Risk of intraocular haemorrhage with new oral anticoagulants
Reviewed by Sofia Rokerya

The authors conducted a study to assess the risk of intraocular haemorrhage with warfarin dabigatran, rivaroxaban, apixaban. All reported cases of intraocular haemorrhage (vitreous, choroidal, or retinal) with warfarin and new oral anticoagulants (NOACs) (including dabigatran, rivaroxaban, apixaban) from the World Health Organizations’ Vigibase database from 1968-2015 were collected. A disproportionality analysis to compute reported odds ratios (RORs) and corresponding 95% confidence by comparing the number of events with the study outcomes and study drugs compared with all other drugs reported to Vigibase was used. A harmful signal was deemed for a lower limit of the 95% confidence interval above 1.80. Eighty cases of intraocular haemorrhage (vitreous, choroidal, or retinal) were identified with warfarin and a total of 156 cases of intraocular haemorrhage were identified with NOACs (82 with rivaroxaban, 65 with dabigatran, nine with apixaban). Warfarin had the highest signal of association with choroidal hemorrhage (ROR= 65.40 (33.86–126.30)). Rivaroxaban had the highest signal of association with both retinal and vitreous haemorrhage (ROR=7.41 (5.73–9.59) and ROR= 11.14 (7.37–16.86), respectively). Dabigatran was also significantly associated with retinal and vitreous hemorrhage (ROR=3.78 (2.82–5.08) and ROR= 5.83 (3.66–9.30), respectively). Limitations of the study: Use of a disproportionality analysis demonstrated associations with a rare adverse event, which prior randomised trials were unable to quantify due to limited statistical power (small sample size and short follow-up). Due to reliance on voluntary reporting from patients, healthcare providers and pharmaceutical companies and a lack of comprehensive patient data, results from the spontaneous data cannot provide evidence of causation and are meant to be hypothesis-generating. The study does not take into account age matched control, indication for drug use, or other factors that may correlate with drug usage. No pertinent visits or follow-ups, are included so we have no way of knowing the present status of the reported cases nor how long patients were exposed to the drug before developing intraocular bleeds. Under-reporting – because of the missing data and reluctance to file voluntary reports – would underestimate the true risk of these rare adverse events. The main limitations in comparing between warfarin and NOACs are (1) the length of time for which warfarin has been used as an anticoagulant, (2) differences in pharmacokinetics, and (3) potentially different comorbid conditions in use of NOACs and warfarin, which may affect intraocular bleeding. Warfarin likely presents a higher number of adverse event reports than for NOACs due to the reporting bias mentioned above, which would increase its apparent risk of certain adverse events. Although in the same class of drugs, the mechanism by which NOACs are distributed and eliminated from the body are different from warfarin. Hence, this prevents a direct comparison in dosage and the resulting risk of adverse events. Large epidemiologic studies are needed to better understand the magnitude and timing of risk associated with the drugs in the study. 

Risk of intraocular haemorrhage with oral anticoagulants.
Talany G, Gao M, Etminan M.
EYE
2017;31:628-31.