AMERICAN JOURNAL OF VOLUME 86
OPHTHALMOLOGY
NUMBER 2
AUGUST, 1978
SCANNING E L E C T R O N MICROSCOPY O F INTRAOCULAR LENS AND E N D O T H E L I A L C E L L INTERACTION J O E L SUGAR, M.D.,
AND J E T T I E B U R N E T T ,
Chicago,
M.D.
Illinois
AND S. L A N C E F O R S T O T , Denver,
The increased use of intraocular lenses has led to critical evaluation of their po tential complications. Recent studies 1 - 3 have demonstrated significant endothelial cell loss following intraocular lens im plantation. In a recent report we demon strated that this cell loss is related to endothelial trauma during intraocular surgery. 3 Kaufman and Katz 4 documented in vitro adherence of endothelial cell walls to intraocular lenses in rabbits. The present case reports confirm endothelial cell adherence to intraocular lenses as a mechanism of endothelial cell loss. CASE REPORTS Case 1—A 75-year-old white woman underwent intracapsular lens extraction and intraocular lens implantation with a suture medallion-type lens in her right eye on Nov. 17, 1976. Postoperatively, she had persistent corneal edema and decreased visual acuity in the operated eye. When the patient was referred to us for examination on June 10, 1977, her best corrected visual acuity was R.E.: finger count ing at one foot; L.E.: 6/24 (20/80). The right eye had good Maddox rod perception, color perception, and appreciation of entoptic phenomenon. The pupil lary reactions and extraocular movements were nor mal. Corneal sensitivity was mildly decreased in the From the Department of Ophthalmology, Univer sity of Illinois Eye and Ear Infirmary (Drs. Sugar and Burnett), Chicago, Illinois; and the University of Colorado (Dr. Forstot), Denver, Colorado. Reprint requests to Joel Sugar, M.D., University of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
M.D.
Colorado right eye. On slit-lamp examination, the conjunctiva in the right eye was mildly injected and the cornea showed diffuse epithelial edema, a central stromal thickness of 0.70 mm, 1+ striae, and 3 to 4 + cornea guttata. The anterior chamber was deep and clear. The intraocular lens was in place in the plane of the iris. We observed mild iridodonesis, but no lenscorneal contact. Vitreous was not visible in the anterior chamber. The left eye had a normal conjunctiva, a central stromal corneal thickness of 0.60 mm, and 2 to 3+ cornea guttata. The anterior chamber was deep and clear, and the lens showed moderate nuclear sclero sis. Dilated ophthalmoscopic examination was at tempted on both eyes. T h e view of the right fundus was inadequate for evaluation; the left fundus was normal. On July 11, 1977, a combined penetrating keratoplasty and intraocular lens removal was performed on the right eye. At the time of surgery there was no flattening of the anterior chamber. The patient has done well postoperatively (Figs. 1-4). Case 2—A 75-year-old white woman underwent an intracapsular lens extraction and intraocular lens implantation with a four-loop Binkhorst-type lens on May 17, 1977. A Prolene suture was used to secure the two superior loops through the iridectomy. On the first postoperative day, a small amount of bleeding had occurred from the superior iridectomy, the implant was in good position, and the cornea was edematous. The hemorrhage cleared unevent fully. The corneal edema persisted despite normal intraocular pressures. At the time of referral (Oct. 14, 1977), the patient's best corrected visual acuity was R.E.: 6/120 (20/400); L.E.: 6/15 (20/50). The right eye had good color perception and appreciation of entoptic phe nomenon. The extraocular movements were normal. The left pupil was normal, and the right pupil was atonic and appeared slightly oval. Corneal sensitivi ty was minimally decreased on the right. On slitlamp examination of the right eye, the conjunctiva was normal, the cornea showed diffuse epithelial
AMERICAN JOURNAL O F OPHTHALMOLOGY 86:157-161, 1978
157
158
AMERICAN JOURNAL OF OPHTHAMOLOCY
AUGUST, 1978
•' "V
Fig. 1 (Sugar, Burnett, and Forstot). Case 1, Scan ning electron micrograph shows overall view of suture medallion lens removed from right eye. The superior pole of the lens is in the foreground. An irregularity of the lens surface surrounding the fixation suture apertures (arrows) is not apparent elsewhere on the lens. Bar graph = 1.1 mm (x 17).
edema, eorneal stromal thickness was 0.64 nun, and there were 2+ striae. The anterior chamber was deep except for a peripheral anterior synechia at the 10 o'clock position. The pupil was eccentric toward this area. Vitreous was present between the lens and iris at this position as well, but was not protruding into the anterior chamber. The lens was in the iris
Fig. 2 (Sugar, Burnett, and Forstot). Case 1 (detail from Figure 1), Hole for fixation suture appears in the right foreground (arrow). The smooth lens surface is at the upper left (open arrows). The inter vening area depicts cellular structures in cluster (x 100).
Fig. 3 (Sugar, Burnett, and Forstot). Case 1, Scan ning electron micrograph of cells adherent to the anterior surface of intraocular lens removed from patient. Individual cells are best shown where they are artifactually separated from surrounding cells at the cell junctions (arrows). Cells range from 8 to 14 (i in diameter (x 1,000).
plane; however, minimal iridodonesis was noted and there was no lens-corneal contact. The intraocu lar pressure was 14 mm Hg as measured by Mackay-Marg applanation tonometry. The retina was attached. The macula could not be seen well enough to determine whether cystoid changes were present or not. In the left eye the conjunctiva was normal. The cornea was clear with a thickness of 0.50 mm. Rare pigment deposits but no cornea guttata were ob served. The anterior chamber was deep and clear, and the lens showed moderate nuclear sclerosis. The left fundus was normal. On Dec. 5, 1977, a penetrating kerato.pla.sty and intraocular lens removal were performed on the right eye. At the time oi surgery there was no flattening of the anterior chamber. Following the penetrating keratoplastv, the patient has done well (Figs. 5-9). M A T E R I A L AND M E T H O D S
Case 1—The eorneal specimen and in traocular lens were placed in Trumps fixative. The cornea was routinely proc essed for light microscopy. The intraocu-
VOL. 86, NO. 2
INTRAOCULAR LENS AND ENDOTHELIAL CELLS
Tig. 4 ^Sugai, Burnett, and I'oistot). Cast- 1, Scan ning electron micrograph depicts endothelial cells (asterisks) surrounded by membranous structure on surface of intraocular lens removed from anterior chamber eight months after implantation. Note ad vancing edge of membrane (arrows) (x 1,000).
lar lens was prepared for scanning elec tron microscopy first by air-drying and then by coating the anterior surface with gold using the Polaron DC sputterer. Case 2—The cornea and intraocular
159
Fig. 6 (Sugar, Burnett, and Forstot). Case 2, Scan ning electron micrograph of flattened endotheli al cells adherent to anterior surface of removed in traocular lens (detail of area shown in Figure 5) (x 2,000).
lens were fixed immediately after removal in 2.5% glutaraldehyde with phosphate buffer. The lens and cornea were criticalpoint dried in a series of graded alcohols ascending to 100%. They were then coat ed in the Polaron DC sputterer and exam ined with the scanning electron micro scope. RESULTS
Case 1—CORNEA—The corneal speci men was examined by light microscopy. The epithelium was largely absent. There was edema of the stroma. Descemet's membrane was slightly thickened and focally laminated. The endothelium was absent. INTRAOCULAR LENS—Gross overview
Fig. 5 (Sugar, Burnett, and Forstot). Case 2, Scan ning electron micrograph of four-loop Binkhorsttype lens removed seven months after insertion. Area seen in detail in Figure 6 is indicated as A. Similar cell formations were found in areas B and C (X 20).
of the intraocular lens at x 17 magnifica tion (Fig. 1) showed a large area of sur face irregularity. A higher power view, at 100 x magnification, revealed (Fig. 2) a patchy area of irregularity near the hole in the lens for suture placement. Still higher magnification, at x 1,000 (Figs. 3 and 4), showed the area to be clumps of endothe-
160
AMERICAN JOURNAL OF OPHTHAMOLOGY
Kig. 7 iSug.ii. Bimicll. .IIKI Forstot). Case 2, Endo thelial surface of excised corneal button. The cut edges of epithelium (A), stroma (B), and Descemet's membrane (C) are well demonstrated. The solid arrows point to a portion of Descemet's membrane that is completely denuded of endothelial cells. Open arrows indicate areas of relatively intact endo thelial cells (x 16).
■J9 ;
Fig. 8 (Sugar, Burnett, and Forstot). Case 2, Rela tively normal appearing, although greatly enlarged and thinned, endothelial cells on cornea. Note that cell junctions are adherent in some areas (arrows) and separated in others (x 640).
A U G U S T , 1978
Fig. 9 (Sugar, Burnett, and Forstot). Case 2, En larged degenerating endothelial cells from patient with persistent bullous keratopathy following intra ocular lens implantation. Descemet's membrane is devoid of endothelium in four areas (arrows) (x 600).
Hal cells. Some of the cells appeared to have undergone fibroblastic metaplasia. Surrounding these cells and seemingly insinuated underneath them (Fig. 5) was an irregular membranous structure that appeared to be basement membrane pro duced by the cells or perhaps cytoplasm of endothelial cells. Case 2—INTRAOCULAR LENS—An overview at x 20 magnification showed multiple small collections of material on the anterior surface of the lens (Fig. 5). A higher magnification, x 2,000 (Fig. 6), showed these to be cells with the same configuration as those seen in Figure 3. The cells were separated at their junc tions, which may represent a fixation arti fact or the result of a natural process. CORNEA—As expected, there were ar eas completely devoid of endothelial cells (Fig. 7, arrow) and areas where the endo thelial cells appeared relatively intact (Fig. 8). In a transition zone, intermediate degenerative changes were seen in the
VOL. 86, NO. 2
INTRAOCULAR LENS AND E N D O T H E L I A L C E L L S
endothelial cells (Fig. 9). Similarities were noted between the cells seen on the cornea (Fig. 9) and those seen on the intraocular lens (Fig. 6) in this case. DISCUSSION
In Case 1, endothelial cells that appear to be producing basement membrane were seen on an intraocular lens removed eight months after implantation. Because endothelial cells are in a relatively normal array and are apparently producing base ment membrane, this suggests that these cells were viable and were present for a relatively prolonged period of time on the intraocular lens. In Case 2, apparently viable cells were similarly adherent to the intraocular lens. In both cases these cells apparently adhered to the lens during surgical implantation. Our findings con firm those of Kaufman and Katz 4 and further demonstrate the importance of avoiding endothelial-lens contact during lens implantation to preclude postopera tive corneal edema. This agrees with our previous study 3 and the investigations of Nordlohne, 5 in which he implied that the major cause of corneal edema subsequent
to intraocular lens implantation implant-endothelial contact. 1
161
is
SUMMARY
Scanning electron microscopic evalua tion of two intraocular lenses removed at keratoplasty for pseudophakic bullous keratopathy demonstrated apparently via ble endothelial cells adherent to their surfaces. These presumably adhered to the lens implants at the time of their insertion and confirm this as a mechanism for endothelial damage and subsequent corneal edema from intraocular lens im plantation. REFERENCES 1. Bourne, W. M., and Kaufman, H. E.: Endothe lial damage associated with intraocular lenses. Am. J. Ophthalmol. 81:482, 1976. 2. Forstot, S. L., Blackwell, W. L., Jaffe, N. S., and Kaufman, H. E.: Effect of intraocular lens implanta tion on the corneal endothelium. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83:195, 1977. 3. Sugar, J., Mitchelson, J., and Kraff, M.: Endo thelial trauma and endothelial cell loss from intraoc ular lens insertion. Arch. Ophthalmol. 93:449,1978. 4. Kaufman, H. E., and Katz, J. I.: Endothelial damage from intraocular lens insertion. Invest. Ophthalmol. 15:996, 1976. 5. Nordlohne, M. E.: The Intraocular Implant Lens. Baltimore, Williams and Wilkins, 1975, pp. 100-110.
OPHTHALMOLOGY
NUMBER 2
AUGUST, 1978
SCANNING E L E C T R O N MICROSCOPY O F INTRAOCULAR LENS AND E N D O T H E L I A L C E L L INTERACTION J O E L SUGAR, M.D.,
AND J E T T I E B U R N E T T ,
Chicago,
M.D.
Illinois
AND S. L A N C E F O R S T O T , Denver,
The increased use of intraocular lenses has led to critical evaluation of their po tential complications. Recent studies 1 - 3 have demonstrated significant endothelial cell loss following intraocular lens im plantation. In a recent report we demon strated that this cell loss is related to endothelial trauma during intraocular surgery. 3 Kaufman and Katz 4 documented in vitro adherence of endothelial cell walls to intraocular lenses in rabbits. The present case reports confirm endothelial cell adherence to intraocular lenses as a mechanism of endothelial cell loss. CASE REPORTS Case 1—A 75-year-old white woman underwent intracapsular lens extraction and intraocular lens implantation with a suture medallion-type lens in her right eye on Nov. 17, 1976. Postoperatively, she had persistent corneal edema and decreased visual acuity in the operated eye. When the patient was referred to us for examination on June 10, 1977, her best corrected visual acuity was R.E.: finger count ing at one foot; L.E.: 6/24 (20/80). The right eye had good Maddox rod perception, color perception, and appreciation of entoptic phenomenon. The pupil lary reactions and extraocular movements were nor mal. Corneal sensitivity was mildly decreased in the From the Department of Ophthalmology, Univer sity of Illinois Eye and Ear Infirmary (Drs. Sugar and Burnett), Chicago, Illinois; and the University of Colorado (Dr. Forstot), Denver, Colorado. Reprint requests to Joel Sugar, M.D., University of Illinois Eye and Ear Infirmary, 1855 W. Taylor St., Chicago, IL 60612.
M.D.
Colorado right eye. On slit-lamp examination, the conjunctiva in the right eye was mildly injected and the cornea showed diffuse epithelial edema, a central stromal thickness of 0.70 mm, 1+ striae, and 3 to 4 + cornea guttata. The anterior chamber was deep and clear. The intraocular lens was in place in the plane of the iris. We observed mild iridodonesis, but no lenscorneal contact. Vitreous was not visible in the anterior chamber. The left eye had a normal conjunctiva, a central stromal corneal thickness of 0.60 mm, and 2 to 3+ cornea guttata. The anterior chamber was deep and clear, and the lens showed moderate nuclear sclero sis. Dilated ophthalmoscopic examination was at tempted on both eyes. T h e view of the right fundus was inadequate for evaluation; the left fundus was normal. On July 11, 1977, a combined penetrating keratoplasty and intraocular lens removal was performed on the right eye. At the time of surgery there was no flattening of the anterior chamber. The patient has done well postoperatively (Figs. 1-4). Case 2—A 75-year-old white woman underwent an intracapsular lens extraction and intraocular lens implantation with a four-loop Binkhorst-type lens on May 17, 1977. A Prolene suture was used to secure the two superior loops through the iridectomy. On the first postoperative day, a small amount of bleeding had occurred from the superior iridectomy, the implant was in good position, and the cornea was edematous. The hemorrhage cleared unevent fully. The corneal edema persisted despite normal intraocular pressures. At the time of referral (Oct. 14, 1977), the patient's best corrected visual acuity was R.E.: 6/120 (20/400); L.E.: 6/15 (20/50). The right eye had good color perception and appreciation of entoptic phe nomenon. The extraocular movements were normal. The left pupil was normal, and the right pupil was atonic and appeared slightly oval. Corneal sensitivi ty was minimally decreased on the right. On slitlamp examination of the right eye, the conjunctiva was normal, the cornea showed diffuse epithelial
AMERICAN JOURNAL O F OPHTHALMOLOGY 86:157-161, 1978
157
158
AMERICAN JOURNAL OF OPHTHAMOLOCY
AUGUST, 1978
•' "V
Fig. 1 (Sugar, Burnett, and Forstot). Case 1, Scan ning electron micrograph shows overall view of suture medallion lens removed from right eye. The superior pole of the lens is in the foreground. An irregularity of the lens surface surrounding the fixation suture apertures (arrows) is not apparent elsewhere on the lens. Bar graph = 1.1 mm (x 17).
edema, eorneal stromal thickness was 0.64 nun, and there were 2+ striae. The anterior chamber was deep except for a peripheral anterior synechia at the 10 o'clock position. The pupil was eccentric toward this area. Vitreous was present between the lens and iris at this position as well, but was not protruding into the anterior chamber. The lens was in the iris
Fig. 2 (Sugar, Burnett, and Forstot). Case 1 (detail from Figure 1), Hole for fixation suture appears in the right foreground (arrow). The smooth lens surface is at the upper left (open arrows). The inter vening area depicts cellular structures in cluster (x 100).
Fig. 3 (Sugar, Burnett, and Forstot). Case 1, Scan ning electron micrograph of cells adherent to the anterior surface of intraocular lens removed from patient. Individual cells are best shown where they are artifactually separated from surrounding cells at the cell junctions (arrows). Cells range from 8 to 14 (i in diameter (x 1,000).
plane; however, minimal iridodonesis was noted and there was no lens-corneal contact. The intraocu lar pressure was 14 mm Hg as measured by Mackay-Marg applanation tonometry. The retina was attached. The macula could not be seen well enough to determine whether cystoid changes were present or not. In the left eye the conjunctiva was normal. The cornea was clear with a thickness of 0.50 mm. Rare pigment deposits but no cornea guttata were ob served. The anterior chamber was deep and clear, and the lens showed moderate nuclear sclerosis. The left fundus was normal. On Dec. 5, 1977, a penetrating kerato.pla.sty and intraocular lens removal were performed on the right eye. At the time oi surgery there was no flattening of the anterior chamber. Following the penetrating keratoplastv, the patient has done well (Figs. 5-9). M A T E R I A L AND M E T H O D S
Case 1—The eorneal specimen and in traocular lens were placed in Trumps fixative. The cornea was routinely proc essed for light microscopy. The intraocu-
VOL. 86, NO. 2
INTRAOCULAR LENS AND ENDOTHELIAL CELLS
Tig. 4 ^Sugai, Burnett, and I'oistot). Cast- 1, Scan ning electron micrograph depicts endothelial cells (asterisks) surrounded by membranous structure on surface of intraocular lens removed from anterior chamber eight months after implantation. Note ad vancing edge of membrane (arrows) (x 1,000).
lar lens was prepared for scanning elec tron microscopy first by air-drying and then by coating the anterior surface with gold using the Polaron DC sputterer. Case 2—The cornea and intraocular
159
Fig. 6 (Sugar, Burnett, and Forstot). Case 2, Scan ning electron micrograph of flattened endotheli al cells adherent to anterior surface of removed in traocular lens (detail of area shown in Figure 5) (x 2,000).
lens were fixed immediately after removal in 2.5% glutaraldehyde with phosphate buffer. The lens and cornea were criticalpoint dried in a series of graded alcohols ascending to 100%. They were then coat ed in the Polaron DC sputterer and exam ined with the scanning electron micro scope. RESULTS
Case 1—CORNEA—The corneal speci men was examined by light microscopy. The epithelium was largely absent. There was edema of the stroma. Descemet's membrane was slightly thickened and focally laminated. The endothelium was absent. INTRAOCULAR LENS—Gross overview
Fig. 5 (Sugar, Burnett, and Forstot). Case 2, Scan ning electron micrograph of four-loop Binkhorsttype lens removed seven months after insertion. Area seen in detail in Figure 6 is indicated as A. Similar cell formations were found in areas B and C (X 20).
of the intraocular lens at x 17 magnifica tion (Fig. 1) showed a large area of sur face irregularity. A higher power view, at 100 x magnification, revealed (Fig. 2) a patchy area of irregularity near the hole in the lens for suture placement. Still higher magnification, at x 1,000 (Figs. 3 and 4), showed the area to be clumps of endothe-
160
AMERICAN JOURNAL OF OPHTHAMOLOGY
Kig. 7 iSug.ii. Bimicll. .IIKI Forstot). Case 2, Endo thelial surface of excised corneal button. The cut edges of epithelium (A), stroma (B), and Descemet's membrane (C) are well demonstrated. The solid arrows point to a portion of Descemet's membrane that is completely denuded of endothelial cells. Open arrows indicate areas of relatively intact endo thelial cells (x 16).
■J9 ;
Fig. 8 (Sugar, Burnett, and Forstot). Case 2, Rela tively normal appearing, although greatly enlarged and thinned, endothelial cells on cornea. Note that cell junctions are adherent in some areas (arrows) and separated in others (x 640).
A U G U S T , 1978
Fig. 9 (Sugar, Burnett, and Forstot). Case 2, En larged degenerating endothelial cells from patient with persistent bullous keratopathy following intra ocular lens implantation. Descemet's membrane is devoid of endothelium in four areas (arrows) (x 600).
Hal cells. Some of the cells appeared to have undergone fibroblastic metaplasia. Surrounding these cells and seemingly insinuated underneath them (Fig. 5) was an irregular membranous structure that appeared to be basement membrane pro duced by the cells or perhaps cytoplasm of endothelial cells. Case 2—INTRAOCULAR LENS—An overview at x 20 magnification showed multiple small collections of material on the anterior surface of the lens (Fig. 5). A higher magnification, x 2,000 (Fig. 6), showed these to be cells with the same configuration as those seen in Figure 3. The cells were separated at their junc tions, which may represent a fixation arti fact or the result of a natural process. CORNEA—As expected, there were ar eas completely devoid of endothelial cells (Fig. 7, arrow) and areas where the endo thelial cells appeared relatively intact (Fig. 8). In a transition zone, intermediate degenerative changes were seen in the
VOL. 86, NO. 2
INTRAOCULAR LENS AND E N D O T H E L I A L C E L L S
endothelial cells (Fig. 9). Similarities were noted between the cells seen on the cornea (Fig. 9) and those seen on the intraocular lens (Fig. 6) in this case. DISCUSSION
In Case 1, endothelial cells that appear to be producing basement membrane were seen on an intraocular lens removed eight months after implantation. Because endothelial cells are in a relatively normal array and are apparently producing base ment membrane, this suggests that these cells were viable and were present for a relatively prolonged period of time on the intraocular lens. In Case 2, apparently viable cells were similarly adherent to the intraocular lens. In both cases these cells apparently adhered to the lens during surgical implantation. Our findings con firm those of Kaufman and Katz 4 and further demonstrate the importance of avoiding endothelial-lens contact during lens implantation to preclude postopera tive corneal edema. This agrees with our previous study 3 and the investigations of Nordlohne, 5 in which he implied that the major cause of corneal edema subsequent
to intraocular lens implantation implant-endothelial contact. 1
161
is
SUMMARY
Scanning electron microscopic evalua tion of two intraocular lenses removed at keratoplasty for pseudophakic bullous keratopathy demonstrated apparently via ble endothelial cells adherent to their surfaces. These presumably adhered to the lens implants at the time of their insertion and confirm this as a mechanism for endothelial damage and subsequent corneal edema from intraocular lens im plantation. REFERENCES 1. Bourne, W. M., and Kaufman, H. E.: Endothe lial damage associated with intraocular lenses. Am. J. Ophthalmol. 81:482, 1976. 2. Forstot, S. L., Blackwell, W. L., Jaffe, N. S., and Kaufman, H. E.: Effect of intraocular lens implanta tion on the corneal endothelium. Trans. Am. Acad. Ophthalmol. Otolaryngol. 83:195, 1977. 3. Sugar, J., Mitchelson, J., and Kraff, M.: Endo thelial trauma and endothelial cell loss from intraoc ular lens insertion. Arch. Ophthalmol. 93:449,1978. 4. Kaufman, H. E., and Katz, J. I.: Endothelial damage from intraocular lens insertion. Invest. Ophthalmol. 15:996, 1976. 5. Nordlohne, M. E.: The Intraocular Implant Lens. Baltimore, Williams and Wilkins, 1975, pp. 100-110.
