Corneal endothelial damage after cataract surgery: Microincision versus standard technique

J CATARACT REFRACT SURG - VOL 32, AUGUST 2006

Corneal endothelial damage after cataract surgery: Microincision versus standard technique Rita Mencucci, MD, Claudia Ponchietti, MD, Gianni Virgili, MD, Fabrizio Giansanti, MD, Ugo Menchini, MD

PURPOSE: To compare corneal endothelial changes after phacoemulsification performed with a standard technique versus a bimanual microincision cataract surgery (MICS) technique. SETTING: University ophthalmology department. METHODS: Eighty patients scheduled for routine cataract surgery were randomized into 2 groups; 40 eyes had standard stop-and-chop phacoemulsification (standard group) and 40 eyes had stopand-chop phacoemulsification with microincision surgery (MICS group). Central corneal endothelial cell counts, coefficient of variation in cell size, hexagonality, and pachymetry were assessed preoperatively and 1 and 3 months postoperatively. RESULTS: The mean preoperative cell count in the entire sample was 2245 cells/mm2 G 37 (SE). The mean decreased by 102 cells at 1 month (95% confidence interval [CI], 133 to 71; P<.001) and by 144 cells at 3 months (95% CI, 187 to 102; P<.001). The difference between the standard group and the MICS group was 25 cells at baseline (95% CI, 169 to 120 cells; P Z .739), 19 cells at 1 month (95% CI, 163 to 126; P Z .799), and 19 cells at 3 months (95% CI, 164 to 125; P Z .793). There were no changes in the coefficient of variation or morphology in the overall sample, and the pattern of change did not differ between the 2 groups. Corneal thickness increased by 10.2 mm in the overall sample (95% CI, C4.5 to C16.0; P<.001) and approached baseline values by 3 months with an increase of 3.4 mm (95% CI, 4.1 to 10.8; P Z .372). There was no difference in corneal thickness between the groups. CONCLUSION: No significant differences in corneal endothelial cell loss or endothelial morphology were found between MICS and standard incision techniques. J Cataract Refract Surg 2006; 32:1351–1354 Q 2006 ASCRS and ESCRS

The corneal endothelial cell count diminishes after cataract surgery. The amount of loss depends on the procedure, the type of intraocular lens (IOL) implanted, and intraoperative and postoperative complications.1 Intraoperative endothelial trauma can be caused by corneal deformation,

Accepted for publication February 16, 2006. From the Department of Oto-Neuro-Ophthalmological Surgical Sciences Eye Clinic, University of Florence, Florence, Italy. Presented in part at the ASCRS Symposium on Cataract, IOL and Refractive, Washington, DC, USA, April 2005. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: Rita Mencucci, MD, Department of OtoNeuro-Ophthalmological Surgical Sciences, Eye Clinic, Viale GB Morgagni 85, 50134, Florence, Italy. E-mail: [email protected]. Q 2006 ASCRS and ESCRS Published by Elsevier Inc.

nuclear fragments, IOL contact, and the release of free oxygen radicals.2 More sophisticated instruments, better ophthalmic viscosurgical devices (OVDs), and improvements in IOLs and surgical techniques have decreased iatrogenic trauma.3 Microincision cataract surgery (MICS) creates a smaller wound and decreases tissue heating. Whether the technique causes less damage to the ocular structures, particularly endothelial cells,4 has not been evaluated. This study investigated whether MICS causes less damage to the corneal endothelium than standard phacoemulsification in the immediate postoperative period.

PATIENTS AND METHODS This prospective randomized study comprised 80 patients 60 years and older who had stop-and-chop phacoemulsification 0886-3350/06/$-see front matter doi:10.1016/j.jcrs.2006.02.070

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and IOL implantation. Forty eyes had standard phacoemulsification (standard group), and 40 eyes had MICS phacoemulsification (MICS group). Surgery was performed by the same surgeon (R.M.), who was equally familiar with both techniques. Ethics committee approval was obtained for this study, which followed the tenets of the Declaration of Helsinki. The Lens Opacities Classification System III (LOCS III) was used to grade the cataracts. Cataract hardness, nuclear sclerotic grade II, was the same in both groups, and no patient had systemic or ophthalmologic disease. Exclusion criteria included cataract hardness, ocular comorbidities, and axial length greater than 26.5 mm. Corneal exclusion criteria included corneal dystrophy, corneal scarring, and an endothelial cell count of fewer than 1500 cells/mm2. Preoperatively, the pupils were dilated with tropicamide 1%, phenylephrine hydrochloride 2.5% (Visumidriatic Fenilefrina), and indomethacin (Indocolliri). Topical anesthesia was benoxinate 0.4% eyedrops, and the infusion liquid was fortified balanced salt solution (BSS Plus). A temporal clear corneal incision was made, and sodium hyaluronate 3%–chondroitin sulfate 4.0% (Viscoat) was inserted. Phacoemulsification was performed with the Legacy machine (Alcon Laboratories) and the stop-and-chop technique. A Sensar OptiEdge AR40 IOL (AMO) was implanted in the capsular bag with a dedicated injector. No corneal sutures were used. The standard group had endocapsular phacoemulsification, infusion/aspiration of the soft cortex using a bimanual technique, capsular bag refilling with an OVD, and IOL implantation. The MICS group had 2 clear corneal stab incisions smaller than 2 mm, irrigation with a 19-gauge irrigation chopper (Janach) inserted in 1 incision, and placement of a sleeveless 20-gauge phacoemulsification needle through the other incision. The wound was enlarged to 2.75 mm for IOL implantation. All surgery was uneventful. At the end of surgery, absolute phacoemulsification time (APT), effective phacoemulsification time (EPT), mean ultrasound power, and total volume of BSS used in all cases were recorded (Table 1). Postoperatively, all patients received tobramycin–dexamethasone eyedrops (TobraDex) 4 times a day for 4 weeks. Corneal endothelial morphology was evaluated by measuring mean cell density (cells/mm2); coefficient of variation in cell size (SD/mm2), an objective measure of polymegethism;

hexagonality, an index of pleomorphism; and central corneal thickness (mm). Endothelial cell loss was calculated as follows: ECL (%) Z (preoperative postoperative)/preoperative  100, where ECL is endothelial cell loss, preoperative is preoperative cell count, and postoperative is postoperative cell count. Central corneal endothelial cell counts were performed using a noncontact specular microscope (Cellcheck, Konan Medical, Inc.). Between 50 and 100 endothelial cells were required for analyses. This number was specified to reduce sampling errors.5 Central corneal thickness was assessed with a DGH 500 ultrasonic pachymeter (DGH Technology, Inc.). Patients were examined preoperatively and 1 and 3 months postoperatively. Student t and chi-square tests assessed baseline characteristics between the groups; a P value of 0.05 or less was considered statistically significant. A transition regression model (Markov) was used with a first-order autoregressive term (Stata 8.2 software) for statistical analysis of endothelial parameters.6 RESULTS

All patients completed the trial. There were no statistically significant differences between groups in baseline patient demographic data and surgical parameters (Table 1). Endothelial Cell Density

Figure 1 shows mean endothelial cell counts over time. The mean preoperative endothelial cell density was 2258 cells/mm2 G 52 (SD) in the standard group and 2233 G 52 cells/mm2 in the MICS group; the difference (25 cells/mm2) was not significant (95% confidence interval [CI], 169 to 120); P Z .739). Postoperatively, there was a statistically significant decrease in mean cell density in both groups over baseline values. At 1 month, the decrease was 4.65% in the standard group and 4.43% in the MICS group. At 3 months, the decrease was 6.51% and 6.31%,

Table 1. Patient demographics and surgical parameters.

Parameter Mean age (y) Sex (%) Female Male Mean axial length (mm) Mean ACD (mm) Mean lens thickness (mm) Mean APT (s) Mean EPT (s) Mean US power (%) Mean total BSS volume (mL)

Standard Group

MICS Group

P Value

70.8 G 11.7

72.5. G12.5

.532 .458

76 14 23.1 G 1.9 2.98 G 0.4 4.15 G 0.30 25 G 14 10 G 8 28 G 7 130.7 G 29.8

67 23 22.9 G 1.7 2.95 G 0.7 4.19 G 0.46 29 G 19 11 G 7 34 G 9 107.4 G 11.2

.621 .815 .645 .286 .554 .081 .061

Means G SD ACD Z anterior chamber depth; APT Z absolute phacoemulsification time; BSS Z balanced salt solution; EPT Z effective phacoemulsification time; MICS Z microincision cataract surgery; US Z ultrasound

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Figure 1. Mean cell count at baseline and during follow-up, with standard error bars, and endothelial cell loss during follow-up in the 2 groups (solid line Z standard; dotted line Z MICS).

respectively. There was no statistically significant difference between the groups (Figure 1). The difference in the mean cell loss between the groups was 19 cells/mm2 at 1 month and 3 months; it was not statistically significant (95% CI, 163 to 26; P Z .799 and 95% CI, 164 to 125; P Z .793). When the 95% confidence limits of the estimate at 3 months are converted to cell loss values, differences greater than 7.3% favoring the MICS technique or 5.6% favoring the standard technique could be excluded by our study. In fact, values beyond these limits were outside the confidence interval. Coefficient of Variation

At baseline, the mean coefficient of variation was 34.9 G 7.5 SD/mm2 in the standard group and 31.6 G 7.6 SD/mm2 in the MICS group. The difference between groups reached borderline significance (P Z .047). There was no variation in the follow-up period in the overall sample (P Z.110), and the pattern of change did not differ between the groups (P Z.659). Hexagonality

No difference in baseline mean hexagonality was found (P Z.577). This parameter did not have statistically significant variation during the follow-up in the overall sample (P Z.141) or between the 2 groups (P Z.582). Pachymetry

The mean preoperative pachymetry was 548 G 42 mm in the standard group and 546 G 37 mm in the MICS group; the difference was not significant (P Z.800). At 1 month, the mean increase in corneal thickness was 13.4 mm

in the standard group (95% CI, 4.5 to 22.3; P Z .003) and 7.1 mm in the MICS group (95% CI, 1.8 to 16.0; P Z.120). At 3 months, the increase, which was not significant, was 5.9 in the standard group (95% CI, 3.1 to 14.8; P Z 198) and 0.9 in the MICS group (95% CI, 8.0 to 9.8 mm; P Z.839). There was no interaction between group and time in this model (P Z.553), suggesting no overall technique effect on the change of corneal thickness with time. DISCUSSION

Specular microscopy is a standard technique to determine endothelial cell density and morphology in vivo because it allows a qualitative and quantitative morphometric analysis of the endothelial cells.7 With age, endothelial cell density decreases and cell pleomorphism increases. Each year between 0.5% and 0.8% of cells are lost due to physiological aging.8,9 The normal thickness and transparency of the cornea are maintained by the barrier function and the active fluid pump of the corneal endothelium. Endothelial alterations are considered important parameters of surgical trauma and are essential for estimating the safety of surgical techniques. After cataract surgery, endothelial cell density decreases at a greater rate than in healthy, unoperated corneas. The reported losses vary between 4% and 25%, and the period of increased postoperative endothelial cell loss remains unknown. Endothelial cell loss occurs soon after surgery, continues for at least 10 years after, and may be present throughout the patient’s life.10 The mean rate of endothelial cell loss 2 years after surgery is significantly higher (0.09% per year) than the physiological rate.8,9 Other authors10 believe that 10 years after cataract extraction, central corneal endothelial cell loss continues at a rate of 2.5% per year.

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Trauma reduces cell density, increases the mean cell size, and disarranges the normal morphological pattern. Repair processes involve enlargement of residual cells, amitotic nucleus division, migration, and the rosette phenomenon, which leads to a reduction in cell density, proportional increase in mean cell size, and disruption of the normal hexagonal cell pattern. Analysis of cell shape and pattern is a more sensitive indicator of endothelial damage than cell density alone.11 The normal corneal endothelial cell density is approximately 2500 cells/mm2, with corneal edema and decompensation occurring when cell density falls to 500 cells/mm2 or below.12 Several preoperative and intraoperative parameters (nucleus grade, age, long phacomulsification time, high ultrasound energy) can affect endothelial cell loss after phacoemulsification.13 These parameters were similar within the standard and MICS groups, making the groups homogeneous. Corneal distortion, irrigation solution turbulence, mechanical trauma by instruments, nuclear fragments, IOL contact, and free oxygen radicals can cause corneal damage during cataract surgery. Hyaluronic acid has binding sites on the endothelium and may provide mechanical and chemical protection during surgery.14 The endothelial cell loss in this study is comparable to that in other studies.4,15–17 The aim of this study was to compare endothelial damage after standard cataract surgery and MICS. The MICS technique may require longer surgical times at the beginning of the learning curve, and the use of continuous anterior chamber infusion and more manipulation inside the anterior chamber may cause endothelial damage.18 On the other hand, MICS uses a smaller incision and incurs less tissue heating, probably due to decreased friction between the phacoemulsification probe sleeve and the phacoemulsification tip.19,20 Standard phacoemulsification and MICS require a high degree of control over intraoperative ocular hydrodynamics. Anterior chamber collapses during phacoemulsification can threaten surgical outcomes, and endothelial cells can be damaged by excessive irrigation causing increased turbulence in the anterior chamber. BSS Plus was used as the irrigation solution in both groups and has been reported to induce less corneal swelling than other solutions21 but without an effect on postoperative endothelial cell loss. In MICS, the small wound may cause minimum leakage around the needle. This minimum outflow may help cool the tip, avoiding corneal burn while maintaining the anterior chamber. This facilitates capsulorhexis creation, lens manipulation, and nuclear fragment removal. Microincision surgery is a safe technique that does not appear to cause more damage to the corneal endothelium than standard cataract surgery. Longer follow-up is necessary to investigate its potential benefits.

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