Oral Hedgehog Inhibitor, Vismodegib, for Locally Advanced Periorbital and Orbital Basal Cell Carcinoma: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the efficacy and safety of oral vismodegib (Erivedge; Genentech) in the management of locally advanced orbital and periorbital basal cell carcinoma (BCC). METHODS: A literature search was conducted last in September 2023 in the PubMed database for English language original research that evaluated the effect of oral vismodegib on orbital and periorbital BCC. Sixty articles were identified and 16 met the inclusion criteria. RESULTS: Most studies demonstrated high response rates, with up to 100% of patients responding to the medication in individual studies and initial complete regression occurring in up to 88% of patients. Vismodegib treatment resulted in significant reductions in tumor volume, resulting in globe preservation for most patients. However, in 12% of patients, the response was partial. Recurrences also occurred with substantial frequency, even after an initial complete response. As such, up to 79.4% of patients required surgical intervention, and up to 23% of patients still required exenteration. Use of these agents resulted in reductions in tumor volume that may delay or prevent the need for exenteration in some, but not all, patients. Importantly, molecular analysis of tissue excised after vismodegib therapy revealed persistent tumor in all patients, with frequent accumulation of mutations that may confer resistance to further hedgehog inhibitor therapy. Although most adverse events were rated as level I or II, side effects were common, with up to 100% of patients in studies experiencing at least 1 event. Muscle cramps, alopecia, weight loss, fatigue, and dysgeusia were the most common adverse events, and several patients discontinued therapy because of them. Furthermore, 1 patient died of sepsis that may have resulted from the therapy. CONCLUSIONS: Although level I and II evidence are lacking, most studies indicate a benefit from the use of oral vismodegib to treat orbital and periorbital BCC tumor volume. However, patients should be cautioned about the adverse side effects of treatment and the persistence of tumor cells with mutations that may cause long-term resistance. Use of vismodegib as short-term neoadjuvant therapy may be effective in shrinking tumor volume to reduce surgical morbidity while reducing the frequency and severity of side effects. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Intraoperative Image Guidance in Orbital and Lacrimal Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the efficacy and safety of the use of intraoperative image guidance (IIG) in orbital and lacrimal surgery. METHODS: A literature search of the PubMed database was last conducted in November 2023 for English-language original research that assessed the use of any image guidance system in orbital and lacrimal surgery that included at least 5 patients. The search identified 524 articles; 94 were selected for full-text analysis by the panel. A total of 32 studies met inclusion criteria. The panel methodologist assigned a level II rating to 2 studies and a level III rating to 30 studies. No study met the criteria for level I evidence. RESULTS: Procedures reported on were as follows: fracture repair (n = 14), neoplasm and infiltrate biopsy or excision (n = 6), orbital decompression for Graves ophthalmopathy (n = 3), dacryocystorhinostomy (n = 1), and mixed etiology and procedures (n = 8). Four studies used more than one IIG system. One study that met level II evidence criteria compared the outcomes of orbital fracture repair with IIG (n = 29) and without IIG (n = 29). Borderline better outcomes were reported in the IIG group: 2% versus 10% with diplopia (P = 0.039) and 3% versus 10% with enophthalmos (P = 0.065). The other level II study compared the repair of fractures with navigation (n = 20) and without (n = 20). The group in which navigation was used had a measured mean volume reduction of 3.82 cm3 compared with 3.33 cm3 (P = 0.02), and there was a greater measured reduction in enophthalmos in the navigation group of 0.72 mm (P = 0.001). Although the remaining 30 assessed articles failed to meet level II criteria, all alleged a benefit from IIG. No complications were reported. CONCLUSIONS: A small number of comparative studies suggest that there are improved outcomes when IIG is used in orbital fracture repair, but each study suffers from various limitations. No high-quality comparative studies exist for the management of lacrimal surgery, neoplastic disease, or decompression. Complications attributable to the use of IIG have not been identified, and IIG has not been analyzed for cost savings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

New therapies for unresectable or metastatic cutaneous eyelid and orbital melanoma.

PURPOSE: Newer treatment options offer the promise of improved outcomes for metastatic and unresectable melanoma. This investigation was performed to review these modalities for cutaneous eyelid and orbital disease. METHODS: A search for articles that were related to this subject was performed in the PubMed database, and the bibliographies of these manuscripts were reviewed to ensure capture of the appropriate literature. Data was abstracted and analyzed. RESULTS: Historically, patients who suffer from melanoma of the ocular adnexa have fared poorly. Approaches that employ BRAF and mitogen-associated protein kinase inhibitors, immunotherapy, and novel cellular therapies improve outcomes and survival rates, although the side effect profiles of these agents are problematic. Most of the existing strategies have not explored ocular adnexal disease specifically, and treatment plans are generally adapted from the general cutaneous oncology literature. CONCLUSIONS: Thanks to advances in our comprehension of the cellular biology of the disease, the management of unresectable and metastatic melanoma has evolved considerably over the past several years. Newer modalities will likely continue to improve survival and reduce adverse events.

Safety and tolerability of topical trametinib in rosacea: Results from a phase I clinical trial.

Purpose: Overactivation of the mitogen activated kinase pathway has been associated with rosacea. We hypothesised that inhibitors of this pathway can be repurposed to alleviate rosacea symptoms. Methods: In order to test this hypothesis, we designed a double-blind, randomised, placebo-controlled phase I clinical trial to assess the safety and tolerability of a first-in-kind topical formulation of a MEK kinase inhibitor, trametinib. Subjects applied daily trametinib-containing cream (0.05 mg in 0.5 mL) to one cheek and cream without inhibitor to the other for consecutive 21 days. Skin irritation scores and blood samples were obtained during visits on days 8, 15 and 22. Results: On analysis of high-performance liquid chromatography, no systemic trametinib absorption was detected during this treatment period. Subjects demonstrated a slight but significant improvement in both cheeks, regardless of drug contents. No adverse effects were reported during this time. Conclusions: Topical trametinib was well tolerated at a dose of 0.05 mg per day without meaningful systemic absorption or local adverse events. A dose escalation trial is warranted to determine optimal dosing to treat rosacea while avoiding the adverse effects of systemic treatment.

Effects of Preoperative Intravenous Versus Subcutaneous Tranexamic Acid on Postoperative Periorbital Ecchymosis and Edema Following Upper Eyelid Blepharoplasty: A Prospective, Randomized, Double-Blinded, Placebo-Controlled, Comparative Study.

PURPOSE: To compare the effects of preoperative tranexamic acid (TXA) administered intravenously (IV) versus subcutaneously on postoperative ecchymosis and edema in patients undergoing bilateral upper eyelid blepharoplasty. METHODS: A prospective, double-blinded, placebo-controlled study of patients undergoing bilateral upper eyelid blepharoplasty at a single-center. Eligible participants were randomized to preoperatively receive either (1) 1 g of TXA in 100 ml normal saline IV, (2) 50 µl/ml of TXA in local anesthesia, or (3) no TXA. Primary outcomes included ecchymosis and edema at postoperative day 1 (POD1) and 7 (POD7). Secondary outcomes included operative time, pain, time until resuming activities of daily living, patient satisfaction, and adverse events. RESULTS: By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA), ecchymosis scores were significantly lower on POD1 (1.31 vs. 1.56 vs. 2.09, p = 0.02) and on POD7 (0.51 vs. 0.66 vs. 0.98, p = 0.04) among those that received TXA. By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA), significant reductions in edema scores occurred in those that received TXA on POD1 (1.59 vs. 1.43 vs. 1.91, p = 0.005) and on POD7 (0.85 vs. 0.60 vs. 0.99, p = 0.04). By comparison (IV TXA vs. local subcutaneous TXA vs. no TXA) patients treated with intravenous and local subcutaneous TXA preoperatively were more likely to experience shorter operative times (10.8 vs. 11.8 vs. 12.9 minutes, p = 0.01), reduced time to resuming activities of daily livings (1.6 vs. 1.6 vs. 2.3 days, p < 0.0001), and higher satisfaction scores at POD1 (8.8 vs. 8.7 vs. 7.9, p = 0.0002). No adverse events occurred were reported. CONCLUSION: In an analysis of 106 patients, preoperative TXA administered either IV or subcutaneously safely reduced postoperative ecchymosis and edema in patients undergoing upper eyelid blepharoplasty. While statistical superiority between intravenous versus local subcutaneous TXA treatment was not definitively identified, our results suggest clinical superiority with IV dosing.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

The impact of month and season on the incidence of giant cell arteritis: an Intelligent Research in Sight (IRIS) Registry analysis.

PURPOSE: Previous investigations into the relationship between season and the incidence of giant cell arteritis (GCA) have produced conflicting results. This study aimed to explore the impact of season and new diagnoses of GCA in a more definitive sense by employing the large dataset of the Intelligent Research in Sight (IRIS) database. METHODS: The IRIS Registry was queried to identify new cases of GCA from 2013 to 2021. Statistical analyses were performed to determine the significance of the relationship between the time of year and the incidence of GCA on regional and nationwide bases via Cochran's Q statistical test. RESULTS: A total of 27,339 eyes with a new diagnosis of GCA were identified. Neither the month nor the season of the year correlated with the incidence of GCA, regardless of geographic location within the USA (p > 0.05 for each variable). CONCLUSIONS: In the USA, the incidence of GCA does not appear to vary by month or season. While this finding contradicts certain previous studies that identified a relationship, the cohort of patients identified from the IRIS Registry is much larger than that of previous investigations. Clinicians should be mindful of the possibility of GCA, regardless of the time of the year.

Neutrophil-to-Lymphocyte Ratios Distinguish Idiopathic Orbital Inflammation From Orbital Infectious Disease.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a relatively novel biomarker to distinguish between acute stresses. This study was performed to determine whether the NLR may discern infectious orbital maladies from idiopathic orbital inflammation (IOI). METHODS: The NLR was calculated by a review of the initial blood draws of adult patients who presented to the emergency department at a single academic medical center. Statistical comparisons were performed to identify the significance of these results. RESULTS: Ten patients with IOI, 12 patients with necrotizing fasciitis (NF), and 12 patients with orbital cellulitis (OC) presented to the emergency department. The groups were not statistically significantly different in terms of age or gender. The mean NLRs were 3.48 (standard deviation = 1.80), 13.5 (standard deviation = 14.5), and 8.15 (standard deviation = 6.56) for IOI, NF, and OC, respectively. Patients with IOI had statistically significantly lower NLRs than patients with NF ( p = 0.037) and OC ( p = 0.034). However, the NLRs of patients with OC were not statistically significantly different from those of patients with NF ( p = 0.27). CONCLUSIONS: The NLR appears to distinguish IOI from infectious etiologies, but does not discern between variants of infection. These results should be juxtaposed against appropriate imaging and clinical evaluations, but elevated NLR values may heighten clinicians' concerns for an infectious process and encourage them to initiate appropriate management steps.

Traumatic Orbital Roof Fracture With Superior Rectus Entrapment in a Pediatric Patient.

Pediatric patients often present with orbital fractures after facial trauma, most commonly fractures of the orbital floor. Evaluation of orbital fractures for entrapment of the extraocular muscles is crucial, as urgent surgical exploration and possible repair are needed in these cases. We report a 2-year-old male who presented after a fall with multiple left orbital wall fractures, including a roof fracture. On examination, the patient's OS appeared fixed in an upward gaze. Positive forced ductions revealed clinical concern for entrapment of the superior rectus. The patient was taken to the operating room for exploration, and the entrapped superior rectus muscle was freed from the fracture. The patient subsequently recovered fully with complete extraocular movements. This represents the first reported case of superior rectus entrapment in an orbital roof fracture.

A SEER program study of survival trends in Merkel cell carcinoma of the eyelid: 2000-2019.

PURPOSE: Merkel cell carcinoma of the eyelid (MCCE) is a rare yet aggressive neuroendocrine tumour associated with significant morbidity and mortality. This study aimed to investigate survival trends and demographic factors related to MCCE, 2000-2019, using the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Cases were analysed by demographic parameters, disease properties, and survival. Statistical analyses were performed via a dedicated computerized software package. RESULTS: A total 349 cases of MCCE were identified, accounting for 2% of all MCC cases in the United States during that time. Of note, the incidence of MCCE remained stable over the study period (p = .35). Female patients accounted for 56% of the cases, and males for 44%. White patients accounted for 90.8% of the the cases, and Black patients for 2.9%. MCCE incidence increased with age, with the majority of patients age 85+ (p < .05). Incidence was greatest in metropolitan areas and among those with median incomes >$75,000/year. Income correlated with likelihood of MCCE diagnosis (p < .05). Analysis of 5-year survival data showed 20% of the patients died due to MCCE within 5 years of diagnosis. Of these, the majority died within one year of diagnosis. CONCLUSIONS: Consistent with previous reports, most patients were white, female, and age 85+.Incidence correlated with metropolitan environments and median income. While most patients did not die from MCCE, majority of recorded deaths occurred within one year of diagnosis.

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.

Serologic Evaluations in the Distinction Between Sinusitis-Related Orbital Cellulitis and Periorbital Necrotizing Fasciitis.

PURPOSE: While sinusitis-related orbital cellulitis (SROC) and periorbital necrotizing fasciitis (PNF) share similar clinical presentations, they are managed differently, making rapid recognition of the appropriate clinical entity critical to optimal outcomes. This study was performed to assess whether serologic testing might help clinicians to distinguish between SROC and PNF. METHODS: A retrospective review analysis was used to compare initial complete blood counts and comprehensive metabolic panels among adult patients with SROC and PNF. Statistical evaluations were used to determine the significance of differences between the groups. RESULTS: Thirteen patients with PNF and 14 patients with SROC were identified. The 2 groups were similar in age, gender, and likelihood of immunosuppression ( p > 0.05 for each metric). Mean leukocyte counts were 18.52 (standard deviation = 7.02) and 10.31 (standard deviation = 5.77) for PNF and SROC, respectively ( p = 0.0057). White blood cell levels were above normal limits for 12 patients with PNF (92.3%) and 7 patients with SROC (50%) ( p = 0.017). No other laboratory test was significantly different between the 2 groups. CONCLUSIONS: While the majority of serologic testing was quite similar in patients with either SROC or PNF, leukocyte levels may represent an important clue to distinguish between the two diseases. Clinical evaluation remains the gold standard to make the proper diagnosis, but markedly elevated white blood cell counts should prompt clinicians to at least consider a diagnosis of PNF.

Characteristics of Retrobulbar Hemorrhage Presentation in the Emergency Department.

PURPOSE: To describe demographic and clinical features of emergency department patients presenting with fracture-associated (FA) or fracture-independent retrobulbar hemorrhage (RBH). METHODS: The Nationwide Emergency Department Sample database 2018 and 2019 was used to compare demographic and clinical features of patients with fracture-independent RBH and FA RBH. RESULTS: A total of 444 fracture-independent and 359 FA RBH patients were identified. Demographics such as age distribution, gender, and payer type differed significantly, with young (21-44 years), privately insured males more likely to develop FA RBH and the elderly (65+ years) more likely to develop fracture-independent RBH. Prevalence of hypertension and anticoagulation did not differ, but substance use and ocular-related injuries were more prevalent in the FA RBH. CONCLUSION: Presentations of RBH differ in demographic and clinical features. Further research is needed to explore trends and guide decision-making in the emergency department.

Association of open globe injury characteristics with outcome measures in the emergency department.

PURPOSE: To evaluate the association of demographic and clinical features of emergency department (ED) patients presenting with open globe injuries (OG) with outcomes such as inpatient admission rate, length of stay (LOS), and total cost. METHODS: The Nationwide Emergency Department Sample database 2018 and 2019 was used to analyze the association of demographic and clinical features of OG patients with outcome measures. RESULTS: 8404 OG patients were identified. Medicaid patients were associated with higher ED costs and a higher frequency of extended LOS. The 70+ age group was associated with higher inpatient admission. Frail patients were associated with significantly increased likelihood of inpatient admission, higher likelihood of extended LOS and higher total combined ED cost. Falls and being struck were associated with shorter LOS. CONCLUSION: This study describes the most common demographic and clinical characteristics of OGIs that present to the ED, as well as the association of these characteristics with outcome measures such as inpatient admission rates, LOS, and total cost. The study further identified potential high-risk patients for prolonged length of stay. The findings will better optimize patient care protocols to improve outcomes.

Impact of Season on Incidence of Sinusitis-related Orbital Cellulitis.

PURPOSE: To explore the impact of season on the incidence of presentation to emergency departments with sinusitis-related orbital cellulitis in the United States. METHODS: The National Emergency Department Sample was queried to identify cases of patients with sinusitis-related orbital cellulitis. Patient's age, location, and the month of presentation were recorded. Statistical correlations were analyzed via a dedicated software package. RESULTS: A total of 439 patients with sinusitis-related orbital cellulitis were identified. The overall incidence was higher during the winter months ( p < 0.05); while children were more likely to develop this disease during the winter ( p < 0.05), season was not statistically correlated with its incidence among adults ( p = 0.16). The incidence of orbital cellulitis was higher during the winter in the midwest and south regions of the United States ( p < 0.05 for each region), although this correlation did not apply in the northeast and west ( p = 0.60 and 0.99, respectively). CONCLUSIONS: While sinusitis incidence increases during the winter, the relationship between season and orbital cellulitis is complex and varies by age and geographic location. These findings may help to facilitate screening protocols for this disease and to define staffing issues for emergent ophthalmic care.

SH2 domain-containing protein tyrosine phosphatase-2 is enriched in eyelid specimens of rosacea.

Background: Rosacea is a cutaneous disease that may secondarily affect the ocular surface. Due to the vision threatening, cosmetic, psychological, and work productivity impact, the identification of cellular targets that govern rosacea would enhance our understanding of the biology of the disease and delineate targets for therapeutic manipulation. Objective: To characterize the involvement of SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) in the pathogenesis of rosacea. Methods: Specimens from elective ectropion surgery (n = 20) were processed from patients with rosacea (n = 10) and control patients (n = 10). Immunohistochemistry (IHC) and quantitative western blotting (WB) were performed to identify and quantify the presence of SHP2 and 4G10 (a phosphotyrosine antibody) in rosacea compared to normal tissue. IHC samples were graded according to an intensity scale (0-4). Mann-Whitney statistical analyses were performed via a dedicated computerized software package. Results: On WB, SHP2 was expressed in higher concentrations in rosacea specimens (p < 0.05). On IHC, SHP2 was enriched in the epidermis in rosacea (p < 0.05), although 4G10 levels were not statistically significantly different between the two groups (p > 0.05). Conclusions: SHP2 is enriched in cutaneous specimens of rosacea, suggesting a critical role for this protein in the disease and indicating a modifiable therapeutic moiety.