After cataract surgery, some lens epithelial cells (LECs) may proliferate and migrate from the anterior capsular margin onto the intraocular lens (IOL) to form a membranous sheet.1–8 With a poly(methyl methacrylate) (PMMA) IOL, such membranous proliferation occurs within 4 weeks of surgery in 40% to 80% of patients.3,5,7 The proliferation is less frequent with silicone IOLs, occurring in about 15% of patients within 2 weeks of surgery.3 Most membranes disappear within a few weeks and therefore do not affect visual acuity.3–8
It was recently reported that membranous proliferation of LECs occurs with hydrogel IOLs in about 30% to 70% of eyes.1–3 In some cases, proliferation persisted as long as 1 year postoperatively.1–3 Koch and coauthors1 report 11 eyes (5.6%) that required treatment because of visual symptoms, such as hazy vision, caused by occlusion of the visual axis. The incidence and extent of this membrane was examined in eyes with a PMMA, silicone, or hydrogel IOL. However, these variables were not determined in eyes with an acrylic IOL. We therefore conducted a prospective study to evaluate membranous proliferation on IOLs composed of acrylic, silicone, and PMMA.
Patients and methods
This prospective study comprised 87 eyes of 87 consecutive patients who had cataract surgery at Keio University between September 1999 and April 2000. Patients with ocular disease other than age-related cataract or diabetes mellitus were excluded. Informed consent was obtained from all patients.
In all cases, the surgical technique included a scleral tunnel incision, 5.5 mm continuous curvilinear capsulorhexis (CCC), phacoemulsification and aspiration, and in-the-bag IOL implantation. The patients were randomly assigned to receive 1 of 3 types of IOLs: single-piece PMMA (UV-60SB, Hoya), 3-piece silicone (SI-40, Allergan Medical Optics), or 3-piece acrylic (AcrySof® MA60BM, Alcon Laboratories). These IOLs had a 6.0 mm diameter optic.
Patients who developed intraoperative complications such as posterior capsule rupture were excluded from the study. Eyes in which the margin of the anterior capsule did not completely cover the rim of the IOL optic because of excessive diameter or deviation of the CCC were also excluded.
Postoperatively, all patients received topical ofloxacin (0.3%), betamethasone (0.1%), and diclofenac (0.1%) 3 times daily for 2 months.
The pupil was dilated with tropicamide to allow examination of the IOL optic by slitlamp microscopy 1 and 10 days and 1, 2, and 3 months postoperatively. If proliferation was observed at 3 months, follow-up was continued every 3 months until the membranous proliferation disappeared. Any patient with a follow-up shorter than 2 months was excluded from the study.
The observation of membrane-like cell proliferation onto the IOL optic from the anterior capsule margin was regarded as membranous proliferation of LECs (Figure 1). 1–5 The extent of this proliferation was assessed using a clock-face representation of the IOL optic as the number of hours in which LECs could be identified (Figure 2). The duration was defined as the number of days from the day the membranous proliferation was first observed to the day it resolved.
Data are presented as means ± SD. Differences in age among the 3 groups were evaluated by a 1-way analysis of variance. Differences in the sex of the patients and the incidence of membranous proliferation of LECs were evaluated by the chi-square test. Differences in the extent and duration of the membranous proliferation of LECs were evaluated by the Kruskall-Wallis and Bonferroni tests. A level of P < .05 was considered statistically significant.
No intraoperative complications occurred. Thirteen eyes were excluded from the study because the rim of the IOL optic was incompletely covered by the anterior capsule margin. After this exclusion, the frequency and other features of membranous LEC proliferation on the IOL optic was evaluated in 74 eyes; 25 eyes had an acrylic IOL, 25 had a PMMA IOL, and 24 had a silicone IOL. Table 1 shows the patients' background information. The 3 groups showed no significant difference in age (P = .331,) or sex (P = .271). No severe postoperative complications were noted during follow-up. All patients exhibited good postoperative visual acuity (20/25 or better).
Membranous proliferation occurred within 1 month after surgery in some cases with each type of IOL. During the first 3 months, membranous proliferation of LECs on the surface of the IOL optic was noted in 18 of 25 eyes with an acrylic IOL, 9 of 25 with a PMMA IOL, and 6 of 24 with a silicone IOL. The occurrence was greater with the acrylic IOL than with the other types (P = .0024). The incidence of membranous proliferation peaked between 10 days and 1 month postoperatively and then decreased (Figure 3). There was a significant difference in the incidence of membranous proliferation among the 3 types of IOLs 10 days (P = .0029) and 1 month (P = .0051) postoperatively.
The membranous proliferation disappeared completely within 2 months after surgery on the silicone IOLs and within 3 months on all PMMA IOLs. Proliferation still was present on acrylic IOLs in 4 of 18 eyes at 3 months. Among these 4 eyes, membranous LEC proliferation persisted in 3 eyes at 6 months and in 1 eye at 9 months. At 12 months, all membranous LEC proliferation had completely resolved. The duration of LEC proliferation with the acrylic IOL was significantly longer than with the other 2 IOL types (Figure 4).
The extent of membranous proliferation of LECs peaked between 10 days and 1 month postoperatively (Figure 5). A significant difference was noted in the extent of proliferation among the 3 IOL types at 10 days (P = .0021, Kruskall-Wallis) and 1 month (P = .0073, Kruskall-Wallis). The extent of proliferation on the acrylic IOL was greater than that on the PMMA or silicone IOLs at 10 days. Proliferation was more extensive on acrylic IOLs than on the silicone IOLs at 1 month. However, by 3 months, the prevalence and extent of membranous LEC proliferation on acrylic IOLs decreased (Figures 3 and 5).
Although we found membranous LEC proliferation on all 3 IOL materials, its incidence was significantly higher on the acrylic IOLs. Membranous LEC proliferation on acrylic IOLs persisted longer than on the other 2 types. Proliferation on the acrylic IOLs was more extensive than on the PMMA IOLs 10 day postoperatively and the silicone IOLs at 10 days and 1 month. However, by the third postoperative month, LEC proliferation on all 3 types of IOL had decreased in most cases, and proliferation did not disturb visual acuity.
The incidence and extent of membranous LEC proliferation observed on the PMMA and silicone IOLs in our study are consistent with results in previous reports.3–8 The membranous proliferation on the IOLs did not disturb visual acuity.3–8 It has been reported that membranous proliferation of LECs occurs in 40% to 70% of eyes with a hydrogel IOL.1–3 Some patients had persistent proliferation leading to visual symptoms (eg, hazy vision) caused by occlusion of the visual axis.1 Although in our study the extent of membranous proliferation of LECs on the acrylic IOLs was more severe than on the silicone and PMMA IOLs at 1 month postoperatively, the LECs tended to decrease and did not disturb visual acuity.
In rabbit LECs, extracellular matrix constituents such as fibronectin, type IV collagen, and laminin promote the in vitro adhesion and migration of LECs.9 Of these extracellular matrixes, fibronectin promotes the maximal migration of LECs, whereas type IV collagen promotes the maximal adhesion of LECs in vitro. Fibronectin is present in the aqueous humor of patients with cataract.10 Fibronectin is adsorbed by IOL materials such as silicone, acrylic, and PMMA.11–13 Differences in the affinity of these extracellular matrixes for these IOL materials have been reported.14,15 Fibronectin binds better to acrylic and PMMA IOLs, while laminin binds better to acrylic IOLs.14,15 The greater incidence and extent of the membranous proliferation of LECs on acrylic IOLs than on the other 2 types of IOL materials in our study may reflect a greater affinity of these extracellular matrixes for this IOL, which promotes LEC adhesion and migration.
The cellular reaction on the anterior surface of IOLs mainly involves 3 types of cells: small, large, and lens epithelial.16–18 The first 2 types are inflammatory cells that are related to the foreign-body response to the IOL.16–18 The present study examined only the LECs. However, it has been reported that of acrylic, silicone, and PMMA IOLs, silicone IOLs have more small cells and acrylic IOLs exhibit fewer giant cells.16 These findings suggest that the biocompatibility of the acrylic IOL is superior to that of silicone or PMMA IOLs.16 Hollick and coauthors3 report that hydrogel IOLs have fewer inflammatory cells on the surface than PMMA or silicone IOLs and that they have greater membranous proliferation of LECs. Membranous proliferation on hydrogel IOLs may persist as long as 1 year postoperatively. Patients with hydrogel IOLs with no membranous proliferation of LECs show a greater breakdown in the blood-aqueous barrier than patients with membranous proliferation of LECs. Improved biocompatibility leads to a greater membranous proliferation of LECs on the IOL for a longer period. The better biocompatibility of the acrylic IOL may be responsible for the higher incidence and extent of membranous proliferation of LECs for a longer period, as observed in our study.
In conclusion, we observed membranous LEC proliferation on IOLs made of silicone, PMMA, and acrylic. The incidence, duration, and extent of this proliferation were significantly higher with the acrylic IOLs. However, the LECs on the IOLs eventually decreased and did not disturb visual acuity.
1. Koch MU, Kalicharan D, van-der-Want JJL. Lens epithelial cell layer formation related to hydrogel foldable intraocular lenses. J Cataract Refract Surg 1999; 25:1637-1640
2. Lenis K, Philipson B. Lens epithelial growth on the anterior surface of hydrogel IOLs; an in vivo study. Acta Ophthalmol Scand 1998; 76:184-187
3. Hollick EJ, Spalton DJ, Ursell PG. Surface cytologic features on intraocular lenses; can increased biocompatibility have disadvantages? Arch Ophthalmol 1999; 117:872-878
4. Nagamoto T, Hara E. Postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. J Cataract Refract Surg 1995; 21:208-211
5. Ibaraki N, Ohara K, Miyamoto T. Membranous outgrowth suggesting lens epithelial cell proliferation in pseudophakic eyes. Am J Ophthalmol 1995; 119:706-711
6. Amon M, Menapace R, Radax U, Freyler H. In vivo study of cell reactions on poly(methyl methacrylate) intraocular lenses with different surface properties. J Cataract Refract Surg 1996; 22:825-829
7. Pande MV, Spalton DJ, Marshall J. In vivo human lens epithelial cell proliferation on the anterior surface of PMMA intraocular lenses. Br J Ophthalmol 1996; 80:469-474
8. Wolter JR. Continuous sheet of lens epithelium on an intraocular lens: pathological confirmation of specular microscopy. J Cataract Refract Surg 1993; 19:789-792
9. Olivero DK, Furcht LT. Type IV collagen, laminin, and fibronectin promote the adhesion and migration of rabbit lens epithelial cells in vitro. Invest Ophthalmol Vis Sci 1993; 34:2825-2834
10. Vesaluoma M, Mertaniemi P, Mannonen S, et al. Cellular and plasma fibronectin in the aqueous humour of primary open-angle glaucoma, exfoliative glaucoma and cataract patients. Eye 1998; 12:886-890
11. Chen G, Imanishi Y, Ito Y. Effect of protein and cell behavior on pattern-grafted thermoresponsive polymer. J Biomed Mater Res 1998; 42:38-44
12. Fabrizius-Homan DJ, Cooper SL. A comparison of the adsorption of three adhesive proteins to biomaterial surfaces. J Biomater Sci Polym Ed 1991; 3:27-47
13. Vaudaux PE, Waldvogel FA, Morgenthaler JJ, Nydegger UE. Adsorption of fibronectin onto polymethylmethacrylate and promotion of Staphylococcus aureus adherence. Infect Immun 1984; 45:768-774
14. Linnola RJ, Sund M, Ylönen R, Pihlajaniemi T. Adhesion of soluble fibronectin, laminin, and collagen type IV to intraocular lens materials. J Cataract Refract Surg 1999; 25:1486-1491
15. Johnston RL, Spalton DJ, Hussain A, Marshall J. In vitro protein adsorption to 2 intraocular lens materials. J Cataract Refract Surg 1999; 25:1109-1115
16. Hollick EJ, Spalton DJ, Ursell PG, Pande MV. Biocompatibility of poly(methyl methacrylate), silicone, and AcrySof intraocular lenses: randomized comparison of the cellular reaction on the anterior lens surface. J Cataract Refract Surg 1998; 24:361-366
17. Pande MV, Spalton DJ, Kerr-Muir MG, Marshall J. Cellular reaction on the anterior surface of poly(methyl methacrylate) intraocular lenses. J Cataract Refract Surg 1996; 22:811-817
18. Ravalico G, Baccara F, Lovisato A, Tognetto D. Postoperative cellular reaction on various intraocular lens materials. Ophthalmology 1997; 104:1084-1091