Wendy W. Lee

Objectives: To validate claims-based algorithms for identifying thyroid eye disease (TED) cases and assess whether machine learning can improve case identification in a large, linked real-world dataset. Methods: Using a large, linked database from Komodo Health^® and Academy IRIS^® Registry, we evaluated six rule-based algorithms incorporating Graves’ disease (GD), eye symptoms and signs. The IRIS Registry’s curated data, based on confirmed TED diagnoses from medical notes, served as the reference standard. Additionally, we developed supervised machine learning models using demographic, diagnostic, procedural, and medication data. Feature selection was performed using recursive feature elimination to rank predictive codes and construct a simplified, interpretable model. Cross-validation was used to assess model performance and compare performance with the rule-based algorithms. Results: The rule-based algorithms demonstrated a trade-off between sensitivity and specificity, with some achieving high specificity but limited sensitivity. Algorithm 1 had the highest sensitivity (48.7%) but lower specificity (59.9%) and PPV (75.8%). Algorithms 2–5 demonstrated higher specificity (87.2–93.5%) but lower sensitivity (17.8–27.0%). Algorithm 6 improved sensitivity (33.4%) compared to Algorithms 2–5 while maintaining high specificity (86.8%) and a strong PPV (86.7%). Machine learning models demonstrated similar trade-offs. One model achieved improved specificity (77.2%) with sensitivity of 49.3%, outperforming Algorithm 1 in specificity while matching its sensitivity. Another model maximized specificity (91.7%) and PPV (89.8%) at a reduced sensitivity of 28.5%. These results highlight the flexibility of machine learning models in adjusting performance to address different research objectives. Conclusions: This study evaluated existing rule-based algorithms for identifying TED cases in claims data, revealing trade-offs between sensitivity and specificity. Machine learning models provide additional flexibility, allowing performance to be tailored to specific research use cases. While no single method consistently outperformed others across all metrics, both rule-based and machine learning approaches demonstrated value in improving TED case identification using real-world data sources.

Purpose: Xanthelasma palpebrarum (XP) is a common periocular lesion often regarded as benign. However, its potential association with systemic lipid dysregulation and cardiovascular disease remains controversial. This study aimed to evaluate the relationship between XP, dyslipidemia, and major cardiovascular outcomes using a large-scale, electronic health record dataset. Methods: This retrospective propensity score–matched cohort study used de-identified electronic health record data from TriNetX, a global federated research network. Adults aged 20 to 85 years with and without XP were identified between August 5, 2005, and August 5, 2025. XP cases were matched 1:1 to controls without XP based on age, sex, comorbidities, and other covariates. Primary outcomes included the incidence of hyperlipidemia and major adverse cardiovascular events. Secondary measures included lipid profile values and use of lipid-lowering medications. Cox proportional hazards models estimated hazard ratios (HRs) for outcomes, adjusted for demographics and comorbidities. Results: A total of 40,096 patients (20,048 with XP; 20,048 controls) were included in the analysis. The mean age at index was 53.7 years in both groups. Male sex accounted for 28.3% of the XP cohort and 28.4% of the control group. Lipid profiles differed significantly between groups. Compared with controls, patients with XP had higher rates of hyperlipidemia (32.2% vs. 27.6%; p < 0.0001) and major adverse cardiovascular event (13.0% vs. 11.4%; p < 0.0001), while all-cause mortality was not significantly different in unadjusted comparisons (3.1% vs. 3.3%; p = 0.27). In Cox proportional hazards models, XP was associated with increased risk of hyperlipidemia (HR: 1.38; 95% CI: 1.35–1.41; p < 0.0001), major adverse cardiovascular event (HR: 1.26; 95% CI: 1.22–1.31; p < 0.0001), and a statistically significant but small elevation in all-cause mortality (HR: 1.09; 95% CI: 1.01–1.17; p = 0.0324). Conclusions: XP is significantly associated with atherogenic lipid profiles, greater use of lipid-lowering medications, and increased risk of cardiovascular events. Recognition of XP during routine ophthalmic examinations may provide an opportunity for early cardiovascular risk stratification.

Purpose: To evaluate whether blepharoptosis is associated with an increased risk of incident falls and fractures among adults. Methods: This retrospective cohort study utilized data from the TriNetX Health Research Network (January 2004 to January 2024). Adults aged 18 years or older diagnosed with blepharoptosis were matched 1:1 with controls who underwent an ophthalmologic examination without any abnormal findings. Exclusion criteria included severe ocular pathology, low vision/blindness, or falls/fractures within 6 months before the diagnosis. The primary outcomes were incident falls and fractures within 1 year, assessed using risk ratios (RRs) and Cox regression. Results: A total of 119,101 matched patient pairs were analyzed. At 2 weeks postdiagnosis, patients with blepharoptosis had a significantly increased risk of falls (RR, 1.53; confidence interval [CI]: 1.18–1.98; p < 0.01) and fractures (RR, 2.46; CI: 2.02–3.00; p < 0.01). Fracture risk remained elevated at 3 months and was most pronounced in the skull, facial, and cervical regions (RR, 2.87; 95% CI: 2.32–3.55; p < 0.01). By 1 year, patients who underwent blepharoptosis repair (15.4%) had a significantly lower fall risk compared to those who did not (RR, 0.65; 95% CI: 0.54–0.77; p < 0.01), with multivariable analysis showing an 89% risk reduction (hazard ratio, 0.11; 95% CI: 0.02–0.83; p = 0.03). Conclusions: Blepharoptosis is associated with an increased risk of falls and fractures, particularly among older adults. Surgical correction mitigates this risk, suggesting a potential role for blepharoptosis repair in fall prevention strategies.

Purpose: The purpose of this study is to evaluate whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) is associated with periorbital changes in patients with type 2 diabetes mellitus (T2DM) or obesity. Methods: A retrospective cohort study was conducted using the TriNetX Research Network database. Patients with T2DM treated with insulin or other antidiabetic agents and who were GLP-1RA naive served as the T2DM control group. The obesity control group included patients with obesity (body mass index ≥30 kg/m ² ) who neither had bariatric surgery nor T2DM and were GLP-1RA naive. Study groups included patients with T2DM or obesity treated with GLP-1RAs. Rates of blepharoptosis, brow ptosis, dermatochalasis, ectropion, and entropion were recorded alongside their respective rates of surgical repair as well as the frequency of rhytidectomy and botulinum A toxin use. Outcomes were assessed at 3 and 20 years postdrug approval for the obesity and T2DM study groups, respectively. Results: Patients with T2DM using any GLP-1RA were significantly more likely to develop brow ptosis ( p < 0.001) and receive botulinum toxin A ( p = 0.001) compared to controls. Patients with obesity using a GLP-1RA were significantly more likely to develop brow ptosis ( p = 0.004), dermatochalasis ( p < 0.001), and receive botulinum toxin A ( p < 0.001). Patients with obesity on a GLP-1RA were significantly more likely to undergo brow ptosis repair ( p = 0.001), blepharoptosis repair ( p < 0.001), blepharoplasty ( p < 0.001), and rhytidectomy ( p = 0.011) compared to controls. Conclusions: GLP-1RA use by patients with obesity or T2DM resulted in significant periorbital changes and subsequent repair. When compared to their respective controls, patients using GLP-1RAs for obesity observed more periorbital changes than those with TD2M, likely secondary to excess adipose tissue accumulation and loss.

Purpose: To evaluate 20-year multi-institutional trends in endoscopic dacryocystorhinostomy (EN-DCR) versus external dacryocystorhinostomy (EX-DCR) for acquired nasolacrimal duct obstruction, including comparative long-term revision rates. Methods: A retrospective cohort study was performed using the TriNetX federated research network. Annual surgical volumes and revision rates at 1, 10, and 20 years were analyzed for patients undergoing EN-DCR or EX-DCR. Propensity-score matching controlled for demographic and clinical characteristics. Joinpoint regression identified trends and significant shifts in procedural rates over time, expressed as annual percent change (APC) for specific intervals and average APC overall. Results: A total of 14,135 DCR procedures (9,948 EX-DCR, 4,187 EN-DCR) were performed on 12,623 patients. Over the study period, EX-DCR decreased from 87.1% to 60.0% (average APC, –1.9%; p < 0.05), with a greater decline noted after 2018 (APC, –3.9%; p < 0.01). Conversely, EN-DCR increased from 12.9% to 40.1% (overall average APC, +4.9%; p = 0.08), showing significant growth after 2012 (APC, +4.4%; p < 0.01). Surgical revision rates were similar at 1 (EX-DCR 9.0% vs. EN-DCR 8.6%, risk ratios = 1.04, p = 0.61), 10 (EX-DCR 14.5% vs. EN-DCR 13.6%, risk ratios = 1.06, p = 0.31), and 20 years (EX-DCR 14.7% vs. EN-DCR 13.7%, risk ratios = 1.07, p = 0.25). Overall success rates, defined as no surgical revision, were between 85.3% and 91.4% for both approaches. Conclusion: Over the past 20 years, endoscopic DCR has gained popularity, with steadily increasing use and comparable revision rates to external DCR.

Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing/secreting M2 MACs (CD206⁺IL-10⁺). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFNγ (100 IU/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFNγ significantly reduced the number of CD68⁺MACs, M2 CD206⁺MACs, and immunoinhibitory CD206⁺IL-10⁺MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFNγ largely reversed the IFNγ-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15Rα), we successfully silenced IL-15Rα in human skin ex vivo. Indeed, co-administration of IL-15Rα siRNA abrogated the rhIL-15 protection of M2 CD206⁺MACs against IFNγ, but not of the CD206⁺IL-10⁺MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206⁺IL-10⁺MACs in human skin under IFNγ-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15Rα agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs.

Purpose: As the use of hyaluronic acid fillers continues to increase for clinical and aesthetic purposes, associated complications continue to rise as well. Excess hyaluronidase is often used to dissolve filler, which has its own set of adverse effects. This study analyzes 22 commercially available fillers to delineate the lowest single dose of recombinant human hyaluronidase (RHH) required to fully dissolve each filler within 6 hours across 3 trials. Methods: 0.2 ml aliquots of each of 22 hyaluronic acid fillers were placed in wells. A single dose of RHH, titrated to a minimum volume of 0.45 cc, was administered to the center of the aliquot, to a maximum of 140 units. RHH amounts were as follows: 0, 2.5, 5, 10, 20, 40, 60, 80, 100, 120, or 140 units RHH. Bird’s eye and lateral photographs were taken to monitor dissolution progress at several time points over the 6-hour period to monitor aliquot height and appearance changes. Filler aliquots were left undisturbed for 6 hours, after which dissolution was confirmed by stirring the aliquot on video recording. This process was repeated 3 times per filler to determine the minimum dose of RHH required to consistently dissolve each aliquot. Results: For each of the 22 fillers, the minimum dose of RHH required for dissolution was identified with consistent results across 3 trials, demonstrating reliability. Juvéderm Volbella, Juvéderm Vollure, Juvéderm Skinvive, Restylane-L, Restylane Lyft, and Restylane Silk were identified as the least resistant fillers, requiring ≤20 units to dissolve. Resilient hyaluronic acid (RHA) 2, RHA 3, RHA 4, Belotero Volume, Juvéderm Ultra XC, Juvéderm Volux, Restylane Kysse, and Revanesse Versa were classified as most resistant, requiring ≥120 units to dissolve. Conclusions: This study identifies the minimum single dose of RHH from 2.5 units/0.2 ml to 140 units/0.2 ml for dissolution of 22 different hyaluronic acid fillers over 6 hours. These results paired with previous studies help elucidate the dissolution profiles of each filler in the context of their rheological properties, further informing physicians on how to optimally dissolve different hyaluronic acid fillers in a clinical setting. Video Abstract {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Abstract","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_ejd2p2g3"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Abstract","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_altk1id6"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Abstract","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_qo8ak33o"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Abstract","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_v3jchkii"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video Abstract","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_0sqb02hf"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]}

Epithelioid hemangioendotheliomas (EHs) are rare vascular tumors originating from bone or soft tissue. An 81-year-old woman with inoperable EH of the right orbit presented with right-sided decreased vision, proptosis, and facial numbness secondary to a frontotemporal soft tissue mass. Imaging revealed a heterogeneous enhancing mass surrounding the right sphenoid bone extending into the right orbit and right temporal intracranial fossa. The biopsy of the lesion was consistent with EH. The patient received orbital radiation with improvement in her proptosis, vision, and tumor size. However, 20 months later, she developed metastatic spread and her brief improvement rapidly worsened to require eventual enucleation. Orbital EH is rare, with few case reports in the literature. Treatment typically involves complete excision, although adjuvant radiation has been rarely reported. This case highlights rare orbital EH treated initially with radiotherapy with good effect, potentially indicating a role for this palliative therapy in extensive disease.