The prevalence of anophthalmic socket syndrome and its relation to patient quality of life.

BACKGROUND: Following removal of the eye, soft tissue changes of the eyelids and orbit may develop into an anophthalmic socket (AS) syndrome, which is often attributed to orbital volume deficiency. While adequate primary orbital volume replacement is nowadays standard of care, patients may still present with facial asymmetry. The aim of this study is to provide insights into these changes and their impact on patient quality of life (QoL). METHODS: Cross-sectional study of 59 patients with longstanding ocular prosthetic wear after enucleation or evisceration surgery. The alignment, function, and laxity of the eyelids of the anophthalmic side were compared to those of the fellow side. The QoL was assessed with a 4-item questionnaire specific for the prosthetic condition. The different aspects of AS syndrome were analysed in relation to disease-specific and prosthetic data and to the patient QoL scores. RESULTS: Clinical AS syndrome was prevalent in 53% of patients with acquired anophthalmia. The anophthalmic side was statistically significantly different from the fellow side for the known AS syndrome features such as superior sulcus depression, margin reflex distance 1, and enophthalmia, but also for new features such as levator muscle function and lagophthalmia (P < 0.05). The difference was correlated with duration of prosthetic wear, prior orbital radiotherapy, and size of the prosthesis (P < 0.05). QoL scores were not correlated to the separate features of AS syndrome, except for a positive correlation between wearing comfort of the prosthesis and upper eyelid ptosis (P < 0.05). CONCLUSION: Patients with an ocular prosthesis show a relatively high prevalence of one or more distinct clinical features of AS syndrome, which do not negatively affect patient QoL. These findings underscore the importance to tailor prosthetic and surgical treatment to the patient's perceived QoL rather than to the objective clinical findings.

An application of data mining to identify potential risk factors for anophthalmia and microphthalmia.

BACKGROUND: We examined a large number of variables to generate new hypotheses regarding a wider range of risk factors for anophthalmia/microphthalmia using data mining. METHODS: Data were from the National Birth Defects Prevention Study, a multicentre, case-control study from 10 centres in the United States. There were 134 cases of "isolated" and 87 "nonisolated" (with other major birth defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with delivery dates October 1997-December 2011. Using random forest, a data mining procedure, we compared the two case types with controls for 201 variables. Variables considered important ranked by random forest were included in a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals. RESULTS: Predictors for isolated cases included paternal race/ethnicity, maternal intake of certain nutrients and foods, and childhood health problems in relatives. Using regression, inverse associations were observed with greater maternal education and with increasing intake of folate and potatoes. Odds were slightly higher with greater paternal education, for increased intake of carbohydrates and beans, and if relatives had a childhood health problem. For nonisolated cases, predictors included paternal race/ethnicity, maternal intake of certain nutrients, and smoking in the home the month before conception. Odds were higher for Hispanic fathers and smoking in the home and NSAID use the month before conception. CONCLUSIONS: Results appear to support previously hypothesised risk factors, socio-economic status, NSAID use, and inadequate folate intake, and potentially provide new areas such as passive smoking pre-pregnancy, and paternal education and ethnicity, to explore for further understanding of anophthalmia/microphthalmia.

Survey of Ocular Prosthetics Rehabilitation in the United Kingdom, Part 1: Anophthalmic Patients' Aetiology, Opinions, and Attitudes.

PURPOSE: Ocular prostheses are constructed to aid cosmetic, functional, and psychological rehabilitation of anophthalmic patients. Part-1 of this study aimed to evaluate anophthalmic patients' opinions, attitudes, and experience about aspects related to their postfit ocular prostheses. METHODS: One hundred sixty questionnaires were delivered to anophthalmic patients inquiring about different information such as age, gender, occupation, eye-loss cause, prosthesis type, prosthesis-wearing frequency, prosthesis-cleaning frequency, and problems encountered. A total of 126 questionnaires were returned (response rate was 78.8%). Data was analyzed using SPSS software (P <0.05). RESULTS: The patients were 74 males and 52 females (57.55 years ±â€Š17.57). Almost 50% of the patients lost their eye due to trauma that was the highest among other causes (P <0.05). High proportion clean their prosthesis daily (37.4%) which was the highest among other cleaning regimes (P <0.05). Almost 30.3% experienced having problems with their prosthetic eye. Patients who clean their prosthetic eye every 6 months have experienced more problems (P <0.05). Majority of patients wear their prosthetic eyes 24 hours (92%) (P <0.05). Half of patients who received a prosthetic eye for the first time experienced problems with it (P <0.05) such as excess discharge (45%), infection (25%), and soreness (20%). However, the problems were independent of prosthesis-type (P >0.05). CONCLUSIONS: Trauma is the most common cause of anophthalmic patients in the North-West of England. Anophthalmic patients are likely to experience problems with their prosthetic eye if they have lost their natural eye due to disease; it is their first prosthesis; or if they clean it once every 6 months.

Frequência de ocorrência de cavidade anoftálmica na região centro-oeste paulista e características dos portadores / Frequency of occurrence of anophthalmic socket in the Middle West region of the state of São Paulo and the carriers characteristics

OBJETIVO: Observar a frequência de ocorrência de casos de cavidade anoftálmica na região centro-oeste paulista e descrever o perfil demográfico dos portadores em estudo populacional. MÉTODOS: Estudo transversal, de caráter observacional e de amostragem aleatória, realizado em 12 cidades da região centro-oeste do estado de São Paulo, para as quais o centro de referência é a cidade de Botucatu. Os participantes foram determinados por sorteio que levou em conta o local de moradia, tendo sido estabelecida uma amostra de 11.453 indivíduos. Todos os exames foram feitos utilizando uma Unidade Oftalmológica Móvel. O protocolo da pesquisa consistiu de dados demográficos e exame oftalmológico completo (anamnese, antecedentes oculares e sistêmicos, antecedentes familiares, avaliação da acuidade visual com e sem correção, tonometria, biomicroscopia, fundoscopia e exame refracional). Todos os dados obtidos foram transferidos para tabela Excel e submetidos à análise descritiva e apresentados como frequência de ocorrência. RESULTADOS: A frequência de ocorrência de cavidade anoftálmica na região centro-oeste paulista foi de 0,96‰. Dentre os sujeitos examinados, foram encontrados 11 casos de cavidade anoftálmica, com acometimento de 0,7‰, no sexo feminino e 1,3‰, do sexo masculino. Dentre as causas de cavidade anoftálmica foram encontradas glaucoma (olho cego doloroso), microftalmia, trauma e endoftalmite. Os indivíduos eram, em sua maioria, de idade superior ou igual a 40 anos, tendo sido encontrado apenas um caso com idade abaixo de 19 anos. CONCLUSÃO: A cavidade anoftálmica ocorreu em 0,96‰ dos habitantes da região centro-oeste paulista, acometendo mais frequentemente os homens e com grande variação de idade de acometimento.

PURPOSE: To observe the frequency of the occurrence of the anophthalmic socket in the Middle West region of the state of São Paulo and to describe the demographic profile of the carriers in a population-based data. METHODS: A cross-sectional study involve a random sampling carried out in twelve cities of the Middle West region of the state of São Paulo, for which the reference center is the city of Botucatu was done. The participators were chosen by assortment which considered the houses of these people. It was established a sampling with 11,453 people. All the exams were realized using a Mobile Ophthalmologic Unit. The research protocol included the demographic data and the complete ophthalmologic exam (anamnesis, ocular and systemic antecedents, familiar antecedents, visual acuity with and without correction, tonometry, biomicroscopy, fundoscopy, and refraction exam). All the data were transferred to an Excel spreadsheet and submitted to a descriptive analysis and were presented by the frequency of the occurrence. RESULTS: Ophthalmic socket frequency in the Middle West region of the state of São Paulo was 0.96‰. We found 11 cases of anophthalmic socket, with involvement of 0.7 ‰ in females and 1.3 ‰, male. The most common causes of anophthalmic socket were glaucoma (blind painful eye), microphthalmia, trauma, and endophthalmitis. The majority of the people were 40 years old or more, and we found just one person younger than 19 years old. CONCLUSION:The anophthalmic socket occurred in 0.96‰ of the habitants of the Middle West region of São Paulo State, occurring mainly in male and with large variety of the affected ages.

Intracranial and extracranial malformations in patients with craniofacial anomalies.

BACKGROUND: Craniofacial structures have an intimate relationship with the central nervous system in the embryologic development period and the developmental abnormalities of the face and skull that are frequently associated with malformations of the central nervous system. Additional intracranial and extracranial malformations in a patient with craniofacial deformity may negatively affect the outcome of the surgery and the quality of life. PATIENTS AND METHODS: A retrospective analysis of a total of 123 patients with craniofacial anomalies was performed. Physical examination notes, ophthalmologic findings, computed tomography, and magnetic resonance imaging reports were retrospectively analyzed, and intracranial and extracranial malformations and ophthalmologic problems in each group were categorized. RESULTS: Of the patients with nonsyndromic craniosynostosis, 29% had intracranial and extracranial malformations. Of them, 17% had ophthalmologic problems. Of the patients with syndromic craniosynostosis, 34% had intracranial and 31% had extracranial malformations. In the patients with craniofacial cleft, 60% had intracranial and 30% had extracranial malformations. The most common intracranial malformations are hydrocephaly, Chiari type 1 malformation, and corpus callosum disorders. CONCLUSIONS: A multidisciplinary approach is essential in the evaluation and follow-up of individuals with craniofacial abnormalities. Conventional radiography and three-dimensional computed tomography of the bony skeleton and axial scanning of the soft tissues is our first-step routine. Brain magnetic resonance imaging should be performed in patients with multiple-suture synostosis, syndromic synostosis, and craniofacial clefts to rule out central nervous system and soft tissue malformations. During the postoperative first year, conventional x-rays are sufficient to evaluate the craniofacial area. Central nervous system disorders may cause major headaches, muscle weakness, hearing problems, extreme fatigue, poor motor coordination, and cognitive and social disabilities even when their intelligence quotient is normal. Therefore, every effort should be performed to search and treat additional malformations. Prevention of additional morbidities improves surgical and social outcomes.

Anophthalmia and microphthalmia.

Anophthalmia and microphthalmia describe, respectively, the absence of an eye and the presence of a small eye within the orbit. The combined birth prevalence of these conditions is up to 30 per 100,000 population, with microphthalmia reported in up to 11% of blind children. High-resolution cranial imaging, post-mortem examination and genetic studies suggest that these conditions represent a phenotypic continuum. Both anophthalmia and microphthalmia may occur in isolation or as part of a syndrome, as in one-third of cases. Anophthalmia/microphthalmia have complex aetiology with chromosomal, monogenic and environmental causes identified. Chromosomal duplications, deletions and translocations are implicated. Of monogenic causes only SOX2 has been identified as a major causative gene. Other linked genes include PAX6, OTX2, CHX10 and RAX. SOX2 and PAX6 mutations may act through causing lens induction failure. FOXE3 mutations, associated with lens agenesis, have been observed in a few microphthalmic patients. OTX2, CHX10 and RAX have retinal expression and may result in anophthalmia/microphthalmia through failure of retinal differentiation. Environmental factors also play a contributory role. The strongest evidence appears to be with gestational-acquired infections, but may also include maternal vitamin A deficiency, exposure to X-rays, solvent misuse and thalidomide exposure. Diagnosis can be made pre- and post-natally using a combination of clinical features, imaging (ultrasonography and CT/MR scanning) and genetic analysis. Genetic counselling can be challenging due to the extensive range of genes responsible and wide variation in phenotypic expression. Appropriate counselling is indicated if the mode of inheritance can be identified. Differential diagnoses include cryptophthalmos, cyclopia and synophthalmia, and congenital cystic eye. Patients are often managed within multi-disciplinary teams consisting of ophthalmologists, paediatricians and/or clinical geneticists, especially for syndromic cases. Treatment is directed towards maximising existing vision and improving cosmesis through simultaneous stimulation of both soft tissue and bony orbital growth. Mild to moderate microphthalmia is managed conservatively with conformers. Severe microphthalmia and anophthalmia rely upon additional remodelling strategies of endo-orbital volume replacement (with implants, expanders and dermis-fat grafts) and soft tissue reconstruction. The potential for visual development in microphthalmic patients is dependent upon retinal development and other ocular characteristics.

The epidemiology of anophthalmia and microphthalmia in Sweden.

Infants with a clinical diagnosis of anophthalmia or microphthalmia were identified from four health registers in Sweden, covering different parts of the period 1965-2001. During the observation period, the rate of anophthalmia decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered rate of microphthalmia increased markedly during the observation period to reach a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified children had a chromosome anomaly. There was no geographical variation in prevalence and infants born in urban or rural districts had, if anything, a lower risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non-eye malformations were more common at anophthalmia (63%) than at microphthalmia (30%). Sex ratio was normal and no statistically significant variation between sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye malformations) could be demonstrated. There was a marked risk increase with maternal age but no certain parity effect, no effect of maternal education, but a possible association with subfertility. Maternal smoking in early pregnancy seemed to increase the risk for anophthalmia or microphthalmia in the absence of a coloboma.

Anophthalmia and microphthalmia in the Alberta Congenital Anomalies Surveillance System.

BACKGROUND: A higher than expected rate of anophthalmia/microphthalmia (A/M) for 1999 was noted in both the Alberta Congenital Anomalies Surveillance System (ACASS) and the Canadian Congenital Anomalies Surveillance System (CCASS). Since this increase was at variance with the previous 19 years, we performed a review to determine whether the increase was true and, if so, the possible explanation. METHODS: We reviewed the records of the cases of A/M in the ACASS together with the accompanying attachments (e.g., consultant, autopsy and chromosome reports) for 1991-2001. In addition, we contacted all 91 registered ophthalmologists in Alberta. Letters were also written to the Edmonton and Calgary offices of the Canadian National Institute for the Blind (CNIB). RESULTS: Sixty cases of A/M were ascertained over the study period. Of the 88 active ophthalmologists in the province, 21 (24%) replied, but no new cases were ascertained from this source. No replies were received from the CNIB. We constructed five categories of clinical phenotypes for the 60 cases: 20 had a chromosomal etiology, 13 had a recognized syndrome or association, 16 had extraocular malformations, 5 had other eye anomalies, and 6 had A/M only. Pregnancy terminations were not included. The higher rate in 1999 was mainly due to cases with a chromosomal etiology or a recognized syndrome or association. There was no indication that a teratogen was causing a cluster of A/M cases, as our annual rates were comparable to those for other jurisdictions not only in Canada but also in other countries. INTERPRETATION: Our review confirmed that the rate of A/M in Alberta in 1999 was high but that the increase was mainly due to five cases of trisomy 13 together with one case associated with a syndrome (Meckel-Gruber). Our findings provide reassurance that there was no environmental cause of clustering of anophthalmia or microphthalmia. This review demonstrates the importance of ongoing population-based surveillance in providing baseline birth prevalence rates for evaluating trends and clusters.

Anophthalmia in litters of female rats treated with the food-derived carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Anophthalmia in litters of pregnant rats treated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a food-derived carcinogen, was incidentally encountered in a risk-assessment study with 2-generation exposure to PhIP. Female Fischer 344 animals were given 200 ppm PhIP in the diet for 4 wk before mating with nontreated males and also during gestation and lactation periods. Mean numbers of newborn rats per litter in control and PhIP-treated groups were 7.9 +/- 2.9 and 7.1 +/- 1.6 in trial 1 and 8.3 +/- 1.9 and 6.1 +/- 2.4 in trial 2. Among 49 (trial 1) and 63 (trial 2) offspring from PhIP-treated dams, 9 (18.4%) and 32 (50.8%) demonstrated anophthalmia, and 1 (2.0%) and 8 (12.7%) demonstrated hydrocephaly. Five of 7 (71.4%) and 13 of 14 (92.9%) dams delivered pups with malformations in trials 1 and 2, respectively. Also, in a previous study that was carried out with the same protocol and that used the Sprague-Dawley strain of rats, anophthalmia and hydrocephaly were observed in 2 and 1 out of 175 pups, respectively, from 100 ppm PhIP-treated dams. No congenital malformations were found in control groups of the same size in either experiment. In addition to having been previously identified as a cause of carcinogenic activity, our findings suggest that PhIP is capable of causing anophthalmia in rats when administered during the gestational period.