Teprotumumab for Thyroid Eye Disease-related Strabismus.

PURPOSE: To assess and quantify teprotumumab's effect on thyroid eye disease-related strabismus by change in measured horizontal and vertical deviations and change in extraocular motility. METHODS: We reviewed a series of patients with thyroid eye disease-related strabismus treated with teprotumumab. Exclusion criteria included age under 18 years, strabismus of alternate etiology, or thyroid eye disease-related reconstructive surgery during the treatment course. Primary outcomes were absolute (prism diopters) and relative (%) differences in horizontal and vertical deviations in primary position at distance, as well as change in ductions of the more affected eye. Secondary outcomes included incidence and timing of strabismus surgery postteprotumumab. RESULTS: Thirty-one patients were included, with mean age 63 years and thyroid eye disease duration 10 months. After teprotumumab, there was 6 prism diopters (39%) mean reduction in vertical deviation (p < 0.001), without significant change in mean horizontal deviation (p = 0.75). Supraduction, abduction, adduction, and infraduction significantly improved in the more restricted eye (p < 0.01, p < 0.01, p = 0.04, and p = 0.01, respectively). Thirty-five percent of patients underwent strabismus surgery posttreatment, at an average 10 months after last infusion. CONCLUSIONS: Teprotumumab produced a statistically significant reduction in vertical but not horizontal strabismus angles in primary position at distance. Extraocular motility in all 4 ductions also improved. A substantial minority of patients still required strabismus surgery following teprotumumab.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Teprotumumab-related Cutaneous Hypersensitivity Reactions.

The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.

Orbital floor reconstruction via autologous radial forearm free flap with palmaris longus tendon.

We describe reconstruction of the orbital floor following suprastructure maxillectomy for resection of maxillary squamous cell carcinoma utilizing an osteocutaneous radial forearm free flap and palmaris longus tendon.

Peripheral ulcerative keratitis secondary to severe hidradenitis suppurativa.

PURPOSE: To describe a unique case of peripheral ulcerative keratitis secondary to isolated, severe hidradenitis suppurativa (HS). OBSERVATION: A 31-year-old male with HS presented with a red painful right eye with best corrected visual acuity of count fingers at 3 feet with peripheral corneal thinning, inferior descemetocele, and adjacent infiltrate. Work-up revealed negative corneal cultures and positive ANA, ANCA, and rheumatoid factor without other autoimmune or rheumatologic history or symptomatology. He was treated with topical corticosteroids with improvement until he was lost to follow-up before tumor necrosis factor-a inhibitor therapy could be started. Upon re-presentation, he was found to have corneal perforation. CONCLUSIONS AND IMPORTANCE: Coexistence of inflammatory eye disease and HS is known but rare, and most commonly manifests as anterior uveitis. Here we present a unique case of peripheral ulcerative keratitis secondary to HS and demonstrate the importance of ophthalmologists' familiarly with this systemic disease and its variety of ocular manifestations.

Teprotumumab for chronic thyroid eye disease.

PURPOSE: To describe the treatment of nine patients with chronic, low clinical activity score thyroid eye disease with teprotumumab. METHODS: A retrospective series of patients with chronic thyroid eye disease (TED) and low clinical activity score (CAS) treated with teprotumumab infusion therapy. Inclusion criteria: adults over 18 years of age with TED for greater than 9 months and CAS of 1 or less. All patients included in the analyses completed a full series of eight infusions. Primary outcome measures included proptosis and eyelid retraction in both eyes. Secondary outcomes included CAS, reported adverse effects, and surgery post-treatment. RESULTS: Nine patients met all inclusion criteria, seven females and two males with mean age of 50.2 years and TED diagnosis of 6.25 years. Three patients had a baseline CAS of 1 and 6 had a CAS of 0. Mean proptosis reduction in the worse eye was 4.0 ± 2.4 mm immediately post-treatment (p = .02). Five out of nine patients had extended follow-up (average 16.8 ± 5.1 weeks) with mean proptosis reduction of 4.2 ± 2.8 mm at last follow-up (p = .03). Mean reduction in eyelid retraction in the worse eye was 0.3 ± 1.6 mm post-treatment (p = .58) and 0.5 ± 0.9 mm at last follow-up (p = .30). Three patients reported infusion-related myalgias, two hair thinning, one exacerbated chronic tinnitus, and one hyperglycemia. CONCLUSIONS: We report clinically and statistically significant proptosis reduction in nine patients with chronic, low CAS TED treated with teprotumumab. Teprotumumab may be an effective treatment option for these patients.

Secondary infection with rhino-orbital cerebral mucormycosis associated with COVID-19.

We report two fatal cases of rhino-orbital-cerebral mucormycosis associated with COVID-19 infection. Both patients had pre-existing diabetes mellitus type 2, were treated with corticosteroids, and developed ketoacidosis. Both patients rapidly declined owing to rapid extension of the infection into the intracranial cavity. We postulate that additional risk factors for opportunistic fungal infection exist in COVID-19 patients including mechanical ventilation and Sars-CoV-2 induced immunosuppression. The ophthalmologist's role is particularly important in the early diagnosis of mucormycosis associated with COVID-19.

Giant Deep Orbital Dermoid Cyst Presenting in Infancy.

ABSTRACT: Orbital dermoid cysts are benign choristomas that are very common in children and occur most often as a lateral or medial mass associated with the frontozygomatic or frontoethmoidal suture line. The authors present an unusual case of an occult giant deep orbital dermoid cyst in infancy that initially presented with a small, benign appearance and central upper eyelid location on clinical exam. Orbitotomy with complete excision prevented further ocular sequelae in this 11-month-old.

Minimal Dissection Direct Frontalis Muscle Advancement Flap for Congenital Ptosis Repair.

BACKGROUND: Frontalis flap advancement is an alternative means of congenital ptosis repair from frontalis suspension utilizing autologous fascia or allogenic implants. Variations in technique, including flap division, location and number of skin incisions, and dissection planes, are described in the literature. MATERIALS AND METHODS: A retrospective case series of patients with congenital myogenic ptosis treated with simplified, minimal dissection frontalis flap advancement involving a single upper eyelid crease incision with dissection in the preseptal and subcutaneous planes without division to mobilize the frontalis flap. Inclusion criteria: pediatric patients age < 18 years with either primary or recurrent congenital ptosis following previous surgical repair. Exclusion criteria: ptosis of neurogenic etiology or postoperative follow-up < 3 months. Primary outcome measures were postoperative margin-reflex distance 1 (MRD1), the difference in MRD1 between surgical and nonsurgical eyelids in unilateral ptosis, and lagophthalmos. Secondary outcome measures included recurrence and complications. RESULTS: Twenty-six patients met inclusion criteria, 24 males and 2 females. Mean postoperative MRD1 at last follow-up was 2.9 ±â€Š1.2 mm and the mean difference in MRD1 between surgical and nonsurgical eyelids at last follow-up was 1.1 ±â€Š1.0 mm. Average lagophthalmos at postoperative month 2 to 5 was 0.6 ±â€Š0.7 mm. One patient demonstrated postoperative lid retraction that required re-operation. Four of 31 eyelids (12.9%) demonstrated ptosis recurrence at 5, 12, or 24 months. CONCLUSIONS: In this retrospective series, the authors report clinically and statistically significant surgical eyelid height improvement and symmetry between nonsurgical and surgical eyelids in congenital ptosis patients treated with minimal dissection direct frontalis flap advancement.

Isolated bifid medial rectus muscle in adult-onset divergence insufficiency esotropia.

We present the case of a 77-year-old woman with adult-onset divergence insufficiency esotropia in which a bifid medial rectus muscle was identified intraoperatively. The patient had no past ocular, medical, syndromic, or traumatic history associated with this isolated horizontal rectus anomaly. Following identification of the bifid muscle, the original surgical plan was altered to asymmetric recession of the superior and inferior medical rectus heads.

Methodologic Differences Across Studies of Patients With Atrial Fibrillation Lead to Varying Estimates of Stroke Risk.

BACKGROUND: Guidelines for anticoagulation in atrial fibrillation (AF) assume that stroke risk scheme point scores correspond to fixed stroke rates. However, reported stroke rates vary widely across AF cohort studies, including studies from the same country. Reasons for this variation are unclear. This study compares methodologies used to assemble and analyze large AF cohorts worldwide and assesses potential bias in estimating stroke rates. METHODS AND RESULTS: From a previous systematic review of AF cohorts, we analyzed studies including at least 5000 patients. We assessed methods used to generate rates of ischemic stroke off anticoagulants, according to a structured inventory of database interrogation methods. Nine studies (497 578 total patients) met our criteria. Overall cohort stroke rates ranged from 0.45% to 7.03% per year. In bivariate study-level analysis, multiple features were associated with higher stroke rates, including AF identified as inpatients versus outpatients (rate ratio 2.60, 95% confidence interval, 1.19, 5.68), and lack of clinical validation of outcome events (rate ratio 4.09, 95% confidence interval, 1.06, 15.70). European studies reported rates more than 4-fold higher than North American studies. International Classification of Diseases (ICD) coding schemes for outcomes varied widely. Multiple high rate features coexisted in the same studies. CONCLUSIONS: Among AF cohort studies, differences in the composition, method of assembly, determination of clinical features and outcomes, and analytic approach were strongly associated with reported stroke rates. Our study highlights the need for standardized and validated methodologies for AF cohort assembly and analysis to generate accurate stroke rates to better support anticoagulation guidelines for patients with AF.

Stability of High-Quality Warfarin Anticoagulation in a Community-Based Atrial Fibrillation Cohort: The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.

BACKGROUND: Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke-preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) ≥70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR ≥70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR ≥70%. METHODS AND RESULTS: Within the community-based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR ≥70% in an initial 6-month period (TTR1; months 4-9), we described the distribution of TTR2 (months 10-15) and assessed multivariable correlates of persistent TTR ≥70%. Of patients with TTR1 ≥70%, 57% persisted with TTR2 ≥70% and 16% deteriorated to TTR2 <50%. Only initial TTR1 ≥90% (adjusted odds ratio 1.47, 95% CI 1.07-2.01) independently predicted TTR2 ≥70%. Heart failure was moderately associated with marked deterioration (TTR2 <50%); adjusted odds ratio 1.45, 95% CI 1.00-2.10. CONCLUSIONS: Nearly 60% of AF patients with high-quality TTR1 on warfarin maintained TTR ≥70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6-month period. Our analyses support watchful waiting for AF patients with initial high-quality warfarin anticoagulation before considering alternative anticoagulants.

GluA2 mRNA distribution and regulation by miR-124 in hippocampal neurons.

AMPA-type glutamate receptors mediate fast, excitatory neurotransmission in the brain, and their concentrations at synapses are important determinants of synaptic strength. We investigated the post-transcriptional regulation of GluA2, the calcium-impermeable AMPA receptor subunit, by examining the subcellular distribution of its mRNA and evaluating its translational regulation by microRNA in cultured mouse hippocampal neurons. Using computational approaches, we identified a conserved microRNA-124 (miR-124) binding site in the 3'UTR of GluA2 and demonstrated that miR-124 regulated the translation of GluA2 mRNA reporters in a sequence-specific manner in luciferase assays. While we hypothesized that this regulation might occur in dendrites, our biochemical and fluorescent in situ hybridization (FISH) data indicate that GluA2 mRNA does not localize to dendrites or synapses of mouse hippocampal neurons. In contrast, we detected significant concentrations of miR-124 in dendrites. Overexpression of miR-124 in dissociated neurons results in a 30% knockdown of GluA2 protein, as measured by immunoblot and quantitative immunocytochemistry, without producing any changes in GluA2 mRNA concentrations. While total GluA2 concentrations are reduced, we did not detect any changes in the concentration of synaptic GluA2. We conclude from these results that miR-124 interacts with GluA2 mRNA in the cell body to downregulate translation. Our data support a model in which GluA2 is translated in the cell body and subsequently transported to neuronal dendrites and synapses, and suggest that synaptic GluA2 concentrations are modified primarily by regulated protein trafficking rather than by regulated local translation.