Teprotumumab for the Treatment of Recalcitrant Thyroid Eye Disease.

PURPOSE: Teprotumumab, an insulin-like growth factor 1 receptor monoclonal antibody, is FDA-approved to treat thyroid eye disease (TED). The initial clinical trials excluded patients with previous orbital irradiation, surgery, glucocorticoid use (cumulative dose >1 gm), or prior biologic treatment. Information on the use of teprotumumab for patients who failed prior therapy is limited. Our purpose is to characterize the efficacy of teprotumumab for the treatment of recalcitrant TED. METHODS: This is a multicenter retrospective study of all patients treated with teprotumumab for moderate-to-severe TED after failing conventional therapy with corticosteroids, orbital radiation, surgical decompression, biologics, or other steroid-sparing medications. Treatment failure was defined as an incomplete response to or reactivation after previous treatment. Only patients who received at least 4 infusions of teprotumumab were included in the analysis. Primary outcome measures comprised proptosis response (≥2 mm reduction in the study eye without a similar increase in the other eye), clinical activity score (CAS) response (≥2-point reduction in CAS), and diplopia response (≥1 point improvement in Gorman diplopia score in patients with baseline diplopia) following treatment. Adverse events and risk factors for recalcitrant disease were also evaluated. RESULTS: Sixty-six patients were included in this study, 46 females and 20 males. Average age was 59.3 years (range 29-93). The mean duration of disease from TED diagnosis to first infusion was 57.8 months. The proptosis, CAS, and diplopia responses in this recalcitrant patient population were 85.9%, 93.8%, and 69.1%, respectively. Patients experienced a mean reduction in proptosis of 3.1 ± 2.4 mm and a mean improvement in CAS of 3.8 ± 1.6. Patients who underwent prior decompression surgery experienced a statistically significant decrease in diplopia response (46.7% vs. 77.5%, p = 0.014) and proptosis response (75.0% vs. 90.9%, p = 0.045) when compared with nondecompression patients. Additionally, there were no significant differences in proptosis, CAS, and diplopia responses between patients with acute (defined as disease duration <1 year) versus chronic (disease duration ≥1 year) TED. While most adverse events were mild to moderate, 4 patients reported serious adverse events related to persistent hearing loss. CONCLUSIONS: Patients with recalcitrant TED demonstrated a significant improvement after teprotumumab in each of the primary study outcomes. The degree of proptosis reduction, diplopia response, and CAS improvement in the recalcitrant group were similar to those of treatment-naïve patients from the pivotal clinical trials. Patients with a prior history of orbital decompression, however, demonstrated poor improvement in diplopia and less reduction in proptosis than surgery naïve patients. These results indicate that teprotumumab is a treatment option for the treatment of patients with TED recalcitrant to prior medical therapies.

Orbital Hemorrhagic Necrosis, Globe Rupture, and Death From Intraorbital Injection of 1% Sodium Deoxycholate in a Murine Model.

PURPOSE: Deoxycholic acid (DCA) 1% is an injectable detergent indicated for submental fat reduction, although clinically it is being injected off-label for orbital fat prolapse. It is known to cause severe inflammation, local nerve dysfunction, and tissue necrosis, all of which could be catastrophic in the orbit and periocular region. This study evaluated the effects of periocular DCA on orbital and ocular adnexal tissues in a murine model. METHODS: Mice were treated via split-face intraorbital injections, subcutaneous injections, and topical cornea application with DCA versus phosphate-buffered saline. Whole heads were fixed, decalcified, and sectioned for orbital histology after 1-7 days. Matched pairs of human globes and mouse globes were immersed in either phosphate-buffered saline or 1% DCA for 72 hours. RESULTS: Six of 11 mice receiving intraorbital DCA injections died within minutes. Surviving mice developed severe orbital inflammatory necrosis. All orbits injected with phosphate-buffered saline were clinically and histologically normal. Six mice were treated with lower concentrations of DCA and all developed variable amounts of orbital inflammation, hemorrhage, and globe necrosis. Mice receiving subcutaneous DCA injection to the lower eyelid showed inflammatory necrosis, edema, and lid malposition. Topical application of DCA to mouse corneas caused no external or histologic changes. Human and mouse globes immersed ex vivo in DCA developed corneal edema and cataract formation without observable scleral changes. CONCLUSION: Intraorbital and periocular injection of DCA can cause devastating complications in a murine model, and significant caution is advised for off-label use in the periocular region.

Orbital Bony Reconstruction With Presized and Precontoured Porous Polyethylene-Titanium Implants.

PURPOSE: Complex bony orbital defects are reconstructively challenging due to loss of intraoperative anatomical landmarks and adjacent support. Presized and precontoured porous polyethylene-titanium implants (Medpor Titan 3D Orbital Floor Implant) are designed to reestablish normal orbital floor and medial wall anatomy and are modeled after anatomically averaged orbits. This is the first study to report clinical outcomes with this implant. METHODS: This retrospective case series reviewed clinical data and outcomes for patients undergoing orbital reconstruction with a presized and precontoured porous polyethylene-titanium orbital implant from January 2016 to June 2018. RESULTS: A total of 34 orbits of 33 patients were identified (mean age: 43 ± 16 years, 70% men). Most bony defects were a result of trauma and included large orbital floor deformities (100%), medial wall defects (74%), disrupted inferomedial struts (68%), and broken posterior ledges (82%). Symptomatic diplopia (73%) and enophthalmos (89%, mean: 3.7 ± 2.1 mm) were common preoperatively. Many cases were revisions (44%). Mean follow up was 7.8 ± 6.7 months. All patients had improved globe positioning, enophthalmos, and hypoglobus. Seven patients had persistent postoperative diplopia: 6 responded to prism therapy and 1 required strabismus surgery. One patient required retrobulbar hematoma drainage and 1 patient required implant explantation due to chronic infection. CONCLUSIONS: Commercially available presized and precon toured porous polyethylene-titanium implants are useful for complex orbital bony defects and can achieve functional improve ments in diplopia, enophthalmos, and extraocular motility with a low incidence of postoperative complications or revisional surgery.

A Modified Hughes Flap for Correction of Refractory Cicatricial Lower Lid Retraction With Concomitant Ectropion.

INTRODUCTION: Correction of lower eyelid retraction commonly involves one or more techniques, including recession of the eyelid retractors, spacer grafts, horizontal lid tightening, and midface lifting. However, patients presenting with cicatricial lower lid retraction following prior eyelid surgery often have scarring and concomitant ectropion or entropion that cause unpredictable wound healing, recicatrization, and suboptimal outcomes. The modified Hughes tarsoconjunctival flap is typically used to repair full-thickness eyelid defects. Prior reports describe treating refractory lower lid retraction with a modified Hughes flap placed beneath the tarsus after full-thickness blepharotomy. We present our experience with a novel surgical technique for treating refractory cicatricial lower lid retraction using a modified Hughes flap above the tarsus after excision of the scarred lid margin. METHODS: Three patients were treated using this technique. The upper edge of the lower eyelid and associated scar tissue are excised. A modified Hughes flap is mobilized and secured above the posterior lamellar remnant. A full-thickness skin graft is placed over the flap. The flap is divided 4-5 weeks later. RESULTS: This surgical technique was employed in all 3 cases. All cases were revisional, with 2 having extensive multioperative histories with multiple unsuccessful reconstructions and lid retraction repairs. All patients had improvement in cicatricial eyelid retraction, lagophthalmos, exposure keratopathy, and resolution of concomitant cicatricial ectropion. CONCLUSIONS: The technique of using a modified Hughes flap to reconstruct above the tarsus with excision of the scarred lid margin was effective in correcting refractory cicatricial lower lid retraction. This procedure can be considered in multioperative cases in which traditional techniques for lower lid retraction repair have failed. Reconstructing a new lid margin reduces the risk of recicatrization and suboptimal results.

Bilateral Poorly Differentiated Adenocarcinoma of the Lacrimal Gland With Tumor Regression After Treatment With Pembrolizumab.

An 85-year-old man presented with a 6-month history of worsening left proptosis and painless ophthalmoplegia. Imaging revealed an extensive intraconal and extraconal tumor extending to the level of the optic foramen, as well as the scalp, cheek, and the nasal bridge. Incisional biopsy was consistent with lacrimal gland adenocarcinoma. The patient underwent a left orbital exenteration followed by immunotherapy with pembrolizumab. The treatment was stopped prematurely after 5 cycles due to development of autoimmune colitis. Four months later, the patient developed new contralateral disease in the right orbit and an incisional biopsy again showed lacrimal gland adenocarcinoma. Following the incisional biopsy, no further treatment was administered, but over the ensuing 6 months, there was dramatic spontaneous regression of the tumor both clinically and radiographically. At 28 months, the patient is still alive with relatively stable disease.

Ocular Considerations in Face Transplantation: Report of 2 Cases and Review of the Literature.

PURPOSE: Periorbital injuries are common in face transplantation (FT) candidates. It is therefore essential that the ophthalmologist play a central role in the multidisciplinary treatment of these patients. In this study, the authors perform a comprehensive review of all procedures involving periorbital components, provide an update for the ophthalmology community regarding the current state of the field, and present 2 cases. METHODS: A comprehensive review of the literature for all FT procedures including periorbital components was performed. The authors also present 2 patients who received FT including periorbital components for extensive facial disfigurement. One patient sustained high-energy avulsive ballistic injury and underwent a total face, double jaw, and tongue transplant in 2012. The second patient received a total face, eyelids, ears, and skeletal subunits transplant for extensive facial burns in 2015. RESULTS: Literature review demonstrated that 22 (54%) of the 41 patients undergoing FT received allografts containing periorbital components. Only 14 cases (64%) reported on the presence of ocular and periocular complications. The most common complications consisted of lower eyelid ectropion and lagophthalmos, and nearly all required revisional procedures. Both patients presented with significant periorbital scarring and demonstrated good visual acuity and aesthetic outcomes at postoperative follow up between 6 and 28 months. CONCLUSIONS: Face transplantation can address extensive facial and periorbital disfigurement with satisfactory functional and aesthetic outcomes. The majority of FT performed to date have included periorbital components, and postoperative ocular and periocular complications are common. It is critical for ophthalmologists to play a central role in the care of these patients.

Odontogenic choristoma presenting as dermolipoma.

A 5-year-old otherwise healthy girl presented to the oculoplastic service with a painless superotemporal subconjunctival mass in the left eye. Visual acuity was within normal limits, and there was no evidence of proptosis or orbital enlargement. Excision was performed to remove the anterior portion of the mass for alleviation of symptoms. On histopathological analysis, the mass was comprised of fibroadipose tissue consistent with dermolipoma and contained a hard nodule found to be a calcified tooth. In the periocular region, odontogenic choristoma (tooth) is a rare lesion, and has been reported to occur within teratomas, dermoid cysts, and displaced oral embryonic epithelium. We describe an unusual case of a tooth occurring within a sporadic dermolipoma. The clinical presentation, examination, management, and histopathology are reviewed.

Ablative Fractional Laser Resurfacing With Laser-Assisted Delivery of 5-Fluorouracil for the Treatment of Cicatricial Ectropion and Periocular Scarring.

PURPOSE: Cicatricial ectropion and periocular scarring can cause significant functional and cosmetic deficits. Surgical treatments can be associated with recicatrization, donor site morbidity, and textural and pigmentary abnormalities. This case series reports on efficacy and safety of a novel nonsurgical approach to treating cicatricial ectropion using ablative fractional laser resurfacing and laser-assisted delivery of 5-fluorouracil. METHODS: A retrospective review was conducted of all patients at a single institution who received ≥3 rounds of ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil. Six patients with cicatricial ectropion and periocular scarring secondary to reconstructive surgery, traumatic lacerations, and facial burns were included. Aesthetic and functional improvement were evaluated via fluorescein staining, tear breakup time, external photography, questionnaires gauging dry eye symptoms, and scar appearance. RESULTS: All patients showed functional improvement based on fluorescein staining (mean improvement 6.0 ± 1.4; p = 0.0007) and other indicators of dry eye. All 4 patients with lagophthalmos improved and 2 showed complete resolution. All patients demonstrated significant cosmetic improvement based on a validated scar assessment questionnaire (mean improvement 37.5 ± 18.9; p = 0.004), and 5 of 6 patients reported improved satisfaction with scar appearance (mean improvement 19.3 ± 12.8; p = 0.014). There were no adverse effects reported. CONCLUSIONS: Ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil appears to be a safe and effective modality for treating the functional and aesthetic abnormalities associated with periocular scarring, yielding results that are difficult to attain through surgery alone. Optimal management of cicatricial ectropion and periocular scarring often requires multimodality treatment, and ablative fractional laser resurfacing with laser-assisted delivery of 5-fluorouracil may be considered as part of a comprehensive approach to managing periocular scars.

Reconstruction of Unilateral Incomplete Cryptophthalmos in Fraser Syndrome.

A full-term baby girl with Fraser syndrome was born with right incomplete cryptophthalmos. On examination, the globe was completely covered with skin with partially formed eyelids laterally. At 3 years of age, she underwent an evisceration with orbital implant and reconstruction of the eyelids and fornices using the pre-existing scleral remnant. Custom ocular prosthetic fitting was performed 5 weeks postoperatively. At 4 years follow up, she continued to successfully retain an ocular prosthesis.

Unilateral Alacrima as a Presenting Symptom of Nasopharyngeal Carcinoma.

Advanced nasopharyngeal carcinoma may present to oculoplastic surgeons and ophthalmologists as epiphora or medial canthus swelling. In contrast, the authors describe an uncommon initial presentation of alacrima in a 30-year-old female with nasopharyngeal carcinoma without invasion of the nasolacrimal sac, duct, or lacrimal gland. The diagnosis was delayed due an initial misdiagnosis of dry eye. Nasopharyngeal carcinoma should be included in the differential for diminished tear production, especially if it presents asymmetrically.

Orbital Perivenous Abscess Complicating the Diagnosis and Management of Orbital Cellulitis.

An 11-year-old female presented with orbital cellulitis, bacterial sinusitis, enlarged left superior ophthalmic vein, dural venous sinuses, and internal jugular vein. The patient underwent endoscopic sinus surgery and was started on intravenous antibiotics and anticoagulation with limited improvement in orbital signs and symptoms. A magnetic resonance imaging/magnetic resonance venography of the orbits and brain revealed a dilated left superior ophthalmic vein with absence of flow but no clearly discernible orbital abscess. Intravenous corticosteroids resulted in dramatic improvement of pain, hypoglobus, proptosis, and extraocular motility, all of which rapidly recurred on discontinuation. Serial imaging revealed progression of what eventually manifested as a well-defined, rim-enhancing peri-superior ophthalmic vein abscess, which was incised and drained with prompt resolution of orbital cellulitis and complete visual recovery.

Secondary Orbital Reconstruction in Patients with Prior Orbital Fracture Repair.

PURPOSE: To evaluate clinical characteristics, preoperative imaging findings, pre- and post-operative outcomes, and satisfaction of patients requiring secondary reconstruction after inadequate primary orbital fracture repair. METHODS: Retrospective review of 13 patients requiring secondary orbital reconstruction following unsatisfactory primary repair. Primary outcomes were postoperative changes in enophthalmos, hypo- or hyper-globus, superior sulcus deformity, and restrictive strabismus. Secondary outcomes included patient satisfaction. RESULTS: Of 13 patients, 9 patients had primary orbital implants, and 4 patients did not. Of the 9 with implants, 6 had inferior displacement posteriorly, 2 had superior displacement posteriorly, and 1 had good position but had entrapped orbital tissues beneath it. Findings from primary surgery included enophthalmos (12/13), hypoglobus (10/13), hyperglobus (1/13), superior sulcus deformity (9/13), restricted supraduction (12/13), and restricted infraduction (7/13). Mean preoperative enophthalmos and hypoglobus were 4.4 ± 2.6 mm and 2.9 ± 1.4 mm, respectively. Secondary reconstruction resulted in mean reduction of enophthalmos by 3.4 ± 1.4 mm (p < 0.001), of hypoglobus by 2.9 ± 1.5 mm (p < 0.001), and of hyperglobus by 1 mm (n = 1). All 9 patients had resolution of their superior sulcus deformity. Of 12 cases with restricted ocular motility, all had improvements in postoperative motility following secondary surgery. Mean improvement in supraduction and infraduction was 1.8 ± 1.0 points (p < 0.001) and 1.4 ± 1.3 points (p = 0.025), respectively. Twelve patients reported being very satisfied or satisfied with secondary surgery; 1 patient was neutral. CONCLUSIONS: This study demonstrates that secondary orbital reconstruction can achieve excellent functional and cosmetic results with high patient satisfaction and minimal complications. Secondary reconstruction of previously repaired orbital fractures should be considered when clinically indicated.

Customised 3D Printing: An Innovative Training Tool for the Next Generation of Orbital Surgeons.

Additive manufacturing or 3D printing is the process by which three dimensional data fields are translated into real-life physical representations. 3D printers create physical printouts using heated plastics in a layered fashion resulting in a three-dimensional object. We present a technique for creating customised, inexpensive 3D orbit models for use in orbital surgical training using 3D printing technology. These models allow trainee surgeons to perform 'wet-lab' orbital decompressions and simulate upcoming surgeries on orbital models that replicate a patient's bony anatomy. We believe this represents an innovative training tool for the next generation of orbital surgeons.

Agreement between Pentacam and IOL master in patients undergoing toric IOL implantation.

PURPOSE: To investigate inter-device agreement between the Pentacam (Optikgerate GmbH, Wetzlar, Germany) and IOLMaster (Carl Zeiss Meditec, Jena, Germany) in measuring corneal power, cylinder, and axis of astigmatism. METHODS: Retrospective case series reviewing the status of eyes after toric IOL implantation to evaluate inter-device agreement in measuring corneal power, cylinder, and axis of astigmatism. RESULTS: Forty-nine eyes from 41 patients were evaluated. Agreement for corneal power and cylinder were deemed good and moderate, with 95% limits of agreement of -1.02 to +1.13 and -1.37 to +1.09 diopters (D), respectively. Agreement for axis of astigmatism was only fair, with a mean absolute difference of 8.9 degrees (range: 0.3 to 37.7 degrees, standard deviation: 8.79 degrees). Thirty percent of eyes had a 10-degree or greater difference in axis measurements, and 13% of eyes had a 20-degree or greater difference in measurements. Analysis by multivariate logistic regression showed higher cylinder powers associated with discrepant corneal power measurements (odds ratio: 3.46, P = .02), and increasing age was associated with discrepant axis measurements (odds ratio: 1.09, P = .03). Overall, there was no significant difference in accuracy predicting postoperative spherical equivalent refraction. CONCLUSIONS: Pentacam and IOLMaster agree well for corneal power but less so for cylinder and axis of astigmatism and thus cannot be used interchangeably.