Intraocular lens (IOL) opacification is a phenomenon in which the optic portion of an IOL inserted during cataract surgery becomes cloudy postoperatively. IOL opacification has been reported since the 1990s. It is observed in approximately 1 in 200 explanted or exchanged IOLs. 5) IOL optic opacification is one of the most common indications for IOL removal and exchange, but its incidence has been decreasing with improvements in materials. 7)
The opacification pattern varies depending on the IOL material.
The onset of opacification can be classified as intraoperative, early postoperative (hours to days), or late postoperative (months to years). If IOL opacification is misdiagnosed as posterior capsule opacification (PCO), unnecessary Nd:YAG laser capsulotomy or vitrectomy may be performed, potentially leading to complications.
Hydrophilic acrylic IOLs are most prone to opacification due to calcification. Hydrophobic acrylic IOLs may develop glistenings, but the impact on visual function is often mild. With current commercially available products, the incidence has decreased due to improved manufacturing processes.
IOL opacification progresses slowly, so it is often asymptomatic in the early stages.
High-magnification slit-lamp examination is key to diagnosis. The opacification pattern varies depending on the IOL material.
Calcium Deposition
Common material: Hydrophilic acrylic IOL
Appearance: Whitening due to calcium phosphate deposition on the surface to interior of the optic. Onset approximately 5 years after implantation.
Impact on visual function: Severe. Often indicates IOL explantation and exchange.
Glistening
Predisposing material: Hydrophobic acrylic IOL
Appearance: Fluid-filled microvacuoles of 1–20 μm appear inside the optic. The essence is aqueous phase separation.
Impact on visual function: Mostly mild, but in advanced cases, explantation and exchange may be effective. Visual function decline is more likely in patients with reduced retinal function such as retinal disease, macular disease, or glaucoma.
SSNG
Predisposing material: Hydrophobic acrylic (occasionally seen in AcrySof®)
Appearance: Microscopic aqueous phase separation of about 100 nm occurs on the inner surface of the optic, appearing as whitish opacity.
Impact on visual function: Minimal, but opacity increases over time.
Anterior segment optical coherence tomography (AS-OCT) is useful for detecting the presence, location, and density of calcification.
The causes of IOL opacification are multifactorial, involving a combination of IOL material properties, ocular local factors, systemic factors, and iatrogenic factors.
IOL opacification after corneal endothelial transplantation (DSAEK, DMEK) or vitrectomy has gained particular attention in recent years.
Belin et al. (2021) retrospectively reviewed 262 eyes with scleral-fixated Akreos AO60 IOLs and found an overall opacification rate of 2% (5/262 eyes), but a significantly higher rate of 25% (4/16 eyes) in eyes that underwent DSAEK (P < 0.01). 6) All 5 eyes with opacification had been exposed to intraocular gas or air.
Aguilera Zúñiga et al. (2025) reported that the opacification rate of hydrophilic IOLs after DMEK reached approximately 9%, and hydrophilic IOL material carried a 65-fold risk compared to hydrophobic material. 4) Rebubbling (repeat gas injection) was an independent risk factor, and approximately one-third of opacified IOLs ultimately required explantation.
In eyes at risk for corneal endothelial failure, selecting IOL materials other than hydrophilic acrylic is recommended in anticipation of future DSEK/DMEK. 7) Additionally, silicone IOLs can become opacified due to silicone oil adhesion during vitrectomy. 7)
Slit-lamp microscopy at high magnification is most important. Carefully observe the IOL optic surface for granular changes or opacification.
The main diagnostic points are as follows:
Contrast sensitivity testing is useful for quantitatively assessing the actual impact of IOL opacification on visual function. Although increased scattered light due to IOL opacification may not be apparent in visual acuity, it can be detected as a decrease in contrast sensitivity.
Definitive diagnosis is possible through precise analysis of the explanted IOL.
| Test method | Detection target |
|---|---|
| Alizarin red staining | Calcium on IOL surface |
| von Kossa staining | Calcium phosphate inside IOL |
| Scanning electron microscopy (SEM) + EDX | Crystal structure and elemental analysis |
Gartaganis et al. (2023) analyzed explanted Carlevale hydrophilic IOLs using SEM-EDX and confirmed a dense layer of hydroxyapatite (HAP) crystals (approximately 10 μm thick) on the anterior surface. 1) HAP formation was due to diffusion of ions (Ca²⁺, PO₄³⁻, OH⁻) into the hydrophilic polymer.
Alferayan et al. (2026) reported rosette-shaped snowflake deposits from an IOL of a patient with gyrate atrophy, and confirmed calcium oxalate crystals that were von Kossa stain positive and birefringent under polarized light. 5) This was the first report of calcium oxalate deposition, rather than calcium phosphate, causing IOL opacification.
IOL opacification is a change in the IOL optic itself, and high-magnification slit-lamp microscopy reveals granular to white opacification on or within the IOL. Posterior capsule opacification occurs on the posterior capsule behind the IOL and is observed as Elschnig pearls or fibrotic changes. Careful observation under mydriasis is important to prevent misdiagnosis.
The only definitive treatment for IOL opacification affecting visual function is IOL explantation and exchange. Severe opacification due to calcium deposition is a clear indication for exchange. Glistening and SSNS often have mild effects on visual function, but in advanced cases, exchange may be effective. Cases requiring IOL explantation due to glistening of hydrophobic acrylic IOLs are extremely rare. 7)
IOL explantation and exchange is a complex surgery with the following complication risks:
Anterior vitrectomy is required in 33% of IOL exchanges. If prior Nd:YAG laser posterior capsulotomy has been performed, this rate increases to 48%, and even in-the-bag fixation may become difficult.
In cases where BAB rupture is suspected, a hydrophobic IOL should be selected to prevent calcification.
Gartaganis et al. (2023) reported a case of hydrophilic Carlevale IOL calcification with Wagner syndrome, where the IOL was exchanged for a PMMA anterior chamber IOL, achieving corrected visual acuity of 20/25 at 3 months postoperatively. 1) The rationale for selection was that no calcification has been reported with hydrophobic materials.
Maguire et al. (2024) reported a case in a patient with Ehlers-Danlos syndrome where a calcified hydrophilic Akreos Fit IOL was exchanged for a 3-piece hydrophobic sulcus IOL, achieving corrected visual acuity of 6/10 at 2 weeks postoperatively. 2)
Transient opacities, such as IOL coating with triamcinolone acetonide (TA) particles, may resolve spontaneously.
Kumar et al. (2024) reported a case where an anterior chamber IOL was coated with TA particles after intravitreal TA injection. 3) With conservative observation, the IOL cleared within 3 weeks, and cystoid macular edema also resolved. Eyes with posterior capsule defects or zonular weakness have a risk of TA particle migration into the anterior chamber.
When DMEK is needed in eyes with a hydrophilic IOL, strategies to prevent gas-induced calcification are being considered.
Aguilera Zúñiga et al. (2025) reported a technique where an inverted phakic posterior chamber lens was temporarily placed in the anterior chamber during DMEK to block direct contact between gas tamponade and the Carlevale IOL. 4) The phakic posterior chamber lens was removed without complications after 2 weeks, and the IOL remained optically clear at 6 months. Corrected visual acuity improved from logMAR 1.00 to 0.22.
Calcification of hydrophilic acrylic IOLs occurs because functional groups (-OH and -COOH) on the polymer surface promote nucleation of calcium phosphate. 1) Ca²⁺ and PO₄³⁻ ions in the aqueous humor diffuse into the hydrophilic polymer and crystallize as hydroxyapatite (HAP; Ca₅(PO₄)₃OH).
According to Neuhann et al., calcification is classified into three groups.
In the SEM-EDX analysis by Gartaganis et al. (2023), a dense layer of HAP crystals approximately 10 μm thick was observed on the anterior surface of the Carlevale IOL. 1) HAP formation reached a depth of about 60 μm from the posterior surface, but no HAP layer was found directly beneath the posterior surface.
Air injection into the anterior chamber during DSAEK/DMEK or SF₆ gas during vitrectomy can directly contact the IOL, causing dehydration and chemical changes that lead to calcium and phosphate deposition at the exposed site. 6) Therefore, calcification after gas exposure is characteristically localized to the center of the optic.
In hydrophobic acrylic IOLs, the water content within the polymer increases with temperature rise in vivo, but when the temperature drops, excess water accumulates in voids within the polymer. This aqueous phase separation is the essence of glistening. It causes light scattering and retinal stray light.
Aqueous phase separation smaller than glistening (about 100 nm) occurs in the subsurface of the optic, causing whitening due to light reflection and scattering. Also called SSNG, it is occasionally seen in AcrySof®, a hydrophobic acrylic material.
Alferayan et al. (2026) reported rosette-shaped calcium oxalate crystal deposits on the IOL of a patient with gyrate atrophy. 5) In gyrate atrophy, OAT enzyme deficiency leads to high ornithine accumulation in the aqueous humor, which may alter its chemical composition and promote calcium oxalate precipitation. This is the first report of calcium oxalate (rather than calcium phosphate) deposition causing IOL opacification.
Aguilera Zúñiga et al. (2025) reported a technique in which, when performing DMEK in eyes with a hydrophilic Carlevale IOL, an inverted phakic posterior chamber lens (-0.5 D, 12.1 mm) is temporarily placed in the anterior chamber. 4) The phakic posterior chamber lens functioned as a barrier to block contact between the SF₆ 20% gas tamponade and the IOL. After two weeks, the phakic posterior chamber lens was removed, and at six months, the Descemet membrane graft remained well attached and the optical clarity of the IOL was maintained. The advantage is that sufficient tamponade can be maintained while avoiding additional surgical invasiveness such as IOL exchange. However, the additional cost of the phakic posterior chamber lens and the need for reoperation for its removal are challenges, and long-term safety data accumulation is needed.
