Distinguishing spheno-orbital metastatic prostate cancer mimicking a meningioma using novel 18F-PSMA PET/CT imaging.

A 78-year-old man presented with acute-onset left temporal pain, eyelid swelling, and double vision. Computed tomography (CT) demonstrated a left sphenoid wing mass with extra-osseous intra-orbital and intracranial extension, thought to be a typical sphenoid wing meningioma by the primary team. The patient was admitted for an urgent craniotomy, which was planned for the following day. However, upon consultation with ophthalmic plastic surgery, concern was raised for an alternative diagnosis given the atypical timeline, inflammatory changes, and uncharacteristic imaging findings of mixed lytic and sclerotic bony changes without hyperostosis on CT and extensive peri-lesional dural thickening and enhancement on magnetic resonance imaging. A serum prostate-specific antigen was elevated to 206 ng/mL. Subsequent positron emission tomography (PET)/CT using 18F-fluorodeoxyglucose radiotracer was negative for metastatic disease. A prostate-specific membrane antigen (PSMA) PET/CT was then obtained and demonstrated extensive metastases. An orbital biopsy revealed poorly differentiated prostatic adenocarcinoma. The significant incongruence between the standard PET/CT and PSMA PET/CT highlights the value of this novel advanced radiographic modality in narrowing the differential diagnosis and determining the extent of disease. Findings of widespread metastasis on the PSMA PET/CT ultimately helped to avoid a large, morbid neurosurgical intervention in this patient, allowing for a minimally invasive orbital biopsy to characterize the tumor for therapeutic targeting.

Change in upper eyelid position after teprotumumab treatment for thyroid eye disease.

PURPOSE: Despite the high prevalence, treatment challenges, and significant impact of eyelid retraction on vision and quality of life among patients with thyroid eye disease, the effects of teprotumumab on eyelid retraction are not fully understood. This study evaluated change in upper eyelid position after teprotumumab. METHODS: A retrospective study of all patients who completed eight teprotumumab infusions at one institution from January 1 2020 to December 31 2022. Primary outcome was change in upper eyelid position immediately after treatment and at most recent follow-up compared to pre-treatment. RESULTS: Among 234 eyes of 118 patients, average margin reflex distance-1 (MRD1) pre-treatment was 5.25 mm (range 0-10.0, SD 1.75), 4.66 mm (1.0-9.0, SD 1.32) immediately post-treatment (p < 0.001), and 4.50 mm (0-10.0, SD 1.52) at most recent follow-up (mean follow-up duration 10.60 months). In total, 136 (58.12%) eyes of 88 patients had MRD1 reduction immediately post-treatment, averaging 1.49 mm (0.5-5.0 mm, SD 0.97). Every 1-mm increase in pre-treatment MRD1 increased the odds of MRD1 reduction by 15.03% (CI 10.52-19.72, p < 0.001) and increased the reduction amount by 0.48 mm (CI 0.39-0.57, p < 0.001). Of 154 eyes of 78 patients with most recent follow-up, 107 (69.48%) eyes had stable or further improved retraction at most recent follow-up compared to immediately post-treatment. CONCLUSIONS: This study found a modest but significant reduction in MRD1 in approximately 60% of eyes, independent of proptosis change, which was sustained by most patients over longer-term follow-up. Higher pre-treatment MRD1 corresponded with greater improvement. These results suggest an overall mild benefit of teprotumumab for upper eyelid retraction.

The Incidence of Strabismus After Upper and Lower Blepharoplasty in the United States.

PURPOSE: To compare the incidence of strabismus after upper and lower blepharoplasty in the United States. METHODS: Retrospective cohort study of adults (age ≥18 years) in the IRIS Registry (Intelligent Research in Sight) who underwent blepharoplasty between January 1, 2013 and December 31, 2020. The primary outcome was the Kaplan-Meier estimated cumulative incidence of strabismus diagnosis and surgery within 3 years of blepharoplasty. Multivariable Cox regression was used to determine the association of blepharoplasty type with strabismus diagnosis and surgery, adjusting for patient age, sex, and geographic region. RESULTS: Blepharoplasty was performed in 368,623 patients (median [interquartile range] age, 69 [63-75] years, and 69% female). Compared with those undergoing upper eyelid blepharoplasty, patients treated with lower eyelid blepharoplasty were slightly younger (median age, 66 vs. 69 years; p < 0.001) and more likely to be female (71% vs. 69%; p < 0.001). There was a greater 3-year incidence of strabismus diagnosis (2.0% vs. 1.5%; p < 0.001) and a greater 3-year incidence of strabismus surgery (0.15% vs. 0.06%; p = 0.003) for individuals undergoing lower vs. upper blepharoplasty. After adjusting for age, sex, and geographic region, lower blepharoplasty was associated with a higher 3-year risk of strabismus diagnosis (HR, 1.49; 95% CI, 1.23-1.81; p < 0.001) and surgery (HR, 2.53; 95% CI, 1.27-5.03; p = 0.008). CONCLUSIONS: This registry-based analysis found that individuals undergoing lower eyelid blepharoplasty were at higher risk of strabismus compared with those undergoing upper eyelid blepharoplasty. Using large databases to understand the incidence of complications of frequently performed procedures may improve ophthalmologists' ability to provide data-driven counseling on surgical risks prior to intervention.

Perceived change in age after functional upper blepharoplasty.

PURPOSE: To evaluate the perceived age of patients before and after functional upper blepharoplasty. METHODS: Retrospective chart review of patients who underwent upper blepharoplasty by a single surgeon at an academic center. The inclusion criterion was having external photographs before and after blepharoplasty. Exclusion criteria included any other concurrent eyelid or facial surgery. Primary endpoint: perceived change in age after surgery as judged by the American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) surgeons. RESULTS: Sixty-seven patients (14 men, 53 women) were included. Mean pre-operative age was 66.9 years (range 37.8-89.4) and mean post-operative age was 67.4 years (range 38.6-89). The mean perceived age pre-operatively was 68.9 years, and the mean perceived age post-operatively was 67.1 years, a change of 1.8 years (p = 0.0001 by two-tailed paired T-test). Inter-rater reliability of the observers was measured by intraclass correlation coefficient of 0.77 for pre-operative and 0.75 for post-operative photos. The decreased perceived age was 1.9 years for women, 1.4 years for men, 0.3 years for Asians, 1.2 years for Hispanics, and 2.1 years for whites. DISCUSSION: Functional upper blepharoplasty by an experienced ASOPRS surgeon was shown to reduce the perceived age of a patient by an average of 1.8 years.

Proptosis Regression After Teprotumumab Treatment for Thyroid Eye Disease.

PURPOSE: This study analyzed the degree and timing of proptosis regression after teprotumumab therapy. METHODS: A retrospective study of all patients who completed 8 teprotumumab infusions at 1 institution from January 1, 2020 to December 31, 2022. Change in proptosis was assessed in millimeters and percentages compared with immediate post-treatment and pretreatment proptosis. RESULTS: Of 119 patients with post-treatment data (mean follow-up 10.56 months, range: 3.05-25.08), 208 (87.39%) eyes of 110 patients had initial proptosis improvement. Of the 78 patients with multiple follow-up visits, 102 (65.38%) eyes of 59 patients had proptosis regression averaging 12.78% (range: 1.85-58.82%) compared with immediately post-treatment or 2.43 mm (0.5-10.0 mm). Eight (7.84%) eyes had initial documentation of regression more than 1 year after treatment, 40 (39.22%) between 6 months and 1 year, and 54 (52.94%) eyes within 6 months with 25 (46.30%) of these continuing to worsen at subsequent follow-up. Forty (25.64%) eyes of 24 patients had more proptosis at most recent follow-up than before teprotumumab, with an average regression of 1.53 mm (0.5-4.0 mm) or 7.74% (1.85-20.69%) of pretreatment proptosis. In comparison, 99 (63.46%) eyes of 54 patients maintained improvement, with reduction averaging 3.13 mm (0.5-11.0 mm) or 13.19% (1.92-41.67%) of pretreatment proptosis ( p < 0.001). CONCLUSIONS: Two-thirds of eyes had regression despite initial teprotumumab response, typically within 1 year of treatment, with ongoing worsening over time. Most patients maintained some proptosis reduction compared with before treatment despite regression, although 25% were worse than pretreatment. The occurrence of regression was independent of the pretreatment duration of clinical thyroid eye disease. Overall, compared with preteprotumumab, there was a greater amount of improvement than regression at most recent follow-up.

Association of Somatic TET2 Mutations With Giant Cell Arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. METHODS: To examine an association between CH and GCA, we analyzed sequenced exomes of 470,960 UK Biobank (UKB) participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. RESULTS: UKB participants with CH had a 1.48-fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (hazard ratio [HR] 2.98, P = 0.00178) and with TET2 mutation (HR 2.02, P = 0.00116). Mutations were detected in 27.2% of our institutional GCA cohort, three of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (odds ratio 4.33, P = 0.047). CONCLUSIONS: CH increases risk for development of GCA in a genotype-specific manner, with the greatest risk being conferred by the presence of mutations in TET2. Somatic TET2 mutations likewise increase the risk of GCA-associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future.

Concurrence of Ocular Cicatricial Pemphigoid in Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: The aim of this study was to report a series of 3 patients with ocular graft-versus-host disease (oGVHD) with progressive cicatricial conjunctival changes who were diagnosed with ocular cicatricial pemphigoid (OCP) after conjunctival biopsy. METHODS: This study was a retrospective case series. RESULTS: Three patients who received hematopoietic stem cell transplantation for hematologic malignancies developed oGVHD and subsequently were diagnosed with OCP. Case 1 was a 73-year-old woman with oGVHD who developed symblepharon and showed positive IgA, IgG, and C3 staining of the basement membrane zone (BMZ) on conjunctival biopsy, consistent with OCP. She was systemically treated with tacrolimus and prednisone with resolution of conjunctival inflammation. Case 2 was a 68-year-old man with oGVHD who developed symblepharon, severe dry eye, and corneal epithelial defect. An initial conjunctival biopsy was negative, but a repeat biopsy performed 10 years later showed positive BMZ IgA and IgG staining. Healing of the epithelial defect was achieved after treatment with high-dose systemic cyclosporine. Case 3 was a 75-year-old woman with oGVHD who had a nonhealing corneal epithelial defect and symblepharon with positive IgA BMZ staining on conjunctival biopsy, consistent with OCP. The patient responded well to methotrexate with healing of the epithelial defect. CONCLUSIONS: Although low-grade conjunctival fibrotic changes may be observed in chronic oGVHD, development of severe and progressive cicatricial changes, including symblepharon formation, should prompt consideration of biopsy to rule out concurrent OCP, the management of which differs from that of oGVHD.

Use of Mitomycin C in Dacryocystorhinostomy: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the adjuvant use of mitomycin C (MMC) during dacryocystorhinostomy (DCR) in adults with primary nasolacrimal duct obstructions (NLDOs) to determine the efficacy in improving functional and anatomic outcomes with an acceptable level of risk. METHODS: A literature search conducted in November 2020 and updated in November 2022 yielded 137 articles. Twenty-four articles met the inclusion criteria and were rated for level of evidence by the panel methodologist. Inclusion criteria required controlled studies on the effect of MMC on outcomes of external, endoscopic endonasal, or diode laser-assisted transcanalicular DCR in adults with primary acquired nasolacrimal obstruction with 6 months minimum follow-up and at least 10 participants. RESULTS: Six of the 24 articles were rated level I evidence, 15 level II , and 3 level III. In primary external DCR, MMC significantly improved functional outcomes in 3 of 9 series. In primary endoscopic endonasal DCR, MMC significantly improved functional outcomes in 1 of 9 series. In revision endoscopic endonasal DCR, MMC significantly improved functional success in 1 of 3 series. The use of MMC did not improve outcomes statistically in any diode laser-assisted transcanalicular DCR studies. Concentrations of MMC ranged from 0.05 to 1 mg/ml, with 0.2 mg/ml used most frequently in 12 series, with duration of application ranging from 2 to 30 minutes. Ostium size was significantly larger in MMC groups than in control groups at 6 months after surgery in 4 of 5 reporting studies. However, these larger ostia did not confer higher functional success rates. Reporting of adverse events related to MMC were rare, with delayed cutaneous wound healing reported in 1 of 750 patients. CONCLUSIONS: Intraoperative use of MMC in external and endoscopic endonasal DCR has been shown to improve functional and anatomic outcomes compared with controls in some series, but there is no agreement on the recommended concentration or application time for MMC in DCR. The data support that MMC use can result in a larger ostium size, decreased granulation tissue formation, and a decreased number of postoperative nasal debridements compared with controls, but this does not translate into improved functional success. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Thermal Pulsation in the Management of Meibomian Gland Dysfunction and Dry Eye: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature to determine the efficacy and safety of thermal pulsation technologies in improving signs or symptoms of meibomian gland dysfunction (MGD) and dry eye compared with no therapy or with conventional warm compress therapy or eyelid hygiene. METHODS: A literature search was conducted in the PubMed database in June 2022 and again in March 2023 to identify all studies in the English language on the use of thermal pulsation to treat MGD or dry eye. The search yielded 59 citations, and 11 articles met all of the inclusion criteria. The panel methodologist then assigned a level of evidence rating for each study; 8 studies were rated level I evidence and 3 studies were rated level II evidence. RESULTS: All included studies evaluated a single 12-minute session using the LipiFlow automated thermal pulsation system (TearScience, Inc, or Johnson & Johnson). Improvements were detected in subjective and objective metrics of MGD or dry eye in patients within 1 to 12 months of thermal pulsation treatment compared with nontreatment. Most of the studies (9/11) reported greater efficacy with thermal pulsation than with standard warm compress therapy and eyelid hygiene. Four of these studies showed relevant industry conflicts of interest. Two of the 4 level I studies without direct industry participation concluded that thermal pulsation treatment was not significantly different from conventional hygiene or warm compress therapy control treatments (in symptoms in one of the studies and in objective findings in the second study). No serious adverse events were reported in any of the 11 studies. CONCLUSIONS: According to the current literature, a single thermal pulsation session may improve subjective or objective parameters of MGD and dry eye safely. However, industry support and participation were present in 4 of the 8 level I studies. The durability beyond several months and cost efficacy remain uncertain. Because the inclusion parameters of this assessment captured only the LipiFlow system, the conclusions are limited to that product. High-quality independent studies are needed to assess the long-term benefits of this intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Reduction in Extraocular Muscle Cross-sectional Area and Correlation With Extraocular Motility and Diplopia Following Teprotumumab for Thyroid Eye Disease.

PURPOSE: To quantify changes in extraocular muscle (EOM) cross-sectional areas (CSA) on orbital imaging in patients with thyroid eye disease before and after teprotumumab treatment, and assess for correlation with clinical outcomes. METHODS: This retrospective study included thyroid eye disease patients treated with teprotumumab who had pre- and post-treatment CT imaging. Reformatted oblique coronal images were created for each orbit in a plane perpendicular to the optic nerve. EOM CSA measurements were performed by 2 radiographic reviewers and averaged. Primary outcomes included change in ratio of total EOM to orbit CSA, and of each individual muscle group to orbit CSA, before and after treatment. Secondary outcomes included subanalysis based on age (≥40, <40 years) and Clinical Activity Score (CAS) (≥4, <4), and comparison with clinical outcomes including CAS, Hertel exophthalmometry, Gorman diplopia score, and extraocular motility. RESULTS: Forty-eight orbits of 24 patients (16 female, mean age 57.9 years) were included. There was a significant reduction in the total EOM to orbit CSA ratio ( p < 0.01) and for each individual rectus muscle to orbit CSA ratio ( p < 0.01 for all groups). Total EOM to orbit CSA ratios were reduced for 21 patients (87.5%); this was statistically significant in 13 patients (54.2%). There was significant improvement in CAS, proptosis, diplopia, and EOM motility ( p < 0.01 for all categories). There was a significant correlation between reduction of EOM CSA, and reduction of diplopia ( p < 0.01) and EOM motility ( p < 0.01). CONCLUSIONS: EOM CSA is significantly reduced following treatment with teprotumumab, and correlates with clinical findings including improvement in extraocular motility and diplopia.

Orbital resection by intranasal technique (ORBIT): A new classification system for reporting endoscopically resectable primary benign orbital tumors.

BACKGROUND: The Cavernous Hemangioma Exclusively Endonasal Resection (CHEER) staging system has become the gold standard for outcomes reporting in endoscopic orbital surgery for orbital cavernous hemangiomas (OCHs). A recent systematic review demonstrated similar outcomes between OCHs and other primary benign orbital tumors (PBOTs). Therefore, we hypothesized that a simplified and more comprehensive classification system could be developed to predict surgical outcomes of other PBOTs. METHODS: Patient and tumor characteristics as well as surgical outcomes from 11 international centers were recorded. All tumors were retrospectively assigned an Orbital Resection by Intranasal Technique (ORBIT) class and stratified based on surgical approach as either exclusively endoscopic or combined (endoscopic and open). Outcomes based on approach were compared using chi-squared or Fisher's exact tests. The Cochrane-Armitage test for trend was used to analyze outcomes by class. RESULTS: Findings from 110 PBOTs from 110 patients (age 49.0 ± 15.0 years, 51.9% female) were included in the analysis. Higher ORBIT class was associated with a lower likelihood of gross total resection (GTR). GTR was more likely to be achieved when an exclusively endoscopic approach was utilized (p < 0.05). Tumors resected using a combined approach tended to be larger, to present with diplopia, and to have an immediate postoperative cranial nerve palsy (p < 0.05). CONCLUSION: Endoscopic treatment of PBOTs is an effective approach, with favorable short-term and long-term postoperative outcomes as well as low rate of adverse events. The ORBIT classification system is an anatomic-based framework that effectively facilitates high-quality outcomes reporting for all PBOTs.

Smoking Is Associated With a Higher Risk of Surgical Intervention for Thyroid Eye Disease in the IRIS Registry.

PURPOSE: To describe the association of smoking status with surgical intervention for thyroid eye disease (TED) at the population-level. DESIGN: Retrospective cohort study. METHODS: This study included all adults (aged ≥18 years) with Graves disease in the Intelligent Research in Sight (IRIS) Registry (January 1, 2013, to December 31, 2020). The primary outcome was surgical intervention for TED, stratified into orbital decompression, strabismus surgery, and eyelid recession surgery. The Kaplan-Meier estimated 5-year cumulative probability for each surgical intervention was calculated. Multivariable Cox regression was used to evaluate the association between smoking status and each surgical intervention, adjusting for age, sex, race, ethnicity, and geographic region. RESULTS: This study included 87,774 patients. Median age was 59 years (IQR, 48-68 years); 81% were female patients. Current smokers had a greater 5-year cumulative probability of orbital decompression (3.7% vs 1.9%; P < .001), strabismus surgery (4.6% vs 2.2%; P < .001), and eyelid recession (4.1% vs 2.6%; P < .001) compared to never smokers. After adjusting for demographic factors, current smokers were at greater risk for orbital decompression (hazard ratio [HR], 2.1; 95% CI, 1.8-2.4; P < .001), strabismus surgery (HR, 2.0; 95% CI, 1.8-2.3; P < .001), and eyelid recession (HR, 1.7; 95% CI, 1.5-1.9; P < .001) than never smokers. Former smokers were at higher risk for each type of surgery for TED, albeit at lower levels than current smokers. CONCLUSIONS: Smoking was associated with increased risk of surgical intervention for TED in the IRIS Registry. Former smokers were at a lower risk than current smokers, supporting the role of smoking cessation on lowering the burden of surgical disease at the population-level.

Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

Dedicated Chalazion Clinic as a Tool for Early Surgical Education in Ophthalmology Residency.

Objective Ophthalmology residency programs aim to improve resident surgical teaching through increased surgical exposure over a 4-year period. Resident-centric surgical clinics across various surgical specialties have been established to help develop surgical autonomy and experience. We present the first demonstration of a resident-centric chalazion incision and drainage clinic (chalazion clinic) in an ophthalmology residency with the goal of increasing early surgical exposure to residents. Design The chalazion clinic was founded in July 2019. It is a once weekly procedure clinic conducted by an ophthalmology resident and supervised by an ophthalmology attending. Patients with chalazia were referred directly to this clinic for evaluation and management, rather than the oculoplastics clinic as they were in the past. Retrospective review of Accreditation Council for Graduate Medical Education (ACGME) case logs of all residents per academic year before and after establishment of the chalazion clinic was performed in order to assess the impact on residents' chalazion procedures numbers per academic year. Setting The study involved a single academic ophthalmology department. Participants Ophthalmology residents of all years were present. Results A resident of any year performed an average of 3.0 chalazion procedures per year in the 2018 to 2019 academic year, 3.8 in 2019 to 2020, and 8.4 in the 2020 to 2021, which represents a 180% increase in procedure numbers per resident. Among post-graduate-year 2s (PGY)2s, the average number of chalazion procedures increased from 2.1 procedure per year to 22.3 per year (961.9% increase). Conclusion To the best of our knowledge, this is the first description of a dedicated resident-centric chalazion clinic in an ophthalmology residency program. PGY2s demonstrated the largest increase in procedural numbers. While chalazion incision and drainage is a minor procedure, increased exposure to surgical procedures early in training could help improve residents' skills and confidence. This clinic provides a proof of concept of a dedicated minor procedure clinic for ophthalmology residents to increase early procedural volume.

Future Projections in Thyroid Eye Disease.

BACKGROUND AND AIMS: This review aims to summarize current and emerging therapies for treatment of thyroid eye disease (TED), in the light of novel understanding of pathogenetic mechanisms, leading to new treatment options and clinical trials. METHODS: We reviewed and analyzed peer-reviewed literature reporting recent translational studies and clinical trials in the treatment of TED. Searches were made at www.pubmed.gov with keywords "thyroid eye disease," "Graves' ophthalmopathy," "thyroid orbitopathy," and "Graves' orbitopathy." RESULTS: Surgery is reserved for rehabilitation in chronic TED or for emergent compressive optic neuropathy. Oral and intravenous glucocorticoid therapy has been used for decades with variable efficacy in acute TED, but results may be temporary and side effects significant. Nonsteroidal oral immunosuppressive agents offer modest benefit in TED. Several immunomodulatory monoclonal antibodies, including rituximab and tocilizumab, have shown efficacy for inactivating TED. Recently, teprotumumab, an insulin-like growth factor 1 receptor (IGF-1R) inhibitor, has demonstrated significant improvement in proptosis, clinical activity score, diplopia, and quality of life in patients with active TED, with good tolerability. Newly proposed TED therapies, currently in preclinical and clinical trial phases, include thyroid-stimulating hormone (TSH) receptor inhibitory drugs, RVT-1401, local anti-vascular endothelial growth factor therapy, IGF-1R drugs delivered subcutaneously and orally, and desensitization to the TSH receptor with modified TSH receptor peptides. CONCLUSION: New, albeit incomplete, understanding of the molecular mechanisms of TED has led to new promising therapies and offered improved outcomes in TED patients. Their full role and their relationship to classical immune suppression should be clarified over the next few years.

Two pediatric cases of reticular corneal epithelial edema associated with netarsudil.

Purpose: To report two pediatric cases of reticular corneal epithelial edema associated with the use of netarsudil ophthalmic solution 0.02%. Observations: In Case 1, a six-year-old male with glaucoma following cataract surgery was treated with netarsudil for thirteen months and developed diffuse reticular corneal epithelial edema on post-operative day one after undergoing transscleral diode cyclophotocoagulation for persistently elevated intraocular pressures. In Case 2, a three-month-old male with bilateral ocular hypertension developed unilateral inferior reticular corneal epithelial edema five weeks after initiation of netarsudil, which had been discontinued in the fellow eye two weeks prior. In both cases, the reticular epithelial edema resolved following cessation of netarsudil. Conclusions and Importance: Netarsudil-associated reticular corneal epithelial edema can occur in infants and young children.