Dr. Vineet Vaishnav, Dr. Shail,
Dr. Vaishali Abhaykumar Vasavada, Dr. Mamidipudi
Ramakrishna Praveen
Authors: Dr. Vineet Vaishnav, Dr. Shail Vasavada, Dr. Vaishali Vasavada, Dr. M.R. Praveen
Iladevi Cataract & IOL Research Center, Raghudeep Eye Clinic, Gurukul Road, Memnagar, Ahmedabad, India.
Address :
Raghudeep Eye Hospital,
Gurukul Road, Memnagar,
Ahmedabad – 380052. India.
E-mail: info@raghudeepeyeclinic.com
A Prospective Evaluation of Posterior Capsule Opacification in Eyes with
Posterior Capsule Plaque – A Case Control Study
Abstract:
Purpose:
To compare the development of posterior capsule opacification (PCO) between eyes with and without posterior capsule plaque after single-piece hydrophobic acrylic intraocular lens (IOL) implantation 5 years postoperatively.
Design: Prospective, observational, case-control study
Methods:
One hundred and one consecutive eyes with posterior capsule plaque (cases) were compared with the same number of cataractous eyes without posterior capsule plaque (controls). A detailed, preoperative evaluation was done to detect the presence of posterior capsule plaque. Histomorphology of posterior capsule plaque evaluated. Postoperatively, digital retroillumination photographic documentation was performed at 1 month, 1, 2, 3 and 5 years and analyzed for PCO using Evaluation of Posterior Capsule Opacification (EPCO) software; EPCO scores and areas were calculated. The development of PCO and the influence of the anterior capsule cover (total on and part on) on the IOL optic was compared.
Results:
Posterior capsule plaque on histomorphology showed a large amount of collagenous, fibrous extracellular matrix and immunofluorescence staining was positive to αSMA. In the development of PCO, there was no difference between cases and controls at 1 month, 1, 2, 3 and 5 years. Between the two groups, there was no difference in the development of PCO within total on cover and within part on cover of the anterior capsule on the IOL up to 5 years.
Conclusion:
The presence of posterior capsule plaque did not increase the incidence of PCO at 5 years.
Key Words: posterior capsule plaque, phacoemulsification, posterior capsule opacification
A Prospective Evaluation of Posterior Capsule Opacification in Eyes with
Posterior Capsule Plaque – A Case Control Study
Introduction
Classically, posterior capsule opacification (PCO) is described as postoperative opacification of the posterior capsule after cataract surgery.1-3 However, intraoperative posterior capsule opacification (PCO), noticed during surgery, is a separate entity and it should not be confused with postoperative PCO and posterior subcapsular cataract.2,4,5 We were the first to describe this morphological variation in adult eyes and we coined the term “posterior capsule plaque” to refer to it. 4 Capsular plaque is a multifocal, dense, white opacity adherent to the internal surface of anterior and posterior lens capsules.
A few authors proposed that during the occurrence of plaque pathogenesis, most of the lens epithelial cells undergo epithelial-mesenchymal transition and transdifferentiate into myofibroblasts .6-8 Also, there is the existence of a significant molecular switch in the composition of extracellular matrix components during epithelial-mesenchymal transition (EMT) and fibrosis .5,9,10 The changes in the extracellular matrix (ECM) component might interfere with the scaffolding required for cell migration. As maintenance of epithelial cell phenotypes and appropriate ECM is necessary for the cells to proliferate and migrate, we believe that any deviation in these conditions do not impart the requisite molecular milieu for cellular proliferation and subsequent posterior migration. It is not known to what extent posterior capsule plaque noted at the end of surgery will contribute to the development of postoperative PCO over time. The present study was designed to assess whether posterior capsule plaque influences the formation of visually significant PCO over time.
Methods:
This prospective, observational case-control study comprised patients who underwent phacoemulsification from June 2005 to June 2006 at the Iladevi Cataract and IOL Research Center. Eyes with uncomplicated age-related cataract coexisting with posterior capsule plaque were designated as Group A or cases (n= 102 eyes). Patients with uncomplicated, age-related cataract without posterior capsule plaque who were otherwise healthy constituted Group B or controls (n=102 eyes). The exclusion criteria were as follows: patients with glaucoma, high myopia (axial length > 27.0 mm), pseudoexfoliation, traumatic cataract, subluxated cataract, and allergy to dilating drops. Patients, who had previously undergone ocular surgeries, were also excluded. Cataract was categorized as nuclear, cortical, posterior subcapsular, and mixed cataract or a combination of cataracts according to the zone of opacification. After dilating the pupils, the participants were subjected to a slit lamp examination to detect the presence or absence of posterior capsule plaque. The slit lamp beam was fixed at a width of 1.0 mm, height of 14.0 mm, and magnification of 8 mm at 100% illumination.11 Evaluation of the plaque through slit lamp examination was standardized in terms of illumination and magnification. The presence or absence of plaque was observed under oblique illumination, where the slit lamp was placed at an angle of 30° to 45°. A single observer recorded all the observations noting down the presence or absence of plaque. All the patients were given preoperative counseling regarding the possibility of occurrence of posterior capsular plaque, following cataract surgery. The patients were also warned about the occurrence of visual disturbances, such as glare at night. They were reassured that not all patients with plaque will require secondary surgical intervention.
. In case surgical intervention was required, the treatment would be Nd-YAG laser capsulotomy, which could be administered in the outpatient department. A single surgeon (A.R.V.) performed all the surgeries using the Infiniti Vision System (Alcon Laboratories, Fort Worth, USA). A standardized surgical technique was used to ensure comparative consistency in all subjects.11 A single-piece hydrophobic acrylic (model: SN60AT, Alcon Laboratories, Forth Worth, Texas) intraocular lens (IOL) was implanted in the capsular bag. Intraoperatively, the presence of plaque was confirmed after performing bimanual irrigation and aspiration. The plaque was recognized as a thickened opacified lesion, firmly adherent to the posterior capsule, distinguishing it from the posterior subcapsular changes, which are located in front of the posterior capsule. The plaque appeared as a diffuse area with a well-demarcated thickened border or as small multiple islands of thickened capsule or as a complete or incomplete ring configuration. (Figure 1a). Capsule polishing of the posterior capsule in Cap Vac mode, with an aspiration flow rate of 5 cc/min and a vacuum of 5 mm Hg, was done in all cases. A single-piece hydrophobic acrylic (model: SN60AT, Alcon Laboratories, Forth Worth, Texas) intraocular lens (IOL) was implanted in the capsular bag. Either on the first postoperative day or within a week, the posterior capsule was examined with maximal mydriasis.(Figure 2a,2b). The same observer made all the postoperative observations.
Observation Procedures
Histomorphology and Immunohistochemistry
In 8 cases after the informed consent was obtained upon institutional approval in eyes with posterior capsule plaque intraoperatively we performed the technique of plaque peeling for small plaques occupying the central visual axis similar to the technique of manual posterior capsulorhexis as described elsewhere 12.(Figure 1b,1c)The posterior capsule plaque was subjected to histomorphology and immunohistochemistry analysis. Eight samples of adult posterior capsule plaque were collected from patients undergoing cataract surgery. The samples were immediately fixed in 2% paraformaldehyde in phosphate buffer saline (PBS). Next the samples were processed to make wax blocks. Sections of 5 mm were cut out with the help of a microtome. These sections were mounted on saline-coated slides and were stained with hematoxylin-eosin. Some sections were also subjected to immunofluorescence localization of alpha smooth muscle actin (aSMA) using appropriate antibodies as described previously.14
Follow-up Examination and Image Acquisition
The patients were asked to return for postoperative follow-up visits at 1 month 1, 2, 3 and 5 years. An examiner, masked to the groups, performed digital retroillumination photo documentation in all the cases at the 1 month follow-up, after maximal pupil mydriasis, at a fixed illumination and magnification. For this purpose, we used a digital camera (Nikon) mounted on a slit lamp (Haag-Streit USA) with an external light and flash light source, which provided coaxial illumination from the flash pack through a fiberoptic cable to the camera. At every follow-up visit thereafter, photo documentation of the posterior capsule was performed by using retroillumination with a widely dilated pupil. The posterior capsule images of each patient taken at every follow-up visit were saved in a separate folder. The eye was considered to have total cover if the overlap of the anterior capsule on the IOL optic was 12 clock hours. If there was an overlap of the anterior capsule on the IOL optic between 1 to 10 clock hours, the eye was considered to have a partial cover. These images gave information about the onset and progression of PCO.
PCO Image Interpretation and Analysis
All the digital images were analyzed for PCO using the EPCO 2000 program. PCO was evaluated for the entire IOL optic. During the analysis, the posterior capsule plaque was identified and not marked for analysis. The boundaries of the posterior capsule as well as each opaque area of the posterior capsule were drawn on the stored images using a computer mouse. The density of opacification was clinically graded as 0 (none), 1 (minimal), 2 (mild), 3 (moderate), or 4 (severe). Individual PCO values (PCO index) were calculated for each image by multiplying the density of opacification with the fraction of the capsule area involved behind the IOL optics. The score was interpreted in terms of EPCO score and EPCO area.
Observations:
The primary observations were to compare, between the two groups, the mean EPCO scores and EPCO area of PCO up to 5 years for the entire intraocular lens (IOL) optic. Further mean EPCO scores and EPCO area were also compared between the two groups to assess the influence of different types of cataract on the development of PCO up to 5 years postoperatively. Mean EPCO scores and EPCO area were also compared between the two groups to gauge the impact of the anterior capsule relationship (total on and part on) on the development of PCO within the anterior capsulorhexis margin. We compared the development of PCO within the total on and part on cover of the anterior capsule on the entire intraocular lens (IOL) optic up to 5 years between the 2 groups. We also evaluated changes in the severity of PCO (EPCO area) at different time periods: between 1 month to 1 year, 1 to 3 years, and 3 to 5 years within cases and controls separately to confirm the intra-individual differences over time.
Results:
The demographic characteristics of the patients are given in table 1. There was no significant difference in the mean age (P =0.35) and axial length (P=0.77) between the two groups. In the present study, nuclear cataract was observed only in the controls. There was a higher incidence of posterior subcapsular cataract (PSC) in the cases as compared with the controls (P<0.001). There was no significant difference in the distribution of mixed cataracts between the two groups. (P=1.000). (Table 1).
Histomorphology and Immunohistochemistry
The posterior capsule plaque was thick due to the presence a large amount of collagenous, fibrous extracellular matrix (ECM) (Figure 3a). Cells were relatively few and scattered in the extracellular matrix (ECM). Nuclei of cells were spindle-shaped (Figure 3b). We have subjected some sections of the posterior capsule plaque to immunofluorescence staining of αSMA, which is a marker of myofibroblast-like cells. All the cells of posterior capsule plaque were positive to αSMA (Figure 3c and 3d).
Comparison of mean PCO (EPCO score and area) within the capsulorhexis margin between the 2 groups:
The comparison of EPCO score and area within the capsulorhexis margin at 1 month, 1, 2, 3, and 5 years postoperatively are given in Table 2. There was no significant difference in EPCO score and area for the entire IOL optic at any follow-up visit between the 2 groups. (Table 2). (Figure 4).
Comparison of mean PCO (EPCO score and area) within the capsulorhexis margin with different types of cataract between the 2 groups:
The comparison of EPCO score and area within the capsulorhexis margin at 1 month, 1, 2, 3 and 5 years postoperatively are given in Table 3. There was no significant difference in EPCO score and area for the entire IOL optic at any follow-up between the 2 groups (Table 3).
Mean PCO Values and the Anterior Capsule Relationship:
Part On
Between the two groups, at any follow-up visit, there was no statistically significant difference in the development of EPCO score and area with part on cover of the anterior capsule on the IOL up to 5 years. (Table 4)
Total On:
Between the two groups, at any follow-up visit, there was no statistically significant difference in the development of EPCO score and area with total on cover of the anterior capsule on the IOL up to 5 years. (Table 4) (Figure 5).
When we examined PCO within the capsulorhexis margin, within cases, we observed that there was a significant increase in PCO (EPCO area) at the following time points: between 1 month to 1 year (P<0.001) and 2 to 3 years (P<0.001). However, there was no significant difference in PCO (EPCO area) between 1 to 2 years and 3 to 5 years. On the other hand, when PCO was examined within controls, there was a significant increase in PCO ( EPCO area) at the following time point: between 2 to 3 years only (P<0.001). There was no significant difference observed between any other time points. (Table 5)
At the 1 year follow-up, only 3 (2.9%) patients underwent Nd:YAG laser capsulotomy in the controls while 6 patients underwent capsulotomy in eyes with coexisting posterior capsule plaque. At 3 years, 8 patients underwent Nd:YAG laser capsulotomy in eyes with coexisting posterior capsule plaque while 5 patients underwent capsulotomy in the control group.
Discussion:
Cataract surgeons have noted the presence of posterior capsule plaque at the time of cataract surgery, since the advent of extracapsular cataract extraction techniques.4,5 We speculate that the development of posterior capsule plaque is due to increased activity of lens epithelial cells. Plaque formation could also be due to longstanding, exaggerated, and advanced biochemical changes, which cause epithelial cells to undergo fibrous metaplasia.10 We now appreciate that PCO is multifactorial and influenced by factors such as age of the patient, presence of concomitant intraocular or systemic diseases, surgical techniques, and IOL design used. However, the question as to whether the PCO develops in eyes with coexistent posterior capsule plaque has not yet been answered. The present study was designed to assess whether posterior capsule plaque contributes to the formation of visually significant PCO over time.
In the present study, irrespective of the type of cataract present in the eye, there was no significant difference in PCO score and area for the entire IOL optic between the two groups at any follow-up visit. Similarly, there was no significant difference in PCO score and area for the entire IOL optic between eyes with different types of cataract in the two groups at any follow-up visit. We found a higher incidence of posterior capsule plaque in eyes with posterior subcapsular cataract when compared with eyes with nuclear and mixed cataracts. In our previous study on adult cataractous eyes, we also found coexistent plaque in approximately 12.5% of cases with PSC.4 Moota and coauthors,14 while evaluating the incidence of and risk factors for residual posterior capsule opacification after cataract surgery, observed that PSC was documented as a significant risk factor for the presence of posterior capsule plaque. The process of plaque formation generally proceeds as a long-term sequel to an original posterior subcapsular cataract. The authors presumed that the epithelial cells underwent fibrotic metaplasia and that the equatorial cells migrated between the posterior capsule and the posterior cortical fibers, where they formed collagen deposits and fibrotic plaques associated with longstanding cataract. In our previous study,5 while evaluating the histopathologic impact of posterior capsular plaque, we documented that the presence of a Masson’s stain clearly confirmed that plaques are composed of collagen. Further spindle-shaped cells, admixed with the newly-formed collagen fibers in the plaques, were arranged parallel to the surface of the posterior capsule. A few authors have proposed that cells occurring in cases of posterior capsular plaque and in fibrous type of chronic posterior capsular opacification are derived from pseudofibrous metaplasia.3,15,16
In the present study, between the 2 groups, irrespective of the relationship of the anterior capsule on the IOL optic (part on or total on), there was no statistically significant difference in the development of PCO score and area at any follow-up within the capsulorhexis margin up to 5 years. The present study supports our notion that when partial anterior capsule overlap was observed, there was a significant increase in the risk of PCO development after implantation of the single-piece AcrySof IOL. The results obtained by placing the edge of the anterior capsule completely over the IOL optic suggest that the lens implant, which is sequestered in the capsular bag, is pushed in a posterior direction due to pressure from the anterior capsule. This force may lead to greater contact between the IOL and the posterior capsule, thereby creating an effective barrier for migrating LECs. From the above observations and literature, we can conclude that only a partial overlap of the anterior capsule over the IOL optic results in an incomplete capsular bend formation thereby causing a gap between the IOL optic and the posterior capsule. This gap provides a channel for the lens epithelial cells to migrate into the posterior capsule causing extensive PCO.17-19 We implanted an AcrySof IOL, because it has excellent biocompatibility. The AcrySof IOL is made of acrylic hydrophobic material. This has an adhesive surface that results in greater IOL optic-capsule adhesion, and also the stronger binding of fibronectin and laminin to acrylate IOLs. This succeeds in creating a tight fit of the posterior lens capsule against the back of the IOL optic creating a shrink-wrap effect. 20-22 Further several authors have ascribed the occurrence of low PCO rates in AcrySof IOLs to the sharp optic edge design.17-19. Linnola et al reported that the stronger binding of fibronectin and laminin to acrylate IOLs could be an explanation for the better adhesion of the AcrySof IOL to the anterior and posterior capsules thereby resulting in lower PCO rates.21,22 The present study emphasizes our notion that when partial anterior capsule overlap was compared between cases and controls, there was no significant difference in the risk of PCO development after implantation of the single-piece AcrySof IOL. Literature reports suggest that this material is associated with a lower degree of PCO formation.17,20-22
In the present study, there was no significant difference in PCO between 3 to 5 years after surgery in both the groups. In our previous study of long-term evaluation with AcrySof®SN60AT IOLs, a significant increase in PCO was observed up to 3 years. PCO stabilized between 3 to 5 years with no evidence of a difference at 5 years. ( Abhay R Vasavada et al ‘Long-term Evaluation of Posterior Capsule Opacification After Implantation of a Single-Piece Hydrophobic Acrylic IOL” poster presented at the American Academy of Ophthalmology in New Orleans, Louisiana, November 16 – 19, 2013.) Another long-term randomized controlled study documented that both the single-piece and the three-piece foldable AcrySof IOLs showed low PCO intensity 5 years after surgery and that there was no significant difference in PCO and YAG rates.23 There are several existing theories concerning PCO prevention. Acrylic hydrophobic material has an adhesive surface that results in greater IOL optic-capsule adhesion, and more rapid capsular bend formation. As a result, the posterior lens capsule is tightly fitted against the back of the IOL optic (in the form of a ‘‘shrink wrap’’).17,20
In the present study, we found a higher incidence of Nd:YAG laser capsulotomy in eyes with coexisting posterior capsule plaque. Postoperatively, these patients with plaque had voluntarily reported disabling visual complaints and had undergone Nd YAG capsulotomy. We believe that most patients in this part of the world, despite the preexistence of posterior capsule plaque after cataract surgery, do not demand an intervention for plaque removal. We recommend performing Nd: YAG capsulotomy, only when the patient requests it. In the present study, we did not find significant differences in the incidence of Nd:YAG laser capsulotomy rates between the two groups. Another factor, which we had to keep in mind, was the conservative approach of surgeons coupled with the mindset of people in this part of the world who prefer to avoid surgical intervention unless it is absolutely warranted. Hence Nd: YAG capsulotomy was performed only when the patient requested it.
We believe that plaque formation and PCO is based on the similarity in their etiologies. Both the conditions take place on the posterior capsule and are associated with the aberrant behavior of LECs. It is well-known that PCO occurs due to uncontrolled proliferation, migration, and differentiation of residual LECs.24-26 Lens epithelial cells on the posterior capsule may either undergo EMT followed by fibrosis, which leads to a fibrous type of PCO, or undergo differentiation into fiber-like cells, which leads to a globular type of PCO.3,25,26 Many types of PCO have a combination of both these events. In the present study, we have examined the histomorphology and immunofluorescence of αSMA in the samples of posterior capsule plaque. We have found that posterior capsule plaque is made up of myofibroblast like cells suspended in the large amount of fibrous ECM, which are the signs of EMT. Our previous study on anterior capsule plaque has also revealed similar findings .13 In patients with plaque, formation of PCO can be attributed to proliferation, migration, and differentiation of three types of cells. The fibrous cells have already undergone terminal differentiation and it is unlikely that they will undergo a fresh round of proliferation and differentiation. Similarly the myofibroblast-like cells suspended in the ECM have also undergone the differentiation process and are unlikely to contribute to the development of PCO. Only cells that can effectively contribute to PCO in these samples are undifferentiated LECs located at the periphery of the plaques.13 Therefore in both cases, subjects with and without plaque have only one type of cells that can contribute to PCO development. This may be the reason why no difference was observed between the incidence and type of PCO in these samples.
This study aimed at prospectively exploring the long-term effects of posterior capsule plaque on the incidence of PCO. It was important for us to implement standardized surgical techniques for in-the-bag AcrySof IOL fixation and postoperative medication so as to ensure that the surgeries were as identical as possible in both groups. This kind of standardization helped us to objectively evaluate whether eyes with posterior capsule plaque run the risk of developing PCO. In conclusion, our study has shown that at the end of 5 years, the presence of posterior capsule plaque did not increase the risk of PCO development when compared against controls.
References:
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Legends for Figures:
Figure 1: An intraoperative representative photograph of an eye with (1a) intraoperative posterior capsule plaque (1b) intraoperative posterior capsulorhexis after posterior capsule plaque peeling (1c) Postoperative IOL in the bag with anterior and posterior capsulorhexis coexisting posterior capsule plaque.
Figure 2: A postoperative representative photograph of an eye with (2a) IOL in the bag with clear capsule (2b) IOL in the bag with coexisting posterior capsule plaque.
Figure 3: Histomorphology and immunofluorescence studies of posterior capsule plaque. The posterior capsule plaque is made of fibrous extracellular matrix (ECM) with few cells with spindle-shaped nuclei (3a & 3b). All cells located within the ECM of posterior capsule plaque are positive for the αSMA, a marker of myofibroblast-like cells (3c & 3d).
Figure 4: A comparative evaluation of postoperative posterior capsule opacification between eyes with posterior capsule plaque (4a, 4b, 4c, 4d) and clear capsule (4e, 4f, 4g, 4h) at 1 month, 1, 3 and 5 years, respectively.
Figure 5: A comparative evaluation of postoperative posterior capsule opacification between eyes with total on of anterior capsule overlap on IOL optic with posterior capsule plaque (5a, 5b, 5c, 5d) and clear capsule (5e, 5f, 5g, 5h) at 1 month, 1, 3 and 5 years, respectively.

