Systemic exposure to intracameral vs topical mydriatic agents: in cataract surgery

Abstract

Objective: The objective of this study was to compare systemic exposure to tropicamide/phenylephrine following intracameral or topical administration before cataract surgery.

Patients and methods: Mydriatics exposure was calculated in patients randomized to intracameral fixed combination of mydriatics and anesthetic ([ICMA]: tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1%, N=271) or mydriatic eye drops ([EDs]: tropicamide 0.5% and phenylephrine 10%, N=283). Additional doses were permitted if required. Mydriatic plasma levels were determined by mass spectrometric HPLC in 15 patients per group before and after administration.

Results: Most ICMA patients (73.6%) received a single dose (200 µL) representing an exposure to tropicamide of 0.04 mg and phenylephrine of 0.62 mg. None of these patients received additional mydriatics. In the control group (three administrations), the exposure was 0.45 (11.3-fold higher than ICMA) and 10.2 (16.5-fold higher) mg. When additional ED was used in this group (9.2% of patients), it was 37.5-fold higher for tropicamide (10 drops, 1.5 mg) and 54.8-fold higher for phenylephrine (10 drops, 34 mg) than the recommended ICMA dose. Tropicamide plasma levels were not detectable at any time point in ICMA patients while it was detectable in all ED patients at 12 and 30 minutes. Phenylephrine was detectable in 14.3% of ICMA patients compared to all ED patients at least at one time point. More ED patients experienced a meaningful increase in blood pressure and/or heart rate (11.2% vs 6.0% of ICMA patients; P=0.03).

Conclusion: Systemic exposure to tropicamide/phenylephrine was lower and cardiovascular (CV) effects were less frequent with ICMA. This could be of particular significance in patients at CV risk.

Keywords: cardiovascular safety; cataract surgery; intracameral mydriasis; systemic influence; topical mydriasis.

Figure 1

Plasma tropicamide levels during surgery for ICMA and reference treatments. Notes: Columns show the proportion of patients with tropicamide levels above the limit of detection and the lines show tropicamide levels (mean ± SD). Blood samples were collected before (T0) and 2 (T1), 12 (T2), and 30 (T3) minutes after injection of ICMA or instillation of reference treatment. Tropicamide was not detected in the plasma of any ICMA-treated patient. Abbreviation: ICMA, intracameral fixed combination of mydriatics and anesthetic.

Figure 2

Plasma phenylephrine levels during surgery for ICMA and reference treatments. Notes: Columns show the proportion of patients with phenylephrine levels above the limit of detection and the lines show phenylephrine levels (mean ± SD). Blood samples were collected before (T0) and 2 (T1), 12 (T2), and 30 (T3) minutes after injection of ICMA or instillation of reference treatment. The phenylephrine analyses for three samples (one from the ICMA group and two from the reference treatment group) were rejected because they were analyzed after the validated stability period for phenylephrine. Abbreviation: ICMA, intracameral fixed combination of mydriatics and anesthetic.