Trametinib for orbital plexiform neurofibromas in young children with neurofibromatosis type 1.

INTRODUCTION: Plexiform neurofibromas (PNF) in neurofibromatosis type 1 (NF1) are usually diagnosed in childhood and can grow rapidly during this period. In 10% of patients, PNF involve the orbital-periorbital area and may cause visual problems including glaucoma, visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression, or keratopathy. Ptosis, proptosis, and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal involves significant risks and mutilation, and regrowth after debulking is not uncommon. Inhibitors of the RAS/MAPK pathway have recently been investigated for their activity in PNF. We administered the oral MEK inhibitor trametinib to five young children with NF1 and PNF of the orbital area, with visual compromise and progressive tumor growth; and followed them clinically and by volumetric MRI. METHODS: Treatment was initiated at a mean age of 26.8 months (SD ± 12.8) and continued for a median 28 months (range 16-51). Doses were 0.025 mg/kg/day for children aged > 6 years and 0.032 mg/kg/day for those aged < 6 years. RESULTS: Volumetric MRI measurements showed a reduction of 2.9-33% at 1 year after treatment initiation, with maximal reductions of 44% and 49% in two patients, at 44 and 36 months, respectively. No change in visual function was recorded during treatment. One child reported decreased orbital pain after 2 weeks; and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails, grades 1-2. CONCLUSIONS: Trametinib can decrease tumor size in some young children with orbital PNF and may prevent progressive disfigurement.

Quality of life after orbito-facial trauma.

In the wake of high incidence of orbito-facial trauma, there has been a growing need to assess not only the visual outcome, but also the psychological impact of the traumatic event. This is a single questionnaire based evaluation of 100 consecutive patients with orbito-facial trauma (blow-out and Le fort type II and III fractures) at six months of trauma. 84% of the patients had a NEI VFQ- 25 score of less than 50, with 49% having a score less than 25, reflecting the grim impact the trauma has on the quality of life. The three parameters of the questionnaire - general health, difficulty with activities and response to vision problems were significantly positively correlated. Quality of life is considerably affected following orbito-facial trauma, disturbing physical, mental and social health. Poor vision is positively correlated with poor general health. Psycho-social impact of trauma needs to be recognized as an important sphere in the management of orbito-facial trauma.

Ciliochoroidal ganglioneuroma in neurofibromatosis type 1: Report of a case and review of the literature.

Orbitofacial neurofibromatosis (OFNF) is considered a variant of neurofibromatosis type 1 (NF1). OFNF most often affects the eye, orbit and one side of the face. It is characterized by the development of relatively aggressive and disfiguring lesions, including plexiform and diffuse neurofibromas. Ciliochoroidal ganglioneuromas have not been previously reported in patients with this syndrome. We report the case of a 50-year-old man with OFNF, ciliochoroidal ganglioneuroma and a large ipsilateral frontoethmoidal encephalocele.

Osseointegrated implants for orbito-facial prostheses: Preoperative planning tips and intraoperative pearls.

PURPOSE: Implant-retained facial prostheses are becoming increasingly sophisticated. We describe our experience with successful implant placement. METHODS: Retrospective case series. Patients with severe unilateral orbital deformity who underwent socket reconstruction with placement of orbital implants were identified. Data on patient age, gender, mechanism of eye, soft tissue, and bone loss, prior reconstructive surgeries and radiation, and orbital imaging were collected and analyzed. RESULTS: Four patients (9 implants) between 2010 and 2014, who had osseointegrated implants placed for orbito-facial prostheses were identified. Three were male, one female. Average age was 59 years (range 34-86). Reason for eye loss was trauma in two patients, exenteration for recurrent rhabdomyosarcoma in one patient, and enucleation for retinoblastoma in one patient. All patients had Vistafix® (Gothenburg, Sweden) osseointegrated titanium implants (4 mm) placed in a 2-stage procedure over a span of 3-6 months with subsequent successful prosthesis fitting. CONCLUSION: Implant-retained orbito-facial prostheses are safe, easy, and reliable. The ideal socket has minimal dead space, robust bone, and soft tissue 4-5 mm in depth. Preoperative planning should consist of: 1) orbit CT; 2) careful clinical exam of the orbital deformity; and, 3) analysis of socket topography. Operative tips for successful implant placement include: 1) 2-3 points of fixation; 2) placement of implants in bone of adequate thickness; and 3) implant placement as a 2-stage rather than 1-stage procedure. There appears to be no difference in outcome in irradiated and non-irradiated sockets in this series, but should be a consideration and discussed with the patient.

Long-term visual outcomes in patients with orbitotemporal neurofibromatosis.

BACKGROUND: The study aimed to review the presentation and long-term visual outcomes of patients with orbitotemporal neurofibromatosis. DESIGN: Retrospective case series. PARTICIPANTS: Patients with orbitotemporal neurofibromatosis presenting from 1981 to 2009. METHODS: Demographic data, examination findings, causes of vision impairment and interventions performed were recorded for each patient from presentation through subsequent follow-up encounters. Visual impairment was defined as an ipsilateral Snellen acuity of <6/12. MAIN OUTCOME MEASURES: The proportion of patients with visual impairment or enucleation, the rate of new vision loss during follow up; and causes for vision loss or enucleation. RESULTS: Thirty-seven patients (17 female) were included. Median presenting age was 15 years (range 2-45) with an average follow up of 7.4 years (range 0.5-20.3). Visual impairment occurred in 54% of patients at presentation. Causes were amblyopia (13 of 37), optic atrophy (4 of 37), previous enucleation/evisceration (2 of 37), and optic nerve glioma (1 of 37). At presentation, 76% of patients had ptosis, and 51% had strabismus. Thirty-one patients had surgery, with an average of two procedures per patient. At final follow up, 62% had visual impairment. The rate of visual decline was 2% per patient-years. Causes of visual decline were two patients with optic nerve atrophy, one with exposure keratitis and one whose cause was unknown. Five blind patients had enucleation. CONCLUSIONS: The first series of orbitotemporal neurofibromatosis to focus on visual outcomes was presented. Vision loss is common, with a high prevalence of amblyopia. Close monitoring from an early age is needed to prevent visual impairment.

Analysis of orbitofacial anthropometry in children with pseudostrabismus.

AIM: The aim of the study was to analyze orbitofacial anthropometric parameters such as inner and outer canthal distances (ICD and OCD), palpebral fissure length (PFL), interpupillary distance (IPD), and canthal index (CI) in children with pseudostrabismus and to compare the measured IPD (mIPD) with calculated IPD (cIPD). MATERIALS AND METHODS: This was a prospective study of sixty children (6 months-18 years) with pseudostrabismus. ICD, OCD, PFL, and IPD were measured by digital Vernier caliper. The formula used was cIPD: 0.21+0.24 ICD+0.58°CD for males and 1.4+0.31 ICD+0.41°CD for females. Values measured by caliper were compared with that calculated by the formula. The formula used was CI: ICD × 100/OCD. Data were analyzed statistically. RESULTS: The mean age was 6.66 ± 3.57 years. Telecanthus was the most common finding (55%). The mean ICD and OCD in males were 30.89 ± 3.33 mm and 87.96 ± 8.09 mm and in females were 30.91 ± 3.05 and 86.22 ± 6.81 mm, respectively. The mean right eye PFL in males was 28.53 ± 2.63 mm and in females was 27.66 ± 2.22 mm and left eye PFL in males was 28.53 mm ± 2.63 and in females was 27.66 ± 2.22 mm. CI in males was 35.10 ± 1.65 and in females was 35.84 ± 1.71. Mean mIPD and cIPD: male - 55.37 ± 4.75 mm and 58.56 ± 5.34 mm, female - 53.32 ± 4.74 mm and 46.26 ± 3.71 mm. A good agreement was found between mIPD and cIPD. CONCLUSION: This study helps in documenting the anthropometric pattern of the orbitofacial parameters in children with pseudostrabismus which can act as reference data. This helps in the management of orbitofacial, craniofacial syndromes/deformities and lid reconstructive surgeries in retaining ethnical features and obtaining better function. In children's spectacle frame 1 and lens making, where measuring IPD is difficult, cIPD can be a simple alternative.

Iatrogenic nasolacrimal duct obstruction after adnexal intervention: An avoidable consequence.

PURPOSE: Isolated cases of nasolacrimal duct obstruction (NLDO) secondary to rhino-orbito-facial reconstructive surgeries have been reported previously. We report the clinical profiles and management outcomes of a series of patients with iatrogenic INDO. MATERIALS AND METHODS: Case records of all patients who presented with secondary NLDO over 5 years were retrospectively analyzed. The case series included seven patients with NLDO secondary to orbito-facial surgeries. RESULTS: The study included six males and one female patient with a mean age of 29 ± 12.58 years. All the patients had a history of road traffic accidents following which they underwent an open reduction and internal fixation by maxilla-facial surgeons. All of them presented to the Ophthalmology outpatient department with epiphora following the surgical intervention. Imaging revealed the implants were responsible for obstructing the nasolacrimal ducts in all seven cases. Five patients underwent external dacryocystorhinostomy while dacryocystectomy was performed in two. Implant removal was necessary for five patients without any compromise on the structural integrity of the orbital walls. CONCLUSION: Precise knowledge of the orbital anatomy, especially that of the lacrimal drainage system is imperative for surgeons performing surgeries in the midface area. A multidisciplinary approach and inclusion of surgeons trained in lacrimal surgeries can prevent such avoidable complications.

Orbital Implants in Orbital Fracture Reconstruction: A Ten-Year Series.

STUDY DESIGN: Retrospective comparative interventional series of all patients who had undergone orbital fracture repair by 2 senior orbital surgeons in a single tertiary trauma center from January 2005 to December 2014. OBJECTIVE: To compare the outcomes of different implants used for various types of orbital fractures. METHODS: Patients were evaluated by age, gender, etiology of fracture, clinical findings, type of fractures, and implant used. Main outcome measures included restoration of premorbid state without morbidity and complications including enophthalmos, diplopia, infraorbital hypoesthesia, and ocular motility restriction 1 year after fracture repair. Implant-related complications were collected for analysis. RESULTS: There were a total of 274 patients with 307 orbits reconstructed. Thirty-three (12.0%) patients sustained bilateral injuries; 58.0% (n = 178) of orbits had simple fractures (isolated orbital floor, medial wall, or combined floor and medial wall). The distribution of implants used were bioresorbable (n = 117, 38.1%) and prefabricated titanium plates (n = 98, 31.9%) depending upon the nature of fracture. Bioresorbables, titanium plate, and porous polyethylene were used significantly more than titanium mesh for simple fractures, and prefabricated anatomic titanium implants were used significantly more than the other implants for complex fractures. There was a statistically significant improvement in diplopia, enophthalmos, ocular motility, and infraorbital hypoesthesia (p-value < 0.001) 1 year following orbital fracture reconstruction. CONCLUSIONS: When used appropriately, diverse alloplastic materials used in orbital fracture repair tailored to the indication aid orbital reconstruction outcomes with each material having its own unique characteristics.

Differential gene methylation and expression of HOX transcription factor family in orbitofacial neurofibroma.

Although most commonly benign, neurofibromas (NFs) can have devastating functional and cosmetic effects in addition to the possibility of malignant transformation. In orbitofacial neurofibromatosis type 1, NFs may cause progressive, disfiguring tumors of the lid, brow, temple, face and orbit. The purpose of this study was to identify biological differences between orbitofacial NFs and those occurring at other anatomic sites. We used Illumina Methylation EPIC BeadChip to study DNA methylation differences between orbitofacial NFs (N = 20) and NFs at other sites (N = 4). Global methylation differences were detected between the two groups and the top differentially methylated genes were part of the HOX (Homebox) family of transcription factors (HOXC8, HOXC4, HOXC6, HOXA6 and HOXD4), which were hypomethylated in orbitofacial NFs compared to the non-orbital NFs. Conversely, LTF (lactoferrin) was relatively hypermethylated in orbitofacial NF compared to non-orbitofacial NF. HOXC8 protein levels were higher in orbitofacial plexiform NFs (p = 0.04). We found no significant differences in the expression of HOXC4, HOXA6, or HOXD4 between the two groups. HOXC8 mRNA levels were also higher in orbitofacial NFs and HOXC8 overexpression in a non-neoplastic human Schwann cell line resulted in increased growth. In summary, we identified gene methylation and expression differences between orbitofacial NF and NFs occurring at other locations. Further investigation may be warranted, given that the HOX family of genes play an important role during development, are dysregulated in a variety of cancers, and may provide novel insights into therapeutic approaches.

Three-dimensional and topographic relationships between the orbital margins with reference to assessment of eyeball protrusion.

This study investigated the topographic relationships among the eyeball and four orbital margins with the aim of identifying the correlation between orbital geometry and eyeball protrusion in Koreans. Three-dimensional (3D) volume rendering of the face was performed using serial computed-tomography images of 141 Koreans, and several landmarks on the bony orbit and the cornea were directly marked on the 3D volumes. The anterior-posterior distances from the apex of the cornea to each orbital margin and between the orbital margins were measured in both eyes. The distances from the apex of the cornea to the superior, medial, inferior, and lateral orbital margins were 5.8, 5.8, 12.0, and 17.9 mm, respectively. Differences between sides were observed in all of the orbital margins, and the distances from the apex of the cornea to the superior and inferior orbital margins were significantly greater in females than in males. The anterior-posterior distance between the superior and inferior orbital margins did not differ significantly between males (6.3 mm) and females (6.2 mm). The data obtained in this study will be useful when developing practical guidelines applicable to forensic facial reconstruction and orbitofacial surgeries.

Identification of the trochlea with reference to the lacrimal caruncle, and its significance as a landmark in orbitofacial surgery.

PURPOSE: The purpose of this study was to identify the location of the trochlea in order to prevent injury during orbitofacial surgery and to determine the reliability of the lacrimal caruncle as a visible external landmark for the trochlea at the superomedial orbital rim. METHODS: Fifty-one orbits from 27 embalmed cadavers were dissected. The lacrimal caruncle and supraorbital notch/foramen were used as external and bony landmarks, respectively. The location of the trochlea was determined with respect to these structures, and the size of trochlea was measured. RESULTS: The trochlea was 3.6 mm wide and 5.6 mm long, with a flange breadth of 5.4 mm. The vertical distance from the apex of the lacrimal caruncle to the superolateral tip of the trochlea was 15.8 mm, and that from the top of the supraorbital notch/foramen to the bottom of the trochlea was 11.4 mm. As the coefficient of variation and standard deviation were smaller for DCT (11.5 and 1.8, respectively) than for DST (17.0 and 1.9, respectively), it appears that the lacrimal caruncle is a reliable landmark. CONCLUSIONS: In contrast to the supraorbital notch, the lacrimal caruncle allows easy identification and serves as a reliable and visible external landmark for the prediction of the location of trochlea. The trochlea was located directly at 15.8 mm (i.e., approximately 1.5 cm) superior to the lacrimal caruncle. This anatomical study has yielded accurate measurements of the location of the trochlea, which may facilitate a safer orbitofacial surgery by preventing morbidity associated with trochlea injury.

Orbital soft tissue surgery for patients with Treacher-Collins or Nager syndrome. A new surgical approach with early correction of soft tissue: prospective study.

Orbitopalpebral anomalies in mandibulofacial dysostosis (Treacher-Collins syndrome) can be difficult to correct surgically and most authors recommend correction of the malar bone after the age of 8 years. We propose a new, early surgical approach for periorbital defects that involves initial implantation of autologous fat and subperiosteal malar lift with a pedicled upper eyelid flap. We prospectively studied 5 children, 3 of whom had previously had orbital reconstruction. Initial fat graft into the periorbital area was followed by a subperiosteal malar lift with lateral canthopexy, and a pedicled upper eyelid flap if needed. Two surgeons independently assessed the patients' characteristics including scleral show before and after operation, antimongoloid palpebral fissures, canthal dystopia, number 6 cleft (Tessier classification), skin quality, and surgical and ophthalmic complications. Before operation 3 patients had had ophthalmic problems. Postoperative evaluation showed improvements in scleral show, canthal dystopia, and skin quality, and correction of antimongoloid palpebral fissures and subcutaneous number 6 clefts. There were no postoperative complications. The proposed protocol gave satisfactory aesthetic and functional results in children with Treacher-Collins syndrome. We recommend that it is considered for periorbital reconstruction in all patients with a mandibulofacial deformity.

Incidence and management of rhinosinusitis after complex orbitofacial reconstruction.

OBJECTIVES/HYPOTHESIS: To examine the sinus-related sequelae of free flap reconstruction for complex orbitofacial defects. STUDY DESIGN: Retrospective chart review. METHODS: Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow-up of ≥ 3 months was available for 49 patients. Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery. RESULTS: The most commonly involved sinuses were the ethmoid (n = 40) and maxillary (n = 38) sinuses, and the anterolateral thigh was the most common flap used (n = 41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow-up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (P = 0.009). Adjuvant radiotherapy and adjuvant chemoradiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (P = 0.045 and 0.016, respectively). CONCLUSION: Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients.

Three-dimensional and topographic relationships between the orbital margins with reference to assessment of eyeball protrusion / 대한해부학회지

This study investigated the topographic relationships among the eyeball and four orbital margins with the aim of identifying the correlation between orbital geometry and eyeball protrusion in Koreans. Three-dimensional (3D) volume rendering of the face was performed using serial computed-tomography images of 141 Koreans, and several landmarks on the bony orbit and the cornea were directly marked on the 3D volumes. The anterior-posterior distances from the apex of the cornea to each orbital margin and between the orbital margins were measured in both eyes. The distances from the apex of the cornea to the superior, medial, inferior, and lateral orbital margins were 5.8, 5.8, 12.0, and 17.9 mm, respectively. Differences between sides were observed in all of the orbital margins, and the distances from the apex of the cornea to the superior and inferior orbital margins were significantly greater in females than in males. The anterior-posterior distance between the superior and inferior orbital margins did not differ significantly between males (6.3 mm) and females (6.2 mm). The data obtained in this study will be useful when developing practical guidelines applicable to forensic facial reconstruction and orbitofacial surgeries.

Rehabilitación protésica de órbita implantosoportada en paciente con secuela de meduloepitelioma teratoide maligno / Implant-supported orbit prosthetic rehabilitation in patient with malignant teratoid medulloepithelioma

La prótesis maxilofacial es «la especialidad odontológica que se dedica a la rehabilitación estética de las estructuras intraorales y extraorales por medios artificiales¼.¹ Una prótesis orbital es un dispositivo artificial que reemplaza la ausencia del ojo y sus anexos (párpados, pestañas y cejas). Ésta es una alternativa a la rehabilitación cuando la reconstrucción quirúrgica no sea viable, o se prefiere por el paciente. Hoy en día, con el avance de la investigación, podemos contar con el uso de los implantes de oseointegración, los cuales hasta el momento han evidenciado ser el medio de fijación óptimo en la rehabilitación protésica craneofacial. El caso clínico que se presenta corresponde a un paciente masculino con secuelas postquirúrgicas orbitofaciales de un carcinoma derivado del sistema nervioso central (meduloepitelioma teratoide maligno), que tiene como principal tratamiento la exenteración del globo ocular y áreas circunscritas que se encuentren afectadas, dejando un defecto orbitofacial, el cual se rehabilitó con una prótesis maxilofacial retenida por implantes integrados al hueso del reborde supraorbitario. El objetivo de este trabajo es dar a conocer el tipo de tratamiento integral que se da a un paciente con estos antecedentes, desde el diagnóstico de la afección, el tratamiento de la misma, así como la rehabilitación protésica del defecto resultante, con lo que se demuestra las ventajas del uso de implantes de oseointegración como medio de retención de la prótesis, y finalmente se observa cómo este tipo de rehabilitación incrementa la apariencia estética del paciente con secuelas quirúrgicas faciales, logrando su reintegración a la sociedad con más confianza y seguridad. Para lograr un tratamiento exitoso y brindarle al paciente el bienestar físico y mental, debemos trabajar en conjunto con un equipo multidisciplinario que resuelva el caso en su totalidad, para finalmente ofrecer los beneficios reales de la rehabilitación protésica con un medio de retención que ha sido, sin duda, una ventaja más que ofrecer para el paciente portador de la prótesis orbitaria. El uso de implantes ha tenido un gran impacto en estos pacientes, dándoles una favorable reintegración a la sociedad, disimulando sus defectos faciales y brindándoles comodidad y seguridad en el ejercicio de sus actividades cotidianas, sin el temor de un posible desprendimiento de su prótesis.

Maxillofacial prosthesis can be described as «the specialty in dental science devoted to the aesthetic rehabilitation by artificial means of intra-and extra-oral structures¼.¹ Orbit prostheses are artificial devices used to substitute the absence of the eye and annex structures (eyelids, lashes and eyebrows). They represent a rehabilitation alternative when surgical reconstruction is either unviable or not preferred by the patient. In our days, in the light of recent research advances, we can make use of bone-integrated implants. To this date they have proven to be the best fixation means in craniofacial prosthetic rehabilitation cases. The clinical case introduced in the present study is that of a male patient exhibiting postsurgical orbital-facial sequels after a carcinoma derived from the central nervous system (CNS) (malignant teratoid medulloepithelioma). Main treatment for this type of carcinoma is ocular globe and circumscribed affected areas exenteration. In this case, this procedure left an orbital-facial defect which was rehabilitated with a maxillofacial prosthesis, fixated to the supraorbital ridge by bone-integrated implants. The aim of the present study was to describe the comprehensive treatment administered to a patient exhibiting this kind of history, from the moment when the condition was diagnosed, its treatment, and the prosthetic rehabilitation of the resulting defect. This study shows the advantages obtained when using bone-integrated implants as a means for prosthesis retention. It is equally observed how this type of rehabilitation greatly improves the aesthetic appearance of patients afflicted with surgical facial sequels, thus achieving a more confident and self-assured reinsertion into society. In order to achieve successful treatment and offer mental and physical welfare to the patient we must work alongside a multi-disciplinary team, to comprehensively solve the case. We can then finally offer the real advantages of prosthetic rehabilitation with a retention means which has proved to be an additional advantage for patients wearing orbital prostheses. Implant usehas bornea great impact in these patients, fostering favorable reinsertion into society, since facial defects are dissimulated and patients can exhibit comfort and security in their day-to-day activities, without fear of a possible prosthesis displacement.