Correlation between intraocular lens hydrophilicity and anterior capsule opacification and aqueous flare

Kensaku Miyake, MD, Ichiro Ota, MD, Sampei Miyake, MD, Kumiko Maekubo, MD

ABSTRACT

Purpose: To study the correlation between a basic parameter of intraocular lens biocompatibility, hydrophilicity, and two clinical parameters, postoperative inflam­mation and anterior capsule opacification.

Setting: Miyake Eye Hospital, Nagoya, Japan.

Methods: Three combinations of IOls that were identical in shape but had distinct contact angles of water were used in this prospective double-masked study: (1) experimental comparison of collagen type IV and poly(methyl methacrylate) (PMMA) IOls in rabbit eyes; (2) clinical comparison of heparin-surface-modified and PMMA IOls; (3) clinical comparison of three foldable IOls, silicone, acrylic, and memory. One of the two IOls being compared in each situation was randomly assigned to both eyes of each animal or patient. At 1 and 3 months postoperatively, the degree of anterior capsule opacification and the amount of flare in the anterior chamber were determined.

Results: In all three comparative situations, greater postoperative inflammation and more rapid anterior capsule opacification was seen in the eyes with hydrophobic IOls.

Conclusion: There was a correlation between the hydrophilicity of an IOl and the severity of postoperative inflammation and the speed of anterior capsule opacifi­cation. J Cataract Refract Surg 1996; 22:764-769

T he correlation between basic and clinical parame­

ters in determining the biocompatibility of an in­

traocular lens (lOL) surface has not been defined. To

date, the biocompatibility of a lens surface has been eval­

uated by measuring its contact angle of water and oil;

studying the surface by electron spectroscopy chemical

analysis, secondary ion mass spectroscopy, or scanning

electron microscopy; 1 identifYing proliferation and ad-

hesion of various cells on the material surface;2 comple­ment activation,3-5 techniques of cytopathology or chemiluminescence,5-7 and observation of cells and de­

posits on the lens surface.8•9

Postoperative inflammation is known to be caused

by surgical trauma to the anterior uvea and by the for­eign-body reaction to the lOL. 10, II Lens capsule opaci­

fication is also considered a form of inflammatory . r II . 12-14 C b I

Reprint requests to Kensaku Miyake, MD, Shohzankai Medical Foun­d4tion, Miyake Eye Hospital, 1070 Kami-5, Higashiozone-cho, Kita­ku, Nagoya 462, Aichi, Japan.

reaction ro owmg surgery. ontact etween ens

epithelial cells (LECs) and a biomaterial induces meta­plasia of the cells, 12-14 leading to biosynthesis of in flam­

matory chemical mediators. 15,16 Based on this theory,

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IOL HYDOPHILICITY AND CAPSULE OPACIFICATION

early postoperative inflammation and metaplasia of LECs may be used as clinical parameters for determining a material's biocompatibility.

Because there are few studies identifying the corre­lation between basic and clinical parameters, we per­formed three comparative studies using the contact angle of water (hydrophilicity) as the basic parameter and early postoperative inflammation and LEC meta­plasia as the clinical parameters. The amount of flare calculated by a laser flare-cell meter and the speed of anterior capsule opacification were used to indicate in­

flammation and LEC metaplasia, respectively.

Materials and Methods

Experimental Comparison of Collagen Type IVand Poly(methyl methacrylate) IOLs

Following a preliminary study13 using the envelope

intercapsular techniques, we performed phacoemulsifi­cation in both eyes of 3 additional mature, pigmented rabbits, providing a total of 10 animals. Both eyes of each animal were randomly given a poly(methyl methacrylate) (PMMA) or a collagen type IV 10L inside the capsule; the anterior lens capsule was not removed.

Since this was a double-masked study, only the control­ler (K. Maekubo) was aware of which lens had been assigned to each animal. All the operations were done by one of the authors (K.M.).

As indicated in Table 1, the shape of the two lens types was identical. Preoperative and intraoperative medication, including antibiotics, mydriatics, and irri­gating solution, were the same in all animals. Each eye

Table 1. Configuration of the implanted IOls.

Optic

Diameter Material (mm) Configuration

Collagen IV* 10.0 Biconvex PMMA* 10.0 Biconvex

HSM 6.5 Biconvex

PMMA 6.5 Biconvex

Silicone 6.0 Biconvex Acrylic 6.0 Biconvex Memory 6.0 Biconvex

*Collagen IV or PMMA lens without haptics PP = polypropylene

Refractive Power (degree)

1.05 1.55

1.55 1.55

1.46 1.55 1.47

received 0.1 % pranoprofen three times on the day of

surgery preoperatively and three times a day for 1 month postoperatively.

The severity of anterior and posterior capsule opaci­fication, examined by slitlamp microscopy, was classi­fied as follows: 1 ° = no or very mild opacification; 3° = milky white to white discoloration of the entire lens

capsule; and 2° = opacification severer than 1 ° but not as severe as 3°. The integrity of the blood-aqueous bar­rier (BAB) function was determined using the laser flare­cell meter (FC-lOOO, Kowa). Both evaluations were

performed at 1 and 3 months postoperatively by one of the authors (S.M.) who did not know which lenses had been implanted.

Clinical Comparison of Heparin-Surfoce-Modified and PMMAIOLs

Twenty-eight consecutive patients over 50 years of age with bilateral cataracts and no other ocular or sys­

temic disorders were included in the study. Informed consent was obtained from all patients preoperatively.

After creating a 5.5 mm frown incision, a continu­ous curvilinear capsulorhexis (CCC) of 5.0 or 5.5 mm diameter was performed, followed by one-handed or two-handed phacoemulsification. The incision was unsutured or closed with one suture. Both eyes of each patient were randomly given a heparin-surface­modified (HSM) (818C, Pharmacia) or a PMMA 10L (818T, Pharmacia), which was placed inside the capsule.

Since this was a double-masked study, only the control­ler (K. Maekubo) was aware of which lens had been assigned to each patient. As indicated in Table 1, the

Contact Angle (degree)

39 66

33 64

99 73 64

Material

PMMA

PMMA

PP PMMA PP

Haptic

Configuration

C

C

C C C

Angle (degree)

10 10

10 10 10

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IOL HYDOPHILICITY AND CAPSULE OPACIFICATION

shape of the HSM 10L was identical to the PMMA 10L. The same surgeons (K.M., 1.0.) performed all the surgeries. Cases with intraoperative or postoperative complications were excluded from the study.

The anti-inflammatory agents 0.1 % fluoro­

metholone and 0.1 % pranoprofen were applied three times preoperatively on the day of surgery and three times a day for 3 months postoperatively. Lens capsule opacification and the BAB function were evaluated as in the experimental comparison.

Clinical Comparison of Silicone, Acrylic, and Memory lOIs

One hundred twenty consecutive patients over 50 years of age with bilateral cataracts were included in the comparison of silicone (SI30NB, Allergan) and acrylic (AcrySof, MA60BM, Alcon) lenses and 40 pa­tients over 50 years of age, in the comparison of acrylic and memory (U940A, ORC) lenses. None of the pa­tients had other ocular or systemic disorders. Informed

consent was obtained preoperatively from all patients. The surgical procedure, as well as the preoperative

and postoperative regimen, was as described in the clin­ical comparison except that the corneoscleral incision

was 3.5 mm long. Both eyes of each patient were ran­domly given a silicone lens in one eye and an acrylic lens in the other or an acrylic lens in one eye and a memory lens in the other. Since this was a double-masked study, only the controller (K. Maekubo) was aware of which lenses had been assigned to each patient. As indicated in Table 1, the only factor that differed significantly among

the three lens types was the contact angle of water. Lens capsule opacification and BAB function were evaluated as in the experimental comparison.

Results

Experimental Comparison of Collagen Type IVand PMMAIOIs

At 1 month postoperatively, anterior capsule opaci­fication did not differ significantly in the two groups (Table 2). At 3 months, however, eyes with PMMA

lenses had significantly greater opacification (P < .01 chi-square test). At 1 and 3 months, posterior lens capsule opacification was similar in both groups.

At 1 month postoperatively, laser flare-cell findings did not differ significantly in the two groups (Table 3). At 3 months, however, eyes with collagen type IV 10Ls had significantly less flare (P < .01, Wilcoxon test).

Clinical Comparison of HsM and PMMA lOIs At 1 month postoperatively, anterior capsule opaci­

fication did not differ significantly in the two groups (Table 2). At 3 months, eyes with HSM lenses had sta­

tistically less opacification (P< .05). At 1 and 3 months, posterior lens capsule opacification was similar in both

groups. At 1 month, laser flare-cell findings did not differ

significantly in the two groups (Table 3). At 3 months, however, eyes with HSM 10Ls had significantly less flare (P< .01).

Table 2. Number of eyes with anterior and posterior capsule opacification.

Anterior Capsule Opacification Posterior Capsule Opacification

1st Month 3rd Month 1st Month 3rd Month

1° 2° 3° 1° 2° 3° 1° 2° 3° 1° 2° 3°

Collagen IV 10 a a 3 4 3 10 a a 8 2 a PMMA 10 a a a a 10 10 a a 7 3 a HSM 12 13 a 10 10 5 25 a a 20 PMMA 8 13 4 5 10 10 25 a a 22 a a Silicone 10 75 25 a 28 73 34 a a 29 6 Acrylic 23 64 23 7 44 50 34 a a 30 6 a Acrylic 8 24 6 1 15 15 38 a a 24 7 a Memory 10 26 2 6 23 2 38 a a 22 8

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IOL HYDOPHILICITY AND CAPSULE OPACIFICATION

Table 3. Aqueous flare amounts.

Photon Counts (1m sec)

1st Month 3rd Month

Collagen IV 56.3:!: 13.2* (n = 10) 25.6 :!: 8.2 (n = 10)

PMMA 81.2 :!: 30.2 (n = 10) 60.2:!: 18.3 (n = 10)

HSM 8.0 :!: 4.2 (n = 25) 7.0 :!: 2.2 (n = 22)

PMMA 8.4 :!: 5.2 (n = 25) 8.1 :!: 2.5 (n = 22)

Silicone 11.8 :!: 7.4 (n = 110) 8.3 :!: 5.0 (n = 101)

Acrylic 8.6 :!: 4.8 (n = 110) 7.1 :!: 5.6 (n = 101)

Acrylic 7.8 :!: 5.2 (n = 38) 7.1 :!: 4.3 (n = 31)

Memory 7.9 :!: 4.8 (n = 38) 7.0 :!: 4.1 (n = 31)

*Mean :!: standard deviation

Clinical Comparison of Silicone, Acrylic, and Memory lOLs

Silicone and Acrylic lOLs. At 1 month postopera­tively, anterior capsule opacification did not differ sig­nificantly in the two groups (Table 2). At 3 months, however, eyes with silicone IOLs had significantly

greater opacification (P < .01). At 1 and 3 months, posterior capsule opacification was similar in both

groups. At 1 and 3 months postoperatively, laser flare-cell

findings were significantly higher in eyes with silicone IOLs (P < .01) (Table 3).

Acrylic and Memory lOLs. At 1 month postopera­tively, anterior capsule opacification did not differ sig­nificantly in the two groups. At 3 months, however, eyes with memory IOLs had significantly less opacification (P < .01). At 1 and 3 months, posterior lens opacifica­tion was similar in both groups.

At 1 and 3 months postoperatively, laser flare-cell findings did not differ significantly in the two groups (Table 3).

Discussion In this study, we compared the hydrophilicity, de­

gree of postoperative inflammation (the amount of an­terior chamber flare), and speed of anterior capsule

opacification of three combinations of IOLs that had

distinct contact angles of water. We found a correlation between the basic and clinical parameters.

Recent studies indicate that lens capsule opacifica-. . . fl . 12-14 B 11 tlon IS an m ammatory reaction. ecause co agen

type IV is the main constituent of the lens capsule and

therefore may be more biocompatible than other IOL materials,17 Miyake and coauthors13 implanted the

same collagen type IV IOL used in the current study in rabbit eyes. Their preliminary finding was that the col­lagen type IV IOL resulted in less inflammation and lens capsule opacification than a PMMA IOL. This was con­firmed in this study. In a study using baboon eyes,15

Miyake and coauthors found that the amount of pros­taglandin E2 in the aqueous humor 1 and 8 days post­operatively was less in eyes having phacoemulsification alone than in eyes in which a PMMA IOL was im­planted inside the lens capsule. Nishi and Nishi 16 re­

ported that LEC metaplasia is related to the amount of prostaglandin E2 and interleukin-l in the culture me­dium. Tsuboi and coauthors18 found a greater amount of flare in the aqueous in the early postoperative period in eyes with a posterior chamber IOL implanted in the capsule than in eyes with the IOL implanted out of the capsule and in eyes with a small CCC diameter. These findings suggest that early postoperative LEC metapla­sia, induced by the biomaterial coming in contact with

cells, leads to biosynthesis of inflammatory mediators, which results in an inflammatory reaction. Based on

this, we decided to use the degree of LEC metaplasia (anterior lens capsule opacification) and the amount of flare (inflammation) as two clinical parameters for de­termining biocompatibility.13

The studies performed by Miyake and coau­thors 13, 17 have confirmed that the collagen type IV 10 L

is more biocompatible than other IOLs. Unfortunately,

present technology does not allow us to coat an ordinary IOL with collagen type IV.

The HSM IOL was developed to try to reduce the f .. fl . 1920 amount 0 postoperative m ammatory reaction. '

Normal eyes and eyes with pathologies such as pseudo­exfoliation syndrome, glaucoma, diabetes, or uveitis that are implanted with this lens have shown less postopera-. . fl . 21-26 Th d 1 tIve m ammatory reaction. e current stu y a so

confirmed that HSM IOLs result in less severe postop­erative inflammation and slower anterior capsule opaci­fication. These findings suggest that this particular lens

may be specifically suitable for eyes vulnerable to post­

operative inflammation. Various types of foldable IOLs have recently been

introduced. Although there are numerous reports re­garding their implantation methods and their role in reducing astigmatism, few studies evaluate their bio-

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IOL HYDOPHILICITY AND CAPSULE OPACIFICATION

compatibility. While some reports discuss severe poste­

rior capsule opacification or inflammatory reactions in eyes with a silicone lens,27-31 few studies compare this

lens with other foldable lenses.32,33 The acrylic lens is

also reported to be clinically acceptable33 but has not been compared with other foldable lenses. The memory

lens is composed of hydrogel and PMMA and clinical

results of hydrogel lens implantation have been report­ed;34,35 no study of the memory lens has been done since

it was just introduced. We believe that our clinical stud­

ies comparing the biocompatibility of these foldable

lenses are significant. We found that the memory lens

was most biocompatible, followed by the acrylic and the

silicone lenses.

As indicated in this study, there was no significant

difference in the degree of posterior capsule opacifica­

tion during the early postoperative period (up to 3 months). In fact, posterior capsule opacification, com­

pared with anterior capsule opacification, is generally a

late postoperative reaction (occurs 1 to 2 years after sur­

gery). Besides the biomaterial (the lens), posterior cap­

sule opacification is related to other factors including the

shape of the anterior capsulotomy, underlying disorders,

drugs administered, and the shape of the lens. Based on

these factors, we used the speed of anterior capsule

opacification (as opposed to posterior capsule opaci­fication) as one of the parameters for determining

biocompatibility. Although there are various basic parameters for de­

termining the biocompatibility of lens materials,I-7 to

date no study has correlated these basic parameters with clinical parameters. In this study, we discovered that the hydrophilicity of a lens did correlate with the severity of

postoperative inflammation and the speed of anterior

capsule opacification. Further studies are necessary to determine how the hydrophilicity relates to proliferation and adhesion of the cells. Once this is identified, we may be able to define how these cellular activities relate to the

clinical parameters.

Conclusion In this study, we identified a correlation between

the hydrophilicity of a biomaterial, which is a basic pa­

rameter, and the inflammatory breakdown of the BAB

(amount of flare) and the speed of anterior capsule

opacification, which are clinical parameters. We found

that hydrophobic lenses induce greater postoperative in-

flammation and more rapid anterior capsule opacifica­

tion. These findings suggest that the contact angle of a

material is a reliable basic parameter. Recognizing this

correlation will be significant in developing more bio­

compatible IOLs in the future.

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