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Hydroxyapatite Formation on Implanted Hydrogel Intraocular Lenses
Arch Ophthalmol. 2001;119:611-614.
Three Chinese patients undergoing implantation with the same hydrogel
intraocular lens (IOL)(Hydroview; Bausch & Lomb Surgical, Claremont, Calif)
developed delayed IOL opacification with unusual clinical features. The IOLs
were made from a 2-hydroxyethylmethacrylate/6-hydroxyhexylmethacrylate (HEMA/HOHEXMA)
copolymer. Opacification was progressive, whitish, and generalized, and developed
4 to 15 months after surgery. The appearance resembled a mature cataract.
All 3 patients showed a significant reduction in vision. There was no response
to Nd:YAG laser treatment, and all 3 IOLs had to be explanted. The explanted
lenses were analyzed with electron microscopy, elemental analysis, Fourier
Transform (FT) Raman spectroscopy, and x-ray diffraction to define the nature
of the opaque material. Results showed electron-dense deposits in the superficial
5 µm of the lenses. The deposits were predominantly composed of calcium
and phosphorus, and x-ray diffraction identified the presence of hydroxyapatite.
The polymer structure of the lens was unaltered.
Report of Cases
Case 1
A 67-year-old man underwent phacoemulsification on his left eye and
IOL implantation in July 1998. He had diabetes, was taking insulin, and suffered
from ischemic heart disease, hypertension, and renal dysfunction. Best-corrected
visual acuity improved from 20/200 before the operation to 20/70 three months
afterward. Opacification of the implant developed 4 months after surgery (Figure 1). Visual acuity dropped gradually
until the patient could perceive only hand motions 6 months postoperatively.
The IOL was explanted in July 1999.
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Figure 1. Slitlamp photograph of patient
1 taken 10 months after surgery. A granular whitish deposit was noted over
the entire intraocular lens. There were Nd:YAG laser pits present. Opacity
also affected the area beneath the anterior capsule.
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Case 2
A 72-year-old woman underwent phacoemulsification on her right eye and
IOL implantation in June 1998. She had diabetes, was taking insulin, and had
had macular grid laser treatment for diabetic macular edema. Her best-corrected
visual acuity went from 20/400 before surgery to 20/100 three months afterward.
Opacification of the IOL developed 9 months after surgery, and best-corrected
visual acuity dropped to 20/200. An IOL exchange was done in August 1999.
Case 3
A 79-year-old man underwent phacoemulsification on his right eye and
IOL implantation in June 1998. He was in good overall health. His best-corrected
visual acuity improved from 20/200 before surgery to 20/50 three months afterward.
Intraocular lens opacification developed 15 months after surgery, and his
visual acuity became perception of hand motions at 17 months. An IOL exchange
was done in December 1999.
All 3 patients were given local anesthesia and underwent clear corneal
phacoemulsification. Sodium hyaluronate/chondroitin sulfate sodium (Viscoat;
Alcon Surgical, Fort Worth, Tex) and balanced salt solution (BSS Plus; Alcon
Surgical) with added adrenaline (0.1 mL of 1:1000 adrenaline in 500 mL BSS
Plus) were used intraoperatively. Acetylcholine chloride (Ciba Vision Ophthalmics,
Atlanta, Ga) was used for patients 2 and 3. No surgical complications were
noted. For 1 month following surgery, all patients received 1% dexamethasone
sodium phosphate and 1% neomycin sulfate eyedrops. We used the same intraoperative
agents to implant about 500 IOLs from 1997 to 1999. Most patients were not
affected by IOL opacification.
Methods
Each explanted lens was submitted to the pathology laboratory in a dry,
sterile container without fixatives. All 3 lenses underwent the same tests.
They were examined under both a dissecting microscope and a light microscope.
Each lens was then cut into several pieces with a razor blade and subjected
to transmission electron microscopy (TEM), scanning electron microscopy (SEM),
elemental analysis, FT Raman spectroscopy, and x-ray diffraction. Several
unused IOLs served as controls.
For TEM analysis, the lens was cut into 1-mm3 blocks and
fixed in a solution of 1.5% cacodylate-buffered glutaraldehyde, postfixed
in a solution of osmium tetroxide, dehydrated in a series of ethanol, and
embedded in a resin block (Polybed 812; Polysciences Inc, Warrington, Pa).
Ultrathin sections were stained with uranyl acetate–lead citrate and
examined with TEM (Philips CM100; Philips Electron Optics, Eindhoven, the
Netherlands) at an accelerating voltage of 80 kV.
For SEM analysis, 1-mm3 blocks of lens material were sampled
and fixed in a solution of glutaraldehyde, postfixed in a solution of osmium
tetroxide, dehydrated in a series of ethanol, and dried with carbon dioxide
in a critical point dryer (Bal-Tec CPD 030; Bal-Tec AG, Liechtenstein). They
were mounted on aluminium stubs and coated with gold and palladium in a sputter
coater (Bal-Tec SCD 005; Bal-Tec AG). The specimens were examined with SEM
(Leica Stereoscan 360; Leica Instruments Ltd, Cambridge, England).
For elemental analysis, 1-mm3 blocks of lens were air-dried
and analyzed with an energy-dispersive spectrometer (Link eXL system; Link
Analytical Ltd, Bucks, England) attached to the Leica Stereoscan 360.
For FT Raman spectroscopy, the sample was studied with an FT Raman spectrometer
(FT-Raman; Bio Rad, Hercules, Calif), and the Nd:YAG laser (1064 nm) was used
as the excitation laser source.
For powder x-ray diffraction, the test was performed with an x-ray diffractometer
(Siemens D5000; Siemens, Munich, Germany) using CuK radiation (wavelength
= 1.5406 Å), and copper was used as the generating source.
Results
Test results were similar for all 3 lenses. The lenses were semi-opaque
on gross examination. Under the dissecting and light microscopes, both the
anterior and posterior surfaces were reticulated, similar to a piece of dried
leather.
With TEM analysis, the explanted lenses showed an undulating surface.
The distance between the top of the elevated area and the bottom of the depressed
area was approximately 10 µm. Electron-dense aggregates, which extended
to a depth of 5 µm, were present along the superficial part of the lenses.
The size of these aggregates varied, with the largest measuring approximately
1 µm. They were larger and more numerous near the surface (Figure 2). The aggregates contained needle-shaped
crystalline deposits, which contrasted with the smooth surface and absence
of deposits in the control IOL.
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Figure 2. Undulating surface of the lens
from patient 1. Clumps of electron-dense deposits containing needle-shaped
crystals were found beneath the surface (transmission electron microscopy,
original magnification x 8600).
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SEM analysis revealed that the explanted lens surfaces were irregular
and had a "cerebriform" appearance, with convolutes of elevated areas alternating
with crevices. This 3-dimensional architecture corresponded to the 2-dimensional
appearance with TEM analysis (Figure 3).
The control IOL revealed a smooth surface.
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Figure 3. Three-dimensional view of the
lens surface from patient 1, showing irregular convolutes of the elevated
area alternating with crevices (scanning electron microscopy, original magnification
x 150).
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Elemental analysis showed calcium, phosphorus, oxygen, carbon, and trace
amounts of sodium and magnesium present on the explanted lenses (Figure 4). Only carbon and oxygen were found
on the control IOL.
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Figure 4. Elemental analysis of the lens
surface from patient 2 showing calcium, phosphorus, oxygen, and carbon.
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The explanted lenses and the control IOL showed essentially the same
features with FT Raman spectroscopy, indicating that they were the same type
of polymer.
With x-ray diffraction, the explanted lenses showed a diffused halo
at approximately 2 = 16°-24° (where 2 describes the
range of angle between the incident x-ray and the test sample), which was
due to the amorphous polymer matrix. The peaks at 2 = 25.9°, 31.9°,
32.1°, and 33.1° (Figure 5)
matched the major diffraction peaks for a typical hydroxyapatite sample.1 These peaks were absent on the control IOL.
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Figure 5. Powder x-ray diffraction pattern
of the intraocular lens from patient 3. The peaks at 2 = 25.9°,
31.9°, 32.1°, and 33.1° matched the major diffraction peaks for
a typical hydroxyapatite sample.
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Comment
Intraocular lens calcification has not been frequently reported. Olson
et al2 reported intraoperative calcification
of the IOL surface. Bucher et al3 reported
the formation of calcium hydroxyapatite on a polyHEMA IOL on the first postoperative
day. The clinical features they reported were very different from the delayed
calcification observed in our patients.
Bucher et al3 attributed IOL calcification
to the use of phosphate-containing solutions during surgery. We used balanced
salt solution and viscoelastics, both of which contained calcium and/or phosphate.
Following surgery, patients were given eyedrops that contained the steroid
dexamethasone sodium phosphate. Materials used during surgery may explain
early postoperative calcification, but this does not necessarily explain calcification
several months afterward.
Normal aqueous humor contains calcium and phosphate.4
This continuous supply of minerals is a more convincing explanation for the
delayed and progressive calcification in our patients. In addition, hydrogels
are permeable to aqueous humor. The small amount of sodium and magnesium detected
probably came from the aqueous carried by the explanted lenses. Carbon and
oxygen were detected in both the explanted lenses and the control. Oxygen
probably existed together with phosphorus in the form of hydroxyapatite. The
presence of carbon may not be abnormal; more investigation is necessary to
clarify its presence in the deposit.
The bulk of deposits were found just beneath the IOL surfaces. The physical
presence of the deposits led to expansion of the superficial layers and subsequent
surface folding, which produced the cerebriform appearance. Hydrogels make
up a large family of polymers, and certain hydrogels are very active in promoting
calcification. Winter and Simpson5 reported
the calcification of synthetic polyHEMA sponges implanted into young pigs.
The calcified IOL reported by Bucher et al3
was also made from polyHEMA. We believe that the calcium affinity of the HEMA/HOHEXMA
copolymer is comparable with that of polyHEMA and is an important factor leading
to IOL calcification.
Most of the IOLs we used remained transparent after implantation. Although
we believe that the calcium affinity of the polymer is responsible for calcification,
this cannot explain its occurrence in only a handful of patients. Multiple
factors might be involved, such as irregularities in IOL manufacturing, interaction
with intraoperative materials, and patient factors such as race and diabetes
mellitus. More investigation is necessary to determine the mechanism of calcification
and the factors involved.
In conclusion, we observed delayed opacification of 3 IOLs that necessitated
explantation 12 to 18 months after implantation. The opacification was caused
by compounds containing calcium and phosphorus, specifically hydroxyapatite.
Irregularly shaped deposits formed beneath the surfaces of the lenses, giving
the surfaces a cerebriform irregularity. The calcium and phosphorus in the
deposits were probably derived from the patients' aqueous humor. We believe
that the affinity of the hydrogel copolymer to calcium was responsible for
the dystrophic calcification in these 3 cases. Why this kind of opacification
occurs in only a handful of patients remains unexplained, and further work
is necessary to define the multiple factors that may be involved.
Alexis Ka Fai Yu, MBBS, FHKAM;
Tony Wai Hung Shek, MBBS, FHKAM
Hong Kong, China
REFERENCES
1. Sugawara A, Antonucci JM, Takagi S, Chow LC, Ohashi M. Formation of hydroxyapatite in hydrogels from tetracalcium phosphate/dicalcium
phosphate mixtures. J Nihon Univ Sch Dent. 1989;31:372-381.
PUBMED
2. Olson RJ, Caldwell KD, Crandall AS, Jensen MK, Huang SC. Intraoperative crystallization on the intraocular lens surface. Am J Ophthalmol. 1998;126:177-184.
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3. Bucher PJ, Buchi ER, Daicker BC. Dystrophic calcification of an implanted hydroxyethylmethacrylate intraocular
lens. Arch Ophthalmol. 1995;113:1431-1435.
ABSTRACT
4. Sears ML. Formation of aqueous humor. In: Albert DM, Jackobiec FA, eds. Principles and
Practice of Ophthalmology. Philadelphia, Pa: WB Saunders Co; 1994:182-205.
5. Winter GD, Simpson BJ. Heterotopic bone formed in a synthetic sponge in the skin of young
pigs. Nature. 1969;223:88-90.
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