Intraocular Lens Opacification

Key points at a glance

1. What is Intraocular Lens Opacification?

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.

Hydrophilic acrylic IOL: Calcium phosphate deposition (calcification)
Hydrophobic acrylic IOL: Glistening, whitening (SSNG)
Silicone IOL: Discoloration
Polymethyl methacrylate (PMMA) IOL: Snowflake degeneration

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.

Q Which type of IOL is most prone to opacification?

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.

2. Main Symptoms and Clinical Findings

Subjective Symptoms

IOL opacification progresses slowly, so it is often asymptomatic in the early stages.

Blurred vision (haze): As opacification progresses, the entire visual field appears hazy.
Visual acuity loss: Calcium deposition can cause significant visual acuity loss.
Glare: Particularly easily induced by glistenings.
Decreased contrast sensitivity: May be noticed even with mild opacification.

Clinical Findings

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.

3. Causes and Risk Factors

The causes of IOL opacification are multifactorial, involving a combination of IOL material properties, ocular local factors, systemic factors, and iatrogenic factors.

Hydrophilic acrylic: Hydroxy groups (-OH) and carboxy groups (-COOH) on the material surface catalyze calcium phosphate crystallization. ¹⁾
Hydrophobic acrylic: Temperature changes cause fluctuations in water content within the polymer, leading to aqueous phase separation (glistening).
IOL manufacturing/storage errors: Poor polymer formation and interaction with packaging materials can also cause primary opacification.

Ocular Local Factors

Breakdown of the blood-aqueous barrier (BAB): prolonged or complex surgery, severe postoperative inflammation, chronic uveitis
Intraocular gas or air exposure during intraocular surgery: DSAEK, DMEK, and vitrectomy are among the most important risk factors
Residual lens cortex: dystrophic calcification due to elevated aqueous humor calcium levels
Asteroid hyalosis: associated with calcification of silicone IOLs; over 85% of calcification cases have ipsilateral asteroid hyalosis
Pseudoexfoliation syndrome: spoke-like opacities on the anterior IOL surface

Systemic Factors

Diabetes mellitus: BAB breakdown and elevated aqueous humor phosphorus levels due to proliferative diabetic retinopathy ⁶⁾
Connective tissue diseases: Ehlers-Danlos syndrome may impair BAB via vascular damage; bilateral secondary calcification has been reported 14 years after IOL implantation ²⁾
Metabolic diseases: Gyrate atrophy (OAT gene mutation) may cause elevated aqueous ornithine leading to calcium oxalate deposition ⁵⁾

Risks Associated with Secondary Surgery

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⁾

Q If vitreous surgery or corneal transplant is planned, are there any points to consider regarding IOL selection?

Hydrophilic acrylic IOLs have a high risk of calcification after exposure to intraocular gas. If future DSAEK, DMEK, or vitreous surgery with gas tamponade is possible, a hydrophobic acrylic IOL is recommended. ⁶⁾

4. Diagnosis and Examination Methods

Clinical Diagnosis

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:

Location of opacity: Distinguish between surface deposits and internal changes. Calcification after gas exposure is often localized to the center of the optic. ⁶⁾
Morphology of opacity: Calcium deposits appear granular to white, while glistenings are observed as punctate bright spots.
Retroillumination: Useful for evaluating the extent and severity of IOL opacification.

Imaging Tests

Anterior segment OCT (AS-OCT): Non-invasively assesses the location and density of calcification. Helps differentiate internal changes from surface deposits.
Slit-lamp photography: Useful for documenting progression over time.

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.

Post-removal specimen analysis

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.

Differential diagnosis

Posterior capsule opacification (PCO): The most important differential diagnosis. If IOL opacification is misdiagnosed as PCO and Nd:YAG laser posterior capsulotomy is performed, subsequent IOL exchange becomes difficult.
Vitreous opacification / vitreous hemorrhage
Anterior capsule epithelial cell proliferation
Opacification between lenses of piggyback IOL

Q How to differentiate IOL opacification from posterior capsule 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.

5. Standard Treatment

IOL Explantation and Exchange

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:

Zonular rupture
Posterior capsule rupture
Corneal endothelial damage

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.

Material Selection for Exchange IOL

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⁾

Conservative Treatment

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.

New Surgical Strategies for Opacity Prevention

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.

6. Pathophysiology and Detailed Mechanisms

Mechanisms of Calcium Deposition

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.

Primary: Due to factors inherent to the IOL itself (polymer properties, manufacturing/packaging issues). Calcium penetrates into the lens interior.
Secondary: Occurs as a result of diseases or surgeries that disrupt the blood-aqueous barrier. Typically involves calcium deposition on the lens surface.
Pseudocalcification: False-positive staining for calcium.

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.

Calcification due to gas/air exposure

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.

Mechanism of glistening

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.

Mechanism of whitening (SSNG)

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.

Special conditions

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.

7. Latest Research and Future Prospects (Research Stage Reports)

Prevention of IOL Opacification During DMEK Using Temporary Phakic Posterior Chamber Lens Barrier Method

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.

8. References

Gartaganis PS, Natsi PD, Gartaganis SP, Koutsoukos PG, Manousakis E, Karmiris E. Explantation of a sutureless scleral fixated Carlevale intraocular lens due to calcification: a clinical and laboratory report. BMC ophthalmology. 2023;23(1):359. doi:10.1186/s12886-023-03102-0. PMID:37587408; PMCID:PMC10433584.
Maguire MJ, Munro DJ, Merz P, et al. Intraocular lens calcification in a patient with Ehlers-Danlos syndrome. Am J Ophthalmol Case Rep. 2024;35:102080. doi:10.1016/j.ajoc.2024.102080.
Kumar K, Agarwal D, Bajaj A, Saha S. Transient anterior chamber intraocular lens opacification by triamcinolone acetonide following intravitreal injection. GMS ophthalmology cases. 2024;14:Doc16. doi:10.3205/oc000248. PMID:39811491; PMCID:PMC11730686.
Aguilera Zúñiga M, Güell JL, Gris Ó, et al. A novel use of temporary ICL during DMEK to prevent gas-induced opacification of a scleral-fixated Carlevale IOL. Am J Ophthalmol Case Rep. 2025;40:102454. doi:10.1016/j.ajoc.2025.102454. PMID:41209839; PMCID:PMC12590035.
Alferayan YA, Hameed ST, Maktabi AMY, Alsaif FF. Intraocular lens opacification in a patient with gyrate atrophy with a subluxated intraocular lens. Am J Case Rep. 2026;27:e950243. doi:10.12659/ajcr.950243.
Belin PJ, Kim JH, Sheikh A, Winokur J, Rhee D, Deramo V. Incidence and Risk of Scleral-Fixated Akreos (AO60) Lens Opacification: A Case Series. Journal of vitreoretinal diseases. 2021;5(2):157-162. doi:10.1177/2474126420946605. PMID:37009087; PMCID:PMC9979051.
Miller KM, Oetting TA, Tweeten JP, et al. Cataract in the Adult Eye Preferred Practice Pattern. Ophthalmology. 2022;129(1):P52-P94.

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