corneal endothelial damage associated by phacoemulsification

CORNEAL ENDOTHELIAL DAMAGE ASSOCIATED WITH PHACOEMULSIFICATION

PERRY S. BINDER, M.D., HARVEY STERNBERG, B.S., M. GARY WICKHAM, P H . D . , AND DAVID M. W O R T H E N , M.D.

San Diego, California

Following its introduction in 19671 and subsequent reports which further described the technique,2 - 4 phacoemulsification rapidly became established as an accepted means of removing cataracts. The Kelman phacoemulsification procedure has similar incidences of complications as those that occur with standard cataract removal techniques,3 - 1 2 but the first 50 cases performed are usually associated with a higher incidence of complications. 2'5>7'9·12

Recently,13 the in vivo effect of irrigation and sonification on the cat endotheli-um was evaluated and it was concluded that the procedure caused no damage. However, the number of corneas examined and the volume of fluid used for irrigation was not specified and no stains for endothelial viability were performed.

The purpose of the present study was to evaluate the effect of the phacoemulsification procedure on the viability of the cat endothelium and to determine which parts of the procedure, if any, were deleterious to the cornea.

MATERIAL AND METHODS

Cats weighing 2.5 to 4.0 kg, randomly selected for age and sex, were anesthetized with intramuscular ketamine hydro-chloride (Ketalar) 25 mg/kg and intramuscular sodium pentobarbital (Nembutal) 20 mg/kg and both eyes were maximally dilated with 1% atropine sulfate, 1%

From the Veterans Administration Hospital and the Division of Ophthalmology, University of California, San Diego, California.

Presented in part at the Association for Research and Vision in Ophthalmology, Sarasota, Florida, April 30, 1975.

Reprint requests to Perry S. Binder, M.D., 3350 La Jolla Village Dr. (112G), San Diego, CA 92161.

cyclopentolate hydrochloride, and 10% phenylephrine ophthalmic drops.

The operations were performed under clean but not sterile conditions. Preopera-tively, the eyes were covered with a plastic drape and the eyelids were separated with a wire eyelid speculum; 4-0 black silk bridle sutures were used for fixation. All surgery was performed using a Zeiss operating microscope and the Kelman phacoemulsification unit at a resonant frequency of 40,000 Hz with a 0.0003-inch stroke. The irrigation fluid used was either Plasmalyte 148 at pH 7.4 or Norm-osol. All surgery was performed by two of us (P.S.B., D.M.W.) after completion of an instructional course in phacoemulsification and, in addition to course work, practice on rabbit and cat eyes before we began.

To determine the effect of the irrigation procedure alone, ten left eyes underwent 15 minutes of irrigation and aspiration by using foot pedal position two only. To determine the effect of lens material rubbing against the corneal endothelium, 11 left eyes underwent a planned extracap-sular cataract extraction employing standard techniques with wound closure, using interrupted 10-0 monofilament nylon sutures.

To determine the total effect of irrigation, nuclear material rubbing against the corneal endothelium, and sonification, 21 right eyes underwent a standard Kelman phacoemulsification procedure14 except that the lens nucleus was partially emulsified in situ before its dislocation into the anterior chamber. The wound was closed with 10-0 monofilament nylon.

Topical 1% atropine sulfate drops and polymyxin B sulfate ointment (Neospor-

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VOL. 82, NO. 1 CORNEAL ENDOTHELIAL DAMAGE 49

in) were applied daily. No corticosteroids were used throughout the study. Cats whose endothelium was possibly touched by the probe tip of the phacoemulsifica-tion hand piece during the procedure were excluded from the study.

Three cats were killed immediately after the operation, and six each were killed four, seven, and 14 days postopera-tively. The eyes were enucleated and the corneas with a scierai rim were removed and stained with para-bitroblue tetrazoli-um1 5 for one hour at 37°C. The corneas were fixed in 2% glutaraldehyde and a 5.5-mm central corneal button was removed with a trephine, punching from the endothelial side over a paraffin block. The central button and the corneoscleral remains were evaluated for the percentage of endothelial cells staining (indicating injury) in a single-blind fashion, and were then prepared for scanning electron microscopy using standard techniques. The specimens were evaluated with a scanning electron microscope at an accelerating voltage of 10 V.

The effect of the procedure was determined by evaluating the clarity of the in vivo corneas at the time of enucleation, the percentage of endothelial cells staining with nitroblue tetrazolium, and the morphologic changes seen with the scanning electron microscope. A cloudy cornea, more than 15% of stained cells, or morphologic disturbances of the endothelial cells were each considered evidence of damage. More than 15% of endothelial

cells staining with nitroblue tetrazolium was used as an indicator of damage because (1) freshly enucleated eye bank eyes have less than 5% staining cells whereas eye bank eyes stored for 16 hours have 10 to 15% staining of endothelial cells,16 and (2) in a series evaluating the corneal endothelium with trypan blue after cataract extraction,17 few cells stained.

R E S U L T S

Group 1—Phacoemulsification (21 right eyes)—The average sonification time was 8.7 minutes (range, 3.7 to 15.3 minutes). The average duration of the phacoemulsification procedure was 30 minutes, and 500 to 750 ml of irrigation fluid was used for each procedure. The average sonification time for the eyes evaluated at four days, seven days, and 14 days postoperatively was 8.3 minutes, and the average sound time for the corneas evaluated immediately after the operation was 11.1 minutes. Four of 21 eyes showed no evidence of damage, and only one of 21 eyes had damage as determined by all three factors (corneal clarity, vital staining, and scanning electron microscopic changes). Fourteen of 21 eyes were clear, and seven were cloudy or opaque at enucleation (Table 1). Nine of 21 eyes had no staining with para-nitroblue tetrazolium, and 12 demonstrated staining involving more than 15% of the endothelial cells (Fig. 1, left).

Of 11 eyes in which scanning electron microscopic studies were performed,

TABLE 1 R E S U L T S O F PHACOEMULSIFICATION IN CATS (RIGHT EYES)

Postoperative Day

14 6 4 0

No. of Eyes

Clinical Evaluation

2 cloudy 2 cloudy 3 cloudy 0 cloudy

Nitroblue Tetrazolium*

Electron Microscopyf

2 injured 4 injured 4 injured 2 injured

2/2 injured 2/4 injured 3/4 injured 1/1 injured

Overall Evaluation


*More than 15% of cells stained in a diffuse pattern. fEleven of 21 eyes were svaluated with scanning electron microscopy.

6 6 6 3

50 AMERICAN JOURNAL OF OPHTHALMOLOGY JULY, 1976

eight showed evidence of cellular damage such as exploded cells, separation of cell borders, irregular surfaces, cellular edema, and loss of cells from Descemet's membrane (Figs. 1, right and 2). Of 14 eyes judged to be clear at enucleation, nine showed endothelial cell compromise based on nitroblue tetrazolium staining and scanning electron microscopic changes. The amount of nitroblue tetrazolium staining decreased as the postoperative course lengthened; however, scanning electron microscopic damage persisted for the duration of the study (Table 1).

Group 2—Irrigation and aspiration (ten left eyes)—All ten eyes were clinically clear at the time of enucleation, but five showed evidence of damage (Table 2). Of the five left eyes that were damaged by 15 minutes of irrigation, four of the fellow right eyes were damaged during the pha-coemulsification procedure, suggesting an equal susceptibility of the endothelial cells to damage.

The major changes seen morphologically were diffuse cellular edema and

exploded endothelial cells, but there were no areas of missing cells which were seen with the complete phacoemulsification procedure (Fig. 3, top). In addition, the areas of staining with nitroblue tetrazolium were diffuse (Fig. 3, bottom); 400 ml of fluid was used for each procedure.

Group 3—Planned extracapsular cataract extraction (11 left eyes)—All but one of the corneas were clear at the time of enucleation, but only three eyes showed no evidence of damage when all factors were analyzed (Table 3). Of the ten corneas that seemed to be clear at enucleation, seven showed some evidence of damage with nitroblue tetrazolium staining and scanning electron microscopy. Both right eyes and left eyes appeared to be equally damaged. Using the extracapsular cataract extraction technique, areas of missing cells were similar to areas of missing cells from the corneal buttons of those cats that had undergone a phacoemulsification procedure (Fig. 4). Ruptured endothelial cells and severe cellular edema were not seen. The nitroblue tetrazolium staining involved irregular areas

Fig. 1 (Binder and associates). Left, Right cornea from cat No. 52 removed immediately after phacoemulsification. Fifty percent of the endothelial cells stained with nitroblue tetrazolium (xl60). Right, Scanning electron micrograph (10 kV, 45-degree tilt) demonstrating loss of endothelial cells, rupture of endothelial cells, and edema of remaining endothelial cells (x 1,000).


Fig. 2 (Binder and associates). Right cornea from cat No. 28 removed 14 days after phacoemulsification. Scanning electron micrograph (10 kV, 45-degree tilt) shows ruptured endothelial cells on the right and swollen endothelial cells on the left with lens material scattered throughout the photograph. A large piece of lens material is seen on the right (x2,000).

compared to the diffuse staining seen with irrigation alone. There was no difference in the results of the surgery performed by the two operating surgeons.

DISCUSSION

The results of this experiment demonstrate the possible sources of corneal

damage from phacoemulsification. Irrigation and aspiration without sonification for 15 minutes using the manufacturer's suggested irrigation fluid (or its equivalent) produced diffuse cellular staining with nitroblue tetrazolium (Fig. 3, bottom) and morphologic damage as seen with the scanning electron microscope

TABLE 2 RESULTS OF IRRIGATION AND ASPIRATION (LEFT EYES)

Postoperative Day

14 7 4 0

No. of Eyes

3 3 2 2

Clinical Evaluation




Electron Microscopyf


Overall Evaluation


*More than 15% of cells stained in a diffuse pattern. fSix of ten eyes were evaluated with electron microscopy.


Fig. 3 (Binder and associates). Top, Left cornea from cat No. 40 removed four days after irrigation and aspiration. Scanning electron micrograph (10 kV, 45-degree tilt) shows ruptured endothelial cells in the lower left hand corner and edematous endothelial cells in the middle and right (x400). Bottom, Left cornea removed from cat No. 21 immediately after irrigation and aspiration. All cells stained with nitroblue tetrazolium (xl60).

(Fig. 3, top) in the cat endothelium in five of ten eyes (Table 2). This damage persisted for as long as 14 days postopera-tively, yet all ten eyes in this series were clinically clear at enucleation (Table 3). A comparison with the fellow right eyes

Fig. 4 (Binder and associates). Top, Left cornea removed from cat No. 52 immediately after an extracapsular cataract extraction. In this scanning electron micrograph (10 kV, 45-degree tilt), endothelial cells are missing in the upper half of the photograph. Remaining endothelial cells are edematous. The red blood cells are from a partial hyphema (x800). Bottom, Left cornea removed from cat No. 28, 14 days after an extracapsular cataract extraction. Scanning electron micrograph (10 kV, 45-degree tilt) shows that the surface of swollen endothelial cells is ruptured and remnants of lens material are over the ruptured cells (x 1,200).

that had undergone a complete phaco-emulsification procedure revealed a similar amount of damage and similar morphologic changes in the endothelium.

The planned extracapsular cataract ex-


TABLE 3 RESULTS OF PLANNED EXTRACAPSULAR CATARACT EXTRACTION (LEFT EYES)

Postoperative Day

No. of Eyes

Clinical Evaluation


Electron Microscopyt

Overall Evaluation

14 7 4 0





*More than 15% of cells stained in a diffuse pattern. tEight of 11 eyes were evaluated with electron microscopy.

traction procedure has nuclear material rubbing against the corneal endothelium when the lens nucleus is expressed. In this experiment, ten of 11 corneas were clinically clear at enucleation; however, eight corneas had endothelial staining and scanning electron microscopic changes suggesting some cellular damage (Table 3). These corneas manifested somewhat different changes than those that were irrigated. For example, they had more irregular areas of staining with nitroblue tetrazolium and areas with loss of endothelial cells (Fig. 4), whereas the irrigated corneas demonstrated more diffuse nitroblue tetrazolium staining (Fig. 3, bottom), diffuse cellular edema, and ruptured cells (Fig. 3, top). As in the irrigation experiment, the fellow right eyes that had undergone the phacoemulsification procedure appeared to have an equal amount and similar damage as compared to the eyes that had extracapsular cataract extractions (Figs. 1, left and 2).

When irrigation and aspiration were combined with nuclear trauma to the endothelium, as may occur with a phacoemulsification procedure, 17 of 21 eyes had endothelial cell changes (Table 1) that we found in both the planned extracapsular cataract extraction procedures and irrigation and aspiration procedures (Fig. 2) (Table 1). Although this is not conclusive evidence, it appears that the irrigation procedure causes some endothelial cell compromise, and the trauma of nuclear material rubbing or ricocheting

on the endothelial surface during the lens dislocation procedure, or both, and the phacoemulsification procedure are other sources of damage.

The results of this experiment suggest that the corneal endothelium is stressed during a phacoemulsification procedure. One may argue that the surgeons were "heavy-handed" and were unexperienced with the phacoemulsification procedure, thereby causing endothelial damage. However, most physicians newly trained in the technique find the procedure takes longer to perform than their own standard cataract extraction and they use more than four minutes of sound time and more than 500 ml of fluid with each procedure. The high incidence of complications reported with the first 50 cases of phacoemulsification appears to reflect the early difficulties encountered with this procedure.

It is not known now if the longevity of the endothelial cells after phacoemulsification will be decreased producing late-onset corneal edema, but to better appreciate the effects of the phacoemulsification procedure, a pachometric study of corneal thickness and in vivo specular microscopy of the endothelial cells may be useful in the future.

SUMMARY

Twenty-one cats underwent standard Kelman phacoemulsification procedures in their right eyes. The left eyes of the same animals underwent a planned extracapsular cataract extraction or irrigation

3 3 4 1


and aspiration for 15 minutes using the Kelman phacoemulsification unit. The corneal endothelium was evaluated at various times postoperatively using a stain for endothelial cell viability and scanning electron microscopy. The results suggested that the irrigation procedure alone is deleterious to the cat endothelium as is the rubbing of nuclear material against the endothelial cells. These two procedures caused additional damage when combined in a routine phacoemulsification procedure.

R E F E R E N C E S

1. Kelman, C. D.: Phacoemulsification and aspiration. A new technique of cataract removal. A preliminary report. Am. J. Ophthalmol. 64:23,1967.

2. : Phacoemulsification and aspiration. A progress report. Am. J. Ophthalmol. 67:464, 1969.

3. : Cataract emulsification and aspiration. Trans. Ophthalmol. Soc. U. K. 90:13, 1970.

4. : Phacoemulsification and aspiration of senile cataracts. A comparative study with intracap-sular extraction. Can. J. Ophthalmol. 8:24, 1973.

5. Hues, D. A., and Hurite, F . G.: Results of the first year's experience with phacoemulsification. Am. J. Ophthalmol. 75:473, 1973.

6. Kelman, C. D.: Symposium on phacoemulsification, summary of personal experience. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:35, 1974.

7. Cleasby, G. W., Fund, W. E., and Webster, R. G., Jr.: The lens fragmentation and aspiration

procedure (phacoemulsification). Am. J. Ophthalmol. 77:384, 1974.

8. Troutman, R. C , Clahane, A. C , Emery, J. M., Fink, A. I., Kelman, C. D., Ryan, S. J., and Welsh, R.: Cataract survery of the cataract-phacoemulsification committee. Trans. Am. Acad. Ophthalmol. Otolaryngol. 79:178, 1975.

9. Hurite, F. G.: The contraindications to phacoemulsification and summary of personal experience. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:14, 1974.

10. Kratz, R. P.: Difficulties, complications, and management. Symposium on phacoemulsification. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:18, 1974.

11. Schaffer, D. M.: Retinal detachment after phacoemulsification. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:28, 1974.

12. Emery, J. M., and Paton, D.: Phacoemulsification: A survey of 2,875 cases. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:31, 1974.

13. Emery, J. M.: Phacoemulsification. In Paton, D., and Emery, J. M. (eds.): Current Concepts in Ophthalmology. St. Louis, C. V. Mosby Co., 1975, pp. 207-225.

14. Little, J. H.: Outline of Phacoemulsification for the Ophthalmic Surgeon. Oklahoma City, Semco Color Press, 1974.

15. Polack, F . M.: Cryopreservation of corneas for penetrating keratoplasty. Am. J. Ophthalmol. 71 : 505, 1971.

16. Pena-Carrillo, J., and Polack, F . M.: Histo-chemical changes in endothelium of corneas stored in moist chambers. Arch. Ophthalmol. 72:811,1964.

17. Norn, M. S.: Pachometric study on the influence of corneal endothelial vital staining. Acta Ophthalmol. 51:679, 1973.

corneal endothelial damage associated by phacoemulsification

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