Reversible Opacification of Intraocular Lens in vitro: Case Report

Abstract

Introduction

We reported a case of late-onset opacification of a hydrophilic acrylic intraocular lens (IOL) that developed years after uneventful phacoemulsification cataract surgery. Remarkably, the calcification-related opacification was successfully reversed in vitro using ethylenediaminetetraacetic acid (EDTA) solution.

Case Presentation

An 86-year-old male presented with a 2-year history of progressive visual decline in the right eye (best-corrected visual acuity: 2/200). Slit-lamp examination revealed posterior capsular opacification (PCO), and B-scan ultrasonography showed dense vitreous opacities, precluding fundus and optical coherence tomography (OCT) examinations. He had undergone cataract surgery with implantation of a Rayner monofocal IOL 10 years ago. As for the treatment of vitreous opacities, PCO, as well as investigating fundus diseases, the pars plana vitrectomy was performed. After PCO removal, fundus visualization remained poor. Intraoperative inspection revealed diffuse opacification of the IOL, which was subsequently explanted. Following removal of IOL, fundus examination revealed non-proliferative diabetic retinopathy and asteroid hyalosis. In vitro, the IOL exhibited homogeneous opacification resistant to mechanical cleaning and soaking in sterile water for 1 week. However, immersion in 4% EDTA gradually restored full optical clarity over the course of 1 month. Scanning electron microscopy (SEM) demonstrated small subsurface pits suggestive of prior crystal deposition. Energy-dispersive X-ray spectroscopy detected mainly carbon (C) and oxygen (O), without significant evidence of calcium (Ca), silicon (Si), or phosphorus (P).

Conclusions

This case highlighted the potential reversibility of hydrophilic IOL opacification through EDTA chelation, suggesting a promising direction for therapeutic management of IOL calcification in vivo in the future.

Introduction

Phacoemulsification cataract surgery remains the most frequently performed ophthalmic procedure worldwide. With the progressive increase in global life expectancy, the functional longevity of intraocular lens (IOL) has been significantly extended. Although uncommon, opacification of IOLs represents a serious long-term complication. Opacification may arise intraoperatively or postoperatively, and when associated with calcific deposition, it may result in irreversible loss of optical transparency [1].

Herein, we report a case of late-onset opacification of a hydrophilic acrylic IOL following an uneventful phacoemulsification cataract procedure. Notably, the calcification has been successfully reversed in vitro through the application of ethylenediaminetetraacetic acid (EDTA) solution.

Case Presentation

An 86-year-old man presented to hospital with a 2-year history of progressively worsening vision in his right eye. Best-corrected visual acuity was 2/200 in the right eye and 12/20 in the left eye. The intraocular pressures (IOP) were both within normal limits. Slit-lamp examination revealed a quiet anterior segment and IOL in both eyes, with posterior capsular opacification (PCO) in the right eye. PCO and vitreous opacity prevented imaging of the fundus and optical coherence tomography (OCT) examinations (shown in Fig. 1a1, a2). B-scan ultrasonography demonstrated dense opacities in the vitreous in right eye and flat retina in the both eyes (shown in Fig. 1a3, b3).

Fig. 1.

Multiple ocular images of the case. Scanning laser ophthalmoscopy (SLO) of the right eye (a1) revealed no discernible fundus details due to significant media opacity, whereas the left eye (b1) showed scattered retinal hemorrhages and exudates, consistent with diabetic retinopathy. OCT of the right eye (a2) was blurred, with only the macular contour visible, suggesting macular edema, while the OCT image of the left eye (b2) was clear and showed mild structural disorganization of the macula. B-scan ultrasonography of the right eye (a3) revealed dot-like opacities within the vitreous body, with a few similar opacities present in the left eye (b3). During surgery, no red fundus reflex was detected in the right eye (c) at beginning. The surgical field remained obscured during pars plana vitrectomy (d), and further inspection identified opacification of the intraocular lens (e). The intraocular lens was removed using a twist extraction technique (f). After removal, the fundus became clearly visible (g), revealing asteroid hyalosis and allowing a detailed examination of the posterior segment. By the end of the procedure, the red fundus reflex could be observed (h).

The patient had a medical history of diabetes mellitus spanning over 2 decades, which had been controlled with insulin therapy and routine follow-up. No other systemic comorbidities were reported, and there was no known family history of ocular or related systemic diseases. Phacoemulsification cataract surgery had been performed in the both eyes, with the right eye on approximately 10 years ago and the left eye 2 years ago, at another institution. Surgical records were unavailable; however, based on the patient’s recollection, a monofocal IOL (Rayner, Hove, UK) had been implanted at both eyes. Except that, the patient denied any history of ocular trauma or intraocular surgeries.

Comprehensive ophthalmic evaluation led to a diagnosis of vitreous opacities and PCO, with a fundus that was barely assessable. The patient subsequently underwent pars plana vitrectomy. During the surgery, the PCO was initially addressed; however, fundus visualization remained significantly impaired, appearing diffusely obscured as if viewed through a translucent veil (shown in Fig. 1d). Further intraoperative assessment revealed a markedly opacified IOL, which was then carefully explanted (shown in Fig. 1e, f). Following IOL removal, fundus visualization markedly improved, allowing continuation of the vitrectomy. The vitreous opacities were identified as asteroid hyalosis (shown in Fig. 1g), and signs consistent with nonproliferation diabetic retinopathy. The diagnosis was revised to include IOL opacification and asteroid hyalosis. The patient returned for follow-up 1 week after surgery with no obvious complications observed but was subsequently lost to follow-up.

The explanted IOL exhibited diffuse, homogeneous opacification, with two haptics appearing as well clouded as the optic (shown in Fig. 2A, a). The opacity could not be removed by gentle wiping with a sterile cotton swab. Then, the IOL was soaked in sterile water for approximately 1 week, but no visible improvement was observed. Subsequently, the lens was immersed in a 4% EDTA solution, obtained using standard blood collection tubes [2]. After 1 week, the solution became slightly turbid, and partial clearing of the IOL was noted (shown in Fig. 2B, b). Over the following week, transparency continued to improve progressively (shown in Fig. 2C, c). By the end of the month, the IOL had regained complete optical clarity (shown in Fig. 2D, d).

Fig. 2.

Photographs of the change of a calcified intraocular lens (IOL) immersed in a 4% ethylenediaminetetraacetic acid (EDTA) solution for one month. Overview image at ×25 magnification (a) and a ×40 magnification (A) image focused on the center exhibited dense, homogeneous white opacification. One week after immersion in EDTA solution, overview images at ×25 (b) and ×40 (B) focused on the center showed noticeable improvement in opacification. Two weeks after immersion, images at ×25 (c) and ×40 (C) focused on the center demonstrated that the IOL appeared nearly clear, with a few small pits visible on the surface. One month after immersion, overview images at ×25 (d) and ×40 (D) focused on the center revealed that the IOL was completely clear, although distinct surface pits remained.

Scanning electron microscopy (SEM) revealed the presence of small subsurface pits, potentially resulting from crystal deposition that led to localized disruption of the lens surface (shown in Fig. 3a, b). Aside from these minor irregularities, the overall surface morphology appeared smooth. Energy-dispersive X-ray spectroscopy (EDS) analysis of the lens primarily detected carbon (C) and oxygen (O), without obvious peaks corresponding to calcium (Ca), silicon (Si), or phosphorus (P) (shown in Fig. 3c).

Fig. 3.

Results of scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) images of the intraocular lens immersed in a 4% ethylenediaminetetraacetic acid (EDTA) solution for one month. SEM images at 1.00 k (a) and 2.00 k (b) magnifications revealed the presence of small subsurface pits. Apart from these minor irregularities, the overall surface morphology appeared smooth. EDS analysis (c) primarily detected carbon (C) and oxygen (O), with no significant peaks corresponding to calcium (Ca), silicon (Si), or phosphorus (P).

Discussion

Since the 1990s, multiple studies have documented cases of late-onset IOL opacification [3]. Although relatively uncommon, late postoperative IOL opacification represents a clinically significant complication. It may manifest in several distinct forms, including glistening, calcification, and snowflake degeneration [4]. Among these, IOL calcification is particularly concerning and may present as surface deposits on the optic or haptics or as intraocular infiltration within the IOL material itself [4, 5].

Calcification of IOL is generally classified into three categories [5]. Primary calcification is attributed to defects introduced during the manufacturing or packaging process and may occur in the absence of any underlying ocular or systemic pathology. In contrast, secondary calcification arises from alterations in the intraocular environment and is frequently associated with systemic or ocular conditions such as diabetes mellitus, uveitis, or prior intraocular surgeries [6]. The third, less common entity is referred to as pseudo-calcification, in which the observed opacification mimics true calcification but is caused by other unrelated factors [5].

Primary calcification of Rayner C-Flex IOL had not been previously reported [5]. Moreover, the observed opacification could not be removed by simple wiping or soaking in standard solutions, indicating a more persistent pathological process. Intraoperatively, asteroid hyalosis was noted, which may be a contributing factor to IOL opacification; however, this condition had been more commonly associated with silicone IOLs [7, 8], suggesting that asteroid hyalosis may not have been the primary cause in this case. The patient had no other history of intraocular surgeries but did have a 20-year history of diabetes mellitus – a well-established risk factor for IOL calcification. We, therefore, hypothesized that the opacification represented a form of secondary calcification, with diabetes being the primary contributing factor.

Although robust evidence to definitively establish that IOL opacification occurs more frequently in hydrophilic IOLs is still lacking, most studies report a higher incidence of opacification in these lenses [4]. Hydrophilic IOLs are typically composed of acrylate copolymers with varying water contents. In the present case, the Rayner IOL is a hydrophilic acrylic lens with an approximate water content of 26%. As the hydration levels increase, the ionization of the polymer’s functional groups becomes more pronounced, potentially promoting calcification by facilitating the formation of complexes with ionized calcium [4]. As well as, hydrophobic acrylic IOLs generally possess smoother surfaces, which have been shown to help prevent PCO [9], meanwhile, this smoother surface may also reduce the likelihood of calcium phosphate deposits on the IOL surface. The accumulation of salts, such as calcium and sodium, can naturally occur due to surface acrylic acid and protein deposition, both of which are influenced by the material’s biocompatibility [2]. Notably, this calcification process was regarded irreversible [4].

Previous studies have identified calcium bicarbonate (Ca(HCO₃)₂) and hydroxyapatite (Ca₅(PO₄)₃(OH)) as potential complexes contributing to IOL opacification, a finding confirmed by SEM and elemental analysis [10]. Based on that, we introduced EDTA, a well-established calcium-chelating agent, as a novel strategy. The 4% EDTA solution, commonly used for the treatment of corneal band keratopathy and reported to be both safe and effective [2], was innovatively applied in this case to address IOL calcification. The results were promising, with complete restoration of IOL transparency. Studies indicated that EDTA, combined with permeability enhancers, can reduce the accumulation of toxic protein adducts and protect against cataract formation in both in vitro and in vivo models [11]. Importantly, EDTA, a metabolically inert, anionic, and hydrophilic chelator with good water solubility, physiological pH, and osmolarity, and is cleared through aqueous humor outflow, which showed the potential for intraocular use [12]. It needs more exploration for these properties in greater detail.

Subsequent analyses using light microscopy, electron microscopy, and EDS techniques confirmed that the opacification had been effectively resolved. The IOL surface appeared nearly smooth, with only minor pits detected, suggesting that calcification had occurred both on the surface and within the subsurface layers. It was reported that calcium compounds can deposit on the surface of hydrophilic acrylic IOLs, while interactions between the IOL material and aqueous humor may lead to subsurface and intrasubstance opacification [13, 14]. For our case, calcification appeared to extend into the subsurface, altering the microstructure of the IOL. It was proposed that the polymer material of IOLs acted like a gel, permitting Ca²⁺, PO₄³⁻, and OH⁻ ions to diffuse into its matrix and when the ion activity product exceeded the solubility limit, hydroxyapatite crystals formed from within the lens and progressing outward [12].

EDS analysis further showed no significant presence of calcium (Ca), silicon (Si), or phosphorus (P) on the IOL surface after EDTA therapy for the calcification, indicating that it was reversible through a simple intervention in vitro. It remains necessary to study the feasibility of using appropriate concentrations and method of EDTA for intraocular management of IOL calcification.

One of the limitations of this case was that anterior chamber and vitreous fluid sampling were not collected at the time of surgery to analysis the characteristics of the biochemical environment. Meanwhile, as no two opacified IOLs were identical, intervention, and analysis were performed on the same IOL. Draw on the SEM findings of literature which have been clearly confirmed the presence of calcification; our primary focus was on evaluating the outcomes following the reversible opacification treatment. Although setting a control was challenging, it could strength the validity of our findings and we plan to do further investigate in future.

In conclusion, the case successfully demonstrated reversible opacification of IOLs in vitro using a 4% EDTA solution. It may provide a basis for exploring the potential therapeutic reversal of IOL calcification in vivo in the future. Nevertheless, more comprehensive studies are required.

Statement of Ethics

This case was approved by the Ethics Committee of the first affiliated hospital of Soochow University (No. 2025628). Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000547601).

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

Yanting Li collected and reviewed the medical records and Bin Chen wrote the original draft of the case report. Yunfeng Lu revised the manuscript and supervised the project.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

All data generated or analyzed and online supplementary material during this case are included in the case report. Further inquiries can be directed to the corresponding author.