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Long-term endothelial cell loss after phacoemulsification: Peribulbar anesthesia versus intracameral lidocaine 1%

Prospective randomized clinical trial

Heuermann, Tim MDa,*; Hartmann, Christian MD, PhDa; Anders, Norbert MD, PhDa

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Journal of Cataract & Refractive Surgery: April 2002 - Volume 28 - Issue 4 - p 639-643
doi: 10.1016/S0886-3350(01)01216-0
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The use of topical anesthesia in cataract surgery has become popular in the past decade. New, minimally invasive surgical techniques and less traumatic surgical procedures have sparked the change in anesthesia techniques for cataract surgery. In 1990, 90% of cataract surgery in the United States was performed using peribulbar or retrobulbar anesthesia, dropping to two thirds in 1998.1 Of the more than one third of surgeons performing cataract surgery using topical anesthesia, 82% used it in combination with intracameral injection of unpreserved lidocaine.1

The major advantages of topical anesthesia in cataract surgery include no painful injection through the skin or conjunctiva, avoidance of the risks and complications of peribulbar and retrobulbar injections,2 preserved ocular motility during surgery, and immediate visual rehabilitation after surgery. Since the introduction of intracameral anesthesia in cataract surgery, many investigational and clinical studies have verified the efficacy and safety of intracameral anesthesia intraoperatively and postoperatively.3–7

Nevertheless, some authors advise caution with the use of intracameral anesthetic agents because of their possible toxic secondary effects on intraocular structures, in particular damage to the corneal endothelium.8,9 Changes in the ultrastructure of corneal endothelial cells and an increase in polymorphism and cellular edema have been reported.8 These alterations also occur with unpreserved lidocaine 1%, the concentration used most often for intracameral anesthesia in cataract.10

This study evaluated whether the intraocular application of unpreserved lidocaine 1% affects endothelial cell loss after phacoemulsification with posterior chamber intraocular lens (IOL) implantation and compared the endothelial cell loss rate with that in patients having peribulbar anesthesia. In contrast to other published clinical studies, we examined the long-term endothelial cell loss with a follow-up of 1.5 to 2.0 years.

Patients and Methods

This controlled prospective randomized clinical trial comprised 78 eyes of 78 patients scheduled for cataract surgery under peribulbar or topical anesthesia. The patients' demographics are shown in Table 1. There was no statistically significant difference in age, sex, or preoperative endothelial cell density between the 2 anesthesia groups.

Table 1
Table 1:
Patient characteristics.

The patients provided written informed consent after they received a thorough explanation of the procedure. All patients were in need of cataract surgery as ascertained using conventional clinical criteria. Exclusion criteria were corneal endothelial dystrophy, a baseline endothelial cell count of fewer than 1500 cells/mm2, or an ocular condition that might interfere with specular microscopy of the corneal endothelium. In addition, deaf patients and those who did not know the spoken language were excluded.

All operations were performed by the same surgeon (N.A.) and comprised phacoemulsification with the Premiere unit (Storz Ophthalmics) and implantation of a poly(methyl methacrylate) posterior chamber IOL in the capsular bag. Patients were randomized in the operating room to have peribulbar or topical anesthesia by the envelope technique. Peribulbar anesthesia was by injection of 6 cc prilocaine chlorhydrate 2% (Xylonest®) in 90 IU hyaluronidase using a 24-gauge cannula; the injection was into the temporal lower quadrant of the lower eyelid. Patients in the topical/lidocaine group received a small amount of lidocaine hydrochloride 2% (Xylocaine®) gel placed on the conjunctiva in the area of the planned incision. Then, 0.15 cc unpreserved lidocaine 1% was injected into the anterior chamber at the beginning of surgery. All patients received 1.15 mg midazolam for sedation and 15 minutes of 35 mm Hg ocular compression. The sclerocorneal incision was made at the steepest corneal meridian. In 9 patients in the peribulbar group and 4 in the lidocaine group, a lateral incision was made to correct astigmatism.

Specular endothelial cell microscopy was performed preoperatively by a single observer unmasked to the anesthesia technique a mean of 20 months ± 5.1 (SD) after surgery using the Zeiss Noncon Robo-CA specular endothelial microscope. A photograph of the central cornea was taken with a video camera attached to the specular microscope. A reference grid was placed over the picture, and 75 cells were identified manually on a monitor. Thereafter, the instrument calculated the cell density in cells per square millimeter by multiplying the appropriate magnification factor. The variation in cell area (ie, polymegethism) and cell shape (ie, pleomorphism) were determined automatically by calculating the frequency of hexagonal cells. Noncontact specular microscopy was used as it provides an accurate evaluation of the safety of surgical procedures.11–14

Taking into account differences found in pilot studies, it was presumed that a minimum of 39 patients were needed in each group to reach a P value less than 0.01 by a power of 0.8 for the main clinical outcome measures. Statistical analysis was by the Mann-Whitney rank sum test with a significance level less than 0.01. This nonparametric test was used because the normality of the underlying population could not be confirmed.


Cataract surgery was uneventful in all cases. There were no intraoperative or postoperative complications.

Table 2 shows the mean phaco time, mean ultrasound power, and mean duration of surgery. The only statistically significant difference between the peribulbar and topical/lidocaine groups was in the mean duration of surgery (P < .01).

Table 2
Table 2:
Intraoperative parameters.

Table 3 shows the preoperative and postoperative endothelial cell measurements. There were no statistically significant differences between the peribulbar and topical/lidocaine groups in the mean preoperative and postoperative endothelial cell counts, mean endothelial cell loss from preoperatively to postoperatively, mean endothelial cell size, and amount of hexagonal cells.

Table 3
Table 3:
Endothelial cell measurements.


The use of topical anesthesia rather than peribulbar or retrobulbar anesthesia in cataract surgery is becoming increasingly popular. Topical anesthesia by subconjunctivally injected anesthetic agents in combination with the sponge technique, instillation of lidocaine gel, or anesthetic eyedrops alone has been described.15,16 In the early 1990s, intracameral injection of unpreserved lidocaine was introduced, and many clinical studies showed it to be a safe and effective local anesthesia technique for cataract surgery.3–7

The toxicity of commonly available topical anesthetic agents is well known. Secondary effects on the corneal surface and corneal epithelium have been reported when local anesthetic agents are used to achieve anesthesia for small-incision corneal surgery or for intraocular pressure measurement by applanation.17,18 With the growing use of intracameral anesthesia, possible alterations of intraocular structures including corneal endothelial cells and the retina19,20 have been reported. Electrophysiological investigations showed no change in the retinal function when intracameral lidocaine 1% is used in cataract surgery.2 Nevertheless, alterations in the electroretinogram after intraocular injection of lidocaine in higher concentrations have been described in animal studies.21

The alteration of the corneal endothelium also depends on the concentration of the anesthetic agent. In in vivo animal studies, Judge and coauthors8 found an increase in corneal thickness up to 25% to 75% and an increase in corneal haze when 0.2 cc unpreserved lidocaine 4% was injected into the anterior chamber; both increases were highly significant. They found no statistically significant changes with unpreserved lidocaine diluted to 0.4%. Others report transient edema in corneal endothelial cells in humans and rabbits after perfusion of the corneal endothelium with unpreserved lidocaine 1%,10 the concentration most surgeons use for intracameral anesthesia in cataract surgery. In addition, they describe a loss of hexagonal conformity and an increase in endothelial cell polymorphism.10

Another factor in endothelial cell damage may be the pH of the anesthetic solution. The corneal endothelial barrier works best with a pH of 6.5 to 8.5. We have taken several measurements when lidocaine 1% is used and found a mean pH between 6.73 ± 0.17, revealing a tendency toward acidity (unpublished data).

Studies of endothelial cell loss after cataract surgery using intracameral injection of lidocaine have a follow-up up to 3 months. Garcia et al.22 compared the postoperative course after cataract surgery with and without intracameral anesthesia of unpreserved lidocaine 1% and found an endothelial cell loss rate of 3.6% and 4.7%, respectively. In a similar study, Carino and coauthors23 found endothelial cell rates of 6.7% and 6.1% 1 month after surgery with and without intracameral anesthesia, respectively. Neither study found a statistically significant difference between anesthesia techniques in endothelial cell size or polymorphism. Elvira et al.24 report an endothelial cell loss rate of 5.9% 3 months after cataract surgery with intracameral injection of 0.3 cc lidocaine 1%.

Our study evaluated long-term endothelial cell loss and found no statistically significant differences between the peribulbar and topical/lidocaine groups 20 ± 5.1 months after surgery. There was no difference in cell morphology; that is, in cell size or the amount of hexagonal cells. Our endothelial cell loss rates of 11.11% and 12.55% with or without intracameral lidocaine injection, respectively, are within the average range 1 to 2 years after cataract surgery with peribulbar anesthesia.25,26

One drawback of our study is that the person performing the postoperative examinations was not masked to the anesthesia technique used, which may have introduced bias. This could have been prevented by using an observer masked to the technique.

An important consideration, especially when comparing in vitro animal studies and in vivo studies, is that immediately after the anesthetic agent is injected into the anterior chamber, it quickly dilutes in the intraocular fluid. Irrigation/aspiration during phacoemulsification further dilutes the agent, which is quickly washed out. Thus, injection of lidocaine 1% into the anterior chamber seems to provide sufficient analgesia without damaging intraocular structures, in particular the corneal endothelium.

In summary, our results show that topical anesthesia combined with intracameral injection of 0.15 cc unpreserved lidocaine 1% is a safe alternative to peribulbar anesthesia in cataract surgery, as evidenced by the postoperative endothelial cell course. After a 20-month follow-up, there were no statistically significant differences between the 2 types of anesthesia.


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© 2002 by Lippincott Williams & Wilkins, Inc.