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Heparin-surface-modified intraocular lenses in pediatric cataract surgery: Prospective randomized study

Basti, Surendra DNBa; Aasuri, Murali K. MDa,*; Reddy, Madhukar K. MSa; Preetam, Padmaja DOTb; Reddy, Sreelakshmi DOTb; Gupta, Satish MDa; Naduvilath, Thomas J.c

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Journal of Cataract & Refractive Surgery: June 1999 - Volume 25 - Issue 6 - p 782-787
doi: 10.1016/S0886-3350(99)00039-5
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Abstract

Atendency toward increased postoperative inflammation in children is well recognized1–3 and is of concern to surgeons considering intraocular lens (IOL) implantation in these patients. The routine use of microsurgical techniques, meticulous cleaning of lens material, and in-the-bag IOL placement have helped decrease the incidence of early postoperative inflammation after pediatric cataract surgery and IOL implantation.4,5 However, eyes that are relatively quiet in the initial weeks after IOL implantation can develop synechias, inflammatory cell deposits on the IOL, and pupillary capture during subsequent evaluation.5 Reactivity of the IOL material is a likely contributor to this low-grade inflammation.

Poly(methyl methacrylate) (PMMA), the lens material used in many IOLs, is not biologically inert.6–8 By modifying the surface, PMMA IOLs can be rendered more biologically compatible. Initial clinical studies of heparin-surface-modified (HSM) IOLs found that they are beneficial in eyes with pseudoexfoliation,9 diabetes, and glaucoma (K.M. Sarri, H. Jyrkkio, H. Seppa, et al., “Cellular Reactions on Heparin Surface-Modified and Regular PMMA IOLs in Patients with Diabetes and Glaucoma; Interim Analysis of Specular Microscopy Findings 1 Week–3 Months Postoperatively,” presented at the IXth Congress of the European Society of Cataract & Refractive Surgeons, Valencia, Spain, September 1991). Zetterström and coauthors10 implanted HSM IOLs in a series of 21 eyes (14 children). Postoperative inflammatory reactions resolved within the first postoperative week, no cellular deposits were observed on the IOL surface, and posterior synechia formation was seen in 1 eye only. Encouraged by this report, we initiated a prospective, randomized, double-masked, controlled study to compare implantation of HSM with that of unmodified PMMA IOLs in children.

Patients and Methods

Children with cataract were considered for the study, which began in March 1996. Inclusion criteria were cataract and eligible for primary implantation of a posterior chamber IOL; age between 2 and 14 years; able to attend all follow-ups; informed consent provided. Exclusion criteria were recurrent or chronic uveitis; corneal pathology potentially impairing IOL visualization; systemic treatment with anti-inflammatory drugs (steroidal or nonsteroidal); surgical complications contraindicating the use of a nonsutured posterior chamber IOL; previous inclusion in the study; current participation in another clinical study.

Institutional review board approval was obtained. All parents provided written informed consent. Computer-generated envelopes were used to randomize the 90 patients eligible for the study to receive either an HSM or an unmodified PMMA IOL. All IOLs were single-piece, all-PMMA with a 6.5 mm biconvex optic and 12.0 mm haptic spread (CeeOn, Model 808 A/C). Extracapsular cataract extraction with IOL implantation (ECCE+IOL) was performed in children 8 years and older. As is our practice,5 children younger than 8 years had primary posterior capsulotomy and anterior vitrectomy (PPC+AV) with ECCE+IOL. All patients were operated on using general anesthesia by 1 of 4 surgeons (S.B., M.K.A., K.M.R., S.G.) experienced in pediatric cataract surgery.

Surgical Technique

A standard technique was used. After intubation, sterile preparation, and draping, a Barraquer wire speculum was inserted and a 6-0 silk superior rectus bridle suture passed. The conjunctiva was opened at the limbus between the 10 and 2 o'clock meridians, and a partial-thickness scleral groove was made with a #11 blade on a Bard-Parker handle. The anterior chamber was entered in the groove at the 11 o'clock position and sodium hyaluronate 1.4% (Healon GV®) injected to fill the anterior chamber.

In the ECCE+IOL group, a central puncture was made in the anterior capsule with a 26 gauge cystotome and a continuous curvilinear capsulorhexis (CCC) performed with a Utrata forceps. Lens material was aspirated with an irrigating/aspirating cannula. Care was taken to completely remove all lens material in all cases. Healon GV was then used to inflate the capsular bag and to fill the anterior chamber. The IOL was inserted in the capsular bag, and the wound was closed with 10-0 monofilament nylon sutures in a continuous shoelace fashion. The anterior chamber was meticulously irrigated at the end of surgery to remove the Healon GV and debris. A subconjunctival injection of 10 mg gentamicin and 2 mg dexamethasone was given and the eye patched.

In eyes that had a PPC+AV, after the lens matter was aspirated as above, the anterior chamber was filled with Healon GV and a central puncture was made in the posterior capsule with the 26 gauge bent cystotome. Healon GV was then injected between the posterior capsule and anterior hyaloid face. Posterior CCC was performed with a Utrata forceps or an automated vitrector. This was followed by a bimanual anterior vitrectomy using a guillotine-type vitreous cutter while the anterior chamber was infused with a 20 gauge cannula. The IOL implantation and wound closure were performed as above.

Intracameral miotics were not used in any eye, and Ringer's lactate solution was used as the infusion fluid in all eyes. Postoperatively, all eyes received topical betamethasone 0.1% every 2 hours, cyclopentolate 1% every 12 hours, and gentamicin 0.3% every 6 hours. Gentamicin was discontinued in 1 week and cyclopentolate, in 2 weeks. The betamethasone was tapered between the second and sixth week to every 4, 6, 8, and 12 hours, and then once a day. No medication was used thereafter.

Postoperative Evaluation

Postoperative evaluations were performed at a mean of 1 week ± 1 day (SD), 1 month ± 1 week, 3 months ± 2 weeks, and 6 months ± 4 weeks. At each visit, after an ophthalmologist's examination, 1 of 2 optometrists (S.R., P.P.) performed visual acuity measurement, slitlamp evaluation, and intraocular pressure recording. Before the first examination, the evaluation methodology and findings of the 2 optometrists were found to be similar.

Anterior chamber reaction was graded using Hogan and coauthors' classification.11 After complete pupil dilation, the entire anterior surface of the IOL optic was evaluated manually under high magnification at a slitlamp biomicroscope (handheld or mounted). The deposits were counted in a systematic fashion to ensure the entire surface was evaluated. In children who did not cooperate during clinical evaluation and refraction, evaluation under anesthesia was performed and the deposits were counted. Pigment dusting alone was disregarded. Cellular deposits were not further subclassified, nor was cell morphology studied by specular microscopy. The extent of synechia formation was documented. Clarity of the central 4.0 mm of the posterior capsule was noted in eyes in the ECCE+IOL group. If postoperative signs of increased inflammation were thought to warrant an alteration or increase in anti-inflammatory medication, this was considered an adverse event and documented as such. In such cases, topical betamethasone was used hourly and cyclopentolate or atropine 1% every 12 hours. Based on clinical response, the medications were decreased and stopped as soon as possible.

Statistical Methods

The effect of the IOL types (HSM or unmodified) was determined by inflammatory cell deposits, synechias, and anterior chamber inflammation using an analysis of covariance, with time as the covariate. Separate regression coefficients with their corresponding significance levels were calculated only for significant time covariates. At each time point, differences between the groups in cell deposits, synechias, and anterior chamber inflammation were tested using the Mann–Whitney U test because of the relatively large variation resulting from the small sample. The occurrence of posterior capsule opacification (PCO) was compared at each time point using the chi-square test with Yates continuity correction.

The effect of the surgery type (ECCE+IOL and ECCE+PPC+AV+IOL) on postoperative inflammatory signs was tested using an analysis of covariance while controlling for IOL type, with time as the covariate. Statistical significance was set at P < .05.

Results

The surgical procedure was uneventful in all except 2 eyes. In 1 patient, in-the-bag IOL implantation was not possible because the capsular bag was small and shrunken. Postoperative findings from this patient were not included in the analysis. In the other patient, posterior capsule dehiscence occurred during injection of Healon GV after cortex aspiration. As there was no vitreous prolapse, the tear was converted to a posterior capsulorhexis and the IOL inserted in the bag. This 12-year-old patient was not considered in the PCO analysis but was in cell deposit, uveitis, and synechia evaluations. In Group 1 (HSM lens), there were 11 ECCE+IOL patients and 32 ECCE+PPC+AV+IOL patients. In Group 2 (unmodified IOL), there were 15 and 31, respectively. Mean age in Group 1 was 6.61 ± 3.11 years and in Group 2, 6.12 ± 2.74 years. Distribution of boys and girls and mean preoperative visual acuities were comparable in the 2 groups.

Follow-up data at 1 week, 1, 3, and 6 months were available in 73, 70, 60, and 68 patients, respectively. Occurrence of inflammatory cell deposits in the 2 groups is shown in Table 1. Eyes in Group 1 had significantly fewer deposits than Group 2 at 1, 3, and 6 months (P = .0001). Prevalences of anterior chamber inflammation and synechias are shown in Tables 2 and 3, respectively. There was no statistically significant difference between the 2 groups (P > .05). Although the occurrence of PCO was not statistically different between the 2 groups, it appeared to be higher in Group 2 (Table 4).

Table 1
Table 1:
Number of cell deposits over time.
Table 2
Table 2:
Anterior chamber flare grade11 over time.
Table 3
Table 3:
Number of synechias over time.
Table 4
Table 4:
Posterior capsule opacification (PCO) in eyes having ECCE+IOL only (≥8 years).

The analysis of covariance showed that the significance of IOL type on cell deposits was P < .0001; on inflammation, P = .298; and on synechias, P = .008. The significance of the covariate (time) was P = .009, P < .0001, and P = .565, respectively.

Regression analysis determined the rate of change within each group. Deposits changed at the rate of −4.91 per month in Group 2, which was statistically significant (P = .02), and −0.74 in Group 1 (P = .30). Inflammation changed at the rate of −0.13 in Group 2 and −0.14 in Group 1. Both were statistically significant (P < .0001). Synechias did not change significantly with time within the 2 groups (P= .565).

At the 1 week postoperative visit, Group 2 had a higher incidence of adverse inflammatory reactions (9/36) than Group 1 (2/34). However, the difference was not statistically significant (P = .0618).

Eyes that had ECCE+IOL were compared with those having ECCE+PPC+AV+IOL within each group to determine whether the PPC+AV technique affected the outcome parameters (Table 5). Analysis of covariance revealed no difference between the 2 types of surgeries in cell deposits and anterior chamber inflammation; however, synechia formation was statistically greater in eyes having ECCE+PPC+AV+IOL.

Table 5
Table 5:
Intergroup comparison of variables.

Reliable best corrected visual acuity recording was possible in 19 of 34 eyes in Group 1 and 16 of 34 in Group 2 at 6 months postoperatively (Table 6). There was no statistically significant difference in the visual acuity results between the groups.

Table 6
Table 6:
Best corrected visual acuity preoperatively and 6 months postoperatively.

Discussion

The cytopathology of IOL implantation has been extensively studied in cadaver eyes8,12 and in vivo.7,13 Three cell types are usually seen on IOLs: small cells, giant cells and erythrocytes, and pigment granules.13 The number of these cells varies significantly between quiet eyes and those that are inflamed.12 Although, in general, it is agreed that these cells represent a foreign-body reaction against the IOL and an endeavor to sequester the IOL from intraocular fluids, their significance in otherwise quiet eyes is unclear.

Our inability to obtain reliable visual acuity readings in many patients did not permit us to evalate the relationship of cell deposits and visual acuity. In a randomized double-masked study of adults, Ygge and coauthors13 compared HSM and unmodified PMMA lenses in adults and found no differences in visual acuity between the 2 groups. It is conceivable, however, that very dense deposit formation will scatter light and interfere with visual acuity. One study14 reported the rapid disappearance of giant cells with time. We noted a decrease in cell deposits over time in our study, too. Our lack of visual acuity readings limits us from drawing meaningful conclusions on the clinical implication of this cell reduction. Future studies on older patients who are at risk of deposit formation might help clarify this.

Eleven eyes in our series had a coagulum over the anterior IOL surface and the pupil 1 week postoperatively. All had relatively quiet eyes on the first postoperative day, and none had greater than grade II anterior chamber inflammation co-existing with the coagulum. All except 2 eyes had complete resolution of the coagulum within 2 weeks of therapy with intensive topical steroids and cycloplegics. These 2 eyes had persisting inflammation and synechia formation up to 5 weeks postoperatively that then resolved. One of these eyes had a grossly decentered, occluded pupil. It is believed that a fibrin coagulum forms secondary to breakdown of the blood–aqueous barrier. However, the actual factor triggering coagulum formation and the reason for the relatively less pronounced associated signs of inflammation are unclear to us. Fortunately, intense topical steroid and cycloplegics were beneficial in resolving the coagulum in most of these cases.

Although we noted significantly higher inflammatory cell deposition in Group 2, the occurrence of anterior uveitis was not higher and the occurrence of posterior synechias was only marginally higher. Low-grade inflammation in eyes with IOLs is likely responsible for these findings. It is possible that such inflammation is significantly more pronounced in eyes with unmodified IOLs. We noted minimal deposit formation in both groups 1 week postoperatively. Thereafter, deposits in eyes with HSM IOLs remained minimal. Eyes with unmodified IOLs, however, had significantly greater deposits 1 month after surgery that decreased temporally thereafter. The topical steroids and cycloplegics were tapered after the evaluation 1 week after surgery. Especially in eyes with unmodified IOLs, it might be prudent to use relatively higher doses of topical corticosteroids during the first postoperative month, even if the eye appears relatively quiet upon clinical examination.

In our series, the incidence of acute anterior uveitis (≥ grade II) during the 1 week postoperative evaluation was 8.5%. This is consistent with the incidence noted in more recent reports4,5 on results of pediatric cataract surgery and is significantly lower than what was consistently reported in the 1980s.1–3 The lower incidence possibly reflects the beneficial effects of currently practiced microsurgical techniques.

Although our findings suggest a lower incidence of PCO in eyes with an HSM IOL, the small number of eyes that developed PCO and the relatively short follow-up of our study undermine accurate evaluation of the influence of HSM IOLs on PCO rates. Our results suggest that it might be useful to study larger number of patients with a longer follow-up to evaluate whether a beneficial effect of HSM IOLs exists and, if so, its extent.

In conclusion, the findings of our study indicate that HSM IOLs are advantageous in children in that inflammatory cell deposit formation is significantly less than in eyes with unmodified PMMA IOLs during the first 6 months after cataract surgery. Also, coagulum occur less frequently in eyes with HSM IOLs.

References

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