Carbonic anhydrase inhibitors(University of Wollongong)

We report a unique case of iris metastasis from epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma, diagnosed solely by cytologic analysis of aqueous humor without tissue biopsy.

A 56-year-old man with a known history of lung adenocarcinoma presented with unilateral iris masses, anterior chamber inflammation, and secondary glaucoma. Intraocular pressure was initially controlled with cataract surgery combined with microhook trabeculotomy. However, the pressure re-elevated despite maximal topical antiglaucoma therapy (including a prostaglandin analog, beta-blocker, carbonic anhydrase inhibitor, alpha-2 agonist, and Rho-kinase inhibitor) and oral acetazolamide. Three sessions of transscleral cyclophotocoagulation were performed. In addition, two intravitreal injections of aflibercept (2.0 mg each) were administered for rubeosis iridis. Aqueous humor obtained via anterior chamber paracentesis immediately before intravitreal injection demonstrated Class V adenocarcinoma cells on cytology, allowing the diagnosis of iris metastasis without iris biopsy.The lesions subsequently enlarged, and similar iris lesions appeared in the fellow eye during the final 1 month before the patient's death. Systemic disease progression became evident during the final 1 month before death, and the patient ultimately succumbed 9 months after the initial visit. Conclusions and Importance: This is among the few reported cases of iris metastasis confirmed solely by aqueous cytology. This case underscores the diagnostic utility of anterior chamber paracentesis as a less invasive yet reliable alternative to iris biopsy in carefully selected patients. It also highlights the clinical course and therapeutic challenges in managing anterior segment metastasis from epithelial tumors such as lung cancer.

Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant neuromuscular disorder characterized by episodic flaccid weakness with hypokalemia. It is primarily caused by mutations in the CACNA1S gene, encoding the voltage-gated calcium channel Cav1.1, and the SCN4A gene, encoding the voltage-gated sodium channel Nav1.4. A unified pathophysiological mechanism proposes that these mutations neutralize positively charged residues in the S4 voltage-sensor segments, generating "gating pore currents" (ω currents). These currents destabilize the resting membrane potential, trigger paradoxical depolarization, and lead to reversible loss of muscle excitability. Genotype-phenotype correlations are evident: CACNA1S mutations typically cause earlier onset and high male penetrance, whereas SCN4A mutations exhibit greater phenotypic heterogeneity and a propensity for interictal weakness. Genetic testing is the gold standard for diagnosis, and a targeted next-generation sequencing (NGS) panel is recommended as the first-tier diagnostic approach. Management focuses on trigger avoidance, acute potassium replacement, and long-term prophylaxis with carbonic anhydrase inhibitors or potassium-sparing diuretics; pregnant patients require a multidisciplinary care model. This review provides a systematic overview of the clinical diagnosis, pathogenesis, genotype-phenotype correlations, and individualized treatment of HypoPP, aiming to serve as a practical reference for its clinical management.