L-Lactate Levels in Aqueous Humor Higher in those with Uveal Melanoma

Aqueous humor L-lactate levels were significantly elevated in eyes with uveal melanoma compared to controls, according to a new study from Johns Hopkins published in American Journal of Ophthalmology. The findings suggest a correlation between L-lactate concentration and tumor mitotic activity, supporting its potential role as a biomarker. This metabolite-based approach could aid in distinguishing malignant lesions from benign nevi and guide earlier clinical intervention. Photo:  Amy Bade, OD. Click image to enlarge. Uveal melanoma (UM) is the most common primary intraocular malignancy among adults in the US. It’s fatal in up to 50% of cases, and only 13% of those with metastatic UM survive more than one year. These statistics make early diagnosis of vital importance. Current diagnostic methods based on clinical appearance and ultrasound are highly accurate for finding medium and large lesions; however, distinguishing small UM from benign nevi is a challenge. Fine-needle aspiration biopsy is commonly used, but its accuracy is questionable; therefore, researchers have looked into alternative biomarkers for earlier clues of UM, drawing from evidence of elevated lactic acid (L-lactate) and L-lactate dehydrogenase (LDH) observed in other cancers and ocular disease. A new study specifically investigated the role of aqueous humor L-lactate and whether higher levels correlated with clinical, pathological and molecular tumor characteristics. Results were recently published in American Journal of Ophthalmology.The study included eyes with UM and controls undergoing cataract surgery at the Wilmer Eye Institute at Johns Hopkins University. L-actate levels were measured from aqueous taken at the time of enucleation for UM (n=34) or controls (n=13). Of the melanoma patients, 64.7% (n=22) were male and 94.1% (n=32) were Caucasian. A total of 23 UM patients (68%) were followed for at least five years. Eighteen patients with melanoma were lost to follow-up. According to the results, the average L-lactate concentration of the aqueous humor was 384 nM ±218 nM in eyes with uveal melanoma and 211.5 nM ±73.10 nM in control eyes. The average aqueous humor L-lactate level for melanoma samples was higher than the maximum L-lactate concentration in control samples. This trend persisted after excluding samples with evidence of radiation retinopathy after brachytherapy L-lactate levels were not different amongst eyes with tumors that had progressed after brachytherapy, that did not progress after brachytherapy but were still enucleated and eyes that were enucleated only. Longer time to analysis from sample acquisition for tumor samples correlated with lower L-lactate levels in melanoma samples, consistent with degradation of L-lactate over time.The authors wrote in AJO, “This study demonstrates that L-lactate was elevated in the aqueous humor of patients with uveal melanoma relative to controls, and that the L-lactate level correlated with tumor mitotic activity seen on histopathology. This correlation is logical given that L-lactate is necessary for cellular proliferation.” However, L-lactate levels didn’t correlate with other prognostic indicators, such as tumor size and gene expression.“The difference in metabolite concentration in the aqueous humor shown here serves as a proof-of-concept for further investigations into the role aqueous humor L-lactate and potentially other metabolite levels can have in clinical decision-making, such as distinguishing whether pigmented uveal lesions are cancerous, and deciding when to begin treatment,” they continued.The study acknowledges limitations, including a small sample size and a bias towards larger melanomas due to the use of enucleated eyes. The authors noted, “Because this investigation studied enucleated eyes, the tumors included were biased towards large melanomas, often too large for brachytherapy and may not reflect L-lactate levels of small melanomas.” Additionally, sample degradation over time may have underestimated the true difference in L-lactate levels. The possibility of elevated L-lactate from non-neoplastic sources like ischemic retina or retinal neovascularization, or from anesthetic medications, is also acknowledged.While additional investigations are warranted, this study sets the stage for identifying molecular biomarkers that predict transformation from an indeterminate lesion to uveal melanoma, subsequently allowing for early intervention, concluded the authors. Click here for the journal source. Miller, Sarah et al. Elevated lactic acid levels in the aqueous humor may be an indicator of uveal melanoma. American Journal of Ophthalmology. September 11, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.