Anterior capsule fibrosis and in-the-bag subluxation of the intraocular lens with a concertina-like folded surface of the lens capsule (arrow).
A, Light microscopy of the capsular bag from patient 8 showing a concertina-like folded lens capsule (arrows) and paucicellular membrane (arrow). LP indicates lens protein. B, Enlarged view of concertina-like folded lens capsule. C, Electron microscopy shows extracellular fibrillary collagen (COL), spindle-shaped nucleus (N), and basal lamina (BL). D, Fibrosis and epithelial metaplasia in the crystalline lens.
Heng LZ, Sandhu R, Snead DRJ, Poulson A, Snead M. Clinicopathologic Correlation of Lens Epithelial Metaplasia and Late Intraocular Lens Dislocation After Repair of Retinal Detachment. JAMA Ophthalmol. 2016;134(7):827–830. doi:10.1001/jamaophthalmol.2016.1184
In-the-bag intraocular lens dislocation is an uncommon but serious complication of cataract surgery in patients with previous repair of retinal detachment. The causative mechanism is currently unknown. We report histologic findings from a retrospective case series from 1993 to 2010 and suggest a possible mechanism to explain this association.
Clinical characteristics of 8 patients presenting with in-the-bag intraocular lens dislocation after repair of retinal detachment were evaluated. Explanted capsular bags from 3 of these patients were compared with pathologic changes of crystalline lenses associated with retinal detachment. Histologic examination of the explanted capsular bags revealed a paucicellular membrane that covered the concertina-like folded surface of the lens capsule. The lens capsule was devoid of epithelial cell nuclei and showed excessive thickening with the presence of spindle-shaped cells, such as fibroblasts. Collagen fibers were noted in the extracellular matrix.
Conclusions and Relevance
Previous studies of crystalline lens pathologic findings associated with retinal detachment have shown changes in the epithelium with migration and subsequent metaplasia of epithelial cells, resulting in excessive thickening of the anterior capsule with a layer of fibrous tissue. In this retrospective series, similar histologic findings were seen, suggesting that zonular dehiscence and lens dislocation may result from progressive capsular contraction secondary to retinal detachment–induced lens epithelial metaplasia.
Spontaneous in-the-bag intraocular lens (IOL) dislocation is an uncommon but serious complication after cataract surgery, with a known incidence of 0.032% to 0.28% in the general population.1- 3 Risk factors for in-the-bag IOL dislocation include trauma, pseudoexfoliation, high myopia, uveitis, previous vitreoretinal surgery, and connective tissue diseases.4- 6 The pathogenesis of this phenomenon has been hypothesized to be secondary to 1 or a combination of the following conditions: zonular dehiscence owing to mechanically weakened zonules, accumulation of exfoliation material in patients with pseudoexfoliation syndrome, or zonular failure from anterior capsule phimosis (otherwise known as capsular contraction syndrome).7,8
Although vitreoretinal procedures have been frequently cited as a risk factor for in-the-bag IOL dislocation, the pathologic basis for this association remains largely unexplored. We report histologic findings from a series of patients with in-the-bag IOL dislocation and suggest a possible mechanism to explain this causal association.
Question Do findings from clinicopathologic studies suggest a possible mechanism for in-the-bag intraocular lens dislocation and retinal detachment?
Findings A clinicopathologic evaluation of 8 patients showed migration and subsequent metaplasia of lens epithelial cells, resulting in abnormal thickening of the anterior capsule with a layer of fibrous tissue.
Meaning These findings suggest that zonular dehiscence and lens dislocation are associated and may result, at least in part, from progressive capsular contraction secondary to rhegmatogenous retinal detachment–induced lens epithelial metaplasia.
A retrospective review was undertaken of case notes from the Vitreoretinal Service at Addenbrooke’s Hospital, Cambridge, England, of consecutive patients between 1993 and 2010 with a history of retinal detachment who underwent surgery for spontaneous in-the-bag IOL dislocation in the same eye as the retinal detachment. Eight such patients were identified (Table). Other than patient 3, who had pseudophakia before repair of the retinal detachment, all other patients developed cataracts after repair of the retinal detachment. Addenbrooke’s Hospital Institutional Review Board waived approval, as the study was a retrospective case series.
Where applicable, written informed consent for tissue analysis for research was obtained, and the capsular bag containing the explanted IOLs from patients 2, 3, and 8 were fixed in glutaraldehyde, processed, and embedded in epoxy resin. Semithin sections (0.5 µm) were cut and stained with toluidine blue and examined using standard slitlamp biomicroscopy.
Similar slitlamp biomicroscopy findings were seen in all 8 patients. All patients demonstrated anterior capsule fibrosis with a thickened and irregular surface and in-the-bag IOL subluxation with a concertina-like folded contraction of the surface of the lens capsule (Figure 1).
Similar pathologic findings were noted in each of the explanted specimens. Figure 1 demonstrates a subluxed IOL (patient 2), and Figure 2 shows the histopathologic changes observed in patient 8. In both patients, a paucicellular membrane covered the concertina-like folded surface of the lens capsule, which contained a residuum of lens protein. The lens capsule itself was devoid of epithelial cell nuclei and showed focally excessive thickening. The cells within the capsular membrane are spindle shaped and are present on the surface of the membrane, with an extracellular matrix separating these cells from the lens capsule. These spindle cells are surrounded by a basal lamina, but the cytoplasm lacked prominent rough endoplasmic reticulum, which would be expected in actively secreting cells such as fibroblasts. The extracellular matrix did, however, contain classic, banded, fibrillary collagen fibers.
Spontaneous in-the-bag IOL dislocation occurred very late (between 3 and 17 years) after routine, uneventful cataract surgery in this retrospective case series of 8 patients who had undergone repair for retinal detachment. Histopathologic examination of the capsular bags from 3 patients showed a layer of extracellular collagenous stroma containing spindle cells on the surface of the lens capsule, associated with a folded concertina-like distortion of the lens capsule. The folding of the lens membrane in comparison with the linear arrangement overlying the membrane suggests a constrictive force from the membrane. In the absence of any other cellular constituent, it seems most likely that the collagenous matrix is produced by the spindle cells within the membrane. The origin of these cells is uncertain from these studies, although true metaplasia of the lens capsule epithelium into a fibroblast-like cell is a likely possibility.
The clinical findings of anterior capsular concertina-like fibrosis correspond with the histologic findings of a thickened capsule that consists of a cellular membrane, comprising a single layer of vacuolated cuboidal cells. These findings suggest the involvement of subcapsular metaplasia of the epithelial lens in the pathogenesis of this complication.
The findings are strikingly similar to those described previously by Scott,9 associating anterior lens epithelial metaplasia and consequent cataract formation as a result of epithelial regulatory dysfunction in patients with giant retinal tears causing retinal detachment. Scott9 noted the phenomena of migration of equatorial and anterior epithelial cells, followed by cell metaplasia with resultant collagen production. Subcapsular epithelial thickening that remains adherent to the capsule was also noted. It is known that retinal pigment epithelium proliferates in response to retinal detachment, migrates into the vitreous, and transforms into fibrocyte-like cells. Scott9 hypothesized that the cause of the lens epithelial metaplasia stems from the same factors that result in retinal epithelial metaplasia.
Two of our 8 patients underwent an extracapsular cataract extraction via the “can opener” capsulotomy technique, and the rest underwent phacoemulsification via continuous curvilinear capsulorrhexis; all the cataract surgical procedures were uneventful. A previous large-scale epidemiologic study did not find any difference between the incidence of late dislocation of in-the-bag IOL between extracapsular cataract extraction and phacoemulsification.10
Based on the current histologic findings, several plausible theories may explain current phenomena associating lens epithelial metaplasia with dislocation of the IOL. First, the current findings may lend support to the theory of capsular contraction syndrome, in which there is imbalance between the centrifugal forces of the zonules, IOL haptics, and metaplastic lens epithelial cells.8 Furthermore, the metaplastic cuboidal cell membrane has been found to undergo myofibroblastic transformation with collagen and fibrous membrane formation, causing contraction, zonular dehiscence, and displacement of the IOL.9 Second, Yasuda et al6 described the loss of zonules after cataract surgery in a patient with IOL dislocation who had previously undergone vitreoretinal surgery. The investigators attributed the IOL dislocation to be a consequence of the combination of damage to the anterior hyaloid membrane and the posterior zonules. In the same study, it was postulated that centripetal contractual forces caused by capsular contraction triggered dialysis of the lens zonules, which may be a secondary effect as a result of capsular contraction syndrome.
In this series, 50% of patients had experienced giant retinal tears and 1 patient had a horseshoe-shaped tear. As such, we are unable to comment on the risk of lens dislocation to retinal detachment secondary to a horseshoe-shaped tear. However, our study found similar appearances to giant retinal tear–associated changes in the crystalline lens of subcapsular metaplasia of the lens epithelium and thickening, which suggests that zonular dehiscence and lens dislocation results from progressive capsular contraction secondary to rhegmatogenous retinal detachment–induced lens epithelial metaplasia.
This clinicopathologic study shows that zonular dehiscence and IOL dislocation may result from progressive capsular contraction secondary to retinal detachment–induced lens epithelial metaplasia.
Submitted for Publication: January 16, 2016; final revision received March 14, 2016; accepted March 15, 2016.
Corresponding Author: Martin Snead, MD FRCS FRCOphth, Vitreoretinal Service, Addenbrooke’s Hospital, Cambridge University Hospital, National Health Service Foundation Trust, Hills Road, Cambridge CB2 0QQ, England (firstname.lastname@example.org).
Published Online: May 26, 2016. doi:10.1001/jamaophthalmol.2016.1184.
Author Contributions: Drs Heng and M. Snead had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Sandhu, Poulson, M. Snead.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Heng, Sandhu, D. R. J. Snead, M. Snead.
Critical revision of the manuscript for important intellectual content: Heng, Sandhu, Poulson, M. Snead.
Statistical analysis: Sandhu.
Obtained funding: Sandhu.
Administrative, technical, or material support: Heng, Sandhu.
Study supervision: Sandhu, Poulson, M. Snead.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.