Intravitreal injection has become an important treatment choice in many vision-threatening diseases. Various pharmacologic agents such as antibiotics, steroids, and antifungal and antiviral drugs can be delivered into the vitreous cavity by this method [
Intravitreal injections are usually performed as an office procedure, and topical and/or local anesthesia is used during the injection. The most common anesthesia techniques are topical anesthetic eye drops, anesthetic-applied pledget placed on the conjunctiva, and subconjunctival anesthetic injection [
Ozurdex (Allergan, Inc., Irvine, CA) is an intravitreal implant containing 700
The indications for intravitreal Ozurdex implantation have broadened in the recent years. Consequently, increasing numbers of Ozurdex implantation are administered. During implantation procedure, patient comfort and eye stabilization are very important to avoid complications related to application; calm and painless patient can allow us to complete Ozurdex implantation without any problem. Some of the surgeons are using subconjunctival anesthesia to reduce the pain that occurs while Ozurdex applicator is penetrating through the sclera on pars plana. It is arguable if subconjunctival anesthesia really reduces pain or causes more conjunctival hemorrhage and edema that could prevent finding the proper injection site and control the leakage after injection.
We conducted a prospective randomized clinical trial comparing the patients’ comfort and pain with or without subconjunctival anesthesia during intravitreal Ozurdex implantation procedure.
This prospective randomized study included 63 patients who were diagnosed as central or branch retinal vein occlusion. The patients underwent intravitreal Ozurdex injection for their macular edema related to their diagnosis. All patients were naïve to any kind of intravitreal injection before enrollment. The Ethical Committee of Kocaeli University Medical Faculty approved this study. After the patients provided a written consent, each patient was randomized into one of the two anesthetic groups. The first group received topical proparacaine drop and 4% lidocaine-applied pledget. The second group received subconjunctival lidocaine injection in addition to the anesthetics in group 1.
First, topical proparacaine hydrochloride ophthalmic solution was instilled in eyes of the patients in both groups. Then proparacaine-applied sterile pledgets were placed into upper and lower conjunctival sac of the patients in both groups for 1 minute. Povidone-iodine was used to prepare the ocular surface for preinjection antisepsis and the periocular area was covered with an ophthalmic drape. A lid speculum was placed. All eyes were irrigated with 10% povidone-iodine after draping. A second irrigation with sterile 0.9% NaCl was performed. The patients in group 1 (31 patients) received subconjunctival lidocaine injection before Ozurdex implantation, and the patients in group 2 (32 patients) did not receive any anesthesia other than topical proparacaine hydrochloride and 4% lidocaine-applied pledget.
This step was followed by the insertion of the Ozurdex implant into the vitreous cavity through the pars plana using a customized, single-use 22-gauge applicator in both groups by the same surgeon. Standard eye calipers were used to measure the distance from the limbus (3.5 mm for the pseudophakic patients, 4 mm for the phakic patients). Injections were performed in the superotemporal quadrant of the each eye.
After the subconjunctival lidocaine application the surgeon assessed the grade of the subconjunctival hemorrhage using a scoring system (none = 0, minor = 1, moderate = 2, and severe = 3).
Approximately 15 minutes after the injection, a masked ophthalmology resident administered a standard questionnaire to evaluate the patients’ pain level during the injection. We used a Visual Analog Pain score survey [
All analyses were performed using SPSS version 16.0. Independent sample
There was no statistically significant difference between the groups in age and gender. The mean age was
Mean pain score comparison between the patients with or without subconjunctival anesthesia showed no statistically significant difference. Mean pain score was
The patients’ pain level was evaluated by using a Visual Analog Pain score survey, where 0 = no pain/no distress and 10 = agonizing pain/unbearable distress. The number of patients in each pain score level is shown below. There was no statistically significant difference in pain score among the groups (
Group 1 | Group 2 | |
---|---|---|
Pain score 0 | 9 | 10 |
Pain score 1 | 12 | 10 |
Pain score 2 | 3 | 6 |
Pain score 3 | 3 | 4 |
Pain score 4 | 1 | 2 |
Pain score 5 | — | — |
Pain score 6 | — | 1 |
Pain score 7 | 2 | — |
Pain score 8 | — | — |
Pain score 9 | 2 | — |
Pain score 10 | — | 1 |
Subconjunctival hemorrhage was higher in subconjunctival lidocaine group (group 1). Mean subconjunctival hemorrhage score in group 1 was
The number of patients in each subconjunctival hemorrhage grade in both groups is demonstrated. The patients that received additional subconjunctival anesthesia (group 1) presented with higher levels of subconjunctival hemorrhage compared to the patients that received only topical and pledged anesthesia (
Subconjunctival hemorrhage | Group 1 | Group 2 |
---|---|---|
Grade 0 | 3 | 10 |
Grade 1 | 12 | 16 |
Grade 2 | 10 | 3 |
Grade 3 | 6 | 2 |
Grade 4 | 1 | — |
There was no relationship between the amount of subconjunctival hemorrhage and pain score of the patients. Pearson’s correlation test did not reveal any statistically significant correlation (
The use of corticosteroids for the treatment of ocular inflammatory diseases was first described in the early 1950s. Corticosteroids have anti-inflammatory, antiangiogenic, and antipermeability properties that make them an important therapeutic option for a variety of posterior segment diseases [
A variety of methods have been proposed that achieve longer duration of pharmacologic effect with lower administration frequency and minimal side effects of the intravitreal steroids. Novel agents including preservative-free and sustained-release intravitreal implants such as Ozurdex are currently approved for ocular use and are being further evaluated for the treatment of RVO, DME, uveitis, and AMD. Due to a potential for greater potency, dexamethasone is being evaluated alone or in combination with anti-VEGFs as promising options in the emerging armamentarium for the treatment of several retinal diseases [
The intravitreal injections are usually administered as a part of the office procedure. In order to maintain a successful injection the patient should be comfortable and relaxed. This can be achieved by a minimally painful injection. The American Society of Retina Specialists Preferences and Trends Survey from 2010 revealed that 25.44% of the retina specialists use topical anesthetic drop, 25.15% use topical viscous anesthetic, 26.33% use topical anesthetic (drop or viscous) + pledget, and 22.19% use subconjunctival injection of anesthetic for intravitreal injections [
Recently, few studies assessed patient comfort using different kinds of anesthetic methods during intravitreal injections. In most of these studies it was found that all of these methods were effective [
In most of these studies, researchers evaluated the anesthetic methods in intravitreal injection of ranibizumab (Lucentis, Genentech), bevacizumab (Avastin, Genentech), or triamcinolone (Kenalog, Bristol-Myers Squibb). In order to perform these injections a smaller sized needle was used (27.5–32 gauges). However, Ozurdex injection is different than other intravitreal injections. It has a larger needle, which is 22 gauges. While inserting the Ozurdex needle it feels blunter. The long axis of the applicator should be held parallel to the limbus, and the sclera should be engaged at an oblique angle with the bevel of the needle up (away from the sclera) to create a shelved scleral path. The tip of the needle is advanced within the sclera for about 1 mm (parallel to the limbus) and then redirected toward the center of the eye and advanced until penetration of the sclera is completed and the vitreous cavity is entered (the package insert is available online at
Kozak et al. compared the gel anesthesia using different needle lumens. They observed no difference between 27.5-gauge and 30-gauge needles, but these needles are also smaller than Ozurdex applicator [
In our study we found higher incidence of subconjunctival hemorrhage in patients that underwent subconjunctival injection. It might be a minor complication; however patients find the appearance of their eyes bothersome. Additionally, it might cause difficulty in injection especially when it is combined with the chemosis. It makes marking the injection site location more difficult [
In conclusion, there are different methods for pain reduction during intravitreal injections. However, there has been no method repeatedly shown to be superior in controlling pain. To the best of our knowledge, this study is the first study that compares the anesthesia techniques in intravitreal Ozurdex implantation. Our study showed that subconjunctival lidocaine injection is not mandatory in reducing pain during Ozurdex implantation. On the contrary, it causes conjunctival bleeding and chemosis in the injection site, which might cause difficulty in injection. We believe that future investigations to compare the local anesthesia techniques should be carried out.
The authors declare that there is no conflict of interests regarding the publication of this paper. The authors have no financial or proprietary interest in any product mentioned in this paper.