Side Effects and Adverse Events After Treatment With Teprotumumab for Thyroid Eye Disease: A Retrospective Observational Case Series.

As the use of teprotumumab for thyroid eye disease (TED) becomes more prolific, there remains a scarcity of literature regarding the associated side effects and adverse events of teprotumumab use. The authors present a single-center retrospective, observational case review of TED patients who received at least a single dose of teprotumumab infusion at the oculofacial plastic surgery service between February 2020 and July 2023. The most predominant recollected side effects were fatigue, brittle nails, dry eye symptoms, hair loss, muscle spasms, and dry mouth. Significant adverse events were limited to two cases of a blood clot and a single case of pulmonary embolism. This is the first retrospective study of patient-reported side effects and adverse events experienced by a cohort of teprotumumab users.

Penetrating colored pencil injury with Clostridium bifermentans pre-septal cellulitis: case report, literature review, and treatment algorithm.

The incidence of penetrating orbital injuries from writing instruments continues to rise in the pediatric population. Such injuries can cause significant visual morbidity and have a lifelong psychosocial impact. While the description of graphite pencil-related orbital trauma management is well demonstrated with over 40 reported cases, a lack of consistent management protocol for colored pencil-related injuries. Here, we report an inadvertent penetrating orbital colored pencil injury with progressive mechanical ptosis and pre-septal cellulitis necessitating urgent orbitotomy, debridement, and washout to reduce inflammatory and infectious burden. The wooden body serves as a nidus for polymicrobial infection, and the unique composition of colored pencil cores may lead to inflammatory processes that require vigilant multidisciplinary surgical and medical management reflected in our literature review.

Structural Limits of Orbital Compliance and Treatment Options for Pathologic Orbital Pressure.

PURPOSE: The integrity of the orbit has a finite structural limit due to the compliance of its tissue. The authors investigate these limits to quantify them and inform the treatment of heightened ocular and orbital pressure. METHODS: Cadaveric study with 12 orbits being volumized before randomization of treatment for pathologic levels of ocular and orbital pressure. First-line and second-line treatment was chosen randomly (lateral cantholysis, superior septolysis, inferior septolysis). Prior to treatment, IOP, orbital compartment pressure, and axial globe projection was measured after delivery of each 1cc aliquot and surgical treatment. RESULTS: Orbital compartment pressure and IOP were well correlated (r = 0.99). The average reduction in IOP after treatment averaged a 56.2 mm Hg reduction in IOP. All treatments were statistically equivalent ( p < 0.01). Loss of compliance (P LOC ) was determined when the mean plus 1 standard deviation of change in IOP/ml volume was achieved with simultaneous change in exophthalmometry of <0.5 mm change/ml added volume, indicating an acceleration in pressure in the face of a steady volume. This criteria was met for 11 of 12 orbits. The 12th orbit missed this threshold by 1 mm Hg in IOP. P LOC occurred at an average IOP of 43.0 mm Hg (±5.8 mm Hg, 90% CI) and after an average injection of 13 ml (±1.4 mm, 90% CI). Additionally, lateral cantholysis, superior septolysis, and inferior septolysis were statistically equivalent in reducing IOP after P LOC . CONCLUSIONS: IOP and orbital compartment pressure are excellent proxies for each other in the authors' model. Orbital compliance is a mathematic phenomenon that can be quantified, as evident in this investigation. P LOC can inform timing for orbital decompressions in the presence of heightened IOP. Multiple procedures can be used to extinguish dangerously high orbital compartment pressure.

Pediatric Orbital Roof Fractures: A Ratio of Orbital Dimensions Correlated to Prevalence of Fracture.

Objective Orbital roof fractures are more likely to occur in younger children, specifically younger than 7 years. Cranium to face ratio decreases with age; however, there is no definition for measurement of the neurocranium or face. We propose using the length of the orbital roof as a measurement of the neurocranium and length of the orbital floor as a tool to estimate midface size. The purpose of this study is to test this measurement as a correlation rate of orbital roof fractures within the pediatric population. Design This is a retrospective study. Setting This study was done at the LeBonheur Children's Hospital. Participants Sixty-six patients with orbital roof fractures were identified and stratified by gender and age, specifically younger than 7 years and 7 years or older. Main Outcome Measures The main outcome measures were orbital roof length, floor length, and ratio thereof. Results Mean orbital roof length was 43.4 ± 3.06 and 45.1 ± 3.94 mm for patients <7 and ≥7 years, respectively ( p = 0.02). Mean orbital floor length was 41.3 ± 2.99 and 47.7 ± 4.19 for patients <7 and ≥7 years, respectively ( p < 0.00001). The mean roof to floor ratio (RTFR) for patients <7 years was 1.051 ± 0.039 and for patients ≥ 7 years was 0.947 ± 0.031 ( p < 0.00001). Conclusion As children age, the relative length of the orbital roof decreases when compared with the orbital floor. The RTFR was more than 1.0 in children younger than 7 years. These differences were statistically significant when compared with children 7 years and older. This measurement shift follows the differences noted in orbital fracture patterns during childhood.

Spontaneous orbital hemorrhage in a case of acute liver failure.

Purpose: To report an unusual case of spontaneous orbital hemorrhage in the setting of DIC and hepatic failure. Observations: A 33-year-old female presented to the Emergency Department (ED) with acute liver failure. During the first week of her hospital admission, she developed unilateral eyelid swelling and proptosis, prompting a consult to ophthalmology. Additional physical examination revealed significantly decreased visual acuity, extraocular muscle restriction, afferent pupillary defect, and increased intraocular pressure. Computed tomography (CT) and ultrasound confirmed the diagnosis of intraorbital hemorrhage. Aggressive management in the form of lateral canthotomy, cantholysis, and septolysis was unable to be performed due to the patient's multiple comorbidities outweighing the potential benefits. Conclusions and importance: This rare phenomenon is unique from previous existing literature in that the timing of the incident limited the therapeutic options for this patient, additional imaging in the form of ultrasound was utilized in the work-up, and to our knowledge this is the second case of spontaneous orbital hemorrhage as a complication of disseminated intravascular coagulation (DIC) caused by hepatic failure.

Long-acting opioid prescribing patterns of ophthalmic plastic surgeons in the medicare Part D database.

PURPOSE: To assess extended release/long acting (ER/LA) opioid prescribing patterns among ophthalmic plastic surgeons in the Centers for Medicare and Medicaid Services (CMS) Part D database. METHODS: A retrospective observational cohort study was conducted on oculoplastic surgeons in the CMS Part D database who prescribed ER/LA opioids from 2013 to 2017. American Society of Ophthalmic Plastics and Reconstructive Surgery (ASOPRS) and non-ASOPRS surgeons were analyzed as groups. Prescribers were also analyzed based on gender and practice experience. RESULTS: Oculoplastic surgeons (64 ASOPRS and 78 non-ASOPRS) were responsible for 1,177 ER/LA opioid prescriptions from 2013 to 2017. ASOPRS members accounted for 4.6% and non-ASOPRS members accounted for 7.5% of all ER/LA opioids prescribed by ophthalmologists over the study period (p= .02). The total number of ASOPRS and non-ASOPRS members prescribing ER/LA opioids decreased by 52% (p= .10) and 58% (p= .07) from 2013 to 2017 respectively. CONCLUSION: ER/LA opioids are indicated for treatment of chronic pain and may be appropriately prescribed by the oculoplastic surgeon in certain circumstances, however due to the higher risk of overdose injury, those circumstances must be defined and justified. While a relatively small number of oculoplastic surgeons (10.6% ASOPRS and 19.6% non-ASOPRS) prescribed ER/LA opioids from 2013 to 2017, non-ASOPRS oculoplastic surgeons wrote 23.5% more ER/LA opioid prescriptions over the study period. Over the 5-year study period there was a general decline in the prescribing of ER/LA opioids by oculoplastic surgeons. Reviewing the prescribing practices of oculoplastic specialists, regardless of professional affiliation, is necessary to understand the role of ER/LA opioids for all of ophthalmology.

Effect of Premature Tube Extrusion for Simple Congenital Nasolacrimal Duct Obstruction: A Comparison of Monocanalicular and Bicanalicular Intubation.

ABSTRACT: The objective of this article is to compare the incidence of premature dislocation of silicone tubes and the effect on treatment success between monocanalicular (MCI) and bicanalicular (BCI) intubation in pediatric patients with simple congenital nasolacrimal duct obstruction. Retrospective comparative case series of 108 eyes of 78 pediatric patients with simple congenital nasolacrimal duct obstruction who underwent probing with either BCI (n = 38 eyes) or MCI (n = 70 eyes) from 2017 to 2020. Premature tube extrusion was defined as any tube removed prior to the 3 month postoperative appointment. Success was defined as resolution of tearing 3 months post tube removal. Ages ranged from 10 months to 5.35 years (mean, 1.95 years; Standard deviation (SD), 0.91). Premature tube extrusion occurred in 15 eyes with BCI and 29 eyes with MCI. Success rates were not significantly different regardless of intubation type between the planned tube removal (90.6%) and the premature tube extrusion cohorts (84.1%), P = 0.89. There was no significant difference in treatment success between the planned tube removal (92.7% MCI, 87% BCI) and the premature tube extrusion cohorts (86.2% MCI, 80% BCI). Complications included 2 infections (1 MCI, 1 BCI) and 2 cases of tube related keratopathy (1 MCI, 1 BCI) that all resolved with tube removal. There were 2 BCI patients that presented to the emergency department for premature tube extrusion. Silicone intubation regardless of stent type is an effective treatment for simple congenital nasolacrimal duct obstruction. There was no significant difference in treatment success between tubes that extrude prematurely, and tubes removed at term based on type of intubation.

Opioid Prescribing Patterns of Optometrists in the Medicare Part D Database.

SIGNIFICANCE: This study aimed to determine the prescription rates and prescribing trends of opioids by optometrists in the Centers for Medicare & Medicaid Services (CMS) part D database from 2013 to 2017 and to assess opioid prescribing patterns of U.S. optometrists in the CMS part D database. METHODS: With internal review board approval, a retrospective observational cohort study was conducted on optometrists listed in the CMS part D database who prescribed opioids from 2013 to 2017. RESULTS: There was an average of 26,477 optometrists in the CMS database from 2013 to 2017, of which 5.9% prescribed opioids. Of those prescribing opioids, optometrists wrote an average of 5.9 opioid prescriptions per year. Those writing greater than 10 opioid prescriptions averaged 24.2 annually. Overall, of opioid prescribing optometrists, opioid prescriptions comprised 7% of prescriptions written per year. CONCLUSIONS: Most optometrists do not prescribe opioids, and the vast majority of those who do write few opioid prescriptions. The total number of optometrists prescribing opioids and the total number of opioid prescriptions declined from 2013 to 2017. Further investigation into the opioid prescribing practices by optometrists will help better understand specific pain needs, as opioid prescribing patterns may differ depending on patient population.

Total or subtotal replacement of tarsal plate by novel silicone plate for upper eyelid reconstruction in malignant tumors.

PURPOSE: : To evaluate the cost, safety, surgical outcome, and efficacy of modified Cutler-Beard eyelid reconstruction utilizing a novel silicone plate as a tarsal plate replacement in the repair of 60% to 100% eyelid defects following the excision of large malignant tumors. METHODS: : A prospective, noncomparative, interventional study of 30 eyes was done over 3 years. Fourteen patients were female, and 16 patients were male. In all the cases, a silicone plate, the synthetic, artificial tarsal plate, was utilized for a total or subtotal replacement of the tarsal plate. The created defect was measured in mm (length and width) and later expressed in percentage. Pre- and postoperative action of levator palpebrae superioris (LPS) was measured. Pre- and postoperative measurements of the margin-to-margin reflex distance (MRD1) were noted. RESULTS: : Preoperative LPS action was 1.23 ± 1.35 mm, whereas postoperative LPS actions at the end of 1 week and 18 months were 11. 8 ± 0.88 mm and 13.53 ± 0. 73 mm, respectively. Preoperative MRD1 was - 3.0 ± 1.144 mm, whereas postoperative MRD1 values at the end of 1 week and 18 months were 2.18 ± 0.27 mm and 4.16 mm ± 0.35, respectively. The mean created defect after the removal of the tumor was 87.3% ±11.10. The mean length of the silicone plate implanted in this study was 27.53 ± 2.48 mm. The follow-up period for the study participants was 18 months. CONCLUSION: : The synthetic novel silicone plate was successful as a tarsal plate replacement. A second surgical site for ear cartilage harvesting is avoided. Cadaver transfer of Achilles tendon carries the risk of transmission of communicable diseases, for example, hepatitis B and HIV. Silicone is an inert, nonreacting, and tissue-tested material, thus eliminating the possibility of graft rejection. This material is readily available and cost-effective. The novel silicone plate is considered to be the most promising alternative material as a tarsal replacement in the future generation.

Postoperative Clinical Outcomes Using Standard Variables Following Levator-Mullerectomy Advancement Blepharoptosis Surgery.

ABSTRACT: The Muller muscle-conjunctival resection is a common technique used to treat blepharoptosis, but there is variability with the target surgical resection and expected postoperative outcomes measured by marginal reflex distance-1 (MRD1). A Levator-Mullerectomy is a novel surgical approach described by Morris et al to incorporate the levator palpebrae superioris in the same incision as the classic Muller muscle-conjunctival resection in the treatment of blepharoptosis. This a retrospective study of patients who underwent Levator-Mullerectomy for ptosis repair showing the clinical outcomes based on MRD1. Statistical analysis was performed using analysis of variance and a nonparametric Kruskal-Wallis test. One hundred-twelve eyes of 83 patients (29 bilateral cases) with a mean age 64.6 years (7-92 years) were included. The types and prevalence of blepharoptosis were involutional (83%), neurogenic (8.0%), traumatic (3.6%), apraxia (2.7%), and congenital (2.7%). There was no significant difference in clinical outcome based on type of blepharoptosis (P = 0.7). Target resection lengths of 8 mm, 10 mm, and 12 mm were compared with postoperative MRD1 change. The mean change in MRD 1 between 8 mm and 10 mm was found to be statistically significant (P = 0.001 for both) but was not statistically significant for the 12 mm resection (P = 0.8). In patients with blepharoptosis and a positive response to 2.5% phenylephrine can benefit from Levator-Mullerectomy with either an 8 mm or 10 mm resection. This novel surgical approach allows surgeons to produce a more predictable and consistent clinical outcome.

Teprotumumab for the Treatment of Active Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).

Essential skin shrinkage: cicatricial ectropion, a histopathologic evaluation and clinical analysis.

Purpose: To describe common risk factors in patients with Essential Skin Shrinkage (ESS) and identify corresponding histopathologic changes in lower eyelids.Methods: A case-control study was performed after an Internal Review Board approval was obtained. Consecutive patients who underwent surgical repair for ectropion with ESS of the lower eyelid were enrolled along with 10 control patients. Informed consent was obtained on all patients. Fitzpatrick skin type, history of sun exposure and non-melanoma skin cancer was obtained along with relevant physical exam findings. Skin samples obtained during surgical repair were evaluated by light microscopy for the extent of dermal actinic change. Statistical analysis was performed.Results: Sixteen study subjects and 10 control patients were enrolled. Subjects were found to be predominantly male, older than controls (p = 0.0011) and have Fitzpatrick skin type (FST) I or II while controls had type I, II or III (p = 0.0221). Hours of sun exposure reported by subjects ranged from 23,165 to greater than 125,000 h, versus 1,459 to 46,890 h in controls (p = 0.0002). Nine of 16 (56%) subjects had a history of skin cancer compared to only 3/10 controls (30%) (p = 0.2475). Histopathologic evaluation using the Fritschi scale for dermal actinic damage identified an average grade of 3.6 for subjects and 2.4 for controls (p = 0.0095).Conclusions: ESS is predominantly seen in male individuals with FST I or II and a history of extensive sun exposure. Histopathologic evaluation shows moderate to severe actinic damage. These individuals frequently have concomitant non-melanoma skin cancer.

Canthal V-plasty for Floppy Eyelid Surgery.

The purpose of this article is to present a modified approach to the reconstruction of the upper and lower eyelids in floppy eyelid syndrome. A retrospective chart review was performed on all floppy eyelid patients who underwent simultaneous tightening of the upper and lower eyelid with a lateral tarsal strip, using a V-shaped incision in the lateral canthus, at University of Tennessee Hamilton Eye Institute from 2011 to 2012. Preoperative symptoms, surgical outcomes, complication rates, and postoperative symptoms were recorded. Nine eyes of 7 patients who underwent surgical correction for symptomatic floppy eyelids were included. All patients noted improvement in symptoms postoperatively, after reduction in the laxity of the upper and lower eyelid. Postoperative complications included buried lashes in the lateral canthus in 1 eye and a pyogenic granuloma in the lateral canthus of 1 eye. An excellent cosmetic outcome was noted in 78% (7/9) of eyes. No patients reported dissatisfaction nor required secondary surgical correction. The lateral canthal "V" incision provides an additional approach in the successful management of floppy eyelid syndrome involving the upper and lower eyelids. The design of the incision allows for excellent exposure of the lateral canthus for shortening of the eyelids with tarsal strip fixation, and it preserves the lateral canthal skin and canthus architecture. Further, the "V" incision is easily continued into the eyelid crease for blepharoplasty and ptosis repair when necessary.

Eyelid Spontaneous Blink Analysis and Age-Related Changes Through High-Speed Imaging.

PURPOSE: To analyze the spontaneous eyelid blink and sphincter closure activity of the orbicularis oculi by measuring the horizontal eyelid movement. METHODS: Individuals 18+ years of age, any ethnicity, and gender were recruited. Participants completed a questionnaire to determine eligibility. Exclusion criteria included the following: history of facial trauma, nerve palsy, surgery, use of periorbital neuromodulators or filler within the past year, thyroid eye disease, and eyelid or ocular surface disease. Data were collected from participants by decade. Eyelid blinks were recorded using the FPS 1000HD. The motions of 3 spontaneous blinks in primary gaze were recorded. All blinks were reviewed and one chosen for most accurate analysis. Horizontal palpebral fissure width and its changes of open and closed eye measurements were taken using National Institute of Health ImageJ software version 2.0. The data were subjected to SAS version 9.4 analysis using paired t test, t test, and linear models. RESULTS: One hundred thirty-six patients were recruited. Fourteen patients were excluded; 122 patients were used in analysis. Ages ranged from 22 to 90 years. Participants were divided into 6 groups according to age (20-29, 30-39, 40-49, 50-59, 60-69, and 70+ years of age). The average horizontal fissure length across all ages was 24.23 mm. Average change in horizontal fissure length decreased 1.42 mm among all ages. There was a statistically significant difference comparing age 20-29 decade to age 70+ decade. CONCLUSIONS: Horizontal fissure length changes with eyelid blink and defines 1 component of the eyelid sphincter.

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.

Necrotic Herpes Simplex Virus Infection of the Nose and Orbit.

This is the first reported case of necrotizing nasal and sinus herpes infection with orbital involvement. A 94-year-old male with a past medical history of hypertension, congestive heart failure, and chronic kidney disease presented with necrotic nasal cellulitis and a red left eye with blurry vision. Onset was 2 weeks prior with an upper lip fever blister. He was admitted to medicine and started on antimicrobials. Maxillofacial computed tomography scan revealed pansinusitis with involvement of bilateral medial orbital walls. Initial nasal biopsy was negative. Repeat biopsy was positive for herpes simplex virus 1. His nose was debrided with full-thickness skin grafting. While there are reports of necrotizing herpes simplex, none were to the extent of our patient nor raised suspicion for invasive fungal sinusitis. Differentiating is important as this patient made a full recovery in comparison to patients with mucormycosis where mortality is often as high as 80%.

Consideration for eliminating conjunctival closure in the enucleation procedure.

To compare post-operative results and complications in patients who undergo enucleation with or without suture closure of the conjunctiva. This was a retrospective chart review study. Review of 50 cases of enucleation surgery at the University of Arkansas for Medical Sciences and Arkansas Children's Hospital between July 2011 and December 2014. Criteria for inclusion in the study were all cases of enucleation that had extraocular muscles attached to a spherical orbital implant with or without conjunctival closure, and at least 2 months of postoperative follow up. Post-operative complications were evaluated. A total of 36 cases fulfilled the criteria for inclusion in the study; 12 cases with direct sutured layered direct closure of Tenon's and then conjunctiva and 24 cases with Tenon's capsule sutured closure but without direct conjunctival sutured closure. No implant complications were identified in either group (p = 1.0). Mean follow-up for all groups was 16.71 months (range 2 to 43 mo., SD 11.94). Mean follow up for the non-closure group was 14.42 months (range 2.25 to 36 mo., SD 10.35). Two cases in the conjunctival closure group developed a conjunctival cyst, affecting prosthesis fit, approximately 3 months postoperatively: no such cysts were identified in the non-conjunctival closure group. Fisher exact test for cyst formation between the two groups was not statistically significant (p = 0.1048). Direct conjunctival closure following enucleation surgery does not appear to increase the risk of extrusion, exposure, or infection. Foregoing direct closure decreases surgical time and reduces cost. It is unclear if this decreases conjunctival cyst formation.

Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).