Purpose Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHR) is cumbersome, but free-text software tools could facilitate efficient searches.

Design Retrospective case series.

Participants 1418 aqueous humor (AH) liquid biopsies from patients undergoing intraocular surgery.

Methods Natural language unstructured free-text EHR searches were performed using the Stanford Research Repository (STARR) cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed.

Main Outcome Measures Biopsy associated intraoperative complications and endophthalmitis.

Results 1418 AH liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50-100μL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was more than seven months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet’s membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis.

Conclusions Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of AH samples for molecular analyses. Natural language free-text EHR searches are an efficient approach to reviewing intraoperative procedures.

The authors have declared no competing interest.

This study was funded by the National Institutes of Health, Bethesda, Maryland, grant numbers: R01EY031952, R01EY031360, R01EY030151, and P30EY026877. The sponsor or funding organization had no role in the design or conduct of this research.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board (IRB) of Stanford University gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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Financial Support: National Institutes of Health, Bethesda, Maryland, grant numbers: R01EY031952, R01EY031360, R01EY030151, and P30EY026877. The sponsor or funding organization had no role in the design or conduct of this research.

Conflict of Interest: No conflicting relationship exists for any author. Running head: Safety of aqueous biopsies during intraocular surgery

Address for reprints: vinit.mahajanstanford.edu

Précis: This study demonstrates that aqueous humor liquid biopsies for molecular analyses can be obtained safely and at large-scale during intraocular surgery.

All data produced in the present study are available upon reasonable request to the corresponding authors.