Introduction

Intraoperative intraocular bleeding can present a major challenge during anterior segment operations, such as cataract surgery. In the presence of significant uncontrollable intraocular bleeding, the surgeon may be unable to proceed if the bleeding cannot be controlled. Furthermore, it can result in post-operative hyphema, which can in turn lead to raised intraocular pressure (IOP) and corneal staining.

Intraoperative anterior chamber bleeding can have various causes, such as iatrogenic iris trauma, abnormal blood vessels or be seemingly spontaneous. A number of intraoperative techniques can be utilised to control intraocular bleeding. A watch and wait approach may lead to spontaneous cessation of bleeding. In cases of significant bleeding or impaired clotting, this may be ineffective. Moreover, if the bleeding does stop naturally, it may restart spontaneously or with further intraocular manuevers. The anterior segment can be tamponaded with viscoelastic, air or saline solution. During significant active bleeding, this may be ineffective. Raising the IOP through tamponading can be painful under topical anesthesia (now used in > 90% of cataract surgery) [1], and is a risk factor for optic disc damage in patients with advanced glaucoma.

Phenylephrine is an α-1 adrenergic receptor agonist which is used in ophthalmology to achieve and maintain pupillary dilation [2]. It is used for pre-operative dilation either in the form of eye drops or a pellet inserted into the inferior fornix. It can also be injected intracamerally to induce or improve pupillary dilatation [2, 3].

In 2016, the first author used intracameral phenylephrine 2.5% to halt the significant iris bleeding during cataract surgery. This manoeuvre succeeded in complete cessation of the bleeding within one minute. Based on this experience, intracameral injection of 0.3 ml phenylephrine 2.5% (undiluted) was used in three consecutive cases of intraocular bleeding during cataract surgery, one of which was combined with CyPass® Micro-Stent insertion. As far as we know, this is the first report of intracameral phenylephrine use intraoperatively to successfully stop intraocular bleeding, enabling safe completion of surgery. We propose that intracameral phenylephrine can be valuable in controlling intraocular bleeding, by causing vasoconstriction until coagulation of the bleeding vessel occurs.

Case Presentations

Compliance with Ethics Guidelines

Informed consent was obtained from all individual participants for being included in the study.

Case 1

A 76-year-old woman presented with reduced vision due to cataract formation in her only eye with useful vision. Relevant examination findings of the operated eye are in Table 1. She therefore underwent cataract surgery [phacoemulsification with intraocular lens (IOL) insertion].

Table 1 Demographics, pre-operative and post-operative findings
Full size table

Intraoperatively, during the irrigation and aspiration of the lens cortex, significant intraocular bleeding started. The cause of this is not certain, but probably due to iris or ciliary body trauma. For five minutes, continued irrigation and aspiration was very challenging due to the continued significant bleeding which appeared to originate behind the iris. Video recording of the case was therefore started (see Video) https://doi.org/10.6084/m9.figshare.7623983. Due to the magnitude of bleeding, it was felt that tamponade would not work. Then 0.3 ml phenylephrine 2.5% (undiluted) was therefore injected intracamerally. As shown in the video recording, further irrigation and aspiration of the anterior chamber revealed that bleeding completely stopped. No further intraoperative bleeding was observed thereafter, and the case was finished successfully.

Case 2

A 78-year-old man on systemic warfarin and tamsulosin tablets had phacoemulsification with IOL insertion. Pre-operative findings are shown in Table 1. Intracameral phenylephrine was used initially to improve pupil dilation. Despite this, iris bleeding occurred at the end of surgery. Intracameral phenylephrine (same concentration as initial injection) was used to control the bleeding. The bleeding point on the iris was seen to stop bleeding about one minute post injection. No further intraoperative bleeding was observed, and the surgery was completed uneventfully.

Case 3

An 82-year-old man on aspirin had left phacoemulsification with IOL and Cypass® Micro-Stent insertion, having had the same procedure (uncomplicated) to his right eye 2 months prior to this. Ab-interno insertion of the CyPass® Micro-Stent into the supraciliary space (second attempt) resulted in significant intraocular bleeding obscuring view of the anterior segment. The bleeding continued despite irrigation and aspiration of the anterior segment. Intracameral phenylephrine was therefore injected, and the bleeding completely stopped within one minute of this injection. Further irrigation/aspiration did not result in more bleeding, and the operation was successfully completed.

Post-operative Findings

In all three cases, hyphema was not detected at any of the post-operative visits. Post-operative findings are summarized in Table 1. Case 1 had low IOP the first two post-operative visits, which returned to normal levels at clinic review day 17 post-operatively (11 mmHg). On examination, no cause for this was found, and there was no evidence of a link to use of intracameral phenylephrine. None of the three patients developed post-operative cystoid macular oedema at up to 2 months follow-up.

Discussion

This appears to be the first report of the use of intracameral phenylephrine for controlling intraocular bleeding during cataract surgery. Physiologically, the observed cessation of bleeding makes sense in light of the known potent vasoconstrictive properties of phenylephrine. Phenylephrine injected intravitreally in rabbits has been shown to result in iris-ciliary vessel vasoconstriction [4].

Topical phenylephrine or Mydriasert® ophthalmic insert was used pre-operatively in all three cases. The latter is removed from the conjunctival fornix a few minutes before the surgery. Animal models have shown that phenylephrine is present in the aqueous humor for at least 2 h following topical drops instillation [5]. Despite this, intraocular bleeding occurred, and was only stopped when phenylephrine was injected intracamerally. There are several explanations for this. Firstly, irrigation and aspiration of anterior chamber fluid may have washed out residual pre-operative phenylephrine. The duration of vasoconstriction has not been studied as far as we know after phenylephrine washout. However, further irrigation and aspiration after intracameral phenylephrine injection (to stop bleeding), did not result in re-bleeding. The efficacy of intracameral phenylephrine may therefore be due to the higher concentration achieved in the aqueous as compared to pre-operative topical application. It is interesting that case 2 had intracameral phenylephrine at the start of surgery yet developed iris bleeding towards the end of surgery. The operation was not prolonged (20 min), suggesting that short duration of action of the first intracameral phenylephrine injection is less likely to explain the bleeding occurring towards the end of surgery. One hypothesis is therefore that the efficacy of phenylephrine is due to the direct vasoconstrictive effect on the exposed bleeding vessel.

There are theoretical concerns regarding vasodilation of the vessel after initial vasoconstriction leading to further intraocular bleeding. This was not observed intraoperatively in these cases, and no hyphema was seen in any of the post-operative visits.

Intraocular adrenaline 0.1% is known to have a vasoconstrictive effect on iris vessels in rat eyes [6]. All three surgical cases had 0.5 ml of adrenaline 1:1000 infused into 500 ml of balanced saline solution (BSS) irrigation solution (i.e., adrenaline 0.1%). Irrigation and aspiration of the anterior segment with this solution did not succeed in halting the bleeding. This case series suggests that intracameral phenylephrine is much more effective in controlling significant intraoperative intraocular bleeding.

Albeit a few sporadic case reports, no significantly increased risk of systemic or post-operative ophthalmological complications have been reported with intracameral phenylephrine 2.5% use [2, 3, 7]. A concentration of 2.5% has been recommended for operating room use [8].

In our case series, 0.3 ml injection of 2.5% phenylephrine was used. A retrospective study found that a 0.6 ml intracameral injection of diluted phenylephrine (0.3 ml phenylephrine 2.5% mixed with 0.3 ml BSS) was not found to be associated with complications in the short- and medium term [7]. Phenylephrine is a vasopressor, however, and there are case reports of cardiovascular complications [9]. Circulatory monitoring of patients for increased blood pressure and heart rate/rhythm changes is therefore advisable.

Although intracameral phenylephrine was not found to be associated with post-operative complications, no corneal endothelial cell counts nor corneal thickness measurements were performed to assess for endothelial toxicity. Also, as this is not a controlled study, it is not possible to state how much faster the bleeding is controlled with phenylephrine as compared with observation.

Conclusion

Intracameral phenylephrine has a potential application for the cessation of anterior chamber bleeding during intraocular surgery. This technique may be particularly helpful in light of the rising trend of combined cataract surgery with minimally invasive glaucoma shunts, in which the risk of intraocular bleeding intraoperatively can be substantially higher.