Purpose To compare the long-term outcomes after intraarterial cytoreductive chemotherapy (IACC) to conventional treatment for lacrimal gland adenoid cystic carcinoma (ACC). Design Retrospective case series. Participants Nineteen consecutive patients treated with IACC, followed by orbital exenteration, chemoradiotherapy, and intravenous chemotherapy. Interventions Analyses of the histologic characteristics of biopsy specimens, extent of disease at the time of diagnosis, diagnostic surgical procedures, incidence of locoregional recurrences or distant metastases, disease-free survival time, response to IACC, tumor margins at definitive surgery, and toxicity and complications. Main Outcome Measures Disease relapse, disease-free survival, and chemotherapeutic complications. Results Eight patients with an intact lacrimal artery had significantly better outcomes for survival (100% vs. 28.6% at 10 years), cause-specific mortality, and recurrences (all p=0.002, log-rank test) than conventionally treated patients from this institution. These eight patients (Group 1) had cumulative 10 year disease-free survival of 100% compared to 50% for 11 patients (Group 2) who had an absence of the lacrimal artery and/or deviated from the treatment protocol (p=0.035) and 14.3% for conventionally treated patients (p<0.001). Likewise, Group 2 was associated with lower cause-specific mortality than the institutional comparator group (p=0.038). Prior tumor resection with lateral wall osteotomy, delay in IACC implementation or exenteration, and failure to adhere to protocol are risk factors for suboptimal outcomes. Conclusions Neoadjuvant IACC appears to improve overall survival and decrease disease recurrence. An intact lacrimal artery, no disruption of bone barrier or tumor manipulation other than incisional biopsy, and protocol compliance are factors responsible for favorable outcomes. The chemotoxicity complication rate is limited and manageable.

Background Teprotumumab, a novel IGF-1R antibody was recently shown to significantly reduce the signs of active Thyroid eye disease (TED). The current study reviews its efficacy in chronic TED. Methods In this retrospective review, consecutive patients with chronic stable TED (>2 years), who had received ≥3 infusions of teprotumumab were included. All patients had measurements of proptosis, and calculation of the CAS and diplopia scores before and after therapy. Five-point strabismus scores were also calculated. Patients who had imaging within 4 months prior to therapy and 6 weeks post therapy underwent orbital 3D volumetric analysis. Results Thirty-one patients met the inclusion criteria. The mean (SD) duration of TED was 81 months (56) and the mean (SD) number of infusions received by each patient was 7 (2). Mean (SD) reduction in proptosis for each study orbit was 3.5 mm (0.4) and 3 mm (0.3) for the fellow orbit. The CAS response was 90% for the study orbit and 87% for the fellow orbit. Of the 15 patients who had diplopia at baseline, 67% had a clinically significant response, while 47% had complete resolution following treatment. Following teprotumumab, mean (SD) reduction of muscle tissue was 2011 mm3 (1847) in the study orbit and 1620 mm3 (1759) in the fellow orbit. The mean (SD) reduction of fat volume was 2101 mm3 (1681) in the study orbit and 1370 mm3 (1181) in the fellow orbit. Conclusion Teprotumumab significantly reduces proptosis, inflammation, diplopia, strabismus and orbital soft tissue volume in patients with chronic TED.

A 45-year-old male presented with active progressive thyroid eye disease refractory to intravenous steroids and right orbital radiation. Visual acuity, left relative afferent pupillary defect, and Humphrey visual field defects were consistent with worsening left dysthyroid optic neuropathy. Orbital MRI demonstrated extraocular muscle enlargement and effacement of the left optic nerve sheath. After 2 infusions of teprotumumab, the patient’s visual acuity, relative afferent pupillary defect, Humphrey visual fields, proptosis, and extraocular muscle size improved. This is the first report of dysthyroid optic neuropathy responsive to teprotumumab, and it supports the need for further studies to better understand the role of teprotumumab in treating sight-threatening thyroid eye disease.

Purpose To study post-interventional findings in patients with dysthyroid optic neuropathy (DON) treated with teprotumumab. Observations In this multicenter observational Case series , patients with DON were treated with teprotumumab, an insulin-like growth factor I receptor inhibitor (10 mg/kg for the first infusion then 20 mg/kg for subsequent infusions, every three weeks for a total 8 infusions). This study included patients with acute and chronic thyroid eye disease (TED) with DON who had failed conventional therapies and were not candidates for surgical decompression. Data collected included best corrected visual acuity (BCVA), color vision, RAPD when present, and orbital CT or MRI. Proptosis, clinical activity score (CAS), Gorman diplopia score (GDS), and Humphrey visual fields (HVF) were also evaluated. Ten patients (6 women, 4 men) with an average age 64 years old were included in this study. Mean follow up after completion of infusions was 15 weeks. Baseline visual acuity (VA) impairment ranged from hand motion (HM) to 20/25 in affected eyes. All patients had pre-treatment orbital CT or MRI that confirmed orbital apex compression. Seventy percent of patients had objective improvement in DON after 2 infusions of teprotumumab measured as significant improvement in visual acuity, resolution of RAPD, or both. After completion of treatment, affected eyes had a mean BCVA improvement of 0.87 logMAR (p=0.0207), proptosis reduction of 4.7 mm (p<0.00001), CAS improvement of 5.25 points (p<0.00001), and GDS improvement of 0.75 points (p=0.160). All 6 patients who presented with an RAPD had resolution or improvement of RAPD. All 7 patients who presented with color vision deficits had normalization or improvement of color vision. Conclusions and Importance Teprotumumab infusions resulted in medical decompression and objective resolution or improvement of dysthyroid optic neuropathy. Most patients had rapid improvement of visual acuity and reversal of RAPD. Post-infusion imaging demonstrated reduction in extraocular muscle size that correlated with improvement in visual dysfunction. However, patients who presented with longstanding severe visual loss had limited improvement. There was no recurrence of DON after completion of teprotumumab in our cohort.

Purpose: The objective of this study is to provide a systematic review of the clinical outcomes of corneal neurotization and present the pathophysiology of corneal wound healing, neurotrophic keratopathy, and corneal neurotization. Methods: A literature review of published articles and meeting abstracts between December 2008 and February 2019 in the English language with the terms “corneal neurotization,” “corneal neurotisation,” “corneal reinnervation,” and “neurotrophic keratopathy” was performed. Reported clinical data before and after corneal neurotization, and surgical techniques, were collected and analyzed. Results: A total of 54 eyes that underwent corneal neurotization were identified. Final Logarithm of the Minimum Angle of Resolution (logMAR) best-corrected visual acuity improved to 0.85 (standard deviation [SD] = 0.65) from 1.25 (SD = 0.71) with a mean improvement of 0.41 (SD = 0.55; p < 0.0001). Central corneal sensation measured using Cochet-Bonnet esthesiometer improved from 2.18 mm (SD = 0.4) to 40.10 mm (SD = 18.66) with a mean filament length change of 38.00 mm (SD = 18.95; p < 0.0001). The median time to the reported maximal sensation return was 8 months (interquartile range 6–10). The most common reported limitation to visual recovery was corneal scarring (31.5%). Children (ages 0–17 years) as compared with adults (ages 18–82 years) had significantly greater final central corneal sensation esthesiometry readings, central corneal sensation return, and improvement in the logMAR best-corrected visual acuity (p < 0.011). Conclusions: Neurotrophic keratopathy disturbs the homeostatic balance of trophic factors and trigeminal nerve reflexes needed to support ocular surface health and corneal healing. Corneal neurotization can significantly improve corneal sensation and visual acuity and should be considered for the treatment of refractory neurotrophic keratopathy, especially in pediatric populations.

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Thyroid eye disease (TED) is a complex disease associated with myriad clinical presentations, including facial disfigurement, vision loss, and decreased quality of life. Traditionally, steroid therapy and/or radiation therapy were commonly used in the treatment of active TED. While these therapies can help reduce inflammation, they often do not have a sustainable, significant long-term effect on disease outcomes, including proptosis and diplopia. Recent advances in our understanding of the pathophysiology of TED have shifted the focus of treatment toward targeted biologic therapies. Biologics have the advantage of precise immune modulation, which can have better safety profiles and greater efficacy compared to traditional approaches. For instance, the insulin-like growth factor-1 receptor (IGF-1R) has been found to be upregulated in TED patients and to colocalize with the thyroid-stimulating hormone receptor (TSHR), forming a signaling complex. Teprotumumab is an antibody targeted against IGF-1R. By inhibiting the IGF-1R/TSHR signaling pathway, teprotumumab may reduce the production of proinflammatory cytokines, hyaluronan secretion, and orbital fibroblast activation in patients with TED. Due to promising phase II and III clinical trial results, teprotumumab has become the first biologic US Food and Drug Administration (FDA)-approved for the treatment of TED. In addition, there are currently ongoing studies looking at the use of antibodies targeting the neonatal Fc receptor (FcRn) in various autoimmune diseases, including TED. FcRn functions to transport immunoglobulin G (IgG) and prevent their lysosomal degradation. By blocking the recycling of IgG, this approach may dampen the body’s immune response, in particular the pathogenic IgG implicated in some autoimmune diseases. Advances in our understanding of the pathophysiology of TED, therefore, are leading to more targeted therapeutic options, and we are entering an exciting new phase in the management of TED. This review will cover recent insights into the understanding of TED pathophysiology and novel treatment options as well as ongoing studies of new potential treatment options for TED.

This report outlines contemporary practice patterns among active American Society of Ophthalmic Plastic and Reconstructive Surgery members in the management of upper and lower eyelid blepharoplasty. It is important to quantify such data periodically to update the membership as to how this common surgical procedure is approached. This also allows eyelid surgeons to compare their practice patterns with a national group specializing in such surgery.