Intravitreal injections represent an excellent, direct-route method to deliver high concentrations of pharmacologic agents into the posterior segment of the eye. However, this method is definitely painful and stressful for the patient. Moreover, patients are required to return on a regular basis for subsequent injections as frequently as every month and these may continue for years. It is clear that the anesthetic option for a sufficient patient comfort is an extremely important factor for a successful overall therapy.
Previous studies suggest that among the anesthetic techniques (including SC and peribulbar injection), topical administration could be considered the gold standard anesthetic method for the office-based intravitreal injection procedure, as it is the most comfortably applied, cost-effective, and easiest to administer [1-4]. Additionally, in a recently published study, Sanabria et al., concluded that topical tetracaine and lidocaine provide similar anesthesia before intravitreal injections and that topical diclofenac does not seem to reduce pain scores after them [5]. In agreement with this conclusion, Yau et al., showed that there was no difference in patient pain experience between the 3 (tetracaine, lidocaine and cocaine) anesthetic options tested [7]. Similarly, Blaha et al., compared lidocaine pledget, topical proparacaine, subconjunctival lidocaine and topical tetracaine without obtaining any significant difference in patient pain experience [8].
Ropivacaine is the S-enantiomer of 1-propyl-2’, 6’-pipecoloxylidide. It is a new, long-acting local anesthetic of the amide type with minimal cardiological and neurological toxic events. Several studies have been done to reveal the scope of ropivacaine for use in various diseases and conditions [6]. In ophthalmology, topical anesthesia with ropivacaine is safe and effective in pterygium surgery. Caccavale et al., showed that the long-lasting anesthesia with this agent permitted performing the surgical procedures with autograft conjunctival graft and fibrin glue to attach the flap with low pain perceived by the patients, low surgical invasivity and short duration of surgery [9]. Moreover, Martini et al., referred that topical ropivacaine performed at least as well as topical lidocaine in efficacy and safety in cataract surgery. It provided sufficient and long-lasting analgesia without the need for supplemental intracameral anesthesia in most cases [10]. In a relative study, Borazan et al., concluded that topical anesthesia with ropivacaine was safe, feasible and more effective than lidocaine in cataract surgery [11].
In our study, we tried to evaluate the effectiveness of the combination of ropivacaine 0.2% and proparacaine 0.5% (AM 1), as a topical anesthetic option, for office-based intravitreal injection procedure and to compare it with proparacaine 0.5% alone (AM 2). We were able to show that both anesthetic methods in an over-all duration of 5 minutes provided satisfactory patient comfort for administration of intravitreal injection. In the 1st group of patients with bilateral same-day intravitreal injection, the combined Anesthetic Method (AM 1) applied in one eye offered a clinically significant advantage in pain compared to proparacaine 0.5% alone applied in the other eye. Both ropivacaine and proparacaine cause reversible inhibition of sodium ion influx, and thereby block impulse conduction in nerve fibres. Moreover, ropivacaine has the property to potentiate this action with dose-dependent inhibition of potassium channels and has a long acting anesthetic outcome [12].
The anesthetic methods (AM 1 & AM 2) were also used in two different groups (2 & 3) of the patients who undertook unilateral intravitreal therapy. Our results suggested that patients of 2nd group had a better pain relief (2.38) than patients of 3rd one (2.66) although this difference was not statistically significant. Interestingly, the vision change was different between these groups. In 2nd group the vision was reduced whereas, in 3rd group, the vision was improved and this result may explain the non-statistical significant difference between the anesthetic methods in these two groups. In a recent study, patients whose vision had improved from their previous injection reported a significantly lower average pain score than those who did not show improvement [13]. Perhaps the mental satisfaction with the knowledge that the treatment was working helped patients overcome the physical pain that they were likely to experience.
Before commencing our study, the only published data on topical ocular surface anesthesia with ropivacaine were cataract and pterygium extraction operations [9-11]. We wished to determine whether ropivacaine as the sole anesthetic could provide satisfactory ocular surface anesthesia for intraocular injection procedure. However, before commencing the study, our impression with ropivacaine 0.02 % was that it provoked patient’s itching and burning sensation topically. Hence, we opted for a combination of proparacaine 0.05% with ropivacaine 0.02%, as ropivacaine is not currently available in ophthalmic solution. It should be interesting to try out an ophthalmic solution of ropivacaine in the future, as the sole anesthetic for intravitreal injections, avoiding the relative topical adverse effects.
To date, our study validates the reports that topical anesthesia can be considered as the gold standard anesthetic method for intravitreal injections. Moreover, we conclude that the combination of proparacaine 0.5%-as short acting anesthetic-with ropivacaine 0.2%-as long acting anesthetic-seems to be an effective anesthetic option which provides patients with high rates of pain control and overall satisfaction during the office based intravitreal injection procedure and may be superior to proparacaine 0.5% alone. A future production of ropivacaine’s ophthalmic solution should be considerably useful and could provide another efficient way of topical anesthesia for several ocular operations.