Methods
This prospective randomized clinical trial was approved by the Miami Veterans Affairs Medical Center Institutional Review Board and was HIPAA compliant. The study was registered with ClinicaTrials.gov (Identifier NCT01087489). Patients requiring frequent ranibizumab intravitreal injections for various indications as part of their routine clinical care were recruited to partake in this study. The primary goal of the trial was to compare pain control with 2 anesthetic techniques. IOP rise with and without globe decompression was a secondary outcome measure.
Patients requiring bilateral ranibizumab injections were randomly assigned to a different preparation method in each eye, and the injections were administered on the same day. Patients requiring unilateral ranibizumab injection were randomly assigned to one of the anesthetic methods and then received the alternate anesthetic prep with the next injection at a future visit.
The 4% liquid lidocaine applied with cotton swabs and 3.5% lidocaine gel were administered per standard protocols as described below.
4% Liquid Lidocaine Preparation
Two drops each of 0.5% proparacaine, 4% lidocaine, and 5% liquid povidone-iodine were instilled, and a 10% povidone-iodine swab was gently applied to the lids and lashes. A standard style sterile speculum was placed between the lids. Five percent liquid povidone-iodine was then applied over the entire ocular surface. Next, 3 sterile cotton swabs soaked in liquid 4% lidocaine were applied with moderate pressure to the area designated for injection in the inferotemporal quadrant to produce a visible circular indentation on the globe. Each cotton swab was pressed against the eye for 60 seconds. The cotton swabs were alternated with an additional drop of 5% povidone-iodine to the chosen area of injection. The injection was then performed by the same treating physician (N.G.) according to the routine technique. A sterile caliper was used to mark the distance from the limbus, followed by a drop of 5% betadine to this area, and a 0.05 mL ranibizumab injection into the vitreous cavity using a sterile 32-G needle attached to a 1 mL syringe. A sterile cotton swab was then used to momentarily cover the site (without applying any pressure) as the needle was withdrawn to limit egress of the vitreous.
3.5% Viscous Lidocaine Ophthalmic Gel Preparation
Two drops each of 0.5% proparacaine and 5% povidone-iodine were placed on the eye. Sixty seconds later, 2 drops of preservative-free 3.5% lidocaine hydrochloride ophthalmic gel (Akten; Akorn Inc.) were placed over the ocular surface and into inferior fornix. The patient was asked to gently close the eye for 7 minutes. A 10% povidone-iodine swab was gently applied to the lids and lashes. A standard style sterile speculum was placed between the lids and the gel was rinsed from the eye with an antibiotic (polymixin or gentamicin). Five percent liquid povidone-iodine was then applied over the ocular surface and allowed to remain in contact with the eye for 60 seconds. Next, the injection was performed by the same treating physician (N.G.) according to the routine technique as described in the previous preparation, including momentarily covering the site of injection without applying any pressure on the globe as the needle was withdrawn.
Both preparations were performed by the same technician on the same patient to avoid variability in technique. The amount of appropriate ocular compression was gauged by creating a visible indentation in the area of swab application. Same speculum style was utilized in both methods, which was removed before the first postinjection IOP reading. The injections were given by the same treating physician. For both preparations, optic nerve perfusion was assessed by confirming postinjection finger-counting vision.
The IOP was recorded before any ocular manipulation (baseline) and immediately after the injection by the same technician as often as possible. IOP was monitored every 5 minutes until the reading decreased to ≤30 mm Hg. No eyes received pressure-lowering medication or anterior chamber paracentesis before or after the injection.
The Tonopen (Reichert Technologies, New York, NY) was used for IOP measurements to minimize the effects on the cornea. Corneal staining was one of the outcome measures in the trial.[13] The Tonopen has a relatively small surface area and does not require the use of fluorescein dye, unlike applanation tonometry. To improve measurement accuracy, the Tonopen was calibrated and the measurements were repeated until a reliability of 5% was achieved.
The IOP elevations from baseline were compared between anesthetic methods with paired t tests. A P-value of 0.05 was considered statistically significant. Software utilized for statistical analysis is IBM SPSS PASW Statistics version 17.0.
