Histological examination of primary posterior capsule plaques

ARTICLE

Histological examination of primary posterior capsule plaques Zsolt Biro´, MD, PhD, La´szlo´ Kereskai, MD, Alexis Tsorbatzoglou, MD, PhD, Abhay R. Vasavada, MS, FRCS, Andra´s Berta, PhD, DSc

PURPOSE: To understand the source and evolution of the cellular elements of posterior capsule plaques. SETTING: Department of Ophthalmology, University of Sciences, Faculty of Medicine, Pe´cs, Hungary. METHODS: In 24 eyes of 24 patients, the primary fibrotic plaques were carefully peeled off the posterior capsule with forceps and sent for histological examination. The samples were stained with hematoxylin-eosin and with picrosirius to demonstrate collagen content. RESULTS: Most plaques were found in elderly patients with mature cataracts. However, one was found in a patient with congenital cataract. The histological examination revealed different stages of plaques, permitting discrimination of early (cellular), transitional, and late (fibrotic) stages. The plaques in the early stage contained cuboidal cells with nuclei; collagen deposition led to the development of the transitional stage; and further collagen deposition led to the fibrotic stage. There was no significant correlation between the maturity of the cataract and the plaque stage, but other factors such as previous eye surgery (vitrectomy, glaucoma surgery), long-standing diabetes mellitus (DM), and a high degree of myopia appeared to contribute to the development of plaques. CONCLUSIONS: Primary posterior capsule plaques were found primarily in elderly patients with mature cataracts but were also present post vitrectomy in those who had DM from a young age and had early stages of cataract. In the early plaque stage, cells with nuclei were found. It follows that plaques are capable of proliferation at this stage, aggravating visual disturbance. Therefore, removing the plaques by peeling from the posterior capsule or by posterior capsulorhexis during surgery is suggested. J Cataract Refract Surg 2007; 33:439–442 Q 2007 ASCRS and ESCRS

Posterior capsule opacification is a common and wellknown postoperative complication of extracapsular cataract extraction, including phacoemulsification, whether the intraocular lens is placed in the capsular bag. Opacification develops by proliferation or with the migration of epithelial cells and, usually, with metaplasia. During surgery, after the opacified lens has been removed, a well-circumscribed primary fibrotic plaque can sometimes be seen on the posterior capsule, which is too firmly attached to be removed by simple polishing or ‘‘capsular vacuum cleaning.’’ The phenomenon was first described by Vasavada et al.,1 who called it ‘‘posterior capsule plaque.’’ One option for removing the plaque is to find its border with a pair of capsulorhexis forceps and carefully peel it off the posterior capsule. In this study, we examined the removed plaques using histological methods. Q 2007 ASCRS and ESCRS Published by Elsevier Inc.

PATIENTS AND METHODS This prospective study comprised 24 eyes of 24 patients who had a well-circumscribed primary posterior capsule plaque that was removed during phacoemulsification cataract extraction under topical anesthesia. The mean age of the 6 men (25%) and 18 women (75%) was 68.3 years (11 to 91 years). Only 1 patient was younger than 50 years; he was 11 years old. Five patients were between 50 and 60 years, 6 were between 61 and 70 years, 8 were between 71 and 80 years, 3 were between 81 and 90 years, and 1 was older than 90 years. Three patients had diabetes mellitus (DM) and 1, Parkinson’s disease. In 15 eyes (62%), the cataract was mature and in 9 (38%), intumescent. The ophthalmic history of the patients revealed that 1 had a pars plana vitrectomy, 3 had glaucoma, and 1 had a trabeculectomy. One patient was monocular, 3 were highly myopic (axial length O26.0 mm), and 1 0886-3350/07/$dsee front matter doi:10.1016/j.jcrs.2006.11.014

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had pseudoexfoliation syndrome. There was no traumatic cataract among the patients, but 1 had a congenital cataract. The fibrotic plaques were attached to the posterior capsule so firmly they could not be removed by the conventional techniques of polishing or ‘‘vacuum cleaning’’ the posterior capsule using a low (5 to 20 mm Hg) vacuum. The capsular bag and anterior chamber were filled with an ophthalmic viscosurgical device (hydroxypropyl methylcellulose 2% [Adatocel]), and the clear corneal wound was enlarged to 4.1 mm with a ShortCut Slit Knife (Alcon) for implantation of a foldable posterior chamber intraocular lens (IOL). Before the IOL was implanted, the margin of the posterior capsule plaque was found with a pair of Corydon capsulorhexis forceps (Moria), and the plaque was peeled from the posterior capsule. The sample was put in buffered formaldehyde 4% and sent to the Department of Ophthalmology for histological examination. During the routine examination, serial slides were made from the tissue samples, which were embedded in paraffin. Besides hematoxylin–eosin (H&E) staining, picrosirius staining was used to demonstrate the collagen fibers. The samples were examined under a light microscope, and those stained with picrosirius were examined by a polarization microscope to demonstrate the amount of collagen. The histological slides were photographed for documentation. RESULTS In the study, primary posterior capsule plaques were found primarily in elderly patients. The rate was basically the same in patients with mature cataract and those with intumescent cataract. Based on the histological findings, the samples could be separated into 3 developmental stages. In 10 cases, the plaques almost exclusively contained cellular elements. The cells formed a few layers; they had

Figure 1. Primary posterior capsule plaque in the early or cellular stage. It contains basically no (or a very small amount of) collagen but many nucleated cells (H&E staining). Because of the many nucleated cells, the plaque is capable of proliferation.

a regular, round nucleus and were mostly cuboidal. There was a narrow eosinophilic margin on the capsular side of the cells, which contained minimum amounts of collagen or no collagen (none was detected by picrosirius staining). This was called the early or cellular stage (Figure 1). In 11 plaques, the cellular elements of the plaque had decreased. Longitudinal fibrocytic or fibroblastlike cells appeared instead of the cuboidal cells, and collagen fibers started to form in the eosinophilic matrix. At this stage, some cellular elements were present, but there was also more collagen. This was called the transitional developmental stage (Figure 2). In the transitional stage, the plaque was not much thicker than that in the cellular stage.

Accepted for publication November 22, 2006. From the Department of Ophthalmology (Biro) and the Department of Pathology (Kereskai), University of Sciences, Faculty of Medicine, Pe´cs, and the and the Department of Ophthalmology (Tsorbatzoglou, Berta), Medical University of Debrecen, Hungary; and the Raghudeep Eye Clinic (Vasavada), Ahmedabad, India. No author has a financial or proprietary interest in any material or method mentioned. Corresponding author: Zsolt Biro´, MD, PhD, Department of Ophthalmology, University of Sciences, Faculty of Medicine, H-7643, Pe´cs, Ifjusa´g Street 13, Hungary. E-mail: [email protected].

Figure 2. In the transitional stage, the number of nucleated cells is significantly reduced and the collagen content increased (H&E staining).

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Figure 3. In the fibrotic stage, collagen accumulation and the absence of nucleated cells are characteristic. Left: H&E staining. Right: Picrosirius staining.

In 3 samples, the plaques formed a dense collagenous tissue; the thickness increased significantly, and the plaques contained no cellular elements. This was called the late or fibrotic stage (Figure 3). According to the new classification, of the 24 examined plaques, 10 were in the early or cellular stage, 11 in the transitional stage, and 3 in the late or fibrotic stage. Of the plaques harvested from mature cataracts, 8 were in the early cellular stage, 6 in the transitional stage, and 1 in the fibrotic stage; of the progredient cataract plaques, 3 were early cellular, 4 transitional, and 2 fibrotic. Among the 3 fibrotic plaques, 2 were in men. In men, there was also 1 transient and 3 early plaques. The plaques were found more frequently in women. Of those in women, 7 were in the early cellular stage, 10 in the transitional stage, and 1 in the fibrotic stage. Twelve patients were older than 70 years; in 6, the plaques were in the early stage; in 5, in the transitional stage; and in 1, in the fibrotic stage. The rate was similar in patients younger than 70 years: Four plaques were in the early stage, 6 in the transitional stage, and 2 in the fibrotic stage. In the 3 diabetic patients, the plaques were in 3 different stages. One eye had prior pars plana vitrectomy and another prior trabeculectomy. These patients (54, 57, and 62 years old) were younger than the other patients, and their cataracts were intumescent. Two of the 3 most severe fibrotic plaques were in these patients; the third was in a monocular patient who had had DM for 32 years. A high degree of myopia ( 16.0, 17.0, and 20.0 diopters) was revealed in 3 patients; 1 had a fibrotic plaque and 2 had transitional plaques. Apart from these patients, there was no

significant difference in the plaque stages with mature and progredient cataracts. DISCUSSION In 1977, Vasavada et al.1 described the posterior capsule plaque found during extracapsular cataract extraction. In this Indian series, the authors found plaques in about 10% of patients, mainly those with mature cataracts (27.3%) or with posterior cortical cataracts (12.5%); plaques were found rarely in nuclear sclerosis (5.1%). The phenomenon was significantly more common in patients older than 50 years. 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. The morphology examinations revealed that the plaques affected the center in only one third of cases; in two thirds, the plaques were located peripherally and did not affect visual acuity. Histological examinations were not performed. According to our histological findings, 3 developmental stages of plaques appear to exist. In the earliest stage, the plaque contains mostly cellular elements. These cells form a few layers; they have a regular, round nucleus and are mainly cuboidal cells. There is a narrow eosinophilic margin on the capsular sides of the cells, which contains minimum amounts of collagen or no collagen that is detected by picrosirius staining. We call this the early or cellular stage. Later, the cellular elements of the plaques decrease; longitudinal fibrocytic or fibroblast-like cells appear instead of the cuboidal cells, and collagen fibers start to form

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in the eosinophilic matrix. At this stage, cellular elements are present but there is collagen as well. We call this the transitional stage. At this stage, the plaque is not much thicker than in the cellular stage. Later, the plaques form a dense, collagen-fiber–containing tissue, their thickness significantly increases, and they do not contain cellular elements. We call this the late or fibrotic stage. It is well known that the lens capsule consists of collagen type IV and laminin.2 We have found only 1 article dealing with the histological examination of plaques.3 In this study, lenses removed by intracapsular cataract extraction were examined, and it was found that the plaques that stained positively with Masson trichrome dye consisted of collagen. It was presumed that these plaques were formed on the posterior capsule by migration and pseudofibrotic metaplasia of the epithelial cells. From the literature,4 it is also known that the lens epithelial cells under the anterior capsule are capable of proliferation, and this may lead to fibrotic plaque formation under the anterior capsule. This phenomenon has been called pseudofibrotic metaplasia. It is assumed that posterior capsule plaques can be formed by the same pathological mechanism.4–7 According to the literature, posterior capsule plaques are found 3 times more often in eyes that have had pars plana vitrectomy than in eyes that have not had vitrectomy.8–10 A posterior capsule plaque was found during surgery in an 8-year-old child with congenital cataract, and the authors suggested using trypan blue 0.1% to dye the plaque so the colored plaque could be easily seen and removed without damage to the posterior capsule.11 In our series, 97% of the patients were older than 50 years. We do not have specific reliable information relating to the duration of the plaques. Therefore, it is difficult to correlate different histopathological stages with plaque duration. We do not think the histopathological stages were associated with the ease or difficulty of surgical removal. We do not suggest polishing the posterior capsule plaque, as this can lead to posterior capsule break. If

it cannot be peeled off the posterior capsule, a posterior capsulorhexis can be done. The other possibility is to let it remain on the capsule. Even plaques located centrally do not always cause visual problems for the patient.1,3 If it does, performing a neodymium:YAG laser capsulotomy is another possibility but we suggest waiting at least 6 months after surgery to do this. REFERENCES 1. Vasavada AR, Chauhan H, Shah G. Incidence of posterior capsular plaque in cataract surgery. J Cataract Refract Surg 1997; 23:798–802 2. Zhang X-H, Sun H-M, Yuan J-Q. Extracellular matrix production of lens epithelial cells. J Cataract Refract Surg 2001; 27: 1303–1309 3. Peng Q, Hennig A, Vasavada AR, Apple DJ. Posterior capsular plaque: a common feature of cataract surgery in the developing world. Am J Ophthalmol 1998; 125:621–626 4. Font RL, Brownstein S. A light and electron microscopic study of anterior subcapsular cataracts. Am J Ophthalmol 1974; 78: 972–984 5. Apple DJ, Solomon KD, Tetz MR, et al. Posterior capsule opacification. Surv Ophthalmol 1992; 37:73–116 6. Green WR, McDonnell PJ. Opacification of the posterior capsule. Trans Ophthalmol Soc UK 1985; 104:727–739 7. Spaulding AG, Asbury T, Wander AH. Phacopathology: (1) duplication of posterior lens capsule, (2) total lens capsule stripping. Trans Am Ophthalmol Soc 1974; 72:282–301 8. Chang MA, Parides MK, Chang S, Braunstein RE. Outcome of phacoemulsification after pars plana vitrectomy. Ophthalmology 2002; 109:948–954 9. Grusha YO, Masket S, Miller KM. Phacoemulsification and lens implantation after pars plana vitrectomy. Ophthalmology 1998; 105:287–294 10. Pinter SM, Sugar A. Phacoemulsification in eyes with past pars plana vitrectomy: case-control study. J Cataract Refract Surg 1999; 25:556–561 11. Sharma N, Gupta V, Vajpayee RB. Trypan-blue-assisted posterior capsule plaque removal [letter]. J Cataract Refract Surg 2002; 28:916–917

First author: Zsolt Biro´, MD, PhD