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.

The purpose of this study was to noninvasively test the hypothesis that dysregulated photoreceptor metabolism occurs with early retinal degeneration in dark-reared Pde6brd10 mice.

Postnatal day 23 (P23) phosphodiesterase (PDE) mutant (Pde6brd10) mice, P23 wild-type (WT) mice were continuously dark-reared, and 2-month-old dark-adapted (DA) C57BL/6J WT mice were studied following acute injection of the carbonic anhydrase inhibitor acetazolamide (ACZ) or saline control. Two optical coherence tomography (OCT) metabolic biomarkers were measured: (i) external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness, a proxy for subretinal space acidosis, and (ii) the profile shape aspect ratio of the hyper-reflective band just distal to the ELM (band 2), a proxy for mitochondrial configuration within photoreceptor inner segments. Retinal laminar thicknesses were also assessed.

P23 Pde6brd10 mice responded to ACZ with ELM-RPE contraction, but no change in band 2 profile shape aspect ratio; outer nuclear layer thickness was subnormal. In contrast, P23 WT mice showed no change in either OCT metabolic biomarker following ACZ administration. DA 2-month-old WT mice showed ELM-RPE contraction with ACZ; band 2 profile shape aspect ratio increased in male mice, with no change in female mice.

P23 Pde6brd10 mice with limited rod atrophy had biomarker values suggestive of dysregulation of RPE fluid/ion transport but with stable rod mitochondrial configuration following ACZ. DA 2-month-old male WT mice biomarkers were responsive to ACZ in a manner similar to those in light-adapted 2-month-old male WT mice; the difference in biomarker response pattern in female WT mice suggests a possible hormonal influence.