Abstract
Background
Intraocular lens calcification is a rare but significant late complication that primarily affects hydrophilic acrylic intraocular lenses. Systemic metabolic disorders, particularly diabetes mellitus and end-stage renal disease, are recognized risk factors because they promote breakdown of the blood–aqueous barrier and alter calcium–phosphate metabolism, creating a favorable environment for intraocular calcification.
Case presentation
A 58-year-old woman with a more than 20-year history of diabetes mellitus and end-stage renal disease receiving dialysis presented with progressive visual decline in her left eye. Slit-lamp examination demonstrated marked opacification of a hydrophilic acrylic intraocular lens. The opacified lens was explanted and replaced with a retropupillary iris-claw intraocular lens. Scanning electron microscopy revealed dense rosette-like crystalline deposits on both intraocular lens surfaces with calcification thickness of 7.55–16.7 μm. Energy dispersive spectrometry demonstrated calcium and phosphorus (69.69% and 30.31%), consistent with hydroxyapatite. The patient’s systemic evaluation demonstrated hyperphosphatemia and elevated parathyroid hormone levels. Following surgery, best-corrected visual acuity improved from 6/30 to 6/12.
Conclusions
This case highlights the critical role of systemic metabolic derangements in promoting secondary calcification of hydrophilic acrylic intraocular lens. Careful selection of intraocular lens materials, favoring hydrophobic acrylic or polymethyl methacrylate lenses, is recommended in high-risk patients to prevent this complication.
Keywords: Diabetes mellitus, End-stage renal disease, Hydrophilic acrylic IOL, Hyperphosphatemia, Intraocular lens calcification, Rosette-pattern
Introduction
Intraocular lens (IOL) opacification due to calcification is a recognized complication primarily affecting hydrophilic acrylic materials [1, 2]. This pathology is classified into primary calcification, involving manufacturing or packaging defects, and secondary calcification, which is associated with the intraocular environment factors or systemic comorbidities [1]. Clinical evidence increasingly suggests that systemic conditions disrupting the blood-aqueous barrier, such as diabetes mellitus (DM), significantly increase the risk of secondary calcification [1, 2]. Furthermore, recent in vitro models have demonstrated a clear association between elevated phosphate concentrations and the acceleration of calcium phosphate crystal formation within the IOL polymer matrix [3]. We report a case of severe rosette-pattern IOL calcification in a patient with end-stage renal disease (ESRD) and long-standing DM, highlighting the biochemical drivers underlying this pathology.
Case history and presentation
A 58-year-old female presented with a progressive blurring of vision in the left eye (OS) for an unknown duration. Her medical history was significant for diabetes mellitus of over 20 years’ duration and end-stage renal disease. She had undergone peritoneal dialysis (PD) for 11 years before transitioning to hemodialysis (HD) three months prior to presentation. Systemic laboratory evaluation revealed hyperphosphatemia (serum phosphate, 6.5 mg/dL) and markedly elevated intact parathyroid hormone (iPTH) levels (1719.9 pg/mL). Serum calcium levels were within the normal range (total calcium, 9.7 mg/dL; ionized calcium, 5.49 mg/dL). Serum alkaline phosphatase and creatinine levels were elevated at 203 U/L and 9.23 mg/dL, respectively. The estimated glomerular filtration rate (eGFR) was 4.5 mL/min/1.73 m², consistent with stage 5 chronic kidney disease. Ocular history included cataract surgery in the left eye approximately 10 years ago with the implantation of a hydrophilic IOL (Rayner 100 C). The right eye was prosthetic following retinal detachment surgery 20 years prior. On examination, her best-corrected visual acuity (BCVA) in the left eye was 6/30. Slit-lamp biomicroscopy and anterior segment optical coherence tomography (AS-OCT) revealed significant IOL opacification. Due to the visual impairment, the patient underwent removal of the opacified lens and the insertion of a retropupillary iris-claw lens (Artisan, + 18.5D). Following the procedure, the BCVA OS improved to 6/12.
Analysis method
The explanted IOL was subjected to morphological and chemical analysis. The specimen was prepared with a 1 nm carbon coating and analyzed using Scanning Electron Microscopy (SEM) (Hitachi SU8220, Instrumentation Center at National Taiwan University) and Energy-Dispersive X-ray Spectroscopy (EDS) (Bruker EDS, Instrumentation Center at National Taiwan University). SEM was utilized to examine the ultrastructure of the deposits on the anterior and posterior surfaces as well as cross-sections of the lens. EDS was performed to determine the elemental composition of the opacifying material.
Analysis results
Slit-lamp examination of the anterior segment revealed multiple round, radially striated crystalline deposits clustered within the pupillary area, appearing as rosette-pattern opacities against a dark background (Fig. 1A). Retroillumination further accentuated these deposits, enhancing their rosette-like architecture (Fig. 1B). Microscopic evaluation of the explanted IOL showed numerous spherical, whitish crystalline aggregates distributed on both the posterior and anterior surfaces, with the posterior surface more clearly visualized in focus (Fig. 1C). At higher magnification, these deposits exhibited well-defined concentric and radial crystalline arrangements, forming characteristic rosette-like configurations (Fig. 1D).
Fig. 1.

Crystalline deposits observed in the anterior segment under slit-lamp and microscopic examination. (A) Slit-lamp photograph showing multiple round, radially striated crystalline deposits clustered within the pupil, appearing as rosette-pattern opacities against a dark background. (B) Retroillumination highlighting the same deposits, enhancing their radial spoke-like architecture and revealing varying sizes and densities. (C) Microscopic examination of the extracted IOL reveals numerous spherical, whitish crystalline aggregates on both the posterior (in focus under the microscope) and anterior surfaces, exhibiting a characteristic radiating rosette pattern. (D) Higher-magnification microscopic image showing the detailed structure of the deposits, composed of concentric and radial crystalline arrangements forming rosette-like configurations (scale bar = 100 μm)
Further characterization using SEM of the explanted IOL revealed dense crystalline deposits distributed over both the anterior and posterior surfaces of the optic (Fig. 2). Low-magnification SEM demonstrated a characteristic rosette-pattern architecture composed of radially arranged crystalline plates forming polygonal aggregates (Fig. 2A). Higher-magnification imaging revealed a distinct lamellar organization with layered interfaces between adjacent crystalline plates, accompanied by prominent surface ridges and fracture lines (Fig. 2B). Examination of individual deposits showed heterogeneous surface morphology, with transitions from relatively smooth regions to rough, nodular crystalline areas, including representative structures measuring up to approximately 16.7 μm (Fig. 2C). Cross-sectional SEM further delineated the internal architecture and thickness of the deposits, demonstrating layered structures with measured thicknesses of approximately 5.70 μm and 7.55 μm (Fig. 2D). Elemental mapping by SEM-EDS demonstrated the spatial distribution of major elements, including oxygen, calcium, phosphorus, and carbon, with clear co-localization of calcium and phosphorus within the crystalline regions (Fig. 3A and B). EDS further confirmed the elemental composition, showing prominent peaks corresponding to calcium and phosphorus, along with oxygen and carbon, consistent with a calcium phosphate–based material (Fig. 3C and D). Quantitative elemental analysis demonstrated normalized mass percentages of 69.69% for calcium and 30.31% for phosphorus. These findings are consistent with the formation of crystalized hydroxyapatite rosettes [Ca₅(PO₄)₃OH], the characteristic calcium phosphate phase observed in advanced secondary IOL calcification.
Fig. 2.

Scanning electron microscopy (SEM) characterization of crystalline deposits. (A) Low-magnification SEM image demonstrating a rosette-pattern architecture composed of radially arranged crystalline plates forming polygonal aggregates (scale bar = 300 μm). (B) Higher-magnification view highlighting the lamellar structure and layered interfaces between adjacent crystalline plates, with visible ridges and fracture lines (scale bar = 50 μm). (C) Surface morphology of an individual deposit showing a transition from a relatively smooth region to a rough, nodular crystalline surface; a representative feature measuring approximately 16.7 μm (scale bar = 40 μm). (D) Cross-sectional SEM image revealing the thickness and internal structure of the deposit, with layer thicknesses measuring approximately 5.70 μm and 7.55 μm (scale bar = 40 μm)
Fig. 3.

SEM morphology and elemental composition analysis of crystalline deposits. (A) Scanning electron microscopy (SEM) image showing the interface between a smooth substrate and an overlying crystalline deposit with a layered, radially organized structure (scale bar = 100 μm). (B) Corresponding elemental mapping demonstrating the spatial distribution of major elements, with oxygen (green), calcium (red), phosphorus (blue), and carbon (yellow), including co-localization of calcium and phosphorus within the crystalline deposits. (C) Energy-dispersive X-ray spectroscopy (EDS) spectrum confirming the elemental composition, with prominent peaks corresponding to calcium (Ca) and phosphorus (P), along with oxygen (O) and carbon (C), consistent with calcium phosphate–based material. (D) Data from Energy-dispersive X-ray spectroscopy spectral analysis
Discussion
This case underscores the susceptibility of hydrophilic acrylic IOLs to secondary calcification in the setting of systemic metabolic dysregulation. Hydrophilic materials, typically composed of poly (2-hydroxyethyl methacrylate) (PHEMA), possess a relatively high water content (18–38%) and contain hydrophilic functional groups (e.g., hydroxyl and carboxyl groups) that confer a net negative charge [4]. This physicochemical environment promotes calcium ion attraction and facilitates nucleation and precipitation of calcium phosphate once the solubility threshold is exceeded [5]. The patient’s systemic comorbidities were central to the pathogenesis. Long-standing DM is known to disrupt the integrity of the blood–aqueous barrier, resulting in altered aqueous humor composition, including elevated levels of phosphate, calcium, and serum proteins such as albumin [2, 6]. Concurrently, ESRD complicated by hyperphosphatemia (6.5 mg/dL) provides a sustained systemic source of phosphate ions. Pehere et al. reported a similar case of intraocular lens calcification in an infant; however, unlike the present case, the serum phosphate level was normal [7]. Ward and colleagues also analyzed crystal deposits forming on hydrophilic acrylic intraocular lenses, which were composed of hydroxyapatite layered with amorphous calcium phosphate, using X-ray, Raman, and SEM-EDS analyses. However, their samples showed different compositional ratios and crystal morphologies [8]. In our case, the patient with ESRD had undergone peritoneal dialysis for 11 years, followed by hemodialysis for more than three months prior to presentation. Elevated phosphate concentrations have been shown to accelerate ionic diffusion into the IOL polymer matrix, where interaction with calcium ions promotes hydroxyapatite crystal formation. During the 11-year period of peritoneal dialysis, the local intraocular microenvironment likely played a critical role in secondary calcification. Taken together, the combined effects of diabetes-related barrier dysfunction and ESRD-associated metabolic imbalance likely established a pro-calcifying aqueous milieu. The selection of a retropupillary (Artisan) lens composed of polymethyl methacrylate (PMMA) is therefore appropriate, as materials with low water content (1–4%), including PMMA and hydrophobic acrylics, demonstrate greater resistance to calcification.
In addition, the influence of DM on aqueous humor phosphate levels and subsequent IOL calcification can be explained by several interrelated mechanisms. The disruption of the blood–aqueous barrier in DM patients permits the influx of serum constituents into the anterior chamber [9], leading to increased intraocular concentrations of phosphate and calcium. Furthermore, a large clinical study by Kim et al. demonstrated that aqueous humor phosphate concentrations were approximately 1.2-fold higher in diabetic patients and increased to 1.4-fold in those with proliferative diabetic retinopathy [6]. Therefore, this elevation correlates positively with the severity of retinal microvascular damage, reflecting progressive metabolic dysregulation within the ocular environment.
Ultimately, this hyperphosphatemic state drives secondary IOL calcification. When the local concentrations of calcium and phosphate exceed the solubility product within the hydrophilic polymer matrix, these ions diffuse into the lens material and precipitate as hydroxyapatite crystals [Ca₅(PO₄)₃OH], forming rosette-like structures. Progressive mineral deposition leads to diffuse opacification of the optic and consequent visual impairment.
Conclusion
This case highlights the association between long-standing diabetes mellitus, end-stage renal disease, and calcification of hydrophilic acrylic intraocular lenses, likely resulting from blood–aqueous barrier disruption and hyperphosphatemia that promote hydroxyapatite deposition. Careful preoperative risk assessment and selection of hydrophobic acrylic or polymethyl methacrylate intraocular lenses should be considered in high-risk patients to reduce the risk of calcification and the need for complex IOL exchange.
Acknowledgements
The authors acknowledge Ms. Ya-Yun Yang of the Instrumentation Center at National Taiwan University for her technical assistance with SEM-EDS analysis.
Author contributions
PKL and HSF collected the data and prepared the first draft. PKL and YJL conducted the SEM-EDS analysis, prepared the figures, and revised the manuscript. All authors reviewed and approved the final manuscript. ChatGPT was used for grammar and language editing.
Funding
This study was funded by the National Council of Science and Technology in Taiwan (NSTC 114-2314-B-030-006).
Data availability
Original data for this study are available from the corresponding author upon reasonable request.
Declarations
Ethical approval
Not applicable.
Patient consent for publication
The participant has agreed to and signed the written informed consent form for her personal or clinical details along with any images to be published in this study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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Data Availability Statement
Original data for this study are available from the corresponding author upon reasonable request.
