Complications arising in the lens capsule after cataract surgery are broadly classified into three types based on the behavior of lens epithelial cells (LECs). This article provides a comprehensive overview of these three conditions.
| Condition | Abbreviation | Main mechanism | LEC status |
|---|---|---|---|
| Anterior capsule contraction syndrome | ACCS | Excessive contraction and fibrosis of the CCC opening | Excessive proliferation |
| Capsular block syndrome | CBDS | Fluid accumulation between the IOL and posterior capsule | Metaplasia and proliferation (late type) |
| Dead bag syndrome | — | Loss of structural support of the capsule and late IOL dislocation | Complete disappearance |
Anterior Capsular Contraction Syndrome (ACCS) is a complication that occurs after phacoemulsification and intraocular lens (IOL) implantation. It refers to excessive contraction and fibrosis of the anterior capsular opening created by continuous curvilinear capsulorhexis (CCC).
First reported by Davison in 1993 1). Also called Capsule Contraction Syndrome (CCS) or anterior capsular phimosis.
According to ESCRS guidelines, the postoperative incidence is 0.47–3.3% 2), but some reviews report 1.4–14% 1), with onset most common within 3–30 weeks after surgery. Slight contraction of the opening is normal even in eyes without pathological changes, and contraction of about 10–20% usually does not cause clinical problems. However, excessive contraction progresses in eyes with specific risk factors.
Capsular Bag Distension Syndrome (CBDS) is a complication in which the capsular bag becomes sealed due to adhesion between the anterior surface of the IOL optic and the anterior capsule edge, leading to fluid accumulation between the IOL and the posterior capsule and distension of the posterior capsule. Also called capsular block syndrome (CBS). First reported by Davison in 1990 10).
The incidence is estimated at about 0.73% 6), and onset has been reported from a few weeks to 33 years after surgery 6). Based on Miyake et al.’s classification 5, 7), it is divided into three types: intraoperative (high irrigation pressure during hydrodissection), early postoperative (residual viscoelastic material), and late postoperative (metaplasia and proliferation of residual lens epithelial cells).
Dead Bag Syndrome is a condition in which all lens epithelial cells disappear after cataract surgery, resulting in the capsule being unable to hold the IOL on the optical axis. First named and reported by Dr. Samuel Masket. The capsule remains clear and thin but loses structural support, leading to late IOL dislocation 9). The incidence of IOL malposition is reported as 0.2–3%, and the onset of late dislocation ranges from 4.5 to 16 years after surgery 9).
The postoperative incidence varies by study but is reported to be about 0.47–3.3%. It occurs more frequently in eyes with risk factors such as zonular weakness or pseudoexfoliation syndrome.
ACCS is often asymptomatic until the condition progresses.
Observation of the CCC opening with a slit-lamp microscope is fundamental.
Mild to Moderate
Reduction of the opening: The created CCC window visibly shrinks and often becomes non-circular.
Fibrous thickening: White opaque tissue forms along the anterior capsule edge.
Fold formation: Radial folds (wrinkles) are observed in the anterior capsule.
Severe
Complete occlusion of the opening: The visual axis is completely blocked. Fibrous plaque fills the opening.
IOL decentration/tilt: The IOL becomes decentered or tilted due to a decrease in the capsular equator diameter.
IOL dislocation: The IOL dislocates together with the capsule due to excessive traction on the zonules.
If postoperative blurred vision, decreased visual acuity, or impaired pupillary function is observed, actively check for signs of ACCS. Mydriatic examination allows more accurate assessment of the degree of opening deformation and fibrous opacity.
The main symptoms of CBDS are gradual visual decline, blurred vision, and myopic shift, often without eye pain. Slit-lamp examination typically reveals turbid fluid accumulation between the IOL and the posterior capsule.
Early Postoperative Type
Anterior IOL displacement: The IOL shifts forward due to posterior capsule distension.
Shallow anterior chamber: Reflects forward movement of the lens-iris diaphragm.
Elevated intraocular pressure: May occur due to a pupillary block-like mechanism.
Clear to milky fluid: Originates from retained ophthalmic viscosurgical device (OVD).
Late Postoperative Type
Milky to turbid fluid: Homogeneous or heterogeneous white opacity behind the IOL.
Associated posterior capsule opacification (PCO): Fibrous changes may occur on the posterior capsule.
Soemmering ring: May be observed as an accumulation of residual cortex and epithelial cells.
Normal intraocular pressure and anterior chamber depth: Often not accompanied by elevated intraocular pressure or shallow anterior chamber.
According to Vlasenko’s classification, CBDS is classified into four types: type 1 (clear capsule and clear fluid), type 2 (homogeneous milky fluid), type 3 (fluid accumulation with posterior capsule opacification), and type 4 (opaque contents with posterior capsule opacification). In the late stage, hidden endophthalmitis caused by Propionibacterium acnes (P. acnes) may be present, requiring attention7).
The main symptom is painless progressive vision loss, and refractive error worsens as the IOL gradually shifts9). Onset occurs several to more than ten years after cataract surgery.
Slit-lamp examination reveals the following characteristic findings:
Case reports suggest that IOL support becomes unstable in a clear, thinned capsule9).
Posterior capsule opacification (PCO) is the most common cause, but other conditions to differentiate include anterior capsule contraction syndrome (contraction and fibrosis of the anterior capsule), capsular block syndrome (fluid accumulation behind the IOL), and dead bag syndrome (IOL displacement in a clear capsule). In addition to slit-lamp examination, anterior segment OCT and UBM are useful for differentiation.
Several pre-existing diseases are associated with the development of ACCS2, 3).
The material and design of the IOL affect the incidence of ACCS.
CBDS occurs through different mechanisms depending on the time of onset. Intraoperative type is caused by high perfusion pressure during hydrodissection, early postoperative type is mainly due to incomplete removal of ophthalmic viscosurgical devices (OVD) from the capsule, and late postoperative type is primarily driven by metaplasia and proliferation of residual lens epithelial cells and osmotic gradients5, 6, 7).
The following risk factors have been identified:
The exact etiology of dead bag syndrome remains unclear, but the following risk factors have been suggested9).
The most common cause of late IOL dislocation is pseudoexfoliation syndrome (prevalence 5–20%)9), but an important distinguishing feature from dead bag syndrome is that pseudoexfoliation syndrome shows residual lens epithelial cells and Soemmering ring formation.
The diagnosis of ACCS in post-cataract surgery patients is based on the presence of anterior capsule contraction confirmed by slit-lamp microscopy. It may or may not be accompanied by a decrease in best-corrected visual acuity compared to postoperative levels.
| Examination Method | Purpose |
|---|---|
| Slit-lamp examination | Evaluate the shape, size, and fibrosis of the CCC opening |
| Dilated examination | Assess overall opening deformation and IOL displacement |
| Ultrasound biomicroscopy (UBM) | Three-dimensional evaluation of IOL deformation and confirmation of zonular status |
Regular measurement of the CCC opening size allows early detection of progressive contraction.
Suspect CBDS in patients complaining of decreased vision after cataract surgery (regardless of postoperative duration). Slit-lamp examination confirms turbid fluid accumulation between the IOL and posterior capsule. Anterior segment OCT is useful for quantitative assessment of IOL displacement, and UBM is superior in cases of marked distention or when the posterior capsule is not visible 5, 6, 7).
Differential diagnoses include ordinary posterior capsule opacification (opacification of the posterior capsule adherent to the posterior surface of the IOL without fluid space), chronic endophthalmitis due to P. acnes, and pupillary block glaucoma.
Slit-lamp examination confirms IOL displacement along with a clear, thin, and lax capsular bag, and absence of fibrosis or opacification 9). Differentiation from pseudoexfoliation syndrome (with residual lens epithelial cells and fibrotic changes) and true exfoliation syndrome (with lamellar peeling of the capsule) is important. If the capsule is removed, histological confirmation of complete absence of lens epithelial cells and lamellar peeling of the capsule at the zonular attachment site is performed 9).
The first-line treatment for mild to moderate ACCS is Nd:YAG laser anterior capsulotomy (relaxing incision), which can be performed easily on an outpatient basis.
Key points of the procedure are as follows.
Note that circular excision (removing the annular capsular tissue) is not recommended because the excised fragments may deposit in the angle and cause elevated intraocular pressure.
To prevent intraocular pressure elevation, instill apraclonidine hydrochloride (Iopidine) 1 hour before and immediately after the procedure.
Recent studies report that the ring YAG laser method (ring YAG) has a significantly higher capsular bag relaxation rate (94.4% vs 66.7%) and better safety than conventional radial incision methods1). There are also reports of femtosecond laser-assisted capsulotomy for the treatment of capsular contraction1).
This is an invasive surgery indicated for cases with severe fibrosis causing marked capsular thickening and significant IOL decentration. After incising the capsule with capsular scissors, a tearing maneuver is performed with forceps1).
Xu et al. reported that CBRS performed in 25 CCS patients resulted in significant improvement in postoperative visual acuity compared to preoperative values1).
This is indicated for severe cases with dense fibrous plaques where Nd:YAG laser and vitrectorhexis are ineffective. Bimanual dissection and peeling of the fibrous membrane using 23-gauge trocars have been reported, achieving visual axis clearance and visual recovery3).
The first-line treatment for CBDS is Nd:YAG laser posterior capsulotomy, which is also described in the AAO Cataract in the Adult Eye PPP (2021) 8). An incision is made in the posterior capsule to drain the accumulated fluid into the vitreous cavity, restoring the IOL to its original position. The prognosis is excellent; the cloudy fluid disappears after a few laser shots, and vision quickly returns to baseline.
The treatment strategy by type according to the Vlasenko classification is as follows.
| Type | Treatment strategy |
|---|---|
| Type 1 | Observation |
| Type 2 | Symptomatic → YAG capsulotomy; asymptomatic → observation |
| Type 3 | YAG capsulotomy |
| Type 4 | YAG capsulotomy. If inflammation occurs, consider topical anti-inflammatory drugs + surgical aspiration. |
When the posterior capsule is invisible due to cloudy fluid, treatment with conventional Nd:YAG laser is difficult. Posterior capsulotomy using a femtosecond laser with intraoperative OCT has been reported as an option for severe late-stage CBDS at the case report level 5).
When the posterior capsule is invisible or endophthalmitis due to P. acnes is suspected, a surgical approach combining PPV and posterior capsulotomy is selected. In cases of late CBDS or infection, reports have described vitrectomy combined with posterior capsule management6, 7).
Treatment is selected according to the degree of IOL subluxation.
| Degree of subluxation | Treatment | Remarks |
|---|---|---|
| Mild | Observation | Monitor visual changes and progression of dislocation |
| Moderate to severe | IOL repositioning | In-the-bag fixation or scleral fixation |
| Severe / capsular damage | IOL exchange | Remove IOL-capsule complex and insert secondary IOL |
For IOL subluxation within the capsule due to dead bag syndrome, IOL repositioning has been reported 9). If capsular damage is severe or the IOL itself is problematic, the IOL-capsule complex is removed and a secondary IOL is inserted.
Nd:YAG laser is a painless outpatient procedure that takes a few minutes. In most cases, a single treatment is effective, and recurrence is rare. However, if fibrosis is severe, multiple sessions or surgery may be required.
The core of ACCS pathophysiology is the proliferation and fibrotic metaplasia of lens epithelial cells (LECs) remaining in the capsule after surgery 1, 3).
When LECs are stimulated by surgical trauma, they produce fibrosis-promoting cytokines such as TGF-β, FGF, interleukin-1, and interleukin-6 1). These cytokines alter the microenvironment of the aqueous humor, causing LECs to secrete collagen fibers.
LECs undergo epithelial-mesenchymal transition (EMT) and differentiate into myofibroblasts 1, 3). Myofibroblasts express α-smooth muscle actin (α-SMA) filaments and proliferate and extend from the CCC edge onto the IOL surface. This process generates two complementary mechanisms of anterior capsule contraction.
TGF-β acts as a “master regulator” of EMT, and after cataract surgery, disruption of the blood-aqueous barrier activates TGF-β1). The TGF-β/Smad pathway is involved in the pathogenesis of both ACCS and posterior capsule opacification (PCO). Smad7 protein is attracting attention as an EMT suppressor1).
When anterior capsule contraction occurs, an imbalance between the centripetal force from the anterior capsule edge and the centrifugal force from the zonules is important3). In eyes with weak zonules, the centripetal force dominates, making contraction and fibrosis more pronounced. In high myopia, the concentration of TGF-β2 in the aqueous humor increases, promoting the transformation of LECs into myofibroblasts4).
MMP-2 plays an important role in TGF-β2-mediated matrix contraction and posterior capsule opacification. Inhibition of MMP-2 is being studied as a novel therapeutic strategy for ACCS and PCO1).
The core of the pathophysiology of late-onset CBDS involves two mechanisms: metaplasia and proliferation of residual LECs, and osmotic gradient5, 6, 7).
Metaplasia and proliferation pathway: Residual LECs at the equator undergo fibroblast-like metaplasia and begin to proliferate. LECs produce extracellular matrix such as collagen type IV, and the residual cortex swells and liquefies, leading to accumulation of a milky white turbid fluid within the capsule (called lacteocrumenasia)7). Analysis of the fluid from treated cases has detected large amounts of α-crystallin by electrophoresis.
Osmotic gradient pathway: The osmotic gradient between the hyperosmolar contents inside the capsule and the hypoosmolar aqueous humor promotes fluid influx, accelerating capsular distension6).
Early postoperative type is caused by the sealing effect of residual OVD due to its high viscosity and high osmolarity, while intraoperative type results from excessive distension of the posterior capsule due to high-pressure injection during hydrodissection.
In dead bag syndrome, contrary to ACCS, LECs are completely absent, so no postoperative cellular responses (PCO, anterior capsule contraction) occur9).
The main reason is the presence or absence of risk factors. In eyes with pseudoexfoliation syndrome, diabetes, high myopia, or uveitis, LEC are more easily activated and zonules are fragile, making the balance between centripetal and centrifugal forces prone to disruption. Additionally, the material and design of the IOL used affect the incidence rate. Interestingly, when LEC are completely absent, it leads to the contrasting complication of dead bag syndrome.
Intraoperative 360° anterior capsule polishing may reduce LEC adhesion to the capsule and suppress postoperative capsular deformation. One report found that the anterior capsule opening area was larger in the polished group compared to the non-polished group at 12 months 1). However, the effect on posterior capsule opacification (PCO) is inconsistent across studies, and no definitive conclusion has been reached at this time 1).
Aspirin has been shown to potentially suppress the EMT process of LEC. In a human lens capsule model, the EMT inhibitory effect was enhanced in an aspirin concentration-dependent manner 1). Application to IOL-mounted drug delivery systems is being considered.
Resveratrol may suppress TGF-β2-induced fibrosis-related gene expression and reduce LEC proliferation on the posterior capsule. It has been shown to inhibit capsular wrinkling and is attracting attention as a future candidate for preventing PCO and ACCS 1).
G-CSF (granulocyte colony-stimulating factor) has been reported to promote proliferation, migration, EMT, and extracellular matrix synthesis in human lens epithelial cells (HLEC-B3). Regulation of G-CSF expression may be a target for PCO treatment 1).
Insertion of a capsular tension ring (CTR) in eyes with weak zonules has been reported to prevent postoperative IOL decentration and tilt, as well as to suppress anterior capsule contraction 4).
Antibiofouling IOLs that suppress LEC adhesion, photodynamic inhibition IOLs for LECs, and micropattern surface IOLs are under development, and are expected to be applied to prevent capsular opacification and contraction in the future 1).
Femtosecond lasers have been used for anterior capsulotomy, nuclear fragmentation, and corneal incisions in cataract surgery, but their application to CBDS is a relatively new attempt 5). Intraoperative OCT-guided femtosecond laser posterior capsulotomy has been reported as a candidate for severe late-stage CBDS where conventional Nd:YAG laser is not applicable. Equipment cost and access issues are limiting factors 5).
The exact pathogenesis of dead bag syndrome remains unknown, and elucidating the molecular mechanisms leading to LEC loss is a future challenge 9). Some case reports suggest an association with systemic conditions, but at present this remains hypothetical 9). Studies are needed on the optimal extent of capsular polishing and the balance between LEC preservation and prevention of posterior capsule opacification.
