Björn Lundgren

Formation of free radicals during phacoemulsification

During phacoemulsification cavitation bubbles are formed. These bubbles are believed to be one source of damage to corneal endothelium seen after phacoemulsification. Free radicals are induced whenever cavitation bubbles implode. The aim of this study was to confirm the initiation of free radicals by phacoemulsification and to correlate the power of ultrasound in the phacoemulsification process to the amount of free radicals formed, using both in vitro and in vivo techniques. The formation of free radicals was determined by adding luminol to a buffer and measuring the chemoluminescence in vitro and in rabbit eyes (Lumacounter 2080 or a single-photon-counting apparatus) during phacoemulsification. The data obtained show that free radicals are formed during phacoemulsification and that the amount of free radicals correlates with the power of ultrasound. Furthermore, the radical formation could be inhibited by the radical scavengers SOD, Healon and Healon GV. These results were achieved both in vitro in the test tube and in vivo in rabbit eyes. By showing that the addition of SOD to the irrigation buffer during phacoemulsification decreases the corneal endothelial cell damage, we show that free radicals could have a role in postoperative complications seen clinically.

Inflammatory response in the rabbit after phacoemulsification and intraocular lens implantation using a 5.2 or 11.0 mm incision

Purpose: To study the effect of two incision sizes, 5.2 and 11.0 mm, on the inflammatory response in rabbit eyes after lens extraction with phacoemulsification. Setting: S:t Erik’s Eye Hospital, Stockholm, and Pharmacia, Uppsala, Sweden. Methods: Bilateral endocapsular phacoemulsification was performed on 32 rabbits. The wound was enlarged to 5.2 mm, and a poly(methyl methacrylate) intraocular lens (IOL) was implanted in the capsular bag. In each rabbit, one eye was selected at random and the wound in that eye enlarged to 11.0 mm. In both eyes the wound was sutured with a 9‐0 polypropylene continuous suture. The number of white blood cells (WBCs) and prostaglandin E2 (PGE2) in the aqueous humor were measured at days 1, 3, 7, and 28 postoperatively. Corneal thickness was also measured by pachymetry. Results: The number of WBCs at day 3 and the PGE2 levels at days 1, 3, and 7 were significantly higher in eyes with 11.0 mm incisions than in eyes with 5.2 mm incisions. One week after surgery, the corneas in the eyes with 11.0 mm incisions were significantly thicker than in those with 5.2 mm incisions. Conclusion: The results indicate that incision size is an important factor in the inflammatory response following phacoemulsification and IOL implantation in the rabbit eye.

Ocular growth in newborn rabbit eyes implanted with a poly{methyl methacrylate) or silicone intraocular lens

Purpose: To examine eye growth in lensectomized infant rabbits implanted with a poly(methyl methacrylate) (PMMA) or a silicone intraocular lens (IOL). Setting: S:t Eriks Eye Hospital, Karolinska Institute, Stockholm, Sweden. Methods: Two groups of 3‐week‐old rabbits were used. In Group 1 (n = 13), lensectomy was performed in both eyes. In one randomly selected eye, a +30 diopter (D) heparin‐surface‐modified (HSM) PMMA IOL was implanted in the capsular bag; the other eye was left aphakic. In Group 2 (n = 10), a +21 D HSM PMMA IOL was implanted in one randomly selected eye and a +21 D silicone IOL was implanted in the other. Axial length, corneal diameter, corneal thickness, and intraocular pressure (IOP) were measured in all eyes preoperatively and 1, 2, and 3 months after surgery. The wet mass of the after‐cataract was measured 3 months after surgery. The ciliary body with the ciliary processes and the peripheral retina were examined histologically after formalin fixation. The two IOL types were compressed to 7.0 mm, corresponding to the diameter of the 3‐week‐old rabbit lens. Results: In Group 1, the axial length was significantly decreased in the eye with an HSM PMMA IOL compared with the fellow aphakic eye (P < .01, two‐way analysis of variance [ANOVA]). No significant difference in corneal diameter, corneal thickness, or IOP was found between the eyes. The wet mass of the dissected after‐cataract was significantly less in the eye implanted with an IOL. Two animals had an elevated IOP with secondary glaucoma in their aphakic eye and were excluded from the study. In Group 2, axial length in eyes with the HSM PMMA IOL was less than in the eyes with the silicone IOL (P < .25, two‐way ANOVA). No difference in corneal diameter, corneal thickness, or IOP was found. The amount of after‐cataract was not altered. Histologically, the eyes with the HSM PMMA IOL showed retinal degeneration, neovascularization of the ciliary body accompanied by a large number of inflammatory cells, and tumid ciliary processes. The eyes with the silicone IOL showed only minor changes. The aphakic eyes presented even less histological change. The compression test demonstrated that three times the compression force was needed to squeeze the HSM PMMA lens than the silicone IOL. Conclusion: The results suggest that in the young rabbit eye, implanting a regular‐size HSM PMMA IOL destroys intraocular tissues and reduces eye growth significantly. Replacing the PMMA IOL with a silicone IOL improves the ocular growth.

Secondary cataract. An in vivo model for studies on secondary cataract in rabbits.

Abstract Secondary cataract formation is the most common postoperative complication following cataract surgery. To study different methods preventing the secondary cataract formation a relevant animal model is required. An in vivo rabbit model for studies on the prevention of secondary cataract formation is presented. The lens nucleus and cortex were removed by phacoemulsification, and two months later the growth of the secondary cataract was estimated by scoring on a scale from 0–4, both central and peripheral, and by measuring the wet mass of the dissected secondary cataract. The model seems to be a relevant way to study different concepts for the prevention of secondary cataract formation.

After-cataract and ocular growth in newborn rabbit eyes implanted with a capsule tension ring

Purpose: To examine after‐cataract and eye growth in lensectomized newborn rabbits implanted with capsule tension rings of different sizes. Setting: S:t Eriks Eye Hospital, Karolinska Institute, Stockholm, Sweden. Methods: Two groups of 24‐day‐old rabbits were used. In Group 1 (n = 9), lensectomy was performed in both eyes. In one randomly selected eye, an open poly(methyl methacrylate) (PMMA) capsule tension ring with a 7.0 mm diameter and 0.13 mm thickness was implanted in the capsular bag. The other eye was left aphakic. In Group 2 (n = 10), an open PMMA capsule tension ring with a 10.0 mm diameter and 0.13 mm thickness was implanted in one randomly selected eye, and the other eye was left aphakic. Axial length, corneal diameter, corneal thickness, and intraocular pressure (IOP) were measured in all eyes preoperatively and 1, 2, and 3 months after surgery. The wet mass of the after‐cataract was measured at 3 months. Three Group 1 eyes and four Group 2 eyes developed secondary glaucoma and were excluded from the study. Results: Axial growth did not differ significantly between the eyes implanted with the 7.0 mm ring and the aphakic eyes (mean difference 0.01 mm; F3;15 = 0.02; P>.25). Corneal diameter also did not differ (two‐way analysis of variance [ANOVA]). Axial length growth was less in the eyes implanted with the 10.0 mm ring than in the aphakic eyes (mean difference 1.05 mm; F3;15 = 2.06; P < .25). The average decrease in corneal diameter growth was 1.0 mm in the implanted eyes. Growth in the eyes with the 10.0 mm ring was significantly less than in the eyes with the 7.0 mm ring (P = .05, Wilcoxon rank‐sum test). Corneal thickness and IOP did not differ significantly between eyes (F3;15 = 0.6; P>.25; two‐way ANOVA). Amount of after‐cataract did not differ significantly between the aphakic eyes and the eyes implanted with the 7.0 mm ring. It was significantly less in the eyes with the 10.0 mm ring than in those with the 7.0 mm ring (Wilcoxon signed‐rank test) and in the aphakic eyes (P < .025, Wilcoxon rank‐sum test). Conclusion: In the young rabbit eye, a 10.0 mm capsule ring reduced the eye growth compared with both the aphakic eye and the eye implanted with a 7.0 mm ring. The 10.0 mm ring also inhibited the production of after‐cataract compared with the production in the aphakic eye and the eye implanted with the 7.0 mm ring.

Development of Posterior Capsule Opacification in the Rabbit

Purpose: The aim of the present study was to characterize the development of after-cataract in the rabbit by measuring its wet weight, protein, DNA and glycosaminoglycan (GAG) contents and using Scheimpflug and slitlamp analysis. Further, aqueous humor (AqH) leukocytes, protein and lens epithelial cell proliferation activity were determined. Methods: AqH was collected and capsular bags including after-cataract were dissected free on days 0, 1, 7, 14, 28 and 56 after cataract surgery. The wet weights were determined and the contents of DNA, protein and GAG in the capsular bags including after-cataract were analyzed. AqH was analyzed for leukocytes, protein and proliferative activity. In another set of experiments, rabbit eyes were analyzed by the Scheimpflug technique and slitlamp examination on days 0, 1, 7, 14, 28 and 56 after cataract surgery. The wet weight of the capsular bag with the after-cataract was also determined. Results: An increase was found in the wet weight (480%) and the contents of protein (221%), DNA (945%) and GAG (336%) of the capsular bags including after-cataract during the experimental period. In the AqH, all 3 variables measured, leukocytes, protein and proliferative activity, reached their highest levels on day 1 after surgery. In the second set of experiments, the wet weight of the capsular bag including after-cataract increased by 391% during the 56-day experimental period. Posterior capsule opacification (PCO), as measured by Scheimpflug analysis, increased from 0.8 to 81.7% and the scores of Elschnig’s pearls as well as fibrosis, analyzed by slitlamp, increased from 0.0 to 2.8 and 3.0, respectively. Conclusions: This study shows that the same components that are reported to be important in human PCO are also components of PCO in the rabbit. Thus, the rabbit model seems to accurately reflect human PCO development, and because PCO develops much faster in rabbits that would make the rabbit model suitable for studies to elucidate human PCO development.

Effect of 3-piece AcrySof and downsized heparin- surface-modified poly(methyl methacrylate) intraocular lenses in infant rabbit eyes

Purpose: To evaluate after‐cataract formation, ocular growth, and intraocular lens (IOL) behavior in lensectomized infant rabbit eyes implanted with a downsized heparin‐surface‐modified poly(methyl methacrylate) (HSM PMMA) IOL with long haptics or a 3‐piece AcrySof® IOL (Alcon Laboratories, Inc.). Setting: St. Eriks Eye Hospital, Stockholm, Sweden. Methods: Clear lens extraction was performed in both eyes of 3‐week‐old rabbits. In Group 1 (n = 9), a downsized HSM PMMA IOL with long haptics was implanted in 1 eye and in Group 2 (n = 9), a 3‐piece AcrySof IOL was implanted in 1 eye. The fellow eyes remained aphakic. Results: The amount of after‐cataract was significantly less in the eyes with the IOLs than in the aphakic eyes. The eyes with the HSM PMMA IOL had significantly less after‐cataract than those with the AcrySof IOL. No significant difference in axial length was noted between the IOL eyes and the aphakic eyes in either group. In the eyes with the 3‐piece AcrySof IOL, there was anterior movement of the optic with occlusion of the pupil. Conclusions: Eyes with the HSM PMMA IOL and the AcrySof IOL had less after‐cataract than the aphakic eyes. The HSM PMMA IOL, however, inhibited after‐cataract production significantly better than the AcrySof IOL. The 3‐piece AcrySof IOL was seriously deformed in the infant rabbit eyes and caused occlusion of the pupil. Surgeons should be cautious in implanting this AcrySof IOL in the eyes of newborns or in eyes with severe microphthalmia.

Lack of correlation between intraocular inflammation and after-cataract formation in the rabbit eye

Purpose: To determine whether an increased or reduced inflammatory response following cataract surgery influences the development of after‐cataract. Setting: Department of Preclinical Ophthalmology, Pharmacia, Uppsala, Sweden. Methods: Rabbits that had had cataract surgery were given endotoxin, ovalbumin, dexamethasone, or diclofenac. Aqueous humor, leukocytes, and prostaglandin E2 (PGE2) were analyzed, and the wet weight of the after‐cataract was determined. Results: The wet weight of the after‐cataract was unaffected by endotoxin and 67% lower in the eyes treated with ovalbumin than in the control eyes on day 56. Aqueous humor concentrations of leukocytes and PGE2 were 94% and 87% lower in the group treated with dexamethasone than in the control group on day 7, and the concentration of PGE2 was 98% lower in the diclofenac group; however, the wet weight of the after‐cataract was unaffected by both treatments. Conclusion: This study suggests that an increased inflammatory response does not increase the development of after‐cataract and a reduction in the inflammatory response does not reduce the development of after‐cataract.

Phacoemulsification and lens implantation in rabbit eyes: Capsular bag versus ciliary sulcus implantation and 4.0 versus 7.0 mm capsulorhexis

Purpose: To compare the effects of intraocular lens (IOL) implantation in the capsular bag versus the ciliary sulcus and of a 4.0 versus 7.0 mm continuous curvilinear capsulorhexis (CCC) on postoperative inflammation and after‐cataract formation. Setting: St. Erik’s Eye Hospital, Karolinska Institute, Stockholm, Sweden. Methods: Trial 1 comprised 40 rabbits that had CCC, endocapsular phacoemulsification, and a poly(methyl methacrylate) 10L implanted in the capsular bag in one eye and the ciliary sulcus in the fellow eye. In Trial 2,‐40 rabbits had a 4.0 mm CCC in one eye and a 7.0 mm CCC in the fellow eye followed by phacoemulsification and IOL implantation in the capsular bag. White blood cell (WBC) counts and prostaglandin E2 (PGE2) concentrations in aqueous humor were determined at 1, 3, 7(8), 28, and 56 days postoperatively. Wet mass of the dissected after‐cataract was measured at day 56. In Trial 1, wet mass of the iris‐ciliary body was measured at each observation. Results: In Trial 1, WBC counts at day 1 were higher with a sulcus‐fixated IOL (P = .05). The median wet mass of the dissected after‐cataract was 108.5 mg in eyes with a sulcus‐fixated IOL and 62.5 mg in eyes with a capsule‐fixated IOL (P = .01). In Trial 2, WBC counts at day 8 were significantly higher in eyes with a 7.0 mm CCC than in those with a 4.0 mm CCC (P < .05) There was no significant difference in the amount of after‐cataract. Conclusions: The results indicate that IOL implantation in the capsular bag causes less inflammation and after‐cataract formation than sulcus fixation and that using a large CCC does not affect the total amount of after‐cataract but may enhance the inflammatory response.

PGE2 and leucocyte levels in aqueous humor after lens extraction and intraocular lens implantation

In order to study the inflammatory response after cataract surgery and intraocular lens implantation the leukocyte (WBC) and prostaglandin E(2) (PGE(2)) levels in aqueous humor were measured in rabbit eyes at different time points (1, 3, 7, 14 and 28 days) postoperatively. In the first group lenses were implanted in the anterior chamber of the eye, without lens extraction, while in the second group the lens was removed and the IOL was placed in the capsular bag. A third group of animals was injected with 10 ng endotoxin into the vitreous in order to induce an inflammation of the uvea. In the endotoxin group high levels of WBC and PGE(2) were observed at 24 h postoperatively, followed by a decrease over time. In the intraocular lens groups WBC and PGE(2) were detected at all time points, and at higher levels compared to the endotoxin group. The WBC was high at day 1 and 3, declined over time, and then increased at day 28 postoperatively. The PGE(2) level was highest at day 3 in rabbits with anterior chamber lenses, while it peaked at day 7 in the animals with IOLs implanted in the capsular bag. In animals with the extracapsular lens extraction without an implanted IOL, the levels of WBC and PGE(2) decreased over time, and were statistically lower after one week compared with animals with an IOL placed in the capsular bag. The results demonstrate that the inflammatory response after cataract surgery persists for at least one month, probably due to surgical trauma and foreign body reactions. PGE(2) and WBC could be used to study postoperative trauma and biocompatibility of different IOL materials and designs.