Head/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine.

Head and neck paragangliomas (HNPGLs) are tumors of parasympathetic origin that occur at variable locations and are often secondary to germline mutations in succinate dehydrogenase (SDH) subunit genes. Occasionally, these tumors produce catecholamines. Here, we assessed whether different locations of HNPGLs relate to the presence of SDHx mutations, catecholamine production and other presentations. In this multicenter study, we collected clinical and biochemical data from 244 patients with HNPGLs and 71 patients without HNPGLs. We clarified that jugulotympanic HNPGLs have distinct features. In particular, 88% of jugulotympanic HNPGLs arose in women, among whom only 24% occurred due to SDHx mutations compared to 55% in men. Jugulotympanic HNPGLs were also rarely bilateral, were of a smaller size and were less often metastatic compared to carotid body and vagal HNPGLs. Furthermore, we showed that plasma concentrations of methoxytyramine (MTY) were higher (P < 0.0001) in patients with HNPGL than without HNPGL, whereas plasma normetanephrine did not differ. Only 3.7% of patients showed strong increases in plasma normetanephrine. Plasma MTY was positively related to tumor size but did not relate to the presence of SDHx mutations or tumor location. Our findings confirm that increases in plasma MTY represent the main catecholamine-related biochemical feature of patients with HNPGLs. We expect that more sensitive analytical methods will make biochemical testing of HNPGLs more practical in the future and enable more than the current 30% of patients to be identified with dopamine-producing HNPGLs. The sex-dependent differences in the development of HNPGLs may have relevance to the diagnosis, management and outcomes of these tumors.

Initial Ten Years of Experience with the Intravitreal Dexamethasone Implant: A Retrospective Chart Review.

PURPOSE: To evaluate the initial ten years of results from the intravitreal dexamethasone implant (DEX) in patients treated for retinal vein occlusion (RVO), diabetic macular edema (DME) or uveitis. METHODS: Retrospective chart review of patients receiving DEX since its FDA approval. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure and cataract status were collected. Baseline data were collected from the initial DEX and post-treatment data at the visit at least four weeks after the last DEX. RESULTS: In total, 315 eyes received 1216 DEX over 63.9±4.6 weeks. In the branch RVO (n=90), central RVO (n=59) and DME (n=62) cohorts, BCVA improved significantly (p<0.05). The uveitis (n=154) cohort did not have a significant change in BCVA, 0.62±0.04 to 0.61±0.04 logMAR (p=0.34). Younger patients, vitrectomized eyes, and eyes without a history of glaucoma were associated with significantly better BCVA outcomes in the uveitis cohort (p<0.05). Overall, CMT decreased significantly from 376.6±6.8 to 322.7±5.0 µm (p<0.05). Intraocular pressure increased significantly (p<0.001) and the percentage of patients requiring anti-glaucoma medications increased from 33.0% to 67.6%. Of phakic eyes, 58.8% (n=63) had cataract progression or underwent surgery with those who underwent surgery experiencing a significant improvement in BCVA (p<0.05). CONCLUSION: Repeated DEX over extended follow-up offers significant anatomic benefits to all cohorts. Visual benefits are only seen in RVO, DME and select uveitis demographics.