Cataract surgery with intraocular lens (IOL) implantation has undoubtedly advanced at a remarkable pace since the development of phacoemulsification. Complications have decreased, and expectations for positive results have risen. Yet with the continued pursuit of perfection through new techniques and devices arises a small but significant risk for new complications. Late in-the-bag IOL subluxation or dislocation is a rare but serious complication that occurs on average 8.5 years after implantation.1 The incidence has been rising since the advent of continuous curvilinear capsulorhexis (CCC) and is most likely caused by factors such as zonular weakness and zonular stress that can occur during surgery or postoperatively in association with capsule fibrosis.2–6
In previous studies of late in-the-bag IOL subluxation or dislocation performed at the University of Utah, Salt Lake City, Utah, USA, pseudoexfoliation (PXF) was a significant associated condition.1,7,8 Complete histopathologic analysis of selected specimens represented by capsular bags containing an IOL or an IOL and a capsular tension ring (CTR) sometimes showed the presence of PXF material, even if there were no clinical history or evidence of PXF.1,8 We hypothesized that the prevalence of PXF might be higher in late postoperative in-the-bag IOL subluxation or dislocation than the rate reported based on the clinical diagnosis of this condition. Therefore, in the current study, complete histopathologic analysis of a large series of capsular bags from such cases, consecutively explanted in the same center at the University of Frankfurt, Germany, was performed.
Materials and methods
An institutional review board sanctioned the study design, data collection, storage, and processing. This retrospective study was designed to analyze IOL–capsular bag complexes subluxated (within the retropupillary space or anterior vitreous) or dislocated (posterior vitreous) after cataract surgery. The specimens were represented by capsular bags containing an IOL or an IOL and a CTR. The majority of the specimens were explanted by the same surgeon in Germany (T.K.). Some of the specimens were explanted by another surgeon from the same center (F.H.).
Consecutive explantation specimens from December 2011 through June 2013 were submitted to the John A. Moran Eye Center, University of Utah, immersed in fixative (10% neutral buffered formalin). Pathologic evaluation was completed for IOL design and material composition and any notable pathology. All specimens were analyzed macroscopically, and gross photographs were taken using a camera (model D40 with an AF Micro Nikkor 55 mm 1:2.8 lens, Nikon Corp.) mounted on an MP-4 Land Camera (Polaroid). They were then analyzed microscopically under light microscopy (Olympus BX40). Photomicrographs were taken with an Olympus microscope digital camera (model P20) mounted with a U-TV0.5xC-3 C-mount video port attached to the light microscope for photodocumentation.
All specimens were then processed for complete histopathologic evaluation. After dehydration and embedding in paraffin, multiple 3 μm thick sections were cut and stained with Masson trichrome. The focus of histopathologic analysis was for the presence or absence in each specimen of an amorphous substance on the outer surface of the anterior capsule in an “iron-filing” pattern, which strongly suggests PXF material. This was performed by 1 observer masked to the presence or absence of a clinical diagnosis of PXF. Surgeons were also asked to submit a case summary with each specimen by answering a questionnaire regarding the patient’s age, sex, history leading to subluxation or dislocation, associated ocular conditions, and dates of IOL implantation and explantation. Chart review, when obtainable, confirmed the survey data.
The 2 German surgeons submitted 40 specimens from 40 patients (no bilateral cases) resulting from subluxation or dislocation between December 2011 and June 2013. The specimens were represented by explanted subluxated or dislocated capsular bags containing an IOL (n = 37) or an IOL–CTR (n = 3). There were 14 men and 26 women. The mean patient age was 77.05 years ± 9.99 (SD) at explantation, which was performed a mean of 12.0 ± 4.8 years after implantation. Two specimens were explanted because of subluxation and 38 because of dislocation into the posterior segment.
The IOLs in this series included 3-piece hydrophobic acrylic (n = 13), 1-piece hydrophobic acrylic (n = 7), 3-piece silicone (n = 6), 1-piece hydrophilic acrylic (n = 6), 3-piece hydrophilic acrylic (n = 2), and 1-piece poly(methyl methacrylate) (PMMA) (n = 6) designs; all CTRs were PMMA, generally manufactured by Morcher GmbH or Acri.Tec/Carl Zeiss Meditec AG. Figure 1 shows gross photographs of examples of the specimens analyzed in this study.
According to available patient history, associated ocular conditions were identified as follows: PXF (n = 13; 3 cases with glaucoma), previous vitrectomy or retina surgery (n = 5), myopia (n = 4), retinitis pigmentosa (n = 1), Marfan syndrome (n = 1), and history of trauma (n = 1).
Although some areas of the capsular bags were disrupted on explantation in some specimens, proliferative or regenerative material contained within the capsular bag (Soemmering ring formation) could be graded as mild, moderate, and severe. Soemmering ring formation was mild in 8 specimens, moderate in 18 specimens, and severe in 14 specimens. Excessive contraction of the capsular bag with capsulorhexis phimosis was observed in 24 specimens. Explantation was performed a mean of 11.58 ± 4.45 years after implantation in eyes with capsulorhexis phimosis.
Histopathologic analysis of the specimens showed 26 specimens with evidence of PXF. This is in contrast to 13 specimens having an associated clinical history or evidence of PXF. Explantation was performed a mean of 11.88 ± 5.21 years after implantation in eyes with histopathologic evidence of PXF. All specimens with clinical histories of PXF were found to have histopathologic evidence of the same. Of the 14 specimens without histopathologic evidence of PXF, 1 was from an eye with retinitis pigmentosa, 2 had previous pars plana vitrectomy, 1 had a history of trauma, 1 had associated Marfan syndrome, 2 had high myopia, and 4 were from patients aged between 75 years and 93 years at explantation. Of the 24 specimens with capsulorhexis phimosis, 17 had histopathologic evidence of PXF (Figure 2). However, in some cases with extreme capsulorhexis phimosis, sometimes leading to flexing of the IOL haptics anteriorly, no signs of PXF were found (Figure 3).
We have received an increasing number of specimens in our laboratory related to in-the-bag IOL subluxation or dislocation.1,7–9 The findings in 86 consecutive cases sent for pathological analysis were described in 2009.1 The series included specimens submitted between 2000 and 2008; 2 of the specimens were submitted before 2003 and all others between 2006 and 2008. The mean time from surgery to spontaneous IOL dislocation was 8.5 years. Associated conditions included PXF (50%), previous vitreoretinal surgery (19%), history of trauma (6%), uveitis (2%), and none or unknown (23%). None of the specimens contained an accompanying CTR, which indirectly suggested the efficacy of this device in preventing this complication.1
In a follow-up study, 23 specimens corresponding to explanted subluxated or dislocated capsular bags containing a CTR and an IOL were evaluated.8 Explantation was performed a mean of 81.5 ± 32.2 months after implantation. Available information on associated ocular conditions included PXF (74%), glaucoma (17%), vitrectomy or retina surgery (13%), and trauma (4%). Excessive contraction of the capsular bag with capsulorhexis phimosis was observed in 11 specimens, 1 with an associated history of vitrectomy, 7 with an associated history of PXF, and 3 with an associated history of glaucoma. One of the eyes in this series had implantation of a 1-piece hydrophilic acrylic IOL; excessive capsule fibrosis led to capsulorhexis phimosis and anterior flexing of the IOL haptics despite the presence of a CTR. Explantation was performed a mean of 72.1 ± 41.3 months after implantation (approximately 6 years) in eyes with capsulorhexis phimosis.8
It is not surprising that the mean explantation time was shorter in the series of 23 specimens containing a CTR (6.8 or 6.0 years, without or with capsulorhexis phimosis, respectively)8 than in the series of 86 specimens without a CTR (8.5 years),1 considering that CTRs are usually implanted when zonular weakness is observed before or during surgery. This has also been reported in other series by different authors.10 Stress to the zonular fibers during CTR insertion cannot be ruled out. In the 2 previous studies,1,8 histopathologic assessment was completed in selected specimens only. This included 3 cases with a CTR for which histopathology showed material consistent with PXF, while there was no history or clinical signs of this condition.8 We hypothesized therefore that the prevalence of PXF in subluxation or dislocation series might be higher than the rate based on clinical history and/or clinical examination. Therefore, we performed this study, showing PXF material histopathologically in 26 specimens, while clinical history and examination suggested PXF in 13 cases. All specimens with a clinical history of PXF had histopathologic evidence of this condition.
Multiple conditions likely play a role in contributing to inherent zonular weakness and instability. The most commonly correlated conditions include PXF syndrome, previous vitreoretinal surgery, trauma, and myopia. Additional causes include connective tissue disorders (homocystinuria; Marfan, Ehler-Danlos, or Weill-Marchesani syndromes) and retinitis pigmentosa.2–6,10–12 Pseudoexfoliation is a condition in which abnormal extracellular matrix and basement membrane structural and metabolic proteins are deposited into virtually all structures in the anterior chamber.13 These accumulations mechanically weaken the zonular lamella and impair zonular anchoring to the epithelial basement membrane at both its origin and insertion.14 Because zonular fibers are mainly composed of elastic fibers and patients with PXF have an increase in elastinolysis, the disease likely also enzymatically weakens the zonules.15
Studies have evaluated the rate of PXF in specific populations—Scandinavian countries,16,17 Arabic countries,18 the Bantu tribes of South Africa,19 Japan,20 and India21,22—with variable results. In our current study, all patients were white and originally from Germany or neighboring Eastern European countries. Pseudoexfoliation is also thought to have a factor of inheritance associated with lysyl oxidase-like 1-associated variants.23 Lysyl oxidase-like 1 is a member of a gene family that plays an important role in elastin metabolism. It remains controversial whether regions with a high prevalence of PXF confer a risk as a result of genetics or geographic location because more recent prospective studies report an association with latitude, suggesting complex interactions between inheritance and environmental factors. However, a clear association with increasing age has been reported in multiple studies, and a variable relationship with the female sex exists.24–26 Results in our study show a nearly 2:1 female predilection. Pseudoexfoliation can be a difficult clinical diagnosis, with many cases going unnoticed until well advanced.27
Histopathologic and electron microscopy analyses have identified subclinical cases of PXF in conjunctival biopsies and in crystalline lenses from patients with senile cataracts.28,29 Prince et al.28 categorized a group of patients as who showed no evidence of PXF on the lens capsule in either eye as “PXF suspects.” In their study, inferior bulbar conjunctival biopsies were performed on 4 eyes with PXF, 5 fellow eyes, and 23 PXF-suspect eyes, and specimens were examined by transmission electron microscopy. In 8 suspect eyes, biopsy specimens showed PXF, suggesting that it is more prevalent and possibly responsible for a greater proportion of glaucoma than previously suspected.28 In a study by Dark and Streeten,30 the authors reported that in many older patients, a layer of subtle opacification on the anterior lens capsule, appearing as a ground-glass film, was observed biomicroscopically. Lens capsule material obtained at cataract extraction was studied in patients with and without the film. On scanning electron microscopy (SEM), the film appeared as a friable incomplete fibrillar layer with rolling of the edges, suggesting loose attachment. Ultrastructurally, its component fibrils were from 3.0 to 6.0 nm in diameter, similar to the finer fibrils in PXF material.30 Our study represented by a large series of 40 capsular bags consecutively explanted because of subluxation or dislocation confirms these findings, with a significant clinical underdiagnosis of PXF when compared with histopathologic diagnosis (1:2). A limitation of our study is that ultrastructural evaluations (transmission and SEM) were not performed. Perhaps this would have yielded an even higher PXF rate than the rate found based on histopathologic analyses.
In this current study, as well as in previous studies,1,8 capsulorhexis phimosis was a significant finding in relation to late in-the-bag subluxation or dislocation and PXF. Of the 24 specimens with capsulorhexis phimosis, 17 had histopathologic evidence of PXF. Phimosis exerts a tractional force on the capsular bag that is transmitted to the zonular fibers.5 Capsule contraction syndrome might lead to zonulysis by itself; however, any capsule fibrosis might transmit increased force into the zonular apparatus. The case shown in Figure 3 is of particular interest. Constriction of the capsular bag secondary to fibrosis caused significant anterior flexing of the haptic elements of the implanted 1-piece hydrophilic acrylic IOL. Histopathologic analysis showed dense anterior subcapsular fibrosis and fibrous metaplasia of the anterior lens epithelial cells (LECs); however, no signs suggestive of PXF were found. This case raises concerns related to the continuously evolving indications for implantation of highly flexible IOLs (eg, microincision IOLs), in particular in patients with no clear predisposition to zonular weakness and, accordingly, excessive capsular bag contraction.
Bilateral late in-the-bag dislocations have been reported, suggesting that it is important to pay particular attention to the unaffected eye in patients who have had a late in-the-bag dislocation.4,8,31 Without intervention, minimally displaced IOLs might eventually completely dislocate; therefore, early management is ideal.3,10 Anterior relaxing capsulotomy incisions can be performed as a preventive measure when phimosis is first noticed. A study suggests that to minimize the chances of complications that would arise if the IOL dislocated completely, surgical correction should be performed within 1 month.2 In cases with open-loop and plate-haptic IOLs with holes without excess residual cortical material or excessive phimosis, repositioning may be safer than exchange if the displaced IOL is noted early enough.10 Standard CTRs do not prevent capsulorhexis phimosis or late dislocation.8,32,33 Studies34,35 describe surgical repositioning techniques in the presence of a CTR. In cases of profound zonular weakness, devices designed for scleral fixation should be considered.36,37,A A more recently published study38 describes a promising surgical technique to prevent late in-the-bag dislocation in at-risk patients. The technique is based on the combined effect of multiple historical methods to maximize IOL and capsular bag stabilization during and after surgery. Seventy patients who had predisposing factors such as PXF, uveitis, retinitis pigmentosa, and long axial length had the procedure. After a small CCC was created, iris hooks were used to help stabilize the capsular bag during hydrodissection and phacoemulsification. A CTR was then placed in the bag, followed by a foldable acrylic multipiece IOL placed in the sulcus. The optic of the IOL was then captured by the anterior capsulorhexis opening. No intraoperative or postoperative complications were reported.
In summary, as shown in this study, PXF is likely present in a much larger percentage of patients who have late in-the-bag IOL dislocation than the number currently detected clinically. Increased understanding of this disease process and its potentially detrimental effects in patients can guide surgeons in choosing the most appropriate preventive measures in patients who are at highest risk for late in-the-bag dislocation and minimize the potentially devastating postoperative complications.
What Was Known
- Pseudoexfoliation is an important risk factor for late in-the-bag IOL subluxation/dislocation. The prevalence of this condition in these cases might be higher than the rate reported based on clinical diagnosis alone.
What This Paper Adds
- This study represented by a large series of 40 capsular bags consecutively explanted because of subluxation/dislocation confirmed a significant clinical underdiagnosis of pseudoexfoliation compared with the histopathologic diagnosis.
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Other Cited Material
A. Rosenthal KJ. Improving surgical outcomes with capsular tension rings. Rev Ophthalmol. 2001;8(5):47-55.