Prenatal diagnosis of Sex determining region Y -box transcription factor 2 anophthalmia syndrome caused by germline mosaicism using next-generation sequencing: A case report.

Background: Sex determining region Y box transcription factor 2 (SOX2) mutations lead to bilateral anophthalmia with autosomal dominant human inheritance. SOX2 mutations could result in severe ocular phenotypes usually associated with variable systemic defects. Most patients described with SOX2 anophthalmia syndrome possessed de novo mutations in this gene. Case Presentation: In this case report, we describe 2 brothers with mental retardation and bilateral anophthalmia caused due to SOX2 germline mosaicism in unaffected parents. Next-generation DNA sequencing was carried out to determine the family's possible cause of genetic mutation. Sanger sequencing was performed on the patients and their parents. Prenatal diagnosis was done in both pregnancies of the older brother's wife via chorionic villus sampling. A novel heterozygous pathogenic frameshift deletion variant (exon1:c.58_80del:p.G20fs) was identified in the SOX2 gene, which was confirmed by Sanger sequencing in both affected brothers and did not exist in healthy parents, indicating germline mosaicism. Conclusion: Most SOX2 mutations known look to arise de novo in probands and are diagnosed through anophthalmia or microphthalmia. Prenatal diagnosis should be offered to healthy parents with a child with SOX2 mutation every pregnancy.

Clinical and histopathological study of a hollow and posteriorly multiperforated polymethylmethacrylate implant in eviscerated rabbit eyes / Análise clínica e histopatológica de um implante de polimetilmetacrilato oco e multiperfurado em sua porção posterior em olhos eviscerados de coelhos

ABSTRACT Purpose: The study aimed to evaluate the clinical and tissue response to a hollow polymethylmethacrylate orbital implant with a multiperforated posterior surface in an animal model after evisceration. Methods: Sixteen New Zealand rabbits had their right eye eviscerated. All animals received a hollow polymethylmethacrylate implant 12 mm in diameter that is multiperforated in its posterior hemisphere. The animals were divided into four groups, and each one had the eye exenterated at 7, 30, 90, and 180 days post-evisceration. Clinical signs were assessed daily for 14 days post-evisceration and then every 7 days until 180 days. Inflammatory pattern, collagen structure, and degree of neovascularization generated with implant placement were analyzed with hematoxylin-eosin, picrosirius red, and immunohistochemistry staining. Results: There were no signs of infection, conjunctival or scleral thinning, or implant exposure or extrusion in any animal during the study. On day 7, the new tissue migrated into the implant and formed a fibrovascular network through the posterior channels. Inflammatory response reduced over time, and no multinuclea­ted giant cells were found at any time. Conclusion: Hollow polymethylmethacrylate orbital implants with a multiperforated posterior surface enable rapid integration with orbital tissues by fibrovascular ingrowth. We believe that this orbital implant model can be used in research on humans.

RESUMO Objetivo: Avaliar a resposta tecidual e clínica a um implante orbitário de polimetilmetacrilato, oco e multiperfu­rado em sua porção posterior em modelo animal após evisceração. Métodos: Dezesseis coelhos da raça Nova Zelândia foram submetidos à evisceração do globo ocular direito. Todos receberam implante oco de polimetilmetacrilato de 12 mm de diâmetro, multiperfurado em sua semiesfera posterior. O estudo foi dividido em avaliação clínica e histopatológica. A avaliação clínica foi diária até 14 dias pós-evisceração e, a cada sete dias, até completar 180 dias. Os animais foram divididos em grupos de quatro animais e cada um foi submetido à exenteração com 07, 30, 90 e 180 dias e depois à eutanásia. A análise histopatológica teve por fim caracterizar o padrão inflamatório, a estrutura do colágeno e o grau de neovascularização. Para isso, além da tradicional coloração pela hematoxilina-eosina, utilizou-se o corante Picrosirius Red (PSR) e imuno-histoquímica com o marcador CD 34. Resultados: Não houve sinais de infecção, afinamento conjuntival ou escleral, exposição ou extrusão do implante em nenhum animal durante o estudo. Já no sétimo dia, o tecido neoformado migrou para dentro do implante formando uma rede fibrovascular através dos canais posteriores. A resposta inflamatória diminuiu ao longo do tempo avaliado e não foram encontradas células gigantes multinucleadas. Conclusão: O implante analisado permite a sua integração aos tecidos orbitários pelo crescimento fibrovascular em seu interior. Os autores acreditam que este modelo de implante orbital pode fazer parte de testes com humanos.

Recurrent Fetal Anophthalmia Caused by retinoids acid gene 6 mutations: Correlation between prenatal ultrasonography, magnetic resonance imaging, and pathology.

OBJECTIVE: Anophthalmia is an extreme form on the spectrum of anophthalmia-microphthalmia (A/M) syndrome. Most articles define fetal microphthalmia by an ocular diameter (OD) less than fifth percentile. Diagnosis of fetal microphthalmia using only orbital measurements such as interocular distance (IOD), and OD may neglect the presence or morphology of the fetal lens, hence failing to identify abnormalities of the fetal globe. CASE REPORT: We hereby present a case of isolated fetal anophthalmia in two consecutive pregnancies from the same mother. Both fetuses presented as full-sized globes with absence or small size of lens under fetal ultrasound examination. Magnetic resonance imaging and pathology of the second fetus further revealed a thorough view of the underdeveloped globes. Whole exon sequencing (WES) analysis for the parents-fetus trio revealed compound heterozygous mutations of the retinoids acid gene 6 (STRA6). CONCLUSION: Detailed examination for intraocular structures including fetal lens, in addition to orbital measurements by ultrasound is crucial for diagnosis of diseases in the A/M spectrum.

Clinical Congenital Anophthalmos and Microphthalmos-Experiences of Patients and Their Parents after More than 10 Years of Treatment.

Congenital clinical anophthalmos and blind microphthalmos describe the absence of an eye or the presence of a small eye in the orbit. Between 1999 and 2013, 97 children with anophthalmos or microphthalmos were treated with self-inflating, hydrophilic gel expanders at the Rostock Eye Clinic. More than a decade later, this study investigated the perspective of patients and parents regarding the treatment, the surgical outcome, and the emotional and social well-being of the patients. A total of 22 families with 16 patients sighted in the other eye and six patients blind in both eyes participated. Questionnaires were developed, including items on physical, emotional, social, and medical aspects. The patients felt emotionally stable and integrated into their social environment, with no major limitations reported by the majority. These statements were confirmed by most of the parents. Parents (67%) indicated that the success of the operation was already apparent after the first intervention and that the current situation did not play a role in the patients' social environment. The study provided new insights into the therapy results, the postoperative care, and the social and emotional stability of the prosthesis-wearing patients, indicating the chosen expander methods as promising in terms of positive postoperative care.

Three-dimensional design of a geometric model for an ocular prosthesis in ex vivo anophthalmic socket models.

PURPOSE: Fitting a customized ocular prosthesis for anophthalmic patients entails an artisanal labour-exhausting process and is standardly based on impression moulding of the socket, which may be anatomically inaccurate. The objective of the study was to design an impression-free socket mould with three-dimensional (3D) technology. METHODS: The ex vivo anophthalmic socket models included one silicone, one fresh pig cadaver head and three fresh-frozen human cadaver heads. After intra-socket application with iodine substance, five observers obtained eighteen low-dose cone beam computed tomography (CBCT) scans and one observer one high-dose CBCT scan of each model. The observers designed non-impression 3D moulds of the socket with 3D software. For the human cadaver sockets 3D geometric models of the ocular prosthesis were rendered from the 3D mould of the socket and the mirrored cornea of the contralateral eye. RESULTS: The posterior surface of the 3D mould was highly accurate, with a mean absolute deviation of 0.28 mm, 0.53 mm, 0.37 mm and mean upper deviation of 0.53 mm, 0.86 mm, 1.17 mm, respectively, for the phantom, pig and human model. The intra- and interobserver repeatability and reproducibility of the 3D moulds and designs was good (<0.35 mm). The largest variation in the 3D geometric model was found at the junction of the 3D mould and mirrored cornea. CONCLUSION: 3D design of an impression-free geometric model for an ocular prosthesis with low-dose CBCT is highly accurate in ex vivo anophthalmic socket models. This novel method is a critical step towards the manufacturing of 3D printed ocular prostheses and requires validation in anophthalmic patients.

A Pilot Clinical Study of Ocular Prosthesis Fabricated by Three-dimensional Printing and Sublimation Technique.

PURPOSE: We sought to evaluate the safety and effectiveness of patient-specific ocular prostheses produced by three-dimensional (3D) printing and the sublimation technique. A comparison with prostheses produced using manual manufacturing methods was then performed. METHODS: To confirm the biological and physiochemical safety, cytotoxicity, systemic acute toxicity, intradermal reaction, and skin sensitization tests were conducted according to the International Organization for Standardization guidelines. The compressive strength of the prostheses was also tested. Further, a case series of three patients who wore the 3D printed prostheses for more than eight hours daily for 4 weeks was executed. Self-assessments by these individuals using a questionnaire and safety evaluations focusing on the occurrence of conjunctival inflammation or allergic reactions according to the Cornea and Contact Lens Research Unit criteria by slit-lamp examination and similarity assessment were completed. RESULTS: The 3D printed ocular prostheses met the necessary qualifications per the biological and physiochemical safety tests, showing the absence of cytotoxicity, acute systemic toxicity, intradermal reactivity, and skin-sensitizing potency. Also, there was no difference in strength test results between previous ocular prostheses and the 3D printed ones. Self-assessment by the patients yielded satisfactory results, with no significant difference in the level of satisfaction reported for the 3D printed and previous handmade ocular prostheses. The 3D printed prosthesis did not trigger any side effects in the conjunctival sac and showed similar objective findings with respect to the color of the iris, sclera, and vessel patterns. CONCLUSIONS: Our study confirms the biologic and physiochemical safety of 3D-printed ocular prostheses created using computer-aided design technology and a sublimation technique. The patients' questionnaires and the judgment of the ophthalmologists/ocularists showed that the 3D printed ocular prosthesis was acceptable in function and appearance through a case series report.

Issues of rehabilitation of the patients with symblepharon using oral mucosal autografts.

PURPOSE: To systematize clinical variants of symblepharon and to analyze rehabilitation availability boundaries in patients with different forms of symblepharons. METHODS: Retrospective analysis of clinical cases included 26 patients with local, subtotal, and total symblepharon (ankyloblepharon) with a normal or anophthalmic orbit. In all patients, symblepharon was operated using split- or full-thickness oral mucosal autografts and their fixation with U-shaped stitches and compression plates. Preoperatively and postoperatively, best-corrected visual acuity, IOP, extraocular motility, results of Schirmer I test, and tear break-up time with slit-lamp biomicroscopy were analyzed, as well as additional ultrasound and electrophysiological studies were performed in some cases. Follow-up period lasted from 1.5 to 6 years. RESULTS: The proposed surgical technique using mucosal autografts in all patients allowed complete anatomical restoration of conjunctival fornices and cavity. It resulted in improvement of visual function in patients with local symblepharon, full restoration of ocular motility in patients with a presence of the eye and provided an opportunity to wear artificial eye in patients with anophthalmia. Nonetheless, loss of conjunctival Krause's and Wolfring lacrimal glands, goblet cells, meibomian glands, and limbal stem cells prevents from further optic keratoplasty in patients with total or subtotal symblepharon on potentially sighted eye. CONCLUSION: The most difficult patients for visual rehabilitation were the ones with subtotal or total symblepharon (ankyloblepharon) on potentially sighted eye due to the loss of conjunctival goblet cells, meibomian glands, and limbal stem cells.

[Computer technologies in diagnostics and treatment of worsening post-enucleation socket syndrome]. / Komp'iuternye tekhnologii v diagnostike i lechenii progressiruiushchego anoftal'micheskogo sindroma.

Enucleation with primary orbital implantation and the use of ocular prosthesis does not exclude the risk of post-enucleation socket syndrome (PESS). Correction of such conditions requires modern visualization methods and software for calculation, modelling and control of the surgery. PURPOSE: To demonstrate the capabilities of modern computer technologies in diagnostics and treatment of patients with worsening post-enucleation enophthalmos. MATERIAL AND METHODS: The retrospective study included 6 patients (4 male and 2 female) aged 29-68 years who exhibited signs of PESS in 2017-2018. To define the orbital condition, patients underwent multispiral computed tomography (MSCT) and magnetic resonance imaging (MRI) followed by image analysis with computed exophthalmometry and step-by-step computed exophthalmometry. Results of these examinations helped construct 3D-models of patients' orbits, which were then used to calculate the parameters of the silicone implants. Patient-specific silicone implants were implanted into their orbits during surgery under general anesthesia. RESULTS: Implantation of the patient-specific silicone implant resulted in increase of the volume behind orbital prosthesis and correction of post-enucleation enophthalmos in all patients allowing them to use thinner, more mobile ocular prosthesis, and restore normal eyelid position. The patients also noted better appearance of the eye and personal comfort. CONCLUSION: Modern visualization methods along with computer analysis and modelling, as well as technologies to produce medical products enable creation of the best suitable patient-specific orbital implants. This allows achieving better clinical results and better quality of life for patients with monolateral anophthalmos.

Prosthesis-socket volume imbalance and dermofat graft rehabilitation in patients with an anophthalmic socket / Os problemas causados pelo desequilíbrio do volume da cavidade da prótese, nos casos de cavidades anoftálmicas, e a sua reabilitação com o enxerto de dermofat

ABSTRACT Purposes: To identify problems caused by prosthesis-socket volume imbalances in anophthalmic sockets; and to evaluate rehabilitation with dermofat graft as a solution. Methods: We retrospectively reviewed medical records of patients operated in our clinic (between May 2011 and June 2016) with dermofat grafts to treat anophthalmic socket-related problems. During the preoperative examinations, ophthalmologists recorded the presence of eyelid problems due to the socket volume deficit, upper and lower fornix deficiency, deepening in the upper eyelid sulcus, epiphora and secretion, lower eyelid laxity, ptosis, entropion, and ectropion. Following the surgical repair, new prosthesis suitable for the resulting socket area were implemented for all the patients. The mean follow-up period was 27.42±16 months (ranging from 10-62 months). On the last control examinations, ophthalmologists recorded solved and unsolved socket problems that were present preoperatively. Results: We included 16 men and 5 women in this study. The mean age was 38.3 ± 18.4 years (range, 5-75 years). The mean duration of preoperative prosthesis use was 9.4 ± 6.8 years (range, 1-30 years). Preoperatively, 7 patients had only orbital volume deficits, and 14 had socket volume displacements in addition to the volume deficits. After the dermofat graft implantations, the remaining deficits were corrected during another surgical session: 6 patients underwent ptosis corrections, 5 lateral canthal suspensions, 5 lower fornix with mucosal graft formations, and 2 upper fornix formations with mucosal grafts. All patients were able to use prosthesis postoperatively. Conclusion: The use of dermofat grafts to correct anophthalmic socket problems caused by orbital volume deficits or volume displacements is an effective, reliable, and reproducible surgical method.

RESUMO Objetivos: Identificar os problemas causados pelo desequilíbrio do volume da cavidade da prótese em cavidades anoftálmicas, e avaliar a reabilitação com enxerto de dermofato como solução. Métodos: Revisamos retrospectivamente os prontuários de pacientes operados em nossa clínica (entre maio de 2011 e junho de 2016) com enxertos de dermofato para tratar problemas relacionados a cavidades anoftálmicas. Durante os exames pré-operatórios, os oftalmologistas registraram a presença de problemas palpebrais devido ao déficit de volume, deficiência de fórnice superior e inferior, aprofundamento no sulco palpebral superior, a epífora e secreção, flacidez palpebral inferior, ptose, entrópio e ectrópio. Após a cirurgia, novas próteses adequadas para a área de encaixe foram implementadas em todos os pacientes. O tempo médio de acompanhamento foi de 27,42 ± 16 meses (variando de 10 a 62 meses). Nos últimos exames de controle, os oftalmologistas registraram problemas corrigidos e não corrigidos da cavidade que estavam presentes no pré-operatório. Resultados: Foram incluídos 16 homens e 5 mulheres neste estudo. A média de idade foi de 38,3 ± 18,4 anos (variação de 5-75 anos). A duração média do uso de prótese pré-operatória foi de 9,4 ± 6,8 anos (variação de 1 a 30 anos). No pré-operatório, 7 pacientes apresentavam apenas déficit orbitais e 14 tinham desvios de volume, além dos déficits de volume. Após os implantes de enxerto de dermoadipação, os déficits remanescentes foram corrigidos durante outra sessão cirúrgica: 6 pacientes foram submetidos a correção de ptose, 5 suspensões de cantal lateral, 5 fórnix inferior com enxerto de mucosa e 2 formações de fórnice superior com enxerto de mucosa. Todos os pacientes foram capazes de usar prótese no pós-operatório. Conclusão: A utilização de enxertos de dermofato para corrigir problemas de anoftalmia causados por déficits de volume orbital ou deslocamento de volume é um método cirúrgico eficaz, confiável e reprodutível.

Abnormal retinal pigment epithelium melanogenesis as a major determinant for radiation-induced congenital eye defects.

Recent studies highlighted a link between ionizing radiation exposure during neurulation and birth defects such as microphthalmos and anophthalmos. Because the mechanisms underlying these defects remain largely unexplored, we irradiated pregnant C57BL/6J mice (1.0 Gy, X-rays) at embryonic day (E)7.5, followed by histological and gene/protein expression analyses at defined days. Irradiation impaired embryonic development at E9 and we observed a delayed pigmentation of the retinal pigment epithelium (RPE) at E11. In addition, a reduced RNA expression and protein abundance of critical eye-development genes (e.g. Pax6 and Lhx2) was observed. Furthermore, a decreased expression of Mitf, Tyr and Tyrp1 supported the radiation-induced perturbation in RPE pigmentation. Finally, via immunostainings for proliferation (Ki67) and mitosis (phosphorylated histone 3), a decreased mitotic index was observed in the E18 retina after exposure at E7.5. Overall, we propose a plausible etiological model for radiation-induced eye-size defects, with RPE melanogenesis as a major determining factor.

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation.

Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.

Microphthalmos-anophthalmos-coloboma (MAC) spectrum in two brothers with Renpenning syndrome due to a truncating mutation in the polyglutamine tract binding protein 1 (PQBP1) gene.

Background: Patients with intellectual disability syndromes frequently have coexisting abnormalities of ocular structures and the visual pathway system. The microphthalmos, anophthalmos, and coloboma (MAC) spectrum represent structural developmental eye defects that occur as part of a syndrome in one-third of cases. Ophthalmic examination may provide important diagnostic clues in identifying these syndromes.Purpose: To provide a detailed and comprehensive description of the microphthalmos, anophthalmos, and coloboma (MAC) spectrum in two brothers with intellectual disability and dysmorphism.Methods: The two brothers underwent a detailed ophthalmic and systemic evaluation. A family pedigree was obtained and exome sequencing was performed in the proband.Results: The two brothers aged 4 and 7 years had intellectual disability, microcephaly, short stature, and characteristic dysmorphic features. Ophthalmic evaluation revealed the presence of the MAC spectrum in both boys. Genetic testing led to the detection of an X-linked hemizygous truncating mutation in the nuclear polyglutamine-binding protein 1 (PQBP1) gene confirming the diagnosis of X-linked recessive Renpenning syndrome.Conclusion: The presence of X-linked intellectual disability and characteristic dysmorphism, in a patient with the MAC spectrum should raise the suspicion of Renpenning syndrome. PQBP1 mutation testing is confirmatory. A comprehensive systemic evaluation is mandatory in all patients with the MAC spectrum and intellectual disability.

Custom wave-shaped CAD/CAM orbital wall implants for the management of post-enucleation socket syndrome.

The satisfactory management of post-enucleation socket syndrome is a major challenge. In addition to enophthalmos and hypophthalmos, the appearance of the supratarsal fold is frequently unsatisfactory. Using a combination of orbital volume reduction by means of custom wave-shaped CAD/CAM implants (1), the implantation of a dermis-fat graft (2), and the fitting of an acrylic eye prothesis (3), an algorithm has been developed that has led to considerable long-term improvements. 10 patients have already been treated by this method. The most important step is the reduction of orbital volume by means of custom wave-shaped CAD/CAM implants. These move the intraorbital soft tissue in an anterior and cranial direction. This considerably reduces the required volume of additional dermis-fat grafts, which are always subject to resorption. The use of an acrylic eye prothesis facilitates the aesthetic and functional correction of this condition and exerts less pressure on the lower eyelid due to its low weight. The method presented here leads to stable and aesthetically pleasing results with a minimum risk of complications. One problem is the exact predictability of the necessary orbital volume reduction by the custom wave-shaped CAD/CAM implants. Further studies and a larger number of cases are required to address this problem.

Orbital Fat Injection: Technique and 5-Year Follow-Up.

BACKGROUND: Orbital volume loss, early or late, is common after placement of an orbital implant or dermis fat graft, and there is currently no satisfactory long-lasting solution. Hyaluronic fillers are relatively easy to administer but are prone to migration and are temporary. Cannula-based orbital fat grafting has not gained the status of standard of care because of perceived low likelihood of success in the near term. This paper describes a technique for fat volume augmentation, its rationale, long-term follow-up, and a description of a complication unique to fat grafting in the orbit. METHODS: Ten consecutive subjects with acquired anophthalmic enophthalmos were enrolled in two IRB (institutional review board)-approved protocols (10.27 and 12.01) undergoing a single session of autologous fat grafting to the orbit using a closed blunt cannula technique. Preoperative photography and non-contrast MRIs (magnetic resonance imaging) were obtained prior, immediately after, and at 1 year after injection. Yearly postoperative photography was performed on subjects with successful results. RESULTS: Three of five subjects in IRB 10.27 clearly showed a clinically apparent increase in orbital volume at 1 year. One subject who failed to show improvement also sustained inadvertent injection into three extraocular muscles; she subsequently volunteered to enter IRB 12.01. Three of five subjects in IRB 12.01 did benefit, showing volume increase at 1 year, including the subject who had experienced intramuscular injection in 10.27. One subject in IRB 12.01 was lost to follow-up. Of the total of ten subjects enrolled, three showed no improvement and one was lost to follow-up; six subjects showed volume improvement at 1 year with two retaining the correction at 5 years and four showing variable diminution over 2-5 years. With the exception of the subject who sustained injection into extraocular muscles, none experienced complications. CONCLUSION: A modified technique is recommended for orbital fat injection distinct from methods used elsewhere in the body. Theoretical limits of volumetric enhancement temper expectations in orbital fat grafting and should inform surgical planning. Cannula-based orbital fat grafting can be done safely and result in a gain of orbital fat volume at 1 year and in some cases up to 5 years. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dermis-fat graft for anophthalmic socket reconstruction: indications and outcomes / Enxerto dermo-adiposo para reconstrução da cavidade anoftálmica: indicações e resultados

ABSTRACT Purpose: To evaluate the outcomes of dermis-fat graft procedure for orbital volume replacement in anophthalmic socket. Methods: A retrospective chart review was performed studying all dermis-fat graft surgeries done at King Khlaed Eye Specialist Hospital in the last 10-year period. Sixty-two anophthalmic socket carriers underwent dermis-fat graft during the study period. Data were collected on characteristics of the patients, postoperative complications, cosmesis, and functional results such as the ability to hold an external prosthesis. Results: Mean age of the patients included in the study was 34.2 ± 9.7 years. There were 38.7% of patients with grade 3 anophthalmic socket, 64.5% of patients had an acquired anophthalmic socket, and dermis-fat graft was performed as a secondary procedure in 61.3% of patients. Postoperative complications included lagophthalmos (22.6%), graft necrosis (17.7%), pyogenic granuloma (12.9%), decreased graft size (12.9%), malpositioned lids (3.2%), and volume deficiency (3.2%). The prosthesis was held in place in 49 patients (79%) preoperatively and in 55 patients (88.7%) postoperatively. Conclusion: Dermis-fat graft is an excellent option for congenital or acquired as well as primary or secondary anophthalmic sockets, with or without contraction. The outcomes are favorable, and complications are rare.

RESUMO Objetivo: Avaliar os resultados obtidos com o uso do enxerto dermo-adiposo para reposição de volume em cavidade anoftálmica. Métodos: Estudo retrospectivo baseado em revisão de prontuários incluindo todas as cirurgias de enxerto dermo-adiposo realizadas nos últimos 10 anos no King Khaled Eye Specialist Hospital, Saudi Arabia. O enxerto dermo-adiposo foi realizado em 62 pacientes no periodo do estudo. Os dados analisados incluíram características dos pacientes, as complicações pós- operatórias e os resultados cosméticos e funcionais, tais como a habilidade de usar prótese externa. Resultados: A média de idade dos participantes foi de 34,2 ± 9,7 anos. Segundo a classificação das cavidades, 38,7% possuíam cavidade grau 3; 64,5% possuíam cavidade anoftálmica adquirida e o enxerto dermo-adiposo foi realizado como procedimento secundário em 61,3% dos pacientes. Após o procedimento 22,6% dos pacientes permaneceram com lagoftalmo, 17,7% tiveram necrose do enxerto, 12,9% desenvolveram granuloma piogênico, 12,9% tiveram redução do tamanho do enxerto, 3,2% permaneceram com as alterações no posicionamento palpebral e 3,2% continuaram com déficit de volume na órbita. Quarenta e nove pacientes (79%) eram capazes de usar prótese externa antes da cirurgia e depois do enxerto dermo-adiposo 55 (88,7%) puderam utilizar prótese externa. Conclusão: O enxerto dermo-adiposo é uma ótima opção para tratamento de cavidades anoftálmicas congênitas ou adquiridas, assim como realizado como procedimento primário ou secundário, em cavidades com ou sem contração tecidual. Os resultados são encorajadores e as complicações são pouco frequentes.

Prenatal diagnosis and implications of microphthalmia and anophthalmia with a review of current ultrasound guidelines: two case reports.

BACKGROUND: Microphthalmia and anophthalmia are rare congenital fetal abnormalities. The combined incidence is estimated at 1 in 10,000 births. These two conditions arise from complex and incompletely understood genetic and/or environmental causes. Prenatal diagnosis is neither frequent nor easy and relies on precise, high-quality ultrasonography. Current antenatal ultrasound protocols for imaging of the fetal eye are inconsistent and inadequate to screen for the spectrum of ocular malformations, and there are no clear guidelines on detection of these rare abnormalities. Our study of two cases highlights the importance of early detection, and we review current practice and suggest a definitive fetal imaging protocol. CASE PRESENTATION: We present two antenatal cases, one each of microphthalmia and anophthalmia, both diagnosed at the morphology scan at our tertiary fetal medicine unit. In both cases, the parents (a 36-year-old woman of Mauritanian ethnicity and a non-consanguineous partner of Nepalese descent, and a 31-year-old Caucasian woman and non-consanguineous Caucasian partner) elected to terminate their pregnancies and made unremarkable recoveries. Subsequent fetal autopsy confirmed the ultrasound scan findings. CONCLUSIONS: We recommend that antenatal ultrasound guidelines are updated to specify use of a curvilinear transducer (2-9 MHz) to image both orbits in the axial and coronal planes, aided by use of a transvaginal probe when the transabdominal approach is inadequate to generate these images. When applicable, three-dimensional reverse-face imaging should be obtained to aid the diagnosis. The presence, absence, or non-visualization of lenses and hyaloid arteries should be documented in reports and these cases referred for a tertiary-level ultrasound scan and fetal medicine review. Imaging of the orbits should occur from 12 weeks' gestation. Magnetic resonance imaging and amniocentesis with chromosome microarray testing may provide additional genetic and structural information that may affect the overall morbidity associated with a diagnosis of microphthalmia or anophthalmia.

Anatomical repair of a bilateral Tessier No. 3 cleft by midfacial advancement.

BACKGROUND: Bilateral Tessier number 3 clefts are extremely rare, and their surgical treatments have not been well established. CASE PRESENTATION: The authors describe the case of a patient with a right Tessier number 3, 11 facial cleft with microphthalmia, a left Tessier number 3 facial cleft with anophthalmia, and cleft palate. We repaired simultaneously the bilateral soft tissue clefts by premaxillary repositioning, cleft lip repair, facial cleft repair by nasal lengthening, midfacial advancement, and an upper eyelid transposition flap with repositioning both the medial canthi. Postoperatively, the patient showed an esthetically acceptable face without unnatural scars. CONCLUSIONS: We achieved good results functionally and esthetically by midfacial advancement with facial muscle reposition instead of traditional interdigitating Z-plasties. The surgical modality of our anatomical repair and 3 months follow-up results are presented.

Characterization of Eyeball Loss in Four Cities of Colombia.

PURPOSE: Describe the socio-demographic characteristics of anophthalmic patients examined at specialized centers of four cities in Colombia to know the different causes of eyeball loss. METHOD: A transversal retrospective study was done of 511 medical records from the specialized practices of four cities in Colombia. Socio-demographic data of patients who were seen between January 2011 and December 2013 were compiled. SOFA Statistics software v1.4.6 was used for this analysis. An analysis throughout the measures of central tendency for numerical variables was developed, and the descriptive statistics were used for the categorical variables. RESULTS: Almost 63% of the data belonged to male patients. Eyeball loss was more frequent in patients over 40 years of age. Fifty-one percent of the patients suffered eyeball loss due to traumatic causes, 40.2% due to pathological causes, and 4.6% due to congenital anomalies. The most frequent specific causes were glaucoma (19%), ocular cancer (15.4%), and home accidents (11,2%). Around 60% of the anophthalmic patients belonged to low socioeconomic level. CONCLUSIONS: It is important to highlight that more than half of the analyzed anophthalmia cases originated in some type of trauma; this means that they could be considered potentially avoidable losses. Complications deriving from glaucoma became the most frequent cause of anophthalmia in the pathological origin group, which suggests a reflection regarding the strategies of early detection of the disease and access to proper treatment. It is also showed the need to develop an efficient system to manage information.

[The potential of ectoprosthetics in rehabilitation of patients with orbital pathology]. / Vozmozhnosti éktoprotezirovaniia v reabilitatsii patsientov s patologiei orbity.

AIM: rectification of indications and contraindications for ectoprosthetics and exploration of its potential as a modern rehabilitation modality. MATERIAL AND METHODS: Here are summarized the results of 89 cases of facial reconstruction with prosthetic means in trauma patients and those who had had congenital or oncological pathology and in whom other methods of rehabilitation were unable to remedy the defect within the orbital region. RESULTS: The indications and contraindications for facial prosthetics as well as the conditions, under which this type of medical and social rehabilitation can be carried out, were clarified. The authors also explained the process of creating an epiprosthesis and how it should be attached to the orbit to have the maximum effect on the existing defects of both the bone and auxiliary apparatus (including eyelid soft tissues, eyelashes, etc.). Because modern ectoprostheses are made of silicone and held in place with magnets, they provide an optimal cosmetic result, so that, regardless of patient's age, no rough defects can be detected on the affected side at a 2-m distance. CONCLUSION: As the production technology develops, the cosmetic appearance of epiprostheses improves and their use broadens.

Surgical Outcomes of Porcine Acellular Dermis Graft in Anophthalmic Socket: Comparison with Oral Mucosa Graft.

PURPOSE: We describe our experience with the Permacol graft in anophthalmic socket reconstruction, and compare it to the autologous buccal mucosal graft, emphasizing the postoperative vascularization and contraction of each graft. METHODS: This was a retrospective comparative study. We measured the time necessary for the graft surface to be completely vascularized, as well as the fornix depth of the conjunctival sac in anophthalmic patients. RESULTS: Ten patients underwent Permacol graft reconstruction, with 44 undergoing buccal mucosal graft reconstruction. Seven eyelids (70%) in the Permacol group had a good outcome, with improvement in lower eyelid position and prosthesis retention. Nine out of 10 eyelids (90%) in this group showed complete vascularization of the graft at 2.6 ± 1.9 months postoperatively, while the grafted buccal mucosa was fully vascularized at 1.1 ± 0.3 months postoperatively (p < 0.01). Postoperative fornix depth in the Permacol group was 9.1 ± 2.2 mm, compared to 14.9 ± 4.5 mm in the buccal mucosal graft group (p < 0.01). Mean increases in fornix depth were 33.1% and 67.9% of the mean vertical length of the implanted graft. CONCLUSIONS: The Permacol graft can be useful as spacer graft material in anophthalmic socket patients. It takes longer to vascularize, and undergoes greater graft shrinkage with time, compared to the buccal mucosal graft.