may be an underlying disease, which requires specific therapy. This literature review article was set out to address the main etiologies related to heterochromia, in addition to describing the anatomy and physiology of the iris color and the pathophysiology of possible alterations.

Manifestaciones oftalmológicas compatibles con el síndrome de Waardenburg / Ophthalmological manifestations compatible with Waardenburg syndrome

RESUMEN El síndrome de Waardenburg es una enfermedad genética, con criterios diagnósticos como la distopia cantorum, las anomalías pigmentarias del iris, el hipertelorismo y la conjunción de las cejas. Se presentan dos casos de una misma familia quienes asistieron a la consulta de Oftalmología con manifestaciones compatibles con el síndrome de Waardenburg. Paciente de 12 años con asociación típica que inclu ye conjunción de las cejas, alteraciones en la pigmentación del iris (iris azul zafiro) y distopia cantorum, a los que se le une el antecedente de hipoacusia. Su madre, paciente de 37 años de edad, quien presenta la asociación típica, inclu ye alteraciones en la pigmentación del cabello (mechón de canas) y del iris (iris azul zafiro), distopia cantorum y antecedente de hipoacusia. El propósito de este estudio fue dar a conocer dos casos de la misma familia con una entidad infrecuente en la especialidad. No obstante, se pueden encontrar manifestaciones oftalmológicas que son compatibles con su diagnóstico, por lo que es elemental dirigir nuestra acción hacia una aten ción en forma interdisciplinaria y una remisión oportuna(AU)

ABSTRACT Waardenburg syndrome is a genetic disorder with diagnostic criteria such as dystopia canthorum, iris pigmentary abnormalities, hypertelorism and synophrys. A case is presented of two members of the same family who attend the ophthalmology service for manifestations compatible with Waardenburg syndrome. The two patients are a 12-year-old girl with a typical association, which includes synophrys, iris pigmentary alterations (brilliant blue iris) and dystopia canthorum, as well as a history of hypoacusis, and her 37-year-old mother, who presents the typical association, which includes alterations in the pigmentation of her hair (a forelock of white hair) and iris (brilliant blue iris), dystopia canthorum and a history of hypoacusis. The purpose of the study is to present two cases from the same family with a condition which is infrequent in the specialty. However, ophthalmological manifestations may be found which are compatible with its diagnosis, which should obviously enough lead to actions aimed at interdisciplinary care and timely referral(AU)

Bilateral clear lens extraction and intraocular lens implantation in a child with microspherophakia and Marfan syndrome / Extração bilateral de cristalino transparente e implante de lente intraocular em criança com microesferofacia e síndrome de Marfan

ABSTRACT We report the case of a 4-year-old boy with Marfan syndrome whose parents reported he had had low visual acuity since birth. On examination, there was microspherophakia and a small subluxation of the lens. The objective refraction was -23.75 - 2.75 x 70 in the right eye and -25.50 -3.50 x 90 in the left eye. Since the microspherophakia and the high myopia severely affected the boy's quality of life, clear lens extraction, anterior vitrectomy, posterior surgical capsulotomy via the pars plana, and intraocular lens implantation were performed. Two years postoperatively, the patient had centered intraocular lenses and a corrected visual acuity of 20/30 in both eyes. The child was satisfied with his vision and was able to study and perform daily activities without visual limitations.

RESUMO Reportamos o caso de um menino de 4 anos de idade com Síndrome de Marfan, cujos pais referiam que o mesmo apresentava baixa acuidade visual desde o nascimento. Ao exame oftalmológico, observou-se microesferofacia e discreta subluxação do cristalino bilateralmente. A refração estática era -23.75 - 2.75 x 70 no olho direito e -25.50 -3.50 x 90 no olho es querdo. Como a microesferofacia e a alta miopia traziam sérios prejuízos à qualidade de vida do paciente, foi submetido à facoemulsificação de cristalino transparente, vitrectomia anterior, capsulotomia posterior via pars plana e implante de lente intrao cular. Em seguimento pós-operatório de dois anos, mantinha lentes intraoculares centradas, eixo visual livre, acuidade visual corrigida de 20/30 em ambos os olhos. Paciente satisfeito com a visão podendo estudar e exercer todas as atividades do dia a dia sem limitações visuais.

Síndrome iridocorneoendotelial: variedad Chandler / Iridocorneal endothelial syndrome in Chandler variety

En el síndrome iridocorneoendotelial se unifican diferentes variaciones clínicas de una misma entidad. El denominador común de todas ellas es una peculiar anormalidad de las células endoteliales, alteraciones del iris y el desarrollo de glaucoma, generalmente unilateral y más común en mujeres. Se presenta un caso clínico de la variedad Chandler, quien acudió a la consulta de catarata, con este diagnóstico en el ojo derecho. Se realiza cirugía de catarata en ambos ojos con excelentes resultados y control de la presión intraocular(AU)

Iridocorneal endothelial syndrome comprises different clinical variations of the same disease. The common features of all them are peculiar anomaly of the endothelial cells, alterations of the iris and the onset of glaucoma, generally unilateral and more common in women. A clinical case of the Chandler variety is presented, which is a woman with cataract, and iridocorneal endothelial syndrome diagnosis on the right eye. Cataract surgery was performed in both eyes with excellent results and control of the intraocular pressure(AU)

Pupilloplasty in a patient with true polycoria: a case report / Pupiloplastia em um caso de policoria verdadeira

ABSTRACT Here we report a case of surgical pupilloplasty in an adult with true polycoria. A 44-year old man was referred to our clinic with a best-corrected visual acuity (BCVA) of 0.5 diopters (D) in his left eye. Biomicroscopy revealed two pupils within a 2.5-mm central zone, with diameters of 1.2 and 1.1 mm. Both pupils had real iris sphincters and responded to light and chemical stimulation. Therefore, we surgically cut the bridge between the two pupils without any intraoperative or postoperative complications. One month after the surgery, BCVA had improved to 0.9 D, and the final pupil was almost round, measuring 2.7 mm in diameter.

RESUMO Relatamos um caso de pupiloplastia cirúrgica em um paciente adulto com policoria verdadeira. Um homem de 44 anos de idade foi encaminhado ao nosso serviço com acuidade visual melhor corrigida (BCVA) de 0,5 em seu olho esquerdo. Biomicroscopia revelou 2 pupilas, dentro de uma zona central de 2,5 milímetros com dimensões de 1,2 mm e 1,1 mm de diâmetro. Ambas as pupilas apresentavam esfíncteres irianos reais que respondiam à luz e a drogas. A ponte entre as 2 pupilas foi cortada cirurgicamente. Não houve complicações transoperatórias ou pós-operatórias. A BCVA melhorou para 0,9, e a pupila ficou quase circunferencial com 2,7 mm de diâmetro, um mês após a cirurgia.

Coexistence of optic pit and coloboma of iris, lens, and choroid: a case report / Coexistência de fosseta óptica e coloboma de íris, cristalino e coroide: um primeiro relato de caso

ABSTRACT A 42-year-old woman was admitted to our clinic with a complaint of glare in both eyes. Biomicroscopic examination of both the eyes revealed iris and lens colobomas in the inferior quadrant. Fundus examination of the right eye revealed an oval and gray inferotemporal optic pit and two choroid colobomas in the inferior quadrant. In the left eye, two choroid colobomas were detected that were inferior to the optic nerve head. Furthermore, a 21-year-old man presented to our clinic for a routine ophthalmologic examination. Bilateral biomicroscopic examination was normal. Fundus examination of the left eye revealed an oval and gray inferotemporal optic pit and a choroid coloboma that was inferior to the optic nerve head. Here we describe optic pits co-occurring with iris, lens, and choroidal colobomas. On the basis of these cases, a defect in the closure of the embryonic fissure is the most plausible etiology of the optic pit.

RESUMO Uma mulher de 42 anos de idade foi internada em nossa clínica com queixa de ofuscamento em ambos os olhos. O exame biomicroscópico revelou coloboma de íris e cristalino no quadrante inferior em ambos os olhos. O exame de fundo do olho direito revelou um fosseta óptica oval e acinzentada na região inferotemporal e dois colobomas coroide no quadrante inferior. No olho esquerdo, dois colobomas de coroide foram detectados inferiormente à da cabeça do nervo óptico. Outro homem de 21 anos apresentou-se em nossa clínica para um exame oftalmológico de rotina. O exame biomicroscópico foi normal, bilateralmente. O exame de fundo do olho esquerdo revelou uma fosseta oval e acinzentada de nervo óptico óptico inferotemporal e um coloboma coroide inferior à cabeça do nervo óptico. Nestes relatos nós descrevemos fossetas ópticas ocorrendo simultaneamente com colobomas de íris, cristalino, e coroide. Com base nestes casos, o defeito no fechamento da fissura embrionária é uma provável etiologia da fosseta óptica.

Baraitser-winter syndrome: an additional Egyptian patient with skeletal anomalies, bilateral iris and choroid colobomas, retinal hypoplasia and hypoplastic scrotum

We report a 3.5 year old male child, second in order of birth of non consanguineous Egyptian parents with Baraitser-Winter syndrome [BRWS]. The patient had bilateral colobomas of the iris and choroid. Our patient had also retinal hypoplasia, which was not reported previously in this syndrome, bilateral congenital ptosis, hypertelorism, moderate mental retardation, short stature, short neck, hyperextensibility of the joints of the hands, talipes equinovarus, kyphoscoliosis and unilateral hypoplastic scrotum and testis

Síndrome de Waardenburg: aspectos oftalmológicos e critérios de diagnóstico: relatos de casos / Waardenburg syndrome: ophthalmic findings and criteria for diagnosis: case reports

OBJETIVO: Descrever as características clínicas e imaginológicas de duas famílias com a síndrome de Waardenburg, sendo uma do tipo I e outra do tipo II, enfatizando as manifestações oftalmológicas, bem como o padrão de herança genética. MÉTODO: Realizou-se um estudo clínico envolvendo as duas famílias afetadas pela síndrome de Waardenburg, sendo, através dos heredogramas, determinado o padrão de herança genética presente. Também foram realizadas análises oftalmológicas abordando a medida da acuidade visual, a presença de distopia cantorum (telecanto), a avaliação da coloração da íris e o mapeamento de retina, além de exames otológicos e dermatológicos. RESULTADOS: O heredograma da família afetada pela síndrome de Waardenburg tipo I revelou um modo autossômico dominante de transmissão. A condição estava presente em 85,71% dos pacientes. A distopia cantorum foi a alteração mais frequente, seguida pela mecha branca na pele da fronte, hipopigmentação da íris e da retina e surdez neurossensorial. A família com síndrome de Waardenburg tipo II apresentou 33,33% dos familiares com a alteração. Nenhum membro apresentou distopia cantorum e hipopigmentação de íris. Três pacientes apresentaram surdez neurossensorial (12,5%), associada ao topete branco e manchas acrômicas confluentes pelo corpo. CONCLUSÃO: O presente estudo mostra a importância do oftalmologista no auxílio do diagnóstico desta rara condição genética, uma vez que inclui alterações oftalmológicas como telecanto, hipopigmentação da íris e retina. A distopia cantorum é o principal critério diagnóstico para diferenciar o tipo I do II e deve ser feita por oftalmologista treinado. As famílias encontram-se em acompanhamento multiprofissional, tendo recebido orientações genéticas e os cuidados referentes à proteção ocular.

PURPOSE: To describe the clinical and imaginological features of two families with Waardenburg syndrome: type I and II, with emphasis on ophthalmic manifestations, as well as the pattern of genetic inheritance. METHODS: We conducted a clinical study involving two families affected by Waardenburg syndrome, and through the pedigree, determined the present pattern of genetic inheritance. Analyses were performed including the measurement of visual acuity, the presence of dystopia cantorum (telecanthus), evaluation of iris color and retinal mapping, as well as dermatological and otological examinations. RESULTS: The pedigree of the family affected by the Waardenburg syndrome type I showed an autosomal dominant mode of transmission. The syndrome was present at 85.71% of patients. The dystopia cantorum was the most frequent feature, followed by the white streak on the skin of the forehead, hypopigmentation of the iris and retina and deafness. The Waardenburg syndrome family type II had 33.33% of family members affected by the syndrome. No member had dystopia cantorum and hypopigmentation of the iris. Three patients had sensorineural hearing loss (12.5%), associated with white forelock and achromatic spots confluent by the body. CONCLUSION: This study shows the importance of the ophthalmologist in aiding the diagnosis of this rare genetic condition, since it includes ocular disorders such as telecanthus, hypopigmentation of the iris and retina. The cantorum dystopia is the main diagnostic criterion to differentiate type I and II syndrome and should be done by a trained ophthalmologist. The families are in medical monitoring, receiving genetic guidelines and care related to eye protection.

Prevalence of plateau iris configuration in primary angle closure glaucoma using ultrasound biomicroscopy in the Indian population.

Purpose: To report the prevalence of plateau iris in patients with primary angle closure glaucoma (PACG), in North India. Materials and Methods: The patients with PACG, attending the glaucoma services at a tertiary care center in North India were included in the study. All patients had undergone Nd-YAG laser peripheral iridotomy at least four weeks prior to inclusion in the study. Four weeks prior to inclusion in the study, none of the patients had used pilocarpine. Ultrasound Biomicroscopy (UBM) images were qualitatively evaluated and plateau iris configuration was defined in an eye if the following criteria were fulfilled in two or more quadrants: anteriorly directed ciliary process supporting the peripheral iris, steep rise of iris root from its point of insertion followed by a downward angulation from the corneoscleral wall, absent ciliary sulcus, and iridotrabecular contact in the same quadrant. Results: One hundred and one eyes were included in the study. There were 63 (62.4%) females and 38 (37.6%) males. The mean age of the patients was 57.8 ± 9.5 years (range: 42 to 78 years). The mean axial length in the study population was 22.2 ± 1.1 mm. The mean spherical equivalent refraction was 0.06 ± 1.12 D. The mean intraocular pressure was 18.5 ± 4.7 mmHg (range: 12 – 24 mmHg). Twenty-nine (28.7%) subjects were diagnosed with plateau iris on the basis of above-defined criteria. Of the 29 eyes, 18 (62.1%) subjects had plateau iris in two quadrants, nine (31.03%) in three quadrants, and two (6.8%) had this configuration in all the four quadrants. Conclusions: Approximately 30% of the eyes with PACG had plateau iris on UBM. Plateau iris was very often the cause for residual angle closure following laser peripheral iridotomy in Indian eyes with PACG.

Bilateral multiple primary iridociliary cysts - a rare case report

Iridociliary cysts are often found in patients as an incidental finding during a routine ophthalmic evaluation and if asymptomatic do not require any treatment per se. However, these are often mistaken as iris melanoma and the patient is managed accordingly causing a great deal of inconvenience to the patient as well as the doctor. A 69 year old male presented to the ophthalmic out-patients department for routine ophthalmic evaluation. On examination, he is best corrected visual acuity was 6/9, N6 in both eyes. Post-mydriasis evaluation showed a Grade II nuclear cataract in both eyes. There was a smooth, pigmented mass with a rounded surface projecting from behind the iris resembling an iris melanoma. On further evaluation, he was found to have multiple ciliary body cysts. Ultrasound biomicroscopy is a valuable technique in diagnosing iridociliary cysts

Single lens to lens duplication: the missing link.

Congenital anomalies of the lens include a wide range from lens coloboma to primary aphakia and doubling of lens. There have been few case reports of double lens; the etiology suggested is metaplastic changes in the surface ectoderm that leads to formation of two lens vesicles and hence resulting in double lens. We report a case with bilobed lens, which raises the possibility of explaining the etiology of double lens.

Síndrome de Íris Plateau: relato de 17 casos / Iris Plateau syndrome: case report of 17 cases

Objetivo: Relatar 17 casos diagnosticados como Síndrome da Íris Plateau (17 olhos), enfocando a apresentação clínica, abordagem diagnóstica e conduta. Métodos: Os pacientes foram diagnosticados como Síndrome de Íris Plateau, baseado nos exames de gonioscopia e biomicroscopia ultra-sônica (UBM), realizados após a iridectomia a laser. Todos os pacientes foram acompanhados por um período de tempo médio de 46,7 + 11,7 meses. Aforma completa da síndrome foi determinada pela presença de crise congestiva recidiva ou teste da prono-posição em quarto escuro positivo. Resultados: No primeiro grupo, oito olhos se apresentaram na primeira consulta com glaucoma agudo. Dois destes olhos apresentaram teste provocativo positivo (2) após a iridectomia e seis deles apresentaramcrise congestiva recidiva durante o tempo de seguimento - síndrome da íris em Plateau completa. No segundo grupo, nove olhos não apresentaram glaucoma agudo, antes ou após a iridectomia, e devido aos achados nos exames de gonioscopia e UBM foram diagnosticados como portadores do mecanismo da íris em Plateau – possíveis casos de síndrome da íris em Plateau incompleta. Mesmo após a realização da iridectomia,dois olhos do segundo grupo apresentaram progressão das sinéquias anteriores periféricas (SAP). Conclusão: Casos de síndrome da íris em Plateau podem evoluir apresentando crise congestiva recidiva e/ou progressão das SAP. A gonioscopia sempre deve ser realizada após a iridectomia a laser a fim de verificar a eficácia do procedimento em abrir o ângulo irido-corneano. Entretanto, estudos prospectivos longitudinais são ecessários para determinar quais os fatores de risco relacionados ao processo de fechamento angularsecundário ao mecanismo da íris em Plateau.

Objective: To report 17 cases of Plateau Iris Syndrome (17 eyes) focusing on clinical presentation, diagnosis approach and treatment. Methods: All patients were diagnosed as iris Plateau syndrome cases based on gonioscopy and ultrasound biomicroscopy (UBM) exam findings, performed after laser iridectomy. The mean follow up time was 46,7 + 11,7 months. The completeform of the syndrome was determined by the presence of recurrent acute angle closure episode or a positive darkroom prone position test. Results: In the first group, eight eyes had an acute angle closure episode at the time of thefirst evaluation. Two of them had a positive dark room prone position test even after iridotomy and six of themhad a recurrent acute angle closure episode during the follow-up period - complete plateau iris syndrome cases.In the second group, nine eyes that did not have an acute attack before or after iridotomy were included. All of themhad gonioscopy and UBM findings compatible with plateau iris mechanisms – possible incomplete plateau iris syndrome cases. We observe progression of peripheralanterior synechiae (PAS) in two eyes of the second group even after iridotomy. Conclusion: Plateau iris syndromecases may develop recurrent acute angle closure episodes and/or further PAS formation. The gonioscopy exam must always be performed after the iridotomy in order to verify the opening of the irido-corneal angle. Further studies should address the risk factors related to the maintenance of the angle closure process even after iridotomy.

Síndrome de Waardenburg: presentación de un caso y revisión de los diferentes tipos / Waardenburg syndrome type I: a case presentation

Introducción. En 1951 Waardenburg describió un nuevo padecimiento de etiología hereditaria, con características clínicas específicas; a partir de entonces, se han publicado más de 1,500 pacientes similares. Caso clínico. Paciente masculino de 14 años de edad, hijo de padres consanguíneos (primos en primer grado), con antecedentes de retardo en el desarrollo psicomotor. A la exploración física se le encontró: talla de 1.58 m, peso de 81.5 kg; con telecanto, heterocromía de iris, sordera neurosensorial y alteraciones en la pigmentación del pelo, pestañas y cejas. Estudio citogenético: cariotipo en linfocitos de sangre periférica y con técnica de bandas G, sin obtenerse evidencias de alteraciones cromosómicas ni estructurales. Conclusión. A pesar de la existencia de consanguinidad de primer grado en la familiar, la herencia corresponde al tipo I del padecimiento. Además, es necesario realizar como complemento al estudio clínico los marcadores genéticos específicos en todos los casos para identificar la variedad y proceder al asesoramiento genético

Manuseio de captura pupilar com laserterapia / Pupillary capture after intraocular lens implantation

O objetivo deste estudo é descrever e avaliar a eficácia da técnica de reposicionamento de lente intra-ocular (LIO), quando ocorre captura pupilar. Através do uso do YAG laser, o procedimento consiste na liberaçäo das sinéquias responsáveis pela deformidade iriana e consequente captura. Observou-se deslocamento posterior espontâneo da LIO em um paciente após laserterapia. O segundo caso descrito, além da utilizaçäo do laser, necessitou de punçäo da câmara anterior na lâmpada de fenda e afastamento posterior da LIO com agulha de insulina e injeçäo intra-camerular de lidocaína 1p/c em ambiente cirúrgico. Este estudo sugere que a técnica de reposicionamento da LIO, com YAG lasere agulha de insulina, é eficaz, segura e frequentemente, näo depende do uso do centro cirúrgico

Síndrome de Chandler. Presentación de un caso clínico / Chandler's syndrome. Case report

El síndrome iridocorneal endotelial incluye la atrofia esencial del iris, el nevo del iris o síndrome de Cogan-Reese y el síndrome de Chandler. Esta patología se caracteriza por anormalidades en la córnea, ángulo de la cámara anterior e iris. En síndrome de Chandler existe una membrana que crece hacia el ángulo produciendo alteraciones en el iris y glaucoma secundario entre otras. El pronóstico de esta enfermedad es incierto aun con tratamiento quirúrgico. Presentamos el caso clínico de una paciente con este síndrome y su evolución a 4 meses después del tratamiento

Surgical management for persistent pupillary membrane with vitreous scissors

Persistent pupillary membranes are common congenital disorders. To reduce the surgical complications, we used vitreous scissors instead of conventionally used Vannas scissors to remove the membrane and reviewed the surgical results. Five eyes of 4 children with persistent pupillary membrane were treated by surgery. Through the 1.5 mm limbal incision, the membrane was removed by using vitreous scissors after intracameral sodium hyaluronate. After 22.6 months follow-up, all pupils of operated eyes were round and no complications associated with the surgery were found. Three eyes showed improved visual acuities after the operation. We suggest that the surgery with vitreous scissors is better than with Vannas scissors.

Síndrome de Waardenburg tipo II: a propósito de dos casos clínicos / Waardenburg's syndrome type II: a propose of 2 clinical cases

El Síndrome de Waardenburg representa la forma más común de sordera congénita; es una condición pleitrópica, autosómica dominante, con penetrancia y expresividad variable. Se describen dos casos clínicos de Síndrome de Waardenburg tipo II. Las principales manifestaciones son la sordera sensorioneural congénita, alteraciones de la pigmentación pilosa y cutánea, puente nasal ancho, hipertricosis de las cejas, mandíbula cuadrada, encanecimiento prematuro y alteraciones neurológicas. Se revisan los criterios de diagnóstico de la enfermedad y los hallazgos asociados descritos de la literatura