Selumetinib in the Treatment of Orbital Plexiform Neurofibroma: A Case Report.

A 4-year-old boy with a known diagnosis of neurofibromatosis 1 (NF1) and a diffusely infiltrative plexiform neurofibroma (PN) of the left orbit was started on selumetinib treatment for progressively worsening amblyopia. The patient first presented with new-onset left ptosis at 11 months old. He subsequently developed refractory anisometropic amblyopia of the left eye, in addition to clinically significant left proptosis and hypoglobus that interfered with glasses wear for his amblyopia treatment. The plexiform neurofibroma was not amenable to surgical resection and selumetinib treatment was initiated 3 years after the initial diagnosis. The patient showed remarkable clinical and radiographic improvement in tumor burden after treatment. Best corrected visual acuity improved from 20/50 to 20/20- in his amblyopic eye. Relative proptosis of the affected eye also improved from 4mm to 2mm on Hertel measurements, which allowed for consistent glasses wear. Adverse effects from the treatment were limited to an acneiform rash, which resolved following dose reduction according to the FDA dosing guidelines.

Teprotumumab and Hearing Loss: Case Series and Proposal for Audiologic Monitoring.

PURPOSE: To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS: Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS: An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS: Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.

Compound Coherent Plane-Wave Ultrasound Imaging of Vascular Malformations of the Orbit.

PURPOSE: Prior color-flow Doppler ultrasound studies of the eye have been performed with systems that exceed US Food and Drug Administration permissible ophthalmic ultrasonic energy limits. The authors report a study of orbital vascular malformations using a novel, Food and Drug Administration compliant, ultrafast compound coherent plane-wave ultrasound device to produce power Doppler images. METHODS: Using a Verasonics Vantage 128 ultrasound engine and a user-developed MATLAB program with a 5-MHz linear-array probe, compound coherent plane-wave ultrasound data were collected on patients with orbital vascular malformations. Real-time color-flow Doppler visualized orbital blood flow. Power Doppler images were produced by post-processing compound coherent plane-wave ultrasound data acquired continuously for 2 seconds. RESULTS: Compound coherent plane-wave ultrasound was performed on 3 orbital vascular malformations (1 venolymphatic malformation, 1 infantile hemangioma, and 1 arteriovenous malformation). Compound coherent plane-wave ultrasound produced a high-resolution depiction of orbital blood flow for orbital vascular malformations with high sensitivity to slow flow. CONCLUSIONS: Analysis of blood flow within orbital lesions informs treatment planning. Compound coherent plane-wave ultrasound is an emerging ultrasound modality that falls within the Food and Drug Administration guidelines for use in the orbit and provides information to characterize orbital vascular malformations.

Doxycycline Injection for Sclerotherapy of Lower Eyelid Festoons and Malar Edema: Preliminary Results.

PURPOSE: To investigate the safety and efficacy of direct, intralesional doxycycline hyclate injection for improving the appearance of cosmetically significant lower eyelid festoons and malar edema. METHODS: An Institutional Review Board approved, retrospective review was performed of 15 consecutive patients with malar edema and/or festoons injected with doxycycline hyclate at a concentration of 10 mg/ml. Pre- and postinjection photographs were reviewed and graded on a scale of 0 to 3 (0: no festoon; 1: small festoon; 2: medium festoon; 3: large festoon) by 2 masked physician observers. Patients were excluded from the final analysis if they received an alternate dose concentration, had incomplete photographic records, or did not follow up. Student t test was used for statistical analysis. RESULTS: Twenty consecutive treatment areas of 11 patients were included in the analysis. Final follow up ranged from 3 to 104 weeks, with a mean follow up of 22.5 weeks. The average (standard deviation) initial festoon grade of 2.5 (0.58) decreased to 0.9 (0.82) with a p value of <0.001. The average number of injections performed per side was 1.4 (range: 1-2). The mean volume per injection was 0.72 ml (range: 0.15-2.0 ml). Commonly documented subjective complaints were burning sensation with injection, pain, bruising, and erythema. There were no other dermatologic or visual complications following treatment. CONCLUSIONS: These preliminary results suggest that intralesional injections of doxycycline hyclate at a concentration of 10 mg/ml may be an effective treatment option for cosmetically significant lower eyelid festoons and malar edema. Future prospective studies with increased patient numbers, increasing concentrations, combination therapies with local anesthetic or regional nerve blocks, and longer follow up are needed to validate these results and determine optimal injection technique.

Predominant Contribution of Superior Rectus-Levator Complex Enlargement to Optic Neuropathy and Inferior Visual Field Defects in Thyroid Eye Disease.

PURPOSE: To compare extraocular muscle volumes in thyroid eye disease patients with and without compressive optic neuropathy. METHODS: A retrospective review of 44 orbital CT scans (28 orbits without compressive disease and 16 orbits with compressive optic neuropathy) was conducted. The extraocular muscle volumes, summated soft tissue volumes, and optic nerve volumes were calculated at a section in the posterior 1/3 of the orbit. The visual fields of the orbits with compressive optic neuropathy were analyzed. RESULTS: The mean combined extraocular muscle/summated soft tissue volume ratio and the mean superior rectus-levator complex/summated soft tissue volume ratio were greater in those with compressive optic neuropathy than in those without compressive optic neuropathy (p = 0.02, 0.008, respectively). The ratio of the mean inferior, medial, or lateral rectus/summated soft tissue volume did not differ significantly between patients with or without compressive optic neuropathy (p values of 0.315, 0.615, and 0.254, respectively). Visual field analysis of the compressive optic neuropathy group demonstrated that 58% of the orbits with visual field defects had inferior field defects. CONCLUSIONS: When measured at a section near the orbital apex, the mean combined muscle/summated soft tissue volume ratio and the mean superior rectus-levator complex/summated soft tissue volume ratio are greater in those with compressive disease than those without. This suggests that the specific enlargement of the superior rectus-levator complex makes a significant contribution to thyroid eye disease-compressive optic neuropathy and may explain the inferior visual field deficits classically found in this group of patients.

The Columbia Thyroid Eye Disease-Compressive Optic Neuropathy Diagnostic Formula.

PURPOSE: Diagnosing thyroid eye disease-compressive optic neuropathy (TED-CON) is challenging, particularly in cases lacking a relative afferent pupillary defect. Large case series of TED-CON patients and accessible diagnostic tools are lacking in the current literature. This study aims to create a mathematical formula that accurately predicts the presence or absence of CON based on the most salient clinical measures of optic neuropathy. METHODS: A retrospective case series compares 108 patients (216 orbits) with either unilateral or bilateral TED-CON and 41 age-matched patients (82 orbits) with noncompressive TED. Utilizing clinical variables assessing optic nerve function and/or risk of compressive disease, and with the aid of generalized linear regression modeling, the authors create a mathematical formula that weighs the relative contribution of each clinical variable in the overall prediction of CON. RESULTS: Data from 213 orbits in 110 patients derived the formula: y = -0.69 + 2.58 × (afferent pupillary defect) - 0.31 × (summed limitation of ductions) - 0.2 × (mean deviation on Humphrey visual field testing) - 0.02 × (% color plates). This accurately predicted the presence of CON (y > 0) versus non-CON (y < 0) in 82% of cases with 83% sensitivity and 81% specificity. When there was no relative afferent pupillary defect, which was the case in 63% of CON orbits, the formula correctly predicted CON in 78% of orbits with 73% sensitivity and 83% specificity. CONCLUSIONS: The authors developed a mathematical formula, the Columbia TED-CON Diagnostic Formula (CTD Formula), that can help guide clinicians in accurately diagnosing TED-CON, particularly in the presence of bilateral disease and when no relative afferent pupillary defect is present.

Nasal Glioma: A Rare Cause of Congenital Inner Canthal Swelling.

Nasal glioma, encephalocele, and ectopic brain are rare congenital anomalies. The terminology applied to these entities has been historically confusing. In many cases, the terms overlap and may be employed synonymously although some authors emphasize their differences. The authors describe herein a child with an inner canthal mass of brain-like tissue that they interpret as nasal glioma, a variety of encephalocele that has lost its connection to the intracranial contents. This research was conducted in conformity with the Helsinki Declaration and Health Insurance Portability and Accountability Act regulations.

IgG4-related orbital disease masquerading as thyroid eye disease, vice versa, or both?

A 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses. Inferior oblique biopsy stained positive for IgG4 with histologic features atypical of TED. The patient received rituximab for presumed IgG4-related orbital disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near complete resolution of EOM restriction, and improved proptosis, the latter two of which are not routinely anticipated in advanced TED. The possible role for B-cell depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying immune-related pathophysiology that is yet to be defined.

Ophthalmic Timolol Hallucinations: A Case Series and Review of the Literature.

PURPOSE: Systemic absorption and central nervous system (CNS) penetration of timolol drops are a well-studied phenomenon, resulting in common side effects such as bradycardia, bronchospasm, fatigue, and confusion. More serious CNS side effects, such as psychosis and depression, however, are rarely attributed to eye drops. We report a case series in which patients developed visual hallucinations secondary to topical ocular timolol use. METHODS: This study is a case series and review of the literature. RESULTS: Four patients with glaucoma developed visual hallucinations while using topical timolol. The patients were all elderly, caucasian females with associated CNS pathology. All patients had resolution of symptoms upon discontinuation and a positive retrial test to confirm the association. CONCLUSIONS: The rarity of this side effect and its anecdotal predilection for elderly, caucasian females with underlying neurological dysfunction, may involve a yet unknown predisposition or hypersensitivity to beta blocker action, such as blood brain barrier disruption leading to increased susceptibility to the medication. This case series highlights an important, although rare, side effect of this medication which clinicians should be aware of especially when using it in elderly patients who may have coexisting CNS pathology. It is important that this side effect be recognized and appropriately managed to prevent otherwise unnecessary investigations and treatment.

Patterns of visual field changes in thyroid eye disease.

This article provides a systematic description of visual field changes in thyroid eye disease-compressive optic neuropathy (TED-CON). A retrospective, non-comparative chart review of patients with TED-CON and documented Humphrey Visual Field 24-2 or 30-2 testing was conducted with IRB approval. Ninety-six visual fields in 68 patients were classified into 7 broad categories (superior, inferior, diffuse, temporal, nasal, central/paracentral, enlarged blind spot) and 17 mutually exclusive patterns from the Ocular Hypertension Treatment Study (OHTS) or "other." Fifty-three of 96 visual fields (55%) showed an inferior defect using the broad categories, with the remaining 6 categories ranging from 2% to 14%. The five most common OHTS patterns were other (28%), partial arcuate (28%), partial peripheral rim (9%), arcuate (8%) and altitudinal (7%). Further sub-classification showed a predominance of inferior visual field defects, ranging from 33% to 93% of each category. Of the 78 visual fields in these five categories combined, 52 (67%) were inferior defects. Inferior defect is the most typical TED-CON-associated visual field change. While the OHTS categories are geared toward classification of glaucomatous patterns, the overall predominance of inferior field defects in TED-CON was clearly demonstrated. These "other" visual field changes showing central inferior defect up to but not crossing the horizontal meridian and not contiguous from blind spot to nasal meridian should be designated as "TED-CON pattern." The high proportion of visual fields falling under the "other" category, however, does demonstrate the need for a more specific and tailored visual field classification system for TED-CON.

Enhanced Fasanella-Servat Procedure for the Graded Repair of Blepharoptosis.

PURPOSE: To describe in detail a technique for a modified Fasanella-Servat procedure that provides a simplified method for graded Mueller muscle excision with minimal and controlled tarsal excision. METHODS: A retrospective study of 71 patients (102 eyelids) who underwent the modified Fasanella-Servat procedure is reported. Measurements include the preoperative, post-phenylephrine, and postoperative margin-to-reflex distance-1, and postoperative upper eyelid height symmetry as determined by the absolute difference between right- and left-sided margin-to-reflex distance-1. Postoperative complications are reported. RESULTS: The average increase in margin-to-reflex distance-1 was 2.4 mm with an average postoperative upper eyelid height symmetry of 0.4 mm. Postoperative asymmetry was 1.5 mm or less in 68 patients, a success rate of 96%. Four patients (6%) exhibited overcorrection, 2 of which required additional surgery. No lagophthalmos or notable eyelid contour abnormalities were seen. CONCLUSIONS: The modified Fasanella-Servat technique offers a simple method to isolate and resect Mueller muscle and a minimal segment of tarsus in a quantitative fashion, allowing for a graded repair of blepharoptosis and thereby decreasing the risk of postoperative overcorrection, lagophthalmos, and eyelid contour asymmetry whilst preserving the bulk of tarsus.

Low-Cost 3D Printing Orbital Implant Templates in Secondary Orbital Reconstructions.

PURPOSE: Despite its increasing use in craniofacial reconstructions, three-dimensional (3D) printing of customized orbital implants has not been widely adopted. Limitations include the cost of 3D printers able to print in a biocompatible material suitable for implantation in the orbit and the breadth of available implant materials. The authors report the technique of low-cost 3D printing of orbital implant templates used in complex, often secondary, orbital reconstructions. METHODS: A retrospective case series of 5 orbital reconstructions utilizing a technique of 3D printed orbital implant templates is presented. Each patient's Digital Imaging and Communications in Medicine data were uploaded and processed to create 3D renderings upon which a customized implant was designed and sent electronically to printers open for student use at our affiliated institutions. The mock implants were sterilized and used intraoperatively as a stencil and mold. The final implant material was chosen by the surgeons based on the requirements of the case. RESULTS: Five orbital reconstructions were performed with this technique: 3 tumor reconstructions and 2 orbital fractures. Four of the 5 cases were secondary reconstructions. Molded Medpor Titan (Stryker, Kalamazoo, MI) implants were used in 4 cases and titanium mesh in 1 case. The stenciled and molded implants were adjusted no more than 2 times before anchored in place (mean 1). No case underwent further revision. CONCLUSIONS: The technique and cases presented demonstrate 1) the feasibility and accessibility of low-cost, independent use of 3D printing technology to fashion patient-specific implants in orbital reconstructions, 2) the ability to apply this technology to the surgeon's preference of any routinely implantable material, and 3) the utility of this technique in complex, secondary reconstructions.

Low-Flow Arterialized Venous Malformations of the Orbit.

PURPOSE: Orbital vascular malformations are classified by their hemodynamic properties, either high or low flow. Low-flow lesions may be simple venous, lymphatic, or combined lymphaticovenous malformations. The authors report a series of cases in which predominantly low flow, venous lesions were unexpectedly noted to have arterial feeders. METHODS: A retrospective chart review of patients identified by the authors as having orbital varices with arterial components was conducted. The authors identified 7 such cases. After careful review, 2 cases were excluded due to inconclusive neuroradiographic findings. The authors review the clinical, radiologic, histopathologic, and surgical information from the remaining 5 cases and discuss their clinical significance. RESULTS: All 5 cases were most consistent with variceal lesions: 3 as clinically distensible lesions and 2 as thrombosed lesions. Additional arterial feeder vessels were noted by angiography (3) or intraoperative visualization (2). The arterial contribution varied from faint vessels to distinct branches of the ophthalmic artery. Ages ranged from 13 to 61 years without predilection for gender. Treatments consisted of excision, embolization, and observation. Two poignant cases are highlighted: the first illustrating that an angiogram in isolation of its clinical picture can be misleading and result in treatment intervention with undue risk, and the second illustrating that inadequate treatment of unrecognized arterial components may contribute to recurrences. CONCLUSIONS: Low-flow orbital variceal lesions may have less prominent, arterial components. This type of combined arterialized venous malformation is largely unrecognized in the ophthalmic literature. Correct identification of these lesions is critical in providing safe, effective, and durable treatment.

Atypical Rapidly Enlarging Orbital Schwannoma.

Orbital schwannomas are typically slow-growing benign tumors that can cause gradual loss of vision, proptosis, and limitation of ocular motility. The authors present an atypical case of a rapidly growing orbital apex schwannoma in a patient with preexisting vision loss secondary to presumed sarcoidal optic neuritis. Contrary to the slowly progressive nature of a typical orbital schwannoma, the lesion was observed to enlarge from radiologically undiscernible to 3.5 cm over 4 years.

Retained strabismus suture material masquerading as nonspecific orbital inflammation.

We report a case of orbital myositis of the superior rectus muscle-levator complex masquerading as nonspecific orbital inflammation but corresponding in location to a known braided polyester "chicken suture" placed 20 years earlier during strabismus surgery. The orbital inflammation was refractory to oral steroids but resolved promptly on surgical removal of the suture material. Although suture material is known to cause foreign body granulomatous reactions, to our knowledge this is the first reported case of a deep, diffuse orbital inflammation attributable to chicken suture placed during strabismus surgery.

Wyburn-Mason Syndrome Associated With Cutaneous Reactive Angiomatosis and Central Retinal Vein Occlusion.

Retinal venous occlusive events are a rare complication of arteriovenous malformations of the retina found in Wyburn-Mason syndrome. The authors present a case of a 28-year-old man diagnosed with Wyburn-Mason syndrome and cutaneous reactive angiomatosis, a reactive angioproliferative disorder induced by vascular occlusion. He developed a central retinal vein occlusion complicated by macular edema and received treatment with intravitreal bevacizumab, which led to resolution of the edema. To the best of the authors' knowledge, this is the first report of an anti- vascular endothelial growth factor agent employed as an effective treatment for macular edema in the setting of Wyburn-Mason syndrome. The association between Wyburn-Mason syndrome and cutaneous reactive angiomatosis is also a novel finding.

Malignant rhabdoid transformation of a longstanding, aggressive, and recurrent orbital angiomyxoma.

A 47-year-old woman presented with a medial orbital tumor initially diagnosed as either a myxoid neurofibroma or myoepithelioma. Over 30 years the tumor recurred seven times and was serially debulked. Careful histopathologic analysis coupled with immunohistochemical studies performed on the last two biopsies established the rare diagnosis of a locally aggressive angiomyxoma (because of its local infiltrative growth) with myofibroblastic features (smooth muscle actin and calponin positivity and desmin negativity). The last recurrence manifested at a shorter interval than the earlier ones, suggesting an accelerating clinical course. By this late stage there was complete blindness, a frozen globe, and extreme, unmeasurable proptosis accompanied by massive chemosis and eyelid fullness. An exenteration was performed, and the orbital contents contained a persistent angiomyxoma, but additionally, another cellular population had emerged-mitotically active cells with a malignant rhabdoid phenotype (round shape, cytoplasmic hyaline/globoid inclusions composed of whorls of compact vimentin filaments as well as epithelial membrane antigen and focal cytokeratin positivity). This is the first orbital case of a rhabdoid transformation of a benign orbital mesenchymal tumor. Shortly after the exenteration, multifocal metastases, notably to the lungs, were found, leading to the introduction of chemotherapy, which was discontinued because of non-responsiveness of the tumor and patient intolerance. After 1 year of follow up, the patient is still alive, but has persistent active disease with widespread metastases and a guarded prognosis.

Reactivation of thyroid associated orbitopathy following trauma with intraorbital foreign body.

A 63-year-old female with mild, bilateral, stable thyroid-associated orbitopathy sustained trauma resulting in glass foreign bodies embedded on the left ocular surface and left lateral orbital extraconal and intraconal space. After 2 orbitotomies including a failed attempt to remove the intraconal foreign body and poor response to oral steroids, she developed severe, progressive left periorbital edema and 9 mm of relative proptosis. Serial, post-operative imaging demonstrated worsening inflammatory changes along the surgical tract, which slowly improved over several months, with simultaneously worsening proptosis and enlargement of the left inferior and medial rectus muscles consistent with worsening thyroid orbitopathy. She subsequently underwent unilateral 3-wall orbital decompression with improvement in her symptoms. Periorbital trauma with orbital foreign bodies and related surgical trauma may result in reactivation of thyroid-associated orbitopathy.