Mechanism of calcification opacification of hydrophilic intraocular lenses

1. Mechanistic Explanation for the Calcification of Hydrophilic IOLs
PS. Gartaganis1,2, P. D. Natsi2, SF. Alimisi1,
SP. Gartaganis,1 PG. Koutsoukos2
1. Department of Ophthalmology, Medical School, University of Patras, Greece
2. Department of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, University of Patras and
FORTH-ICEHT, Greece
I HAVE NO FINANCIAL INTEREST TO DISCLOSE

2. Combination of in vitro model experiments with studied clinical findings, by using scanning
electron microscopy (SEM) and energy dispersive x-ray spectroscopic (EDX) analysis, in order to
obtain better understanding of the mechanism leading to the calcification of hydrophilic IOLs.
Purpose
Opacified Aqua-Sense IOL
Opacified Hydroview IOL

3. Introduction
▵ The late postoperative opacification of some hydrophilic acrylic IOLs is an unusual
complication that leads to progressive visual deterioration.
▵ One The major cause of hydrophilic acrylic IOL opacification appears to be the
calcification.
▵ Calcification of hydrophilic acrylic IOL takes place through is due to the deposition of
calcium phosphate crystallites, either on the IOL surface, or within the optic material
or both, depending on the hydrophilic acrylic IOL designs.1
▵ To restore visual acuity, the only effective treatment is explantation and replacement
of the calcified IOL.
▵ The most common reason for explantation of hydrophilic acrylic lenses is
calcification, sometimes several years past the original implantation surgery.2
▵ The formation of calcium phosphates seems to depend both on the material of
construction of the IOLs and on the local chemical micro-environment of the aqueous
humor in contact with the IOL.
Image Courtesy of Dr. N.Mamalis
“When looking at hydrophilic acrylic
(hydrogel) lenses, we’re finding the most
common reason for explanting is
calcification” (N.Mamalis, June 2019)
1. Werner L. Calcification of hydrophilic acrylic intraocular lenses. Am J Ophthalmol 2008;146(3):341-343. 2. JonesJJ, JonesYJ, Jin GJ. Indications and outcomes of intraocular lens exchange during a recent 5-year period. Am J
Ophthalmol 2014;157(1):154-162

4. Materials and Methods
▵ Description of a number of calcified IOLs seen with some hydrophilic lenses as: Hydroview (Bausch & Lomb), MemoryLens (Ciba Vision),
SC60B-OUV (Medical Developmental Research), and Aqua-Sense (Ophthalmic Innovations International).1
▵ Investigation of the characterization and the kinetics of development of calcified deposits on hydrophilic IOLs with construction of an
experimental model simulating the environment of IOLs into the eye.2
▵ Study of 6 explanted calcified hydrophilic acrylic lenses with a hydrophobic surface.3
▵ Study of 3 hydrophilic acrylic lenses with a hydrophobic surface specimens which were mounted and immersed in simulated aqueous
humor (SAH), by the construction of a special type of reactor, the Eye Chamber Reactor (ECR), at 37oC, pH 7.40, flowing at a rate of
0,2ml/hr.
▵ Construction of a cell to simulate the process and monitor the formation of calcific deposits at the air/SAH/hydrophilic IOL interface, as
in procedures using repeated intracameral injection of air or gas.
1. Gartaganis SP, Kanellopoulou DG, Mela EK, Panteli VS, Koutsoukos PG. Am J Ophthalmol. 2008 Sep;146(3):395-403
2. Drimtzias EG(1), Rokidi SG, Gartaganis SP, Koutsoukos PG. Am J Ophthalmol. 2011 Nov;152(5):824-33. 3. Gartaganis SP, Prahs P, Lazari ED, Gartaganis PS, Helbig H,Koutsoukos PG. Am J Ophthalmol. 2016 Aug;168:68-77

5. Results
lump
Ca
P
Examination of opacified IOLs showed a surface texture characterized of lumps containing salts, formed more likely in
the interior of the IOLs, approximately 30µm from the surface.
* Deposits observed mainly on or near ruptures caused to the IOLs accidentally.
EDS: Morphology of crystalline deposits - Hydroxyapatite (Ca5. (PO4)3OH, HAP).
Deposits were
however observed in
some instances on
the surface of
opacified IOLs,
mainly on or near
ruptures caused to
the IOLs accidentally.

6. Artificial Eye Anterior
Chamber Reactor (ACEACR)
cell for the in vitro
IOL opacification experiment
Results
Optical micrograph of lens surface after
exposure in simulated AH at 37° for 270 days.
Optical micrograph of the interface between air-bubble
and IOL exposed in synthetic AH at 370C for 20 days
Scanning electron microscopy of hydroxyapatite
prismatic crystals at a depth of 233μm
from the surface of lens exposed in
simulated AH at 37° for 270 days.
Scanning electron microscopy of
hydroxyapatite prismatic crystal

7. Discussion
▵ It is interesting to note that the salts were deposited both in the interior and the surface of the IOLs, on or near ruptures.
▵ Chemical analysis of the aqueous humor collected from patients with opacified IOLs and thermodynamic calculations
involving all related chemical species, showed that they were supersaturated with respect to calcium phosphates and
corroborated the findings of the mineral deposited in the IOLs examined.
▵ The aqueous humor may be modeled as a supersaturated calcium phosphate solution from which HAP may form either
directly or through the transformation of less stable transient calcium phosphate phases. This is reinforced This suggestion is
supported by the results of our latest experiments, using the Artificial Eye Anterior Chamber Reactor (ACEACR) for simulating
air/gas pressure in achieving Descemet Membrane Endothelial Keratoplasty (DMEK) surgery.
▵ Investigation and analysis of IOLs with hydrophobic surface confirmed that the issue of calcification`s process initiation is
more over influenced by factors others than supersaturation conditions, such as the construction IOL material (hydrophilic or
hydrophobic nature of the IOLs surface).

8. Discussion
COO
COO
COO
COO
COO COO
COO COO
COO
Ca
Ca Ca Ca Ca Ca
Ca
PO 3 PO 3 PO 3 PO 3
Aqueous humor
The favorable thermodynamic driving force, so that
HAP may formed either directly or through the
transformation of less stable transient calcium
phosphate phases on the surface of IOLs.
Calcification Mechanism
▵ The aqueous humor provides a constant supply of the constituent ions of the precipitating salt and provides the
favorable thermodynamic driving force which boosts calcification.
▵ One factor that may be suggested as playing a central role is that, the IOL’s hydroxyl groups on the polyacrylic
materials may increase and also facilitate nucleation and crystal growth of crystal, either through surface
complexation with calcium ionization or through incorporation of phosphate groups as most of the currently
available hydrophilic acrylic lenses are manufactured from copolymers of acrylates with water content with the
hydroxyl groups, OH-) on the polymer and the water associated with hydrophilic IOLs, ranging from 18% to 38%.

9. Conclusion