Heparin-surface-modified Research Articles

In vivo study of cell reactions on poly(methyl methacrylate) intraocular lenses with different surface properties

Purpose: To evaluate the biocompatibility of three poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) with different surface properties.Setting: University Eye Clinic, Vienna, Austria.Methods: Cell reactions on the surfaces of unmodified, heparin-surface-modified (HSM), and surface-passivated (SP) PMMA IOLs were documented in vivo using a Zeiss specular microscope. Risk factors for such reactions were also determined.Results: During the first postoperative days, small round and spindle-shaped cells were found on all IOLs. Cell density was higher in eyes with increased postoperative inflammation. After several days, epithelioid and foreign-body giant cells were seen on some IOLs. Cells appeared significantly less often on the IOLs with hydrophilic surfaces (HSM) than on those with hydrophobic surfaces (unmodified, SP).Conclusion: The significantly lower incidence of foreign-body reactions on hydrophilic than on hydrophobic IOL surfaces is consistent with the results of previous studies on hydrogel and silicone IOLs.

After-cataract formation in newborn rabbits implanted with intraocular lenses

Purpose: Comparison of the after-cataract formation in newborn rabbits implanted with a heparin-surface-modified (HSM) intraocular lens (IOL), a silicone IOL, or no IOL.Methods: Two groups of 3-week-old rabbits were used. In Group 1 (n = 11), lensectomy was performed in both eyes. One eye was selected at random and an HSM IOL was implanted in the capsular bag; the other eye was left aphakic. In Group 2 (n = 13), lensectomy was performed in both eyes. An HSM IOL was implanted in one eye, a silicone IOL in the other. The wet mass of the dissected after-cataract was determined 3 months after surgery in both groups.Results: In Group 1, the wet mass of the dissected after-cataract was 17.0 ± 6.5 mg (mean ± SEM) in eyes implanted with an HSM IOL and 159.7 ± 17.0 mg in aphakic eyes. This difference was statistically significant (P < .01). In Group 2, the wet mass of the dissected after-cataract was 18.3 ± 4.3 mg in eyes implanted with an HSM IOL and 25.7 ± 5.2 mg in eyes implanted with a silicone IOL. No statistically significant difference was found.Conclusions: In young rabbits, implantation of an IOL in the capsular bag following lensectomy reduced cell proliferation.

Efficacy of Heparin Surface-modified IOLs in Reducing Postoperative Inflammatory Reactions in Patients with Exfoliation Syndrome — a Double-blind Comparative Study

OBJECTIVE: The objective of the study was to evaluate the effect of heparin surface modification of intraocular lenses (HSM IOLs) on postoperative inflammatory reactions in cataract patients with exfoliation syndrome. The primary efficacy variables were the presence on the lens surface of giant cells determined from specular microscopy photographs and the presence of cell deposits determined by slit-lamp. STUDY DESIGN: Prospective, randomized, double-blind clinical study with a follow-up period of 6 months. PATIENTS: The study comprised 58 patients who were randomized into 2 groups: 31 patients received polymethylmethacrylate (PMMA) lenses and 27 patients received HSM lenses. The mean age in the HSM group was 78.1 years and the mean age in the PMMA group was 78.3 years. RESULTS: Giant cells on the lens surface were found in more patients in the PMMA group at all postoperative visits. At 6 months the difference between the groups was statistically significant ( P = 0.023). The maximal density of giant cells patient was significantly greater in the PMMA group compared to the HSM group at 1, 3 and 6 months postoperatively ( P ≤ 0.05). Cell deposits, assessed by slit lamp, were observed in fewer patients in the HSM group ( vs . PMMA) at 1 and 3 months. At 6 months 69% (11/16) of the patients in the HSM group and 84% (21/25), in the PMMA group had a best corrected visual acuity of 0.5 or better. This difference was not statistically significant ( P = 0.25). Overall, the number of postoperative complications was lout. At 6 months no complications were reported. CONCLUSION: The postoperative inflammatory reaction as determined by the presence of giant cells and cell deposits on the lens surface is significantly reduced by heparin surface modification of the IOL in patients with exfoliation syndrome.

Comparison of the postoperative inflammatory response in the normal eye with heparin-surface-modified and poly(methyl methacrylate) intraocular lenses

Evidence that poly(methyl methacrylate) (PMMA) is not inert in the eye has led to the introduction of intraocular lens (IOL) surface modification. In this prospective, double-blind, randomized study, we evaluated the effects of heparin surface modification (HSM) on anterior segment inflammation for one year after endocapsular cataract surgery. Fifty-four eyes were randomized to receive an HSM IOL (29 eyes) or a PMMA IOL (25 eyes) and were assessed postoperatively by corneal endothelial photography, laser flare and cell measurements, fluorophotometry, and IOL surface specular microscopy. Corneal endothelial loss, mean aqueous flare and cells, and fluorophotometry did not differ significantly between the groups, although fewer eyes in the HSM group had high flare values on the first postoperative day. The number of giant cells was significantly less in the HSM group for up to one year after surgery. Although there was no statistical difference in overall visual outcome, more patients in the HSM group (17%, 5/29) achieved a postoperative visual acuity of 20/15 than in the PMMA group (0). These results demonstrate that HSM enhances IOL biocompatibility and these effects are detectable in the low-risk, normal eye.

Heparin Surface-modified IOLs Compared with Regular PMMA IOLs in Patients with Diabetes and/or Glaucoma — 1 year Results of a Double-Blind Randomized Multi-independent Trial

OBJECTIVE: The objective of the study was to compare the inflammatory reaction following cataract surgery in patients with diabetes and/or glaucoma implanted with heparin surface modified (HSM) or PMMA intraocular lenses (IOLs). Specular microphotography and slit lamp evaluation were used to determine the presence of foreign body giant cells and cellular deposits on the IOL surface. The presence of capsular fibrosis, pigment and fibrin or fibrinlike deposits determined by slit lamp were secondary efficacy variables. STUDY DESIGN: The study was performed as a prospective, randomized, double-blind, multi-independent clinical trial with 1 year follow-up. PATIENTS: The study comprised 239 patients with diabetes and/or glaucoma. Of these patients, 122 had diabetes, 103 patients had glaucoma, and 14 patients had both diabetes and glaucoma. The mean age of the patients was 73 (± 9.8) years. RESULTS: At all visits, including the 1 year visit, there was a statistically significant difference in favour of HSM with a lower percentage of patients having giant cells on the IOL surface in the HSM group. Cellular deposits, seen with the slit lamp, were also found in significantly fewer patients in the HSM group at all follow-up visits except at 1 week. Visual acuity, at 1 year, was ≥ 0.5 (20/40) in 72% of the HSM group and in 84% of the PMMA group. The reason for a visual acuity below 0.5 was in most cases related to preoperative pathologies, especially in the diabetic patients in the HSM group. CONCLUSION: The results of this study indicate that heparin surface modification increases the biocompatibility of PMMA IOLs by significantly reducing the postoperative foreign body reaction for at least 1 year following cataract surgery in patients with diabetes and/or glaucoma.

Cataract Surgery Using Heparin Surface-Modified Intraocular Lenses in Fuchs' Heterochromic Uveitis

I prospectively studied cataract extraction with implantation of heparin surface-modified intraocular lenses (IOLs) in 20 patients with Fuchs' heterochromic uveitis. The mean follow up was 14.5 months. Seven episodes of postoperative uveitis occurred, including two with fibrin deposition, but substantial giant-cell adhesion to the IOL was seen in only four cases. A visual acuity of 20/40 or better was achieved in 95% of the eyes despite other causes of visual loss such as vitreous opacities. The use of heparin surface-modified IOLs is suggested for patients with heterochromic uveitis.

In vitro organotypic culture method to evaluate the biocompatibility of heparin-surface-modified intraocular lenses

Using an organotypic culture method, we evaluated the biocompatibility of two kinds of intraocular lenses: conventional poly(methyl methacrylate) (PMMA) and heparin-surface-modified (HSM) PMMA. Chicken corneal endothelium from embryos incubated for 14 days was placed on an agar medium and covered with one of three types of materials: PMMA, HSM PMMA, and a control, Thermanoxa. Experiments at five different times measured cell migration, cell multiplication, and cell adhesion. Scanning electron microscopy showed a low level of corneal endothelial adhesion on the HSM IOL surface. There was a significant difference between the HSM and untreated lenses in migration surface and cell density, with the HSM lenses having better biocompatibility.

Cataract surgery in children with capsulorhexis of anterior and posterior capsules and heparin-surface-modified intraocular lenses

Cataract surgery was performed in 21 eyes in 14 children (one to 12 years, 5.6 ± 4.0 [mean ± SD]). Cataract surgery was standardized and included capsulorhexis of the anterior capsule, irrigation/aspiration of the nucleus and cortex, puncture of the posterior capsule, injection of sodium hyaluronate (Healon GV®, 14 mg/ml) between the posterior capsule and the vitreous, and capsulorhexis of the posterior capsule. At the end of the procedure, a heparin-surface-modified (HSM) poly(methyl methacrylate) intraocular lens (IOL) was implanted in the capsular bag. Follow-up ranged from four to 16 months. No complications such as the appearance of vitreous in the anterior chamber occurred during surgery. A mild postoperative inflammation was seen in all cases. Opacification of the visual axis was seen in one eye ten months after surgery. Posterior synechial formation was seen in one eye. Our results suggest that capsulorhexis of the anterior and posterior capsules with implantation of an HSM IOL in the capsular bag is a safe procedure in children and produces good postoperative results.

Heparin-modified lenses for eyes at risk for breakdown of the blood-aqueous barrier during cataract surgery

To determine the appropriateness of heparin-surface-modified (HSM) lenses in eyes at risk for breakdown of the blood-aqueous barrier, 36 consecutive patients with cataracts associated with chronic recurrent or past uveitis had extracapsular cataract extraction and insertion of an HSM posterior chamber one-piece intraocular lens (IOL). Examinations for implant precipitates (IPs), fibrin membranes, IOL synechias, and visual outcome were done postoperatively. Results show that despite a recurrence of overt uveitis with keratic precipitates in 13 eyes (36.1 %), IN were seen in only six eyes (16.6%) and were generally small and few in number. An acute postoperative fibrin reaction, which is related to blood-aqueous barrier breakdown, occurred in nine eyes. Implant synechias were found in three eyes. We found that HSM provided a cell-free IOL surface in the majority of eyes at high risk for blood-aqueous barrier breakdown and uveitis. Heparin surface modification does not prevent complications but tends to protect the IOL from inflammation changes that might otherwise occur.

Reduced bacterial adhesion to heparin-surface-modified intraocular lenses

Bacterial adherence to intraocular lenses (IOLs) could be the cause of endophthalmitis following cataract surgery and lens implantation. There are previous reports that heparin bound to the surface of poly(methyl methacrylate) (PMMA) IOLs reduces cell adhesion. In this study, the in vitro adherence of Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa to regular PMMA IOLs and to heparin-surface-modified (HSM) PMMA IOLs was investigated. The three bacterial strains attached in significantly lower numbers to HSM-PMMA IOLs than to PMMA IOLs (P < .01). Heparin in solution also inhibited attachment of Staphylococcus epidermidis to regular PMMA IOLs. Heparin may reduce adherence by placing a highly hydrated layer between the bacteria and the IOL surface. Therefore, the use of HSM-PMMA IOLs could diminish the incidence of endophthalmitis.

Does Heparin Surface Modification Affect the Incidence of Inflammatory Related Complications in Patients with Glaucoma Undergoing Endocapsular Cataract Extraction with Posterior Chamber Lens Implantation?

OBJECTIVE: To see if heparin surface modification (HSM) of intraocular lenses affects the incidence of post-operative inflammatory related complications in patients with glaucoma undergoing endocapsular cataract extraction with posterior chamber intraocular lens insertion. STUDY DESIGN: A prospective study of post-operative results at one year follow up. SETTING: Ophthalmic Out-patient Clinic, Royal Hallamshire Hospital, Sheffield. PATIENTS: 34 adult patients with pre-existing glaucoma undergoing cataract surgery were randomly allocated to receive either an HSM lens or a standard PMMA lens. MAIN OUTCOME MEASURES: Pigmented deposits and non-pigmented cellular deposits, iridocapsular adhesions, iridolenticular adhesions, peripheral anterior synechiae. RESULTS: Comparing eyes that received HSM lenses with those receiving standard PMMA lenses, at one year follow up there was no statistically significant difference in the number of clear lenses; the number of non-pigmented cellular deposits per IOL; the amount of pigmented deposits per IOL; or the presence and extent of iridolenticular or iridocapsular adhesions or peripheral anterior synechiae. CONCLUSIONS: Heparin Surface Modification of PMMA lenses in our group of glaucoma patients failed to reveal any significant benefits with respect to inflammatory related complications at one year post-surgery, when compared to standard PMMA lenses.

Incidence of posterior capsule opacification in eyes with exfoliation syndrome and heparin-surface-modified intraocular lenses

Conventional poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) and heparin-surface-modified (HSM) IOLs were implanted after extracapsular cataract extraction in 40 human eyes with exfoliation syndrome. The study was doublemasked and randomized. Two years after surgery 17 cases with HSM IOLs and 15 with PMMA IOLs were examined. We observed that pigment and cell deposits were more frequent on the PMMA than on the HSM IOLs. The incidence of posterior synechia formation was similar in both groups. However, the incidence of neodymium:YAG laser posterior capsulotomy and posterior capsule opacification was more frequent in the PMMA IOL group. Visual acuity did not differ between the two groups before or two years after surgery. The results suggest that in eyes with exfoliation syndrome, implanting an HSM IOL reduces the incidence of posterior capsule opacification often associated with extracapsular cataract extraction.

Cellular reaction following cataract surgery with implantation of the heparin-surface-modified intraocular lens in rabbits with experimental uveitis

The inflammatory response after cataract surgery and intraocular lens (IOL) implantation was studied in rabbits with endotoxin-induced uveitis. On days 1, 3, 7, 14, and 30 postoperatively the rabbits were sacrificed and the number of white blood cells in the aqueous humor and cellular deposits on the IOLs were estimated. On days 14 and 30 the rabbits also had slitlamp examination to study the clinical outcome of the surgery. At day 1 after lens extraction and IOL implantation, the number of white blood cells in the aqueous humorwas significantly lower (P < .05) in eyes with Heparin-surfacemodified (HSM) IOLs (795.2 ± 262.9; mean ± SEM) than in eyes with poly(methyl methacrylate) (PMMA) lenses (1386.5 ± 247.9). No differences were seen at day 3, 7, 14, or 30 postoperatively. The choice of IOL material had no effect on the amount of cell deposits on the IOL surface or on clinical parameters such as anterior synechias, posterior synechias, fibrosis, and posterior capsular opacification. There was a trend toward a greater number of cellular deposits on the PMMA lenses, but this was not statistically significant. This study provides further evidence of improved biocompatibility o£ the HSM PMMA lens, as demonstrated by a decreased acute inflammatory response.

Carbonic anhidrase inhibition and level of zinc in aqueous humor and blood

Purpose: To evaluate the influence of heparin-surface-modified (HSM) versus unmodified poly(methyl methacrylate) (PMMA) intraocular lenses (IOLs) on the blood-aqueous barrier (BAB) in at-risk eyes.Setting: Department of Ophthalmology, Bundesknappschaft's Hospital, Sulzbach, Germany.Methods: This study comprised 100 patients with predisposing risk factors for BAB destabilization (e.g., diabetes mellitus with or without retinopathy, glaucoma, pseudoexfoliation, uveitis). One eye in each patient received an HSM IOL and the fellow eye, a conventional unmodified PMMA IOL after phacoemulsification by the same surgeon. Anterior chamber flare was measured with the Kowa 500 laser flare meter 1 day before and 1 day, 1 and 6 weeks, and 3 months after surgery.Results: For most risk factors, mean flare was lower in the HSM group than in the PMMA group at most follow-ups. Significantly lower flare values (difference between postoperative and preoperative mean values) were seen in eyes with the HSM IOL at 6 weeks (P < .004) and 3 months (P < .003; Student's t-test). In the group with preoperative elevated flare values, the eyes with the HSM IOL had significantly better results 6 weeks (P < .0006) and 3 months (P < .01) postoperatively. The values in the HSM IOL eyes were also significantly higher in the diabetic with retinopathy group at 3 months (P < .003).Conclusion: The results confirm the efficacy of IOL surface modification in reducing postoperative intraocular reaction in at-risk eyes.

Effect of Heparin Surface Modification of Polymethylmethacrylate Intraocular Lenses on Signs of Postoperative Inflammation after Extracapsular Cataract Extraction: One-year Results of a Double-masked Multicenter Study

A heparin surface modified posterior chamber intraocular lens (IOL) was compared with a conventional polymethylmethacrylate (PMMA) IOL regarding postoperative complications caused by inflammation. Five hundred twenty-four patients from 10 different centers were included in a parallel group, double-masked, multicenter study. The cumulative number of patients with inflammatory cellular deposits on their IOLs during the first postoperative year differed significantly in favor of the heparin surface modified group, with 29.8% of the patients having cellular deposits compared with 48.8% of patients in the control group. Cellular deposits were observed most frequently at 3 months after surgery, and the difference between the groups was most pronounced and statistically significant at this time. The same results were seen at 1 year, but the difference was not significant. The number of cellular deposits per patient, however, was significantly lower in the heparin surface modified group at 1 year. Cumulatively, there were significantly more patients with posterior synechiae in the PMMA group than in the heparin surface modified group during the 1-year follow-up. Complications were few and comparable between the groups. The results of this study indicate that heparin surface modification reduces the inflammatory response to PMMA IOLs.

Heparin Surface Modified PMMA Lenses in a Prospective Double Blind Study

Objective: To determine if heparin surface modification of polymethylmethacrylate (PMMA) lenses increases biocompatibility by a measurable amount. Study Design: Prospective double blind study of postoperative results at 1 week, 1, 2 and 6 months after surgery. Setting: Second University Eye Clinic, Vienna. Patients: Forty adult patients were divided into two groups: in 20 cases heparin surface modified (HSM) PMMA lenses were implanted, in the other 20 patients PMMA lenses of the same type but without surface modification were implanted. Main Outcome Measures: Intraocular irritation, macrophage deposits on the lens, visual acuity, tension and postoperative cortisone dosage. Results: All patients with age appropriate fundus achieved a postoperative visual acuity of 0.8 to 1.25. Twenty per cent of the non-HSM lenses were covered with foreign body giant (FBG) cells but no FBG cells were found in the HSM group. Conclusions: There was little difference between the two groups, except in the foreign body giant cell deposits on the lens surface. This suggests that hydrophilization positively influences the compatibility of the artificial lens in the eye.

Fibrinous reaction on implanted intraocular lenses: A comparison of conventional PMMA and heparin surface modified lenses

We studied the fibrinous reaction after intraocular lens (IOL) implantation in the posterior chamber of cynomolgus monkeys. In 50% of the eyes, we implanted an IOL made of conventional poly(methyl methaerylate) (PMMA); in the remaining eyes we implanted a PMMA IOL. with a heparin modified surface. Two, 4, 8, and 18 weeks after surgery the eyes were examined by slitlamp for fibrinous reactions on and around the IOL surface. At weeks 4, 8, and 18 there was a marked decrease in fibrinous reaction in the eyes with a heparin surface modified IOL. The results of this study accord with earlier findings that heparin surface modification improves the biocompatibility of the IOL.

Intraocular lenses.

I have again reviewed the current state of the art in intraocular lens design in what has been a year of consolidation rather than dramatic discoveries. In foldable lenses, silicone reigns supreme, but there is the promising development of high-refractive-index foldable acrylic lenses. Heparin surface modification is now accepted as valuable in high-risk eyes, but there remains a question mark over surface passivation value. Small-incision lenses continue to proliferate with the design of new haptics to facilitate insertion after circular tear capsulorhexis. Some doubt has been raised concerning the optical qualities of ovoid lenses. Anterior-chamber myopic lenses for phakic myopic patients remain controversial. However, an increasing volume of data concerning their advantages and disadvantages is now available.

Comparison of Heparin Surface Modified and Ordinary PCLs: A Japanese Study

In a Japanese study, we confirmed that heparin surface modification of IOLs reduces IOL surface inflammatory cells and deposits at first and third postoperative months. This has already been proved in Caucasian eyes. Further, laser flare cell measurement was used for quantitative evaluation of post-implant surgical inflammation. We found that heparin surface modification also has favourable effects upon blood-aqueous barrier function particularly at early postoperative periods.

In-the-bag Implantation of Heparin Modified Posterior Chamber Lenses

In a prospective study, heparin surface modified posterior chamber lenses were implanted into the capsular bag in 50 patients with an average age of 74.1 years. The exact positioning of the biconvex, one-piece lens in-the-bag is a prerequisite for good centration and an optimal result. The hydrophilization of the originally hydrophobic PMMA material is achieved by heparin surface modification and results in decreased inflammation. The aim of this study was to investigate the postoperative behaviour of the HSM posterior chamber lens implanted in the bag, with special consideration given to intraocular inflammation. In the postoperative follow-up time of 5 to 10 months, 100% of the patients with physiological fundus reached a postoperative visual acuity of 0.7 or better.