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Lens epithelial cell reaction after implantation of different intraocular lens materials
Lens Epithelial Cell Reaction after Implantation of Different Intraocular Lens Materials Two-Year Results of a Randomized Prospective Trial Daniele Tognetto, MD,1 Lisa Toto, MD,1 Giorgia Sanguinetti, MD,1 Paolo Cecchini, MD,1 Odilla Vattovani, MD,1 Stefano Filacorda, PhD,2 Giuseppe Ravalico, MD1 Purpose: To determine the influence of intraocular lens (IOL) material on anterior capsular opacification and membrane growth over the anterior IOL surface in patients who have undergone standardized small-incision cataract surgery and foldable IOL implantation in the capsular bag. Design: Randomized controlled trial. Participants: Eighty-eight cataract patients (88 eyes). Methods: Patients were randomly assigned to receive one of four different foldable IOLs after phacoemulsification: Storz Hydroview H60M, Corneal ACR6D, AMO SI40NB, and Alcon AcrySof MA60BM. Examinations on days 7, 30, 90, 180, 360, and 720 after surgery included ophthalmologic examination, slit-lamp biomicroscopy, and photography using red reflex and focal illumination of the anterior IOL surface. Main Outcome Measures: Best-corrected visual acuity was measured at each examination. In addition, the anterior capsule opacification and the membrane growth on the anterior IOL surface were graded according to a subjective method by the same researcher. Results: The fibrosis of the anterior capsule was more frequently observed in the group using Corneal ACR6D and AMO SI40NB. The Hydroview and ACR6D groups showed a higher percentage of cases with membrane growth from the rhexis edge on the anterior IOL surface. AcrySof showed the lowest presence of fibrosis of the anterior capsule, and no membrane growth was noted. Conclusions: Anterior capsule opacification is an index of IOL biocompatibility. The natural location of lens epithelial cells (LECs) precludes the possibility of the IOL’s design influencing the anterior capsule behavior. The local response of LECs varies according to the IOL studied. This may be related to the chemical and physical properties of the materials used in the different IOLs. Ophthalmology 2003;110:1935–1941 © 2003 by the American Academy of Ophthalmology.
Biocompatibility has been defined as the ability of a material to perform with an appropriate host response in a specific biologic application.1 The implanting of intraocular lenses (IOLs) after cataract surgery induces a foreign-body reaction to the IOL and a lens epithelial cells (LECs) response. Both these responses might present different patterns of cell reactivity and are generally considered as indicators of IOL biocompatibility.2–12 The inflammatory
Originally received: August 8, 2002. Accepted: March 21, 2003. Manuscript no. 220546. 1 Eye Clinic, University of Trieste, Trieste, Italy. 2 Department of Production Sciences, University of Udine, Udine, Italy. The authors have no proprietary or financial interest in any product or device discussed in this article, and they have not received any payment as reviewers or evaluators. Reprint requests to Daniele Tognetto, MD, Istituto di Clinica Oculistica, Universita` di Trieste, Ospedale Maggiore, Piazza Ospedale, 1 34129 Trieste, Italy. E-mail: [email protected]. © 2003 by the American Academy of Ophthalmology Published by Elsevier Inc.
cell reaction against the IOL material consists of macrophage-derived cells adhering to the anterior IOL surface. The LECs reaction is characterized by an early response, consisting of anterior capsule opacification (ACO) and membrane growth from the rhexis edge on the IOL surface, which is formed by a sheet of proliferated LECs. LECs proliferation and migration might later lead to posterior capsule opacification (PCO) and the appearance of Elschnig pearls. Histopathologic studies have shown that ACO is due to LEC metaplasia. Contact with IOL biomaterial causes LECs to undergo myofibroblastic changes and to produce extracellular matrix components.13–18 Membrane growth from the capsulorrhexis edge is related to LEC proliferation and migration, giving rise to a layer of cells and extracellular matrix covering the IOL optic.10,19 –24 Suggested risk factors for ACO and membrane growth include pseudoexfoliation syndrome, advanced age, diabeISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(03)00736-X
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Ophthalmology Volume 110, Number 10, October 2003 tes mellitus, uveitis, myopia, pigmentary retinal degeneration, capsulorrhexis size, and IOL design and material.9,11,12,15,21,25– 41 On very rare occasions, ACO and membrane growth can influence visual acuity.25,42,43 IOL dislocation can follow a severe ACO and phimosis.27,40 Anterior neodymium:yttrium–aluminum– garnet laser capsulotomy might be required in cases of severe capsule constriction. In addition, severe ACO impedes the examination or treatment of the peripheral retina.21,40 The aim of our study was to evaluate the influence of different IOL materials on LECs response after phacoemulsification and capsular bag IOL implantation.
Material and Methods A randomized controlled study was carried out. Approval by the Ethics Committee was obtained. Eighty-eight consecutive cataract patients (88 eyes), referred to our Eye Clinic from January to December 1998, were recruited for the study, and informed consent was obtained. All patients underwent a standardized smallincision phacoemulsification with in the capsular bag IOL implantation. Exclusion criteria were other eye diseases, such as glaucoma, uveitis and pseudoexfoliation; previous anterior or posterior segment surgery; intraoperative or postoperative complications; diabetes mellitus; and systemic therapy with antiinflammatory drugs. Each patient was randomly assigned to receive one of four different foldable IOLs: Storz Hydroview H60M (group 1, 25 patients), Corneal ACR6D (group 2, 24 patients), AMO SI40NB (group 3, 18 patients), and Alcon AcrySof MA60BM (group 4, 21 patients). The randomization list was generated by random permutation of the four IOLs in each consecutive block. All lenses are on the market in Europe. Corneal ACR6D lenses are not on the market in the United States; Hydroview lenses have been available in the United States since 2001; AcrySof have been on the market in the United States since 1994. AMO SI40 have been on the market in the United States since 1995. Surgeries were uneventful. All the operations were performed by the same surgeon (DT) with the same technique: a 4.5 to 5 mm capsulorrhexis was carried out after performing a 3.2-mm nearclear corneal incision (0.5 mm behind the limbal vascular arcade). This was followed by a phacofracture in the capsular bag and automated irrigation/aspiration of the cortical remnants. The IOL was implanted in the capsular bag, and the incision sutured with a single 10-0 nylon stitch. Healon GV (Pharmacia & Upjohn, Uppsala, Sweden) was used before performing capsulorrhexis and Provisc (Alcon, Inc., Fort Worth, TX) before the IOL implantation. All patients received the same preoperative and postoperative treatment. Sodium diclofenac, 0.1%, and ofloxacin, 0.3%, eyedrops were instilled four times both the day before and on the morning of surgery. The pupil was dilated with topical 0.5% tropicamide and 10% phenylephrine. At the conclusion of surgery, 4 mg betamethasone was administered subconjunctivally. After surgery, dexamethasone 0.2% eyedrops were instilled four times daily for 2 weeks and then sodium diclofenac 0.1% eyedrops four times daily for 2 months. Six of the 88 patients recruited in the study dropped out because they missed a check-up despite several reminders in writing and by telephone. Twenty-three of the remaining 82 patients belonged to group 1 (Storz Hydroview), 24 to group 2 (Corneal ACR6D), 18 to group 3 (AMO SI40NB), and 17 to group 4 (Alcon AcrySof). Mean age
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Table 1. Grading of Anterior Capsule Fibrosis Grade
Anterior Capsule Fibrosis
0 1
Capsular transparence Moderate: Mild opacification not involving the whole capsule over the IOL optic Severe: Complete whitening of the capsule over the IOL optic, not allowing the visualization of the posterior structures
2
IOL ⫽ intraocular lens.
was 75.1 ⫾ 8.6 years (range, 57– 89 years) in the Storz Hydroview group, 75.9 ⫾ 11.0 years (range, 42– 86 years) in the Corneal ACR6D group, 74.2 ⫾ 10.4 years (range, 41– 84 years) in the AMO SI40NB group, and 68.6 ⫾ 7.6 years (range, 58 – 81 years) in the Alcon AcrySof group. Patients were examined 7, 30, 90, 180, 360, and 720 days after surgery. All the patients in each group who concluded the study completed all of the required visits. The best-corrected visual acuity (BCVA) was measured at each postoperative ophthalmologic examination. After dilating the pupil, the anterior IOL surface was studied. The first step was the observation of the entire anterior IOL surface by slit-lamp biomicroscopy, also using the specular technique to identify membranous growth from the capsular edge and ACO. Photographs of the anterior IOL surface were taken by means of slit-lamp photography using red reflex and focal illumination. Slide film was used, and at least three slides from each patient were studied at each examination. All findings were graded by the same observer not masked to the IOL type, because the IOL design could be identified during examination. ACO and membrane growth on the anterior IOL surface were graded as shown in Tables 1 and 2. The results concerning the anterior capsule were expressed in two ways: (1) the percentage of IOLs with either ACO or membrane growth on the anterior IOL surface at a given postoperative examination; (2) the average grade of both aspects at each examination. Statistical analysis was carried out by comparing the presence and the grade of ACO and membrane growth at 7, 30, 90, 180, 360, and 720 days. The patients’ ages were expressed as mean age ⫾ standard deviation and analyzed using the t test. The Mann–Whitney test was used to compare BCVA expressed as median and range. The n-way frequency and cross-tabulation tables with measures of association (proc freq/measures, SAS [SAS Institute Inc., Cary, NC], 1988) were used to compare the presence of ACO and membrane growth in the four groups. The analysis of variance test for repeated measurements (proc glm, SAS, 1988) was used to compare the average grades of ACO and membrane growth in the four groups.
Table 2. Grading of Membrane Growth from the Capsulorrhexis Edge over the Intraocular Lens Optic Grade
Membrane Growth from the Capsular Edge
0 1 2 3
Absence Mild: membranes extending less than 90° Moderate: membranes extending from 90° to 180° Severe: membranes present over 360°
Tognetto et al 䡠 Lens Epithelial Cell Reaction
Figure 1. Percentage of intraocular lenses with anterior capsule opacification at 7, 30, 90, 180, 360, and 720 days after implantation. The differences between the groups reached statistical significance starting from the 30-day examination up to the 720-day examination (P ⬍ 0.001) (n-way frequency and cross-tabulation tables with measures of association).
Results The groups were not significantly different in age and BCVA. At the 7-day and 720-day examination, the median BCVA was 0.9 in the Corneal ACR6D, AMO SI40NB, and Storz Hydroview H60M groups, whereas it was 1.0 in the Alcon AcrySof group. The percentage of patients with ACO increased continuously over time in the Corneal ACR6D and AMO SI40NB groups. In the Alcon AcrySof and in the in Storz Hydroview H60M groups, it increased up to 180 days and 360 days after surgery, respectively, subsequently stabilizing (Fig 1). At 720 days after surgery, ACO was present in 39.13% of IOLs of group 1 (Storz Hydroview H60 M), 100% of group 2 (Corneal ACR6D), 100% of group 3 (AMO SI40NB), and 29.41% of group 4 (Alcon AcrySof MA60BM). The differences between the groups reached statistical significance starting from the 30-day examination up to the 720-day examination (n-way frequency and crosstabulation tables with measures of association P⬍0.001) (Fig 1). The mean grade of the anterior capsule fibrosis increased during the entire follow-up in the Corneal ACR6D and AMO SI40NB groups. In the Alcon AcrySof and Storz Hydroview H60M groups, it increased, respectively, up to 180 days and 360 days after surgery, subsequently stabilizing (Fig 2, Table 3). Considering all the groups studied, a significant effect of time on ACO formation was observed (P⬍0.0001) (Table 3). The type of IOL had a significant effect on the grade of ACO. At the first examination, the average grade of ACO was significantly higher in the Corneal ACR6D group than the Storz Hydroview H60M, AMO SI40NB, and Alcon AcrySof groups (P⬍0.001). Starting from the 30-day examination and throughout the study, the Corneal ACR6D and AMO SI40NB groups showed a higher average grade of ACO than the other two groups. This difference reached statistical significance (P⬍0.0001) (Table 3). At the 30-day and 90-day examinations, the mean grade of ACO was statistically higher in the AMO SI40NB group than in the Corneal ACR6D group (P⬍0.001) (Fig 2, Table 3). The percentage of IOLs with membrane outgrowth from the capsulorrhexis edge onto the anterior IOL surface increased over time in the Storz Hydroview and the Corneal ACR6D groups up to 360 days after surgery, subsequently stabilizing. At the 720-day
Figure 2. Mean grade of anterior capsule opacification (ACO) at 7, 30, 90, 180, 360, and 720 days after surgery. The Corneal ACR6D and AMO SI40NB groups showed a higher average grade of than the other two groups. This difference reached statistical significance (P ⬍ 0.0001). At the 30-day and 90-day examinations, the mean grade of ACO was statistically higher in the AMO SI40NB group than the Corneal ACR6D group (P ⬍ 0.001) (analysis of variance test for repeated measurements).
examination, it was 86.96% in the Hydroview group and 91.67% in the Corneal ACR6D group. The percentage of patients with membrane growth in the AMO SI40NB group peaked at the 30-day examination (16.67%) and dropped by the 90-day and 180-day examinations (5.56%). Then the membranes disappeared. No patient of the AcrySof group showed membrane growth during the entire follow-up period (Fig 3). The difference between the groups was found to be statistically significant (P⬍0.001). The mean grade of membrane growth increased up to 360 days after surgery in the Hydroview and Corneal groups and then became stable, whereas starting from 90 days after surgery, the AMO SI40NB group showed a decrease in the average grade of membranes, which disappeared completely after 360 days (Fig 4, Table 4). The type of IOL had a significant effect on the grade of membrane proliferation. Starting from the 30-day examination, the Corneal ACR6D and Hydroview groups showed a higher average grade of membrane outgrowth compared with the AcrySof and AMO SI40NB groups. This difference reached statistical significance (P⬍0.0001) (Table 4). Time was observed to have a considerable effect on membrane growth, with an increased growth in the Hydroview and Corneal groups and disappearing in the AMO SI40NB group (P⬍0.0001) (Table 4).
Discussion LECs’ response is an index of IOL biocompatibility. The LECs’ response originates from the LECs that remain beneath the anterior capsule after surgery and is characterized by ACO and membrane growth onto the IOL optic. In this study, ACO was observed in a higher percentage of patients with AMO SI40NB silicone IOL and Corneal ACR6D hydrophilic IOL, with a dense development of fibrosis in both groups. Previous studies described the onset
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Ophthalmology Volume 110, Number 10, October 2003 Table 3. Grade of Anterior Capsule Opacification at 7, 30, 90, 180, 360, and 720 Days After Surgery (Mean and Standard Error) Intraocular Lens Corneal—ACR6D Alcon—Acrysof Storz—Hydroview AMO—SI40NB Effect of time Effect of IOL
7 Days
Standard Error
30 Days
Standard Error
90 Days
Standard Error
0.16a 0.00b 0.00b 0.00b
0.04 0.05 0.04 0.04
0.66b 0.00c 0.17c 1.11a
0.13 0.16 0.13 0.15
0.91b 0.17c 0.34c 1.44a
0.15 0.18 0.16 0.18
180 Days
1.66a 0.35b 0.43b 1.61a 0.0001 0.0001
Standard Error
360 Days
Standard Error
720 Days
Standard Error
0.13 0.16 0.13 0.15
1.66a 0.35b 0.69b 1.66a
0.14 0.17 0.15 0.17
1.83a 0.35b 0.69b 1.77a
0.12 0.15 0.13 0.14
IOL ⫽ intraocular lens. In the same column, the estimated means marked with different letters are significantly different (P ⬍ 0.05). Considering all the groups studied, a significant effect of time on anterior capsule opacification formation was observed.
of ACO after silicone IOL implantation.26,40,41 Georgopoulos et al36 reported the presence of a pronounced fibrosis of the anterior capsule in eyes implanted with a silicone IOL, causing the shrinkage of the capsulorrhexis opening. We observed that membrane growth from the rhexis edge on the anterior IOL surface is more frequent in Storz Hydroview H60M and ACR6D groups. These results confirm the findings of previous studies reporting the growth of an LEC monolayer on the anterior surface of the hydrophilic Hydroview IOL.21,41 Hydrophilic acrylic material seems to be a good scaffold for the growth of epithelial cells.10 –12 To our knowledge there are no data regarding LECs’ behavior in the Corneal ACR6D IOL. This is a hydrophilic IOL with a different level of hydration than Hydroview. The water content is 18% in Hydroview and 26% in ACR6D. This study has revealed the presence of both severe ACO and membrane outgrowth in Corneal IOLs. This finding demonstrates that different hydrophilic materials can cause a specific LEC reaction. The definition of a material as
Figure 3. Percentage of intraocular lenses (IOLs) with membrane growth over the IOL optic at 7, 30, 90, 180, 360, and 720 days after implantation. The percentage of IOLs with membrane outgrowth from the capsulorrhexis edge onto the anterior IOL surface increased over time in the Storz Hydroview and in the Corneal ACR6D groups up to 360 days after surgery. No patient of the AcrySof group showed membrane growth. The difference between the groups was found to be statistically significant (P ⬍ 0.001) (n-way frequency and cross-tabulation tables with measures of association).
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hydrophilic is no longer sufficient to describe the biocompatibility of an IOL. In addition, we noticed the disappearance of small membranes on the AMO SI40NB at the 360-day examination. This is consistent with the finding of Hollick et al,44 describing posterior LECs’ regression with silicone, polymethyl methacrylate and AcrySof IOL. From our data, Alcon AcrySof MA60BM showed the lowest presence of fibrosis of the anterior capsule and no membrane growth. Other authors have reported results consistent with our findings.12,21,26,40 Ursell et al45 reported an anterior capsule stability in eyes implanted with the AcrySof IOL with less incidence of IOL decentration and capsular phimosis. Several factors regarding blood–aqueous barrier (BAB) breakdown, surgical technique, and IOL characteristics have been considered to influence LECs’ response. Some authors believe that inflammatory mediators, either serum-derived after BAB damage or synthesized by macrophages and LECs, can stimulate LEC proliferation and migration.15–17,46 Conversely, it has also been suggested
Figure 4. Mean grade of membrane growth at 7, 30, 90, 180, 360, and 720 days after surgery. The Corneal ACR6D and Hydroview groups showed a higher average grade of membrane outgrowth than the AcrySof and AMO SI40NB groups. This difference reached statistical significance (P ⬍ 0.0001) (analysis of variance tests for repeated measurements).
Tognetto et al 䡠 Lens Epithelial Cell Reaction Table 4. Grade of Membrane Growth at 7, 30, 90, 180, 360, and 720 Days After Surgery (Mean and Standard Error) Intraocular Lens Corneal—ACR6D Alcon—Acrysof Storz—Hydroview AMO—SI40NB Effect of time Effect of IOL
7 Days
Standard Error
30 Days
Standard Error
90 Days
Standard Error
0.91a 0.00c 0.47b 0.16bc
0.12 0.14 0.12 0.14
1.08a 0.00b 1.00a 0.22b
0.13 0.16 0.14 0.15
1.33a 0.00b 1.26a 0.05b
0.14 0.16 0.14 0.16
180 Days
1.62a 0.00b 1.43a 0.05b 0.0001 0.0001
Standard Error
360 Days
Standard Error
720 Days
Standard Error
0.14 0.17 0.14 0.16
1.83a 0.00b 2.21a 0.00b
0.14 0.17 0.15 0.17
1.83a 0.00b 2.21a 0.00b
0.14 0.17 0.15 0.17
IOL ⫽ intraocular lens. In the same column, the estimated means marked with different letters are significantly different (P ⬍ 0.05). Considering all the groups, time was observed to have a significant effect on membrane growth.
that reduced BAB damage is associated with an increased LEC proliferation, leading to LEC outgrowth on the anterior surface.11 No clinical differences in BAB disruption between the groups were observed in this study, and no cases of excessive postoperative inflammation were noted, although we did not measure the anterior chamber cell reaction by means of a laser flare cell meter. ACO occurs in the part of the anterior capsule that is in contact with the anterior surface of the IOL. When the capsulorrhexis is smaller than the IOL optic, the contact of the IOL optics’ material with the anterior capsule induces ACO formation. It has been suggested that the smaller the capsulorrhexis diameter and the larger the area of contact between LECs and the IOL optic, the more severe the ACO to be expected.34 –37 Several authors believe that capsulorrhexis size cannot influence the amount or severity of LEC proliferation but agree that the contact between the capsular edge and the IOL optic is necessary for membrane growth.10,38 In this study, all patients had a capsulorrhexis slightly smaller than the IOL optic, and the capsular edge was in contact with the anterior IOL surface, as is normal practice in our procedure. We demonstrated that this condition might reduce the PCO.47 In our series, no patients had capsular shrinkage or a rhexis that was too small compared with the IOL optic diameter. IOL design has been demonstrated to be one of the main factors influencing PCO.48 –51 Werner et al26,40 suggested that there could be a correlation between IOL design, especially haptic design, and ACO. A higher rate of ACO in plate haptic silicone lenses was observed, suggesting that the large area of contact between LECs and plate haptic lenses stimulates cell proliferation and fibrosis. Schauersberger et al21 found that the sharp-edged optic design has no influence on anterior lens outgrowth. We believe that the IOL design could have not affected LECs’ response in our series. The area of contact between the anterior capsule and the IOL is similar in the four IOLs studied. Moreover, the shape of the optic edge cannot be implicated in ACO and membrane growth development, because the physiologic site of LECs is beneath the anterior capsule and at the equator of the lens. After capsulorrhexis has been performed, part of the anterior capsule covers the IOL optic, and LECs lie directly over the IOL. ACO and membrane outgrowth derive from these cells. Migration of LECs from the equator, as occurs in PCO, is not needed.
Several authors recognize a correlation between the surface tension of the IOL and cell adherence.5,9,52–54 The contact angle is a measure of the surface tension and expresses only the relative hydrophilicity or hydrophobicity of an IOL surface. According to Dick et al,55 the contact angle of AMO SI40NB is different than that of Corneal ACR6D (106.2 versus 64.3 angle °). In our study, these two lenses showed a similar severe ACO development. From this example it can be argued that the relative hydrophilicity or hydrophobicity of an IOL surface seems not to be sufficient to explain the anterior LECs’ behavior in relation to the type of IOL biomaterial. It is well known that within a few minutes of an IOL implantation a protein biofilm deposits on the anterior surface. This layer is composed of different proteins, such as albumin, complement C3, immunoglobulin G, fibrin, collagen type IV, fibronectin, laminin, and vitronectin. Cell adhesion molecules on LECs can bind to this protein scaffold and could affect LEC adhesion, migration, and proliferation.56 – 61 Recent studies have demonstrated that the biomaterial could influence this protein absorption on the IOL surface.62,63 The composition of this film differs according to the chemical composition of the material. It has been demonstrated that AcrySof IOLs adsorb more fibronectin and laminin on their surface than other biomaterials.62– 66 We speculate that, because biomaterial chemistry can determine differential absorption of proteins on IOL surfaces, a specific material-induced relationship between the cell adhesion molecules of the LECs and this proteins occurs. The type of relationship is peculiar to each material, with consequent variable behavior of LECs. The expression of this phenomenon, which takes the form of varying degrees of cell adhesion, spreading, and proliferation onto the lens optic, causes the different clinical patterns observed in IOLs made of different materials. The disappearance of membranes in the silicone IOL we observed could be explained by a protein scaffold peculiar for the silicone optic IOLs, which might be inadequate for the continuing growth of LECs. In conclusion, in eyes without any known risk factor for ACO and membrane formation, the main factor involved in anterior LECs’ proliferation and metaplasia seems to be the relationship between LECs and the IOL biomaterial. The study of anterior LECs’ behavior is crucial, because
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Ophthalmology Volume 110, Number 10, October 2003 it can give us a precise idea of the response of LECs to the IOL material. No other factors affect this response, and it is also crucial to assess the role of the material in influencing the development of PCO. PCO is influenced by several factors, such as surgical technique, cortical cleanup, concomitant eye diseases, IOL material, and IOL design and placement,67 but the role of the material in the LECs’ response can be assessed from the behavior of the anterior LECs themselves.
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18. Kurosaka D, Kato K, Nagamoto T. Presence of alpha smooth muscle actin in lens epithelial cells of aphakic rabbit eyes. Br J Ophthalmol 1996;80:906 –10. 19. Nagamoto T, Hara E, Kurosaka D. Lens epithelial cell proliferation onto the intraocular lens optic in vitro. J Cataract Refract Surg 1996;22(Suppl 1):847–51. 20. Ibaraki N, Ohara K, Miyamoto T. Membranous outgrowth suggesting lens epithelial cell proliferation in pseudophakic eyes. Am J Ophthalmol 1995;119:706 –11. 21. Schauersberger J, Amon M, Kruger A, et al. Lens epithelial cell outgrowth on 3 types of intraocular lenses. J Cataract Refract Surg 2001;27:850 – 4. 22. Wolter JR. Continuous sheet of lens epithelium on an intraocular lens: pathological confirmation of specular microscopy. J Cataract Refract Surg 1993;19:789 –92. 23. Ayaki M, Ohara K, Ibaraki N, et al. The outgrowth of lens epithelial cells onto the anterior capsule after intraocular lens implantation [letter]. Am J Ophthalmol 1993;115:668 –9. 24. Nagamoto T, Hara E. Postoperative membranous proliferation from the anterior capsulotomy margin onto the intraocular lens optic. J Cataract Refract Surg 1995;21:208 –11. 25. Davison JA. Capsule contraction syndrome. J Cataract Refract Surg 1993;19:582–9. 26. Werner L, Pandey SK, Escobar-Gomez M, et al. Anterior capsule opacification: a histopathological study comparing different IOL styles. Ophthalmology 2000;107:463–71. 27. Hayashi H, Hayashi K, Nakao F, Hayashi F. Anterior capsule contraction and intraocular lens dislocation in eyes with pseudoexfoliation syndrome. Br J Ophthalmol 1998;82:1429 – 32. 28. Hayashi H, Hayashi K, Nakao F, Hayashi F. Area reduction in the anterior capsule opening in eyes of diabetes mellitus patients. J Cataract Refract Surg 1998;24:1105–10. 29. Kato S, Suzuki T, Hayashi Y, et al. Risk factors for contraction of the anterior capsule opening after cataract surgery. J Cataract Refract Surg 2002;28:109 –12. 30. Abela-Formanek C, Amon M, Schauersberger J, et al. Results of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses in uveitic eyes with cataract: comparison to a control group. J Cataract Refract Surg 2002;28:1141–52. 31. Kurosaka D, Ando I, Kato K, et al. Fibrous membrane formation at the capsular margin in capsule contraction syndrome. J Cataract Refract Surg 1999;25:930 –5. 32. Hayashi K, Hayashi H, Matsuo K, et al. Anterior capsule contraction and intraocular lens dislocation after implant surgery in eyes with retinitis pigmentosa. Ophthalmology 1998; 105:1239 – 43. 33. Schauersberger J, Amon M, Kruger A, et al. Comparison of the biocompatibility of 2 foldable intraocular lenses with sharp optic edges. J Cataract Refract Surg 2001;27:1579 – 85. 34. Hayashi K, Hayashi H, Nakao F, Hayashi F. Reduction in the area of the anterior capsule opening after polymethylmethacrylate, silicone, and soft acrylic intraocular lens implantation. Am J Ophthalmol 1997;123:441–7. 35. Kimura W, Yamanishi S, Kimura T, et al. Measuring the anterior capsule opening after cataract surgery to assess capsule shrinkage. J Cataract Refract Surg 1998;24:1235– 8. 36. Georgopoulos M, Menapace R, Findl O, et al. Posterior continuous curvilinear capsulorrhexis with hydrogel and silicone intraocular lens implantation: development of capsulorrhexis size and capsule opacification. J Cataract Refract Surg 2001; 27:825–32. 37. Park TK, Chung SK, Baek NH. Changes in the area of the anterior capsule opening after intraocular lens implantation. J Cataract Refract Surg 2002;28:1613–7. 38. Gonvers M, Sickenberg M, van Melle G. Change in capsulor-
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rhexis size after implantation of three types of intraocular lenses. J Cataract Refract Surg 1997;23:231– 8. 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 –74. Werner L, Pandey SK, Apple DJ, et al. Anterior capsule opacification: correlation of pathologic findings with clinical sequelae. Ophthalmology 2001;108:1675– 81. Abela-Formanek C, Amon M, Schild G, et al. Uveal and capsular biocompatibility of hydrophilic acrylic, hydrophobic acrylic, and silicone intraocular lenses. J Cataract Refract Surg 2002;28:50 – 61. Nishi O, Nishi K. Intraocular lens encapsulation by shrinkage of the capsulorrhexis opening. J Cataract Refract Surg 1993; 19:544 –5. Martinez Toldos JJ, Artola Roig A, Chipont Benabent EC. Total anterior capsule closure after silicone intraocular lens implantation. J Cataract Refract Surg 1996;22:269 –71. Hollick EJ, Spalton DJ, Ursell PG, Pande MV. Lens epithelial cell regression on the posterior capsule with different intraocular lens materials. Br J Ophthalmol 1998;82:1182– 8. Ursell PG, Spalton DJ, Pande MV. Anterior capsule stability in eyes with intraocular lenses made of poly(methyl methacrylate), silicone, and AcrySof. J Cataract Refract Surg 1997; 23:1532– 8. Meacock WR, Spalton DJ, Stanford MR. Role of cytokines in the pathogenesis of posterior capsule opacification. Br J Ophthalmol 2000;84:332– 6. Ravalico G, Tognetto D, Palomba M, et al. Capsulorrhexis size and posterior capsule opacification. J Cataract Refract Surg 1996;22:98 –103. Peng Q, Visessook N, Apple DJ, et al. Surgical prevention of posterior capsule opacification. Part 3: intraocular lens optic barrier effect as a second line of defense. J Cataract Refract Surg 2000;26:198 –213. Kruger AJ, Schauersberger J, Abela C, et al. Two year results: sharp versus rounded optic edges on silicone lenses. J Cataract Refract Surg 2000;26:566 –70. Nishi O, Nishi K, Wickstrom K. Preventing lens epithelial cell migration using intraocular lenses with sharp rectangular edges. J Cataract Refract Surg 2000;26:1543–9. Nishi O, Nishi K, Akura J, Nagata T. Effect of round-edged acrylic intraocular lenses on preventing posterior capsule opacification. J Cataract Refract Surg 2001;27:608 –13. Cunanan CM, Tarbaux NM, Knight PM. Surface properties of intraocular lens materials and their influence on in vitro cell adhesion. J Cataract Refract Surg 1991;17:767–73. Cunanan CM, Ghazizadeh M, Buchen SY, Knight PM. Con-
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Biocompatibility has been defined as the ability of a material to perform with an appropriate host response in a specific biologic application.1 The implanting of intraocular lenses (IOLs) after cataract surgery induces a foreign-body reaction to the IOL and a lens epithelial cells (LECs) response. Both these responses might present different patterns of cell reactivity and are generally considered as indicators of IOL biocompatibility.2–12 The inflammatory
Originally received: August 8, 2002. Accepted: March 21, 2003. Manuscript no. 220546. 1 Eye Clinic, University of Trieste, Trieste, Italy. 2 Department of Production Sciences, University of Udine, Udine, Italy. The authors have no proprietary or financial interest in any product or device discussed in this article, and they have not received any payment as reviewers or evaluators. Reprint requests to Daniele Tognetto, MD, Istituto di Clinica Oculistica, Universita` di Trieste, Ospedale Maggiore, Piazza Ospedale, 1 34129 Trieste, Italy. E-mail: [email protected]. © 2003 by the American Academy of Ophthalmology Published by Elsevier Inc.
cell reaction against the IOL material consists of macrophage-derived cells adhering to the anterior IOL surface. The LECs reaction is characterized by an early response, consisting of anterior capsule opacification (ACO) and membrane growth from the rhexis edge on the IOL surface, which is formed by a sheet of proliferated LECs. LECs proliferation and migration might later lead to posterior capsule opacification (PCO) and the appearance of Elschnig pearls. Histopathologic studies have shown that ACO is due to LEC metaplasia. Contact with IOL biomaterial causes LECs to undergo myofibroblastic changes and to produce extracellular matrix components.13–18 Membrane growth from the capsulorrhexis edge is related to LEC proliferation and migration, giving rise to a layer of cells and extracellular matrix covering the IOL optic.10,19 –24 Suggested risk factors for ACO and membrane growth include pseudoexfoliation syndrome, advanced age, diabeISSN 0161-6420/03/$–see front matter doi:10.1016/S0161-6420(03)00736-X
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Ophthalmology Volume 110, Number 10, October 2003 tes mellitus, uveitis, myopia, pigmentary retinal degeneration, capsulorrhexis size, and IOL design and material.9,11,12,15,21,25– 41 On very rare occasions, ACO and membrane growth can influence visual acuity.25,42,43 IOL dislocation can follow a severe ACO and phimosis.27,40 Anterior neodymium:yttrium–aluminum– garnet laser capsulotomy might be required in cases of severe capsule constriction. In addition, severe ACO impedes the examination or treatment of the peripheral retina.21,40 The aim of our study was to evaluate the influence of different IOL materials on LECs response after phacoemulsification and capsular bag IOL implantation.
Material and Methods A randomized controlled study was carried out. Approval by the Ethics Committee was obtained. Eighty-eight consecutive cataract patients (88 eyes), referred to our Eye Clinic from January to December 1998, were recruited for the study, and informed consent was obtained. All patients underwent a standardized smallincision phacoemulsification with in the capsular bag IOL implantation. Exclusion criteria were other eye diseases, such as glaucoma, uveitis and pseudoexfoliation; previous anterior or posterior segment surgery; intraoperative or postoperative complications; diabetes mellitus; and systemic therapy with antiinflammatory drugs. Each patient was randomly assigned to receive one of four different foldable IOLs: Storz Hydroview H60M (group 1, 25 patients), Corneal ACR6D (group 2, 24 patients), AMO SI40NB (group 3, 18 patients), and Alcon AcrySof MA60BM (group 4, 21 patients). The randomization list was generated by random permutation of the four IOLs in each consecutive block. All lenses are on the market in Europe. Corneal ACR6D lenses are not on the market in the United States; Hydroview lenses have been available in the United States since 2001; AcrySof have been on the market in the United States since 1994. AMO SI40 have been on the market in the United States since 1995. Surgeries were uneventful. All the operations were performed by the same surgeon (DT) with the same technique: a 4.5 to 5 mm capsulorrhexis was carried out after performing a 3.2-mm nearclear corneal incision (0.5 mm behind the limbal vascular arcade). This was followed by a phacofracture in the capsular bag and automated irrigation/aspiration of the cortical remnants. The IOL was implanted in the capsular bag, and the incision sutured with a single 10-0 nylon stitch. Healon GV (Pharmacia & Upjohn, Uppsala, Sweden) was used before performing capsulorrhexis and Provisc (Alcon, Inc., Fort Worth, TX) before the IOL implantation. All patients received the same preoperative and postoperative treatment. Sodium diclofenac, 0.1%, and ofloxacin, 0.3%, eyedrops were instilled four times both the day before and on the morning of surgery. The pupil was dilated with topical 0.5% tropicamide and 10% phenylephrine. At the conclusion of surgery, 4 mg betamethasone was administered subconjunctivally. After surgery, dexamethasone 0.2% eyedrops were instilled four times daily for 2 weeks and then sodium diclofenac 0.1% eyedrops four times daily for 2 months. Six of the 88 patients recruited in the study dropped out because they missed a check-up despite several reminders in writing and by telephone. Twenty-three of the remaining 82 patients belonged to group 1 (Storz Hydroview), 24 to group 2 (Corneal ACR6D), 18 to group 3 (AMO SI40NB), and 17 to group 4 (Alcon AcrySof). Mean age
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Table 1. Grading of Anterior Capsule Fibrosis Grade
Anterior Capsule Fibrosis
0 1
Capsular transparence Moderate: Mild opacification not involving the whole capsule over the IOL optic Severe: Complete whitening of the capsule over the IOL optic, not allowing the visualization of the posterior structures
2
IOL ⫽ intraocular lens.
was 75.1 ⫾ 8.6 years (range, 57– 89 years) in the Storz Hydroview group, 75.9 ⫾ 11.0 years (range, 42– 86 years) in the Corneal ACR6D group, 74.2 ⫾ 10.4 years (range, 41– 84 years) in the AMO SI40NB group, and 68.6 ⫾ 7.6 years (range, 58 – 81 years) in the Alcon AcrySof group. Patients were examined 7, 30, 90, 180, 360, and 720 days after surgery. All the patients in each group who concluded the study completed all of the required visits. The best-corrected visual acuity (BCVA) was measured at each postoperative ophthalmologic examination. After dilating the pupil, the anterior IOL surface was studied. The first step was the observation of the entire anterior IOL surface by slit-lamp biomicroscopy, also using the specular technique to identify membranous growth from the capsular edge and ACO. Photographs of the anterior IOL surface were taken by means of slit-lamp photography using red reflex and focal illumination. Slide film was used, and at least three slides from each patient were studied at each examination. All findings were graded by the same observer not masked to the IOL type, because the IOL design could be identified during examination. ACO and membrane growth on the anterior IOL surface were graded as shown in Tables 1 and 2. The results concerning the anterior capsule were expressed in two ways: (1) the percentage of IOLs with either ACO or membrane growth on the anterior IOL surface at a given postoperative examination; (2) the average grade of both aspects at each examination. Statistical analysis was carried out by comparing the presence and the grade of ACO and membrane growth at 7, 30, 90, 180, 360, and 720 days. The patients’ ages were expressed as mean age ⫾ standard deviation and analyzed using the t test. The Mann–Whitney test was used to compare BCVA expressed as median and range. The n-way frequency and cross-tabulation tables with measures of association (proc freq/measures, SAS [SAS Institute Inc., Cary, NC], 1988) were used to compare the presence of ACO and membrane growth in the four groups. The analysis of variance test for repeated measurements (proc glm, SAS, 1988) was used to compare the average grades of ACO and membrane growth in the four groups.
Table 2. Grading of Membrane Growth from the Capsulorrhexis Edge over the Intraocular Lens Optic Grade
Membrane Growth from the Capsular Edge
0 1 2 3
Absence Mild: membranes extending less than 90° Moderate: membranes extending from 90° to 180° Severe: membranes present over 360°
Tognetto et al 䡠 Lens Epithelial Cell Reaction
Figure 1. Percentage of intraocular lenses with anterior capsule opacification at 7, 30, 90, 180, 360, and 720 days after implantation. The differences between the groups reached statistical significance starting from the 30-day examination up to the 720-day examination (P ⬍ 0.001) (n-way frequency and cross-tabulation tables with measures of association).
Results The groups were not significantly different in age and BCVA. At the 7-day and 720-day examination, the median BCVA was 0.9 in the Corneal ACR6D, AMO SI40NB, and Storz Hydroview H60M groups, whereas it was 1.0 in the Alcon AcrySof group. The percentage of patients with ACO increased continuously over time in the Corneal ACR6D and AMO SI40NB groups. In the Alcon AcrySof and in the in Storz Hydroview H60M groups, it increased up to 180 days and 360 days after surgery, respectively, subsequently stabilizing (Fig 1). At 720 days after surgery, ACO was present in 39.13% of IOLs of group 1 (Storz Hydroview H60 M), 100% of group 2 (Corneal ACR6D), 100% of group 3 (AMO SI40NB), and 29.41% of group 4 (Alcon AcrySof MA60BM). The differences between the groups reached statistical significance starting from the 30-day examination up to the 720-day examination (n-way frequency and crosstabulation tables with measures of association P⬍0.001) (Fig 1). The mean grade of the anterior capsule fibrosis increased during the entire follow-up in the Corneal ACR6D and AMO SI40NB groups. In the Alcon AcrySof and Storz Hydroview H60M groups, it increased, respectively, up to 180 days and 360 days after surgery, subsequently stabilizing (Fig 2, Table 3). Considering all the groups studied, a significant effect of time on ACO formation was observed (P⬍0.0001) (Table 3). The type of IOL had a significant effect on the grade of ACO. At the first examination, the average grade of ACO was significantly higher in the Corneal ACR6D group than the Storz Hydroview H60M, AMO SI40NB, and Alcon AcrySof groups (P⬍0.001). Starting from the 30-day examination and throughout the study, the Corneal ACR6D and AMO SI40NB groups showed a higher average grade of ACO than the other two groups. This difference reached statistical significance (P⬍0.0001) (Table 3). At the 30-day and 90-day examinations, the mean grade of ACO was statistically higher in the AMO SI40NB group than in the Corneal ACR6D group (P⬍0.001) (Fig 2, Table 3). The percentage of IOLs with membrane outgrowth from the capsulorrhexis edge onto the anterior IOL surface increased over time in the Storz Hydroview and the Corneal ACR6D groups up to 360 days after surgery, subsequently stabilizing. At the 720-day
Figure 2. Mean grade of anterior capsule opacification (ACO) at 7, 30, 90, 180, 360, and 720 days after surgery. The Corneal ACR6D and AMO SI40NB groups showed a higher average grade of than the other two groups. This difference reached statistical significance (P ⬍ 0.0001). At the 30-day and 90-day examinations, the mean grade of ACO was statistically higher in the AMO SI40NB group than the Corneal ACR6D group (P ⬍ 0.001) (analysis of variance test for repeated measurements).
examination, it was 86.96% in the Hydroview group and 91.67% in the Corneal ACR6D group. The percentage of patients with membrane growth in the AMO SI40NB group peaked at the 30-day examination (16.67%) and dropped by the 90-day and 180-day examinations (5.56%). Then the membranes disappeared. No patient of the AcrySof group showed membrane growth during the entire follow-up period (Fig 3). The difference between the groups was found to be statistically significant (P⬍0.001). The mean grade of membrane growth increased up to 360 days after surgery in the Hydroview and Corneal groups and then became stable, whereas starting from 90 days after surgery, the AMO SI40NB group showed a decrease in the average grade of membranes, which disappeared completely after 360 days (Fig 4, Table 4). The type of IOL had a significant effect on the grade of membrane proliferation. Starting from the 30-day examination, the Corneal ACR6D and Hydroview groups showed a higher average grade of membrane outgrowth compared with the AcrySof and AMO SI40NB groups. This difference reached statistical significance (P⬍0.0001) (Table 4). Time was observed to have a considerable effect on membrane growth, with an increased growth in the Hydroview and Corneal groups and disappearing in the AMO SI40NB group (P⬍0.0001) (Table 4).
Discussion LECs’ response is an index of IOL biocompatibility. The LECs’ response originates from the LECs that remain beneath the anterior capsule after surgery and is characterized by ACO and membrane growth onto the IOL optic. In this study, ACO was observed in a higher percentage of patients with AMO SI40NB silicone IOL and Corneal ACR6D hydrophilic IOL, with a dense development of fibrosis in both groups. Previous studies described the onset
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Ophthalmology Volume 110, Number 10, October 2003 Table 3. Grade of Anterior Capsule Opacification at 7, 30, 90, 180, 360, and 720 Days After Surgery (Mean and Standard Error) Intraocular Lens Corneal—ACR6D Alcon—Acrysof Storz—Hydroview AMO—SI40NB Effect of time Effect of IOL
7 Days
Standard Error
30 Days
Standard Error
90 Days
Standard Error
0.16a 0.00b 0.00b 0.00b
0.04 0.05 0.04 0.04
0.66b 0.00c 0.17c 1.11a
0.13 0.16 0.13 0.15
0.91b 0.17c 0.34c 1.44a
0.15 0.18 0.16 0.18
180 Days
1.66a 0.35b 0.43b 1.61a 0.0001 0.0001
Standard Error
360 Days
Standard Error
720 Days
Standard Error
0.13 0.16 0.13 0.15
1.66a 0.35b 0.69b 1.66a
0.14 0.17 0.15 0.17
1.83a 0.35b 0.69b 1.77a
0.12 0.15 0.13 0.14
IOL ⫽ intraocular lens. In the same column, the estimated means marked with different letters are significantly different (P ⬍ 0.05). Considering all the groups studied, a significant effect of time on anterior capsule opacification formation was observed.
of ACO after silicone IOL implantation.26,40,41 Georgopoulos et al36 reported the presence of a pronounced fibrosis of the anterior capsule in eyes implanted with a silicone IOL, causing the shrinkage of the capsulorrhexis opening. We observed that membrane growth from the rhexis edge on the anterior IOL surface is more frequent in Storz Hydroview H60M and ACR6D groups. These results confirm the findings of previous studies reporting the growth of an LEC monolayer on the anterior surface of the hydrophilic Hydroview IOL.21,41 Hydrophilic acrylic material seems to be a good scaffold for the growth of epithelial cells.10 –12 To our knowledge there are no data regarding LECs’ behavior in the Corneal ACR6D IOL. This is a hydrophilic IOL with a different level of hydration than Hydroview. The water content is 18% in Hydroview and 26% in ACR6D. This study has revealed the presence of both severe ACO and membrane outgrowth in Corneal IOLs. This finding demonstrates that different hydrophilic materials can cause a specific LEC reaction. The definition of a material as
Figure 3. Percentage of intraocular lenses (IOLs) with membrane growth over the IOL optic at 7, 30, 90, 180, 360, and 720 days after implantation. The percentage of IOLs with membrane outgrowth from the capsulorrhexis edge onto the anterior IOL surface increased over time in the Storz Hydroview and in the Corneal ACR6D groups up to 360 days after surgery. No patient of the AcrySof group showed membrane growth. The difference between the groups was found to be statistically significant (P ⬍ 0.001) (n-way frequency and cross-tabulation tables with measures of association).
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hydrophilic is no longer sufficient to describe the biocompatibility of an IOL. In addition, we noticed the disappearance of small membranes on the AMO SI40NB at the 360-day examination. This is consistent with the finding of Hollick et al,44 describing posterior LECs’ regression with silicone, polymethyl methacrylate and AcrySof IOL. From our data, Alcon AcrySof MA60BM showed the lowest presence of fibrosis of the anterior capsule and no membrane growth. Other authors have reported results consistent with our findings.12,21,26,40 Ursell et al45 reported an anterior capsule stability in eyes implanted with the AcrySof IOL with less incidence of IOL decentration and capsular phimosis. Several factors regarding blood–aqueous barrier (BAB) breakdown, surgical technique, and IOL characteristics have been considered to influence LECs’ response. Some authors believe that inflammatory mediators, either serum-derived after BAB damage or synthesized by macrophages and LECs, can stimulate LEC proliferation and migration.15–17,46 Conversely, it has also been suggested
Figure 4. Mean grade of membrane growth at 7, 30, 90, 180, 360, and 720 days after surgery. The Corneal ACR6D and Hydroview groups showed a higher average grade of membrane outgrowth than the AcrySof and AMO SI40NB groups. This difference reached statistical significance (P ⬍ 0.0001) (analysis of variance tests for repeated measurements).
Tognetto et al 䡠 Lens Epithelial Cell Reaction Table 4. Grade of Membrane Growth at 7, 30, 90, 180, 360, and 720 Days After Surgery (Mean and Standard Error) Intraocular Lens Corneal—ACR6D Alcon—Acrysof Storz—Hydroview AMO—SI40NB Effect of time Effect of IOL
7 Days
Standard Error
30 Days
Standard Error
90 Days
Standard Error
0.91a 0.00c 0.47b 0.16bc
0.12 0.14 0.12 0.14
1.08a 0.00b 1.00a 0.22b
0.13 0.16 0.14 0.15
1.33a 0.00b 1.26a 0.05b
0.14 0.16 0.14 0.16
180 Days
1.62a 0.00b 1.43a 0.05b 0.0001 0.0001
Standard Error
360 Days
Standard Error
720 Days
Standard Error
0.14 0.17 0.14 0.16
1.83a 0.00b 2.21a 0.00b
0.14 0.17 0.15 0.17
1.83a 0.00b 2.21a 0.00b
0.14 0.17 0.15 0.17
IOL ⫽ intraocular lens. In the same column, the estimated means marked with different letters are significantly different (P ⬍ 0.05). Considering all the groups, time was observed to have a significant effect on membrane growth.
that reduced BAB damage is associated with an increased LEC proliferation, leading to LEC outgrowth on the anterior surface.11 No clinical differences in BAB disruption between the groups were observed in this study, and no cases of excessive postoperative inflammation were noted, although we did not measure the anterior chamber cell reaction by means of a laser flare cell meter. ACO occurs in the part of the anterior capsule that is in contact with the anterior surface of the IOL. When the capsulorrhexis is smaller than the IOL optic, the contact of the IOL optics’ material with the anterior capsule induces ACO formation. It has been suggested that the smaller the capsulorrhexis diameter and the larger the area of contact between LECs and the IOL optic, the more severe the ACO to be expected.34 –37 Several authors believe that capsulorrhexis size cannot influence the amount or severity of LEC proliferation but agree that the contact between the capsular edge and the IOL optic is necessary for membrane growth.10,38 In this study, all patients had a capsulorrhexis slightly smaller than the IOL optic, and the capsular edge was in contact with the anterior IOL surface, as is normal practice in our procedure. We demonstrated that this condition might reduce the PCO.47 In our series, no patients had capsular shrinkage or a rhexis that was too small compared with the IOL optic diameter. IOL design has been demonstrated to be one of the main factors influencing PCO.48 –51 Werner et al26,40 suggested that there could be a correlation between IOL design, especially haptic design, and ACO. A higher rate of ACO in plate haptic silicone lenses was observed, suggesting that the large area of contact between LECs and plate haptic lenses stimulates cell proliferation and fibrosis. Schauersberger et al21 found that the sharp-edged optic design has no influence on anterior lens outgrowth. We believe that the IOL design could have not affected LECs’ response in our series. The area of contact between the anterior capsule and the IOL is similar in the four IOLs studied. Moreover, the shape of the optic edge cannot be implicated in ACO and membrane growth development, because the physiologic site of LECs is beneath the anterior capsule and at the equator of the lens. After capsulorrhexis has been performed, part of the anterior capsule covers the IOL optic, and LECs lie directly over the IOL. ACO and membrane outgrowth derive from these cells. Migration of LECs from the equator, as occurs in PCO, is not needed.
Several authors recognize a correlation between the surface tension of the IOL and cell adherence.5,9,52–54 The contact angle is a measure of the surface tension and expresses only the relative hydrophilicity or hydrophobicity of an IOL surface. According to Dick et al,55 the contact angle of AMO SI40NB is different than that of Corneal ACR6D (106.2 versus 64.3 angle °). In our study, these two lenses showed a similar severe ACO development. From this example it can be argued that the relative hydrophilicity or hydrophobicity of an IOL surface seems not to be sufficient to explain the anterior LECs’ behavior in relation to the type of IOL biomaterial. It is well known that within a few minutes of an IOL implantation a protein biofilm deposits on the anterior surface. This layer is composed of different proteins, such as albumin, complement C3, immunoglobulin G, fibrin, collagen type IV, fibronectin, laminin, and vitronectin. Cell adhesion molecules on LECs can bind to this protein scaffold and could affect LEC adhesion, migration, and proliferation.56 – 61 Recent studies have demonstrated that the biomaterial could influence this protein absorption on the IOL surface.62,63 The composition of this film differs according to the chemical composition of the material. It has been demonstrated that AcrySof IOLs adsorb more fibronectin and laminin on their surface than other biomaterials.62– 66 We speculate that, because biomaterial chemistry can determine differential absorption of proteins on IOL surfaces, a specific material-induced relationship between the cell adhesion molecules of the LECs and this proteins occurs. The type of relationship is peculiar to each material, with consequent variable behavior of LECs. The expression of this phenomenon, which takes the form of varying degrees of cell adhesion, spreading, and proliferation onto the lens optic, causes the different clinical patterns observed in IOLs made of different materials. The disappearance of membranes in the silicone IOL we observed could be explained by a protein scaffold peculiar for the silicone optic IOLs, which might be inadequate for the continuing growth of LECs. In conclusion, in eyes without any known risk factor for ACO and membrane formation, the main factor involved in anterior LECs’ proliferation and metaplasia seems to be the relationship between LECs and the IOL biomaterial. The study of anterior LECs’ behavior is crucial, because
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Ophthalmology Volume 110, Number 10, October 2003 it can give us a precise idea of the response of LECs to the IOL material. No other factors affect this response, and it is also crucial to assess the role of the material in influencing the development of PCO. PCO is influenced by several factors, such as surgical technique, cortical cleanup, concomitant eye diseases, IOL material, and IOL design and placement,67 but the role of the material in the LECs’ response can be assessed from the behavior of the anterior LECs themselves.
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