C O R N E A L O P A C I F I C A T I O N O C C U R R I N G A F T E R P H A C O E M U L S I F I C A T I O N AND P H A C O F R A G M E N T A T I O N

J U A N J . A R E N T S E N , M . D . , M E R L Y N M . R O D R I G U E S , M . D . ,

A N D P E T E R R . L A L B S O N , M . D .

Philadelphia, Pennsylvania

AND

B A R B A R A S T R E E T E N , M . D .

Syracuse, New York

The use of ultrasound for the disinte-gration of the lens nucleus in extracapsu-lar cataract extraction is a well-accepted technique which has been described else-where . 1 , 2 The incidence of complications is approximately the same as with the conventional intracapsular method. 3 Al-though clinically observed transient or permanent corneal damage has been de-scribed in several repor t s , 3 - 9 histopatho-logical examination of human corneal buttons has not been previously de-scribed. We recently observed four cases of permanent corneal edema and opacifi-cation that had occurred after ultrasonic cataract surgery.

The corneal buttons obtained by pene-trating keratoplasty were examined by light and electron microscopy.

M A T E R I A L AND M E T H O D S

In Case 1, half the corneal button was fixed in 2 . 5 % buffered glutaraldehyde and was processed for scanning electron microscopy ( S E M ) and transmission electron microscopy ( T E M ) . The latter

From the Cornea Service (Drs. Arentsen and Laib-son) and Pathology Department (Dr. Rodrigues), Wills Eye Hospital, Philadelphia, Pennsylvania, and the Departments of Pathology and Ophthalmol-ogy. Upstate Medical Center (Dr. Streeten), Syra-cuse, New York. This study was supported in part by grants from the Pennsylvania Lions Research Foun-dation, the Elizabeth King Trust, the Pennsylvania Oddfellows Visual Research Foundation, and Pub-lic Health Research grant EY01602 from the Nation-al Eye Institute.

Reprint requests to Juan J. Arentsen, M.D., Cor-nea Service, Wills Eye Hospital, 1601 Spring Gar-den St., Philadelphia, PA 19130.

portion was postfixed in 1% osmium te-troxide, dehydrated in ascending concen-trations of alcohols, and embedded in Epon. Thick (1 u.) sections were stained with toluidine blue; thin sections were stained with uranyl acetate and lead ci-trate and examined in an electron micro-scope (Siemens 101).

For S E M , the glutaraldehyde-fixed spe-cimen was postfixed in 1% osmium te-troxide, dehydrated in graded acetones, and dried in a critical point dryer. It was coated with carbon and gold-palladium in a variable speed rotary coater and exam-ined in a scanning electron microscope; the same specimen was reprocessed for T E M .

The other half of the corneal button was fixed in formalin and processed for routine light microscopy. In Cases 2 and 3, the corneal buttons were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin and eosin, PAS, and Masson's trichrome. Representative portions were excised from the paraffin blocks and processed for electron microscopy. 1 0 In Case 4, half the specimen was processed for light micros-copy and the other half for electron mi-croscopy.

C A S E R E P O R T S

Case 1—An 81-year-old white woman had an extracapsular cataract extraction in her left eye in September 1975. The lens was fragmented, using the Shock unit.*

The cornea was edematous immediately after the procedure, and the condition worsened with the development of photophobia, pain, and lacrimation. At the time of the patient's examination in the

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Cornea Service, visual acuity was R.E.: 6/15-3, and L.E.: counting fingers at 15 cm (6 in). Ocular exami-nation revealed an immature nuclear and posterior subcapsular cataract. The left cornea had full-thickness central edema. Numerous folds of Des-cemet's membrane converged to a point located slightly temporal to the center (Fig. 1). The anterior chamber was deep and filled inferiorly with lens cortex. A remnant of lens nucleus was observed in the pupillary area through the sector iridectomy. The posterior capsule was intact and the intraocular pressure was normal. A few cells and a trace of flare were present in the anterior chamber. The patient was treated with topical 0.1% dexamethasone phos-phate (Decadron) eyedrops, four times daily for one month, after which an 8-mm penetrating keratoplas-ty was performed on April 15, 1976.

H I S T O P A T H O L O G Y — T h e opaque corneal buttom measured 8 mm in diameter and showed prominent folds radiating from the center toward the periphery. By light microscopy, the irregularly thinned corneal epithelium displayed moderate intracellular edema and anomalous basement membrane. Fibrous tissue was present between the epithelium and Bowman's layer and considerable stromal edema was noted. Descemet's membrane displayed slight undulations, without guttata (Fig. 2, inset), measured 10 to 12 u. thick, and had two lacerations beneath fibrous nodu-lar areas in the posterior stroma (Fig. 3). A retrocor-neal fibrous membrane was present. Normal endo-thelial cells were not observed.

T R A N S M I S S I O N E L E C T R O N M I C R O S C O P Y — T h e

corneal epithelial cells were connected by desmo-somes. They displayed edema of cytoplasmic orga-nelles, particularly involving mitochondria and endoplasmic reticulum, and contained numerous tonofilaments. Granular chromatin was uniformly distributed throughout the nuclei. The epithelial basement membrane and hemidesmosomes were absent in areas. Bowman's layer displayed random orientation of collagen fibrils. The stromal collagen fibers demonstrated a 30- to 40-nm period and were

Fig. 1 (Arentsen and associates). Case 1. Left eye showing radiating folds of Descemet's membrane (arrows).

separated by edema. Numerous fibroblasts with abundant rough endoplasmic reticulum were pre-sent in the posterior stroma, anterior to folds of thickened Descemet's membrane (Fig. 2). The latter exhibited normal anterior 100- to 110-nm banding.

S C A N N I N G E L E C T R O N M I C R O S C O P Y — H a l f of the

corneal button showed thick folds of Descemet's membrane and inner cornea radiating from the cen-tral area (Fig. 4). A stellate plaque of tissue covering this region tended to wrinkle and separate from the cornea at its edges. Amorphous clumps of debris measuring up to 100 u. in diameter were scattered over the surface. Bare areas displayed a diffuse and regular pitted pattern with 10- to 12-u, areas between the pit-like depressions. The plaque consisted of densely matted fibrils, 25 to 65 nm thick (Fig. 5). At the edge of the plaque a thin film of fibrils continued over a surface devoid of endothelial cells. Occasion-al fibroblast-like cells with long branching processes and the ruffled cell membranes of a migrating cell were visible (Fig. 6) as the fibrillar layer thinned out. Rare lymphocytes, leukocytes, and a flat, 10V to20-|i cell of uncertain type were also present (Fig. 7). The lateral half of the button lacked viable ceils. A variety of curling cellular remnants and a few fibril-lar strands lay on the granular basal lamina.

Case 2—A 69-year-old man had an uneventiful intracapsular cataract extraction in the left eye in 1972 with visual acuity presently corrected to 6/6 (20/20). In February 1976, phacoemulsification was performed in his right eye. The cornea remained edematous from the early postoperative period. On examination at the Cornea Service in July 1976, there was marked foreign body sensation and visual acuity was finger counting at 30 cm (1 ft) with a +11.00 sphere. The cornea was completely edema-tous (Fig. 8), the anterior chamber was deep, and a sector iridectomy was present at 1 o'clock. Cortical remnants were seen behind the pupil, in front of an intact, thickened posterior capsule. No inflammato-ry signs were observed and the intraocular pressure was normal.

On Oct. 2 ,1976, a 7.5-mm penetrating keratoplas-ty combined with a posterior capsulotomy was per-formed.

H I S T O P A T H O L O G Y — T h e cloudy cornea measured 8 mm in diameter and was bisected. Microscopic examination revealed epithelial edema (Fig. 9) with areas of bullous separation from a normal Bowman's layer. Moderate stromal edema was present. Des-cemet's membrane was intact and displayed slight undulations and irregularity of its contour. The endothelium was mostly absent.

Case 3—A 48-year-old white woman had a phaco-emulsification extraction in her left eye in May 1974. She gradually developed corneal edema that pro-gressed, despite the use of 40% glucose ointment at bedtime and 1% prednisolone acetate (Prednefrin Forte) eyedrops four times daily. A soft contact lens failed to alleviate her pain and photophobia. At the time of her examination in the Cornea Service, one year after phacoemulsification, corrected visual acu-ity was R.E.: 6/15 (20/50), and L.E.: hand motions. An immature posterior subcapsular cataract was

796 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1977

Fig. 2 (Arentsen and associates). Case 1. Inset shows a fold of Descemet's membrane (DM) lined by a placoid accumulation of fibrous tissue and cells (asterisk) (PAS, X600). Electron micrograph of the same area showing a fibroblast (F) with prominent rough endoplasmic reticulum (x5,180).

present in the right eye. In the left eye there was full-thickness central corneal edema with numerous folds of Descemet's membrane. The anterior cham-ber was clear superiorly, except for a broad iridovi-treal synechia at 11 o'clock at the incision site. Superficial corneal vascularization was present in this area. In January 1976, an 8-mm penetrating keratoplasty was performed.

HlSTOPATHOLOGY—By light microscopy, the epi-thelium was absent. Bowman's layer was intact and

the stroma showed moderate edema and exhibited focal collagenous areas in the deep stroma. A thin layer of cells and fibrous tissue was present posterior to Descemet's membrane (Fig. 10).

E L E C T R O N MICROSCOPY—Bowman's layer dis-played fibrillar disarray. The stromal collagen fibrils were normal in thickness, but were separated by edema. Descemet's membrane showed 100- to 110-nm anterior banding and occasional abnormal 110-nm banded areas posteriorly. It was lined by a layer

Fig. 3 (Arentsen and associates). Case 1. Lacerations of Descemet's membrane (arrows) in the center of the retrocorneal fibrous plaque (toluidine blue, x 160).

Fig. 4 (Arentsen and associates). Case 1. Stellate fibrous plaque on back of corneal button. Edges are separating from the cornea (arrows). Clumps of probable lens debris adhere to the diffusely pitted surface (SEM, X120).

798 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1977

Fig. 5 (Arentsen and associates). Case 1. Matted fibrillar surface of retrocorneal fibrous plaque (SEM, x22,100). Inset shows junction of plaque (P) and more thinly fibrillar adjacent surface (x2,500).

of collagen with a posterior layer of flattened endothelial-like cells which displayed scant Golgi and rough endoplasmic reticulum and were con-nected by lateral junctional complexes.

Case 4—A 59-year-old man with a 20-year history of retinitis pigmentosa and ten degrees of bilateral central field remaining had an uneventful intracap-sular cataract extraction in his right eye in 1973; visual acuity was 6/9 (20/30) with correction. In February 1975, phacoemulsification was performed in his left eye. During surgery, a sudden collapse of the anterior chamber occurred, the cornea became opaque, and this opacification persisted.

At an examination at the Cornea Service on May 5, 1976, visual acuity in the left eye was light percep-tion with poor projection. The cornea was complete-ly edematous and a dense vascularized scar was present at 12 o'clock, extending from the corneo-

scleral limbus to the center of the pupil. Peripheral anterior synechiae were seen between the 12 and 4 o'clock positions. The pupil was round and the intraocular pressure was normal.

In October 1976, an uncomplicated 8.0-mm pene-trating keratoplasty was performed.

HlSTOPATHOLOGY—The opaque corneal button was 8.0 mm in diameter and was bisected. Micro-scopic examination revealed an irregular corneal epithelium with moderate edema and bullous sepa-ration from Bowman's layer. Subepithelial collagen was focally present between the epithelium and Bowman's layer. The stroma was moderately edema-tous and occasional blood vessels were present. Descemet's membrane was disrupted centrally and a retrocorneal fibrous membrane was present on its posterior surface (Fig. 11). Flattened endothelial cells were present at the periphery. Electron micros-

Fig. 6 (Arentsen and associates). Case 1. Fibroblast-Iike cell with ruffled cell membranes (arrows) that indicate the cell is migrating across the cornea. Scanty fibrils are on bare Descemet's membrane in background (SEM, x3,800).

Fig. 7 (Arentsen and associates). Case 1. Flattened endothelial-like cell on retrocorneal membrane (SEM X4.340).

Fig. 8 (Arentsen and associates). Case 2. Right eye showing central corneal opacification with folds in Descemet's membrane.

Fig. 9 (Arentsen and associates). Case 2. Epitheli-al (arrows) and stromal edema (PAS, x200).

Fig. 10 (Arentsen and associates). Case 3. An irregular retrocorneal fibrous layer (arrow) is adjacent to a fold of Descemet's membrane (DM) (PAS, x600).

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Fig. 11 (Arentsen and associates). Case 4, A layer of subepithelial collagen (C) is anterior to Bowman's layer (arrows). A retrocorneal fibrous membrane (M) is posterior to Descemet's membrane, which is disrupted centrally (asterisk) (PAS, x50). Inset shows site of breaks (arrows) in Descemet's membrane (PAS, x200).

copy demonstrated fibroblasts with prominent rough endoplasmic reticulum and cytoplasmic den-sities in the retrocorneal collagenous zone (Fig. 12).

D I S C U S S I O N

Varying degrees of corneal edema occur in 3 to 5 % of patients after routine intra-capsular cataract extraction depending on age, preexisting corneal disease, and sur-gical complicat ions . 1 1 The incidence of aphakic bullous keratopathy when ultra-sonic devices are used is almost the same as when the conventional intracapsular cataract extraction is u s e d . 3 - 9 In a few of these patients, progression of corneal opacification occurs to a degree that re-quires penetrating keratoplasty.

In an experimental study on the cat cornea, Benolken, Emery, and L a n d i s 1 2

concluded that neither the ultrasonic

emission nor the irrigation-aspiration sys-tems had damaged the corneal endotheli-um, as shown by electron microscopy. Binder and associates , 1 3 however, showed evidence of endothelial damage in cat corneas after phacoemulsification and the use of paranitroblue tetrazolium. Intra-ocular irrigating solutions alone probably play a minor role in endothelial cell dam-age 1 4 * 1 5 that apparently results from the direct trauma of the probe.

Assuming that the requirements for phacoemulsif icat ion 3 , 6 ' 7 are met, the di-rect contact of the probe with the endo-thelium appears to be one of the most important factors producing permanent endothelial damage. Prolonged emulsifi-cation time, intracameral tumbling of the lens nucleus with corneal endothelial contact, cortical remnants, vitreous loss,

802 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1977

Fig. 12 (Arentsen and associates). Case 4. Electron micrograph showing Descemet's membrane (aster-isk) and retrocorneal fibrous membrane (RCFM) (x 7,000).

and anterior synechiae are other possible causes of endothelial damage and corneal edema with this technique.

In Case 1, the presence of a star-shaped striate keratopathy suggested that direct contact with the probe probably damaged the cornea in that area. Histopathologic examination confirmed focal traumatic lacerations of Descemet's membrane,

demonstrating a "peau d'orange" appear-ance posteriorly that corresponded to pit-like depressions on its posterior surface. Normal endothelial cells were not ob-served. The pitted appearance of Des-cemet's surface exhibited a regularity suggesting imprints of detached endothe-lium.1 8 Moderate endothelial edema with scattered loss of endothelial cells has been described as occurring after uncom-plicated phacoemulsification of rabbit and cat eyes.1 4 Placoid and nodular accu-mulation of collagen and fibroblasts ap-peared to correspond to the folds of Des-cemet's membrane observed clinically as well as by SEM. It seems likely that the original surgery and the subsequent in-flammation caused by retained lens mate-rial contributed to the loss of endotheli-um. Whether the curling cell remnants in the peripheral cornea were remnants of endothelial cells, inflammatory cells, or possibly lenticular material is uncertain. Cell debris similar to this and to the larger clumps has been reported adherent to the cornea after phacoemulsification in cats. 1 3

The fibroblast-like migrating cell ap-pears to be the same problematic cell seen on diseased corneal endothelial surfaces by both light and electron microscopy in man and experimental animals.1 7"1 9 It has usually been identified as a metaplastic endothelial cell, although there are diffi-culties in differentiating it from a kerato-cyte or uveal fibroblast.

In Case 3, the presence of lens rem-nants and iridovitreal synechiae probably contributed to the development of endo-thelial damage resulting in corneal ede-ma. Histopathologic examination re-vealed that the folded Descemet's mem-brane with abnormal posterior banding was separated from attenuated endotheli-al cells by a collagenous zone.

In three patients, vitreous touch most likely resulted in the formation of a retro-corneal fibrous membrane (Cases 1, 2 ,

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and 4) ; this was probably enhanced by the endothelial damage caused by direct contact with the probe. Snip, Kenyon, and Green 2 0 noted that the duration of vitre-ous touch at the time of keratoplasty ranged from three months to 12 years. In a study of the rabbit cornea, Fischbarg and Stuart 2 1 suggested that the collagenous (solid) components of the vitreous may have a deleterious effect on the endotheli-al pump mechanism. Boruchoff, 2 2 howev-er, reported that corneovitreal contact oc-curred in 3 % of 100 cases of consecutive bullous keratopathy and concluded that aphakic bullous keratopathy is probably caused by factors other than vitreous touch. Damage to the corneal endotheli-um can result from diverse and nonspe-cific stimuli, including chemical and thermal trauma, postkeratoplasty, uveitis, corneal dystrophies, and pars plana vitrectomy. 2 3* 2 4 It is frequently associated with the development of a retrocorneal fibrous membrane.

Pachymetry and in vivo examination of the corneal endothelium by specular re-flection are useful techniques for the eval-uation of endothelial damage after phaco-emulsification. 2 5

S U M M A R Y

Four patients developed progressive corneal opacification five to eight months after ultrasonic cataract extraction. Trans-mission electron microscopy was per-formed in all patients. Scanning electron microscopy, performed in only one pa-tient, showed radiating folds of Des-cemet's membrane with pits on its poster-ior surface as well as focal traumatic disruption probably caused by probe con-tact. Bullous keratopathy was present in one patient. Two other patients had folds of Descemet's membrane and a thin retro-corneal fibrous layer. All four tumor spec-imens showed secondary epithelial and stromal changes. The common denomina-

tor was the total or partial absence of endothelium or marked alterations of its remnants.

R E F E R E N C E S

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

2. Shock, J. P.: Phacofragmentation and irrigation of cataracts. A preliminary report. Am. J . Ophthal-mol. 74:187, 1972.

3. Kelman, C. D.: Phacoemulsification and aspi-ration of senile cataracts. A comparative study with intracapsular extraction. Can. J. Ophthalmol. 8:24, 1973.

4. Shock, J. P.: Alternative techniques. Phaco-fragmentation, phacocryolysis and irrigation of cata-racts. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:22, 1974.

5. Emery, J. M., and Patón, D.: Phacoemulsificat-ion: a survey of 2,875 cases. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:31, 1974.

6. Hurite, F. G.: The contraindictions of phaco-emulsification and summary of personal experience. Trans. Am. Acad. Ophthalmol. Otolaryngol. 78:14, 1974.

7. Kelman, C. D.: Phacoemulsification and aspi-ration: a report of 500 consecutive cases. Am. J. Ophthalmol. 75:76, 1973.

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

9. Dayton, G. O., and Hulquist, C, R.: Complica-tions of phacoemulsification. Can. J . Ophthalmol. 10:61, 1975.

10. Zimmerman, L. E., Font, R. L., T'so, M. O. M., and Fine, B. S.: Application of electron micros-copy to histopathology diagnosis. Trans. Am. Acad. Ophthalmol. Otolaryngol. 76:101, 1972.

11. Jaffe, N. S., in discussion, Emery, J. M., and Patón, D. (eds.): Current Concepts in Cataract Sur-gery. St. Louis, C. V. Mosby Co., 1974, p. 300.

12. Benolken, R. M., Emery, J. M., and Landis, D. J.: Temperature profiles in the anterior chamber during phacoemulsification. Invest. Ophthalmol. 13:71, 1974.

13. Binder, P. S., Sternberg, H., Wickham, M. G„ and Worthen, D. M.: Corneal endothelial damage associated with phacoemulsification. Am. J . Oph-thalmol. 82:48, 1976.

14. McCarey, B. E., Polack, F. M., and Marshall, W.: The phacoemulsification procedure. 1. The ef-fect of intraocular irrigating solutions on the corneal epithelium. Invest. Ophthalmol. 15:449, 1976.

15. Polack, F.M. , and Sugar, A.: The phacoemul-sification procedure. 2. Corneal endothelial changes. Invest. Ophthalmol. 15:458, 1976.

16. Doughman, D. J . , Van Horn, D., Rodman, W. P., Byrnes, P., and Lindstrom, R. L.: Human corneal endothelial layer repair during organ culture. Arch. Ophthalmol. 94:1791, 1976.

804 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1977

17. Polack, F . M.: Contributions of electron mi-croscopy to the study of corneal pathology. Survey Ophthalmol. 20:375, 1976.

18. Matsuda, H., and Smelser, G. K.: Endothelial cells in alkali burned corneas. Arch. Ophthalmol. 89:402,1973.

19. Waring, C. O., Laibson, P. R., and Rodrigues, M. M.: Clinical and pathologic alterations of Des-cemet's membrane: with emphasis on endothelial metaplasia. Survey Ophthalmol. 18:325, 1974.

20. Snip, R. C , Kenyon, K. R., and Green, W. R.: Retrocorneal fibrous membrane in the vitreous touch syndrome. Am. J . Ophthalmol. 79:233, 1975.

21. Fischbarg, J . , and Stuart, J . : Effect on vitreous

humor on fluid transport by rabbit corneal endothe-lium. Invest. Ophthalmol. 46:22, 1975.

22. Boruchoff, S. A.: Corneo-vitreal contact. Trans. Ophthalmol. Soc. U. K. 95:417, 1975.

23. Rodrigues, M. M., Waring, G. O., Laibson, P. R., and Weinreb, S.: Endothelial alterations in con-genital corneal dystrophies. Am. J . Ophthalmol. 80:678,1975.

24. Kenyon, K. R., Stark, W. J . , and Stone, D. L.: Corneal endothelial degeneration and fibrous prolif-eration after pars plana vitrectomy. Am. J . Ophthal-mol. 81:486, 1976.

25. Bourne, W. M., and Kaufman, H. E.: Cataract extraction and the corneal endothelium. Am. J . Oph-thalmol. 82:44,1976.

OPHTHALMIC MINIATURE

For very fine work, as on the eyelids, Celsus recommends the hair of a woman—a method that has only just died away: the last Deaconess sister to provide her hair for corneal sutures still works at the University Eye Clinic in Geneva.

Guido Manjo; The Healing Hand Cambridge, Mass., Harvard University Press, 1975