- Email: [email protected]
Intracameral triamcinolone acetonide after pediatric cataract surgery
ARTICLE
Intracameral triamcinolone acetonide after pediatric cataract surgery Catherine A. Cleary, FRCSI, Bernadette Lanigan, MBA, Michael O’Keeffe, FRCS
PURPOSE: To assess the use of preservative-free intracameral triamcinolone as an adjunct to topical steroidal agents after pediatric cataract surgery. SETTING: Children’s University Hospital, Dublin, Ireland. DESIGN: Retrospective case series. METHODS: From the 2008 to 2009, intracameral preservative-free triamcinolone 4 mg/0.1 mL (Triesence) was used immediately after cataract surgery. Clinical indices of anterior segment inflammation were assessed at 1, 7, 14, 21 days and at 6 weeks postoperatively. RESULTS: There were no complications secondary to triamcinolone use in 36 eyes of 26 children. In all but 1 case, intracameral triamcinolone was highly effective in controlling postoperative inflammation after pediatric cataract surgery, resulting in quiet eyes with few inflammatory signs (grade 0 to 1). CONCLUSION: Intracameral triamcinolone provided a safe and useful adjunct to topical steroid drops after pediatric cataract surgery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:1676–1681 Q 2010 ASCRS and ESCRS
Although the pathophysiology of fibrinous uveitis after cataract surgery is not well understood, it is thought to be caused by a breakdown of the blood– ocular barrier and an imbalance in the coagulation and fibrinolytic pathways. In the pediatric population, this reaction may be exaggerated by an immature blood–ocular barrier combined with an exuberant healing response.1 Severe fibrinous reaction can lead to poor operative outcomes and long-term morbidity; it is a particular hazard in cataract surgery in infants and is especially an issue after intraocular lens (IOL) implantation.2 Postoperative fibrinous uveitis has
Submitted: March 10, 2010. Final revision submitted: April 20, 2010. Accepted: April 20, 2010. From Doheny Eye Institute (Cleary), University of Southern California, Los Angeles, California, USA; Children’s University Hospital (Lanigan, O’Keeffe), Dublin, Ireland. Corresponding author: Michael O’Keeffe, FRCS, The Eye Clinic, The Children’s University Hospital, Temple Street, Dublin 7, Ireland. E-mail: [email protected].
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Q 2010 ASCRS and ESCRS Published by Elsevier Inc.
been reported in up to 100% of pediatric patients having cataract surgery.3–5 At present, topical and systemic corticosteroid agents are the mainstay of therapy. Moreover, many cases of postoperative uveitis remain poorly controlled despite systemic steroid treatment, leading to clinically significant complications. Complications include secondary membrane formation requiring surgical intervention in up to 27% of children6; this compares with a 3% incidence of severe postoperative fibrinous uveitis in adult populations.7 In this paper, we describe the outcomes in children who received intracameral preservative-free triamcinolone as an adjunct to topical steroid therapy after cataract surgery. PATIENTS AND METHODS Between August 2008 and December 2009, consecutive patients who had pediatric cataract surgery at the Children’s University Hospital, Dublin, received intracameral preservative-free triamcinolone acetonide 4 mg/0.1 mL (Triesence) and intracameral cefuroxime 1 mg/0.1 mL at the end of surgery. In all cases, the parents provided written informed consent. 0886-3350/$dsee front matter doi:10.1016/j.jcrs.2010.04.038
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INTRACAMERAL TRIAMCINOLONE ACETONIDE AFTER PEDIATRIC CATARACT SURGERY
Surgical Technique After general anesthesia was administered and sterile preparation and draping were performed in the usual way, a clear corneal incision was made and an ophthalmic viscosurgical device (OVD) (sodium hyaluronate 1% [Healon]) injected into the anterior chamber. Next, a continuous curvilinear capsulorhexis was created using an Orbit universal diathermy unit (Oertli Instruments AG). The lens nucleus and cortex were aspirated using a bimanual technique. In children younger than 4 years in whom the eye was left aphakic, OVD was injected to deepen the capsular bag and a cystotome used to make an opening in the posterior capsule. A vitrector was inserted through the opening to perform a posterior capsulotomy and anterior vitrectomy. In cases in which an IOL was used, the IOL was first placed in the capsular bag, after which posterior capsulotomy and anterior vitrectomy were performed using the vitrector via a pars plicata sclerotomy located 2.5 mm from the limbus. Corneal wounds were sutured with 10-0 polyglactin (Vicryl), and sclerotomies were sutured using 7-0 glycolide–lactide copolymer sutures (Polysorb). At the end of surgery, all patients received an intracameral injection of cefuroxime 1 mg/0.1 mL and preservative-free triamcinolone 4 mg/0.1 mL using a Rycroft cannula.
Table 1. Grading system used to assess anterior segment inflammation. Score Conjunctival injection Grade 0 Grade 1 Grade 2 Grade 3 Anterior chamber reaction* Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Corneal clarity Grade 0 Grade 1 Grade 2 Grade 3
Postoperative Protocol Postoperatively, all patients were prescribed topical prednisolone acetate 1% (Pred Forte) drops every 2 hours for 1 week followed by every 4 hours for 2 weeks and then 4 times daily for 4 weeks. Patients also received topical chloramphenicol (Chloromycetin) drops every 6 hours for 2 weeks and topical atropine 1% once daily for 1 month. No patient received oral or subconjunctival steroid agents. All patients were examined postoperatively at 1, 7, 14, 21, 28 days and 6 weeks, and monthly thereafter. All examinations were performed using a portable or fixed slitlamp. Table 1 shows the grading system used to assess anterior chamber inflammation. Ten of the children in the study had postoperative intraocular pressure (IOP) measurement under anesthesia, 5 at 3 months and 5 at 6 months.
RESULTS The study comprised 36 eyes of 26 children (10 boys) with a mean age of 5 years (range 6 weeks to 15 years). The mean postoperative follow-up was 8 months (range 3 weeks to 16 months). Table 2 shows the patients’ characteristics, surgical details, outcomes, and complications. Triamcinolone crystals persisted within the anterior chamber for up to 5 days postoperatively. No complications were associated with its use. One eye developed significant postoperative inflammation (Table 3). The mean IOP in 5 eyes at 3 months was 11.8 mm Hg (range 8 to 17 mm Hg) and in 5 eyes at 6 months was 12.0 mm Hg (range 5 to 17 mm Hg). There were no cases of increased IOP. Four patients had a neodymium:YAG posterior capsulotomy. Two patients required surgical capsulotomy to clear the visual axis. In 1 patient with persistent hyperplasia of the primary vitreous and microphthalmos,
Description
White eye Mild conjunctival injection Moderate conjunctival injection Severe conjunctival injection
!5 cells 5–10 cells 10–20 cells 20–30 cells Cells too numerous to count; hypopyon formation Clear cornea; no edema Descemet membrane folds Stromal edema and haze Microcystoid epithelial edema or subepithelial bullae
*Anterior chamber cells were measured with a slit beam 3.0 mm high and 1.0 mm wide at a 45- to 60-degree angle
surgical iridotomies and a surgical capsulotomy were required 4 months after the initial cataract surgery for the treatment of acute iris bombe secondary to adhesions between the iris and the lens capsule and anterior hyaloid. These complications were thought to be due to surgery rather than intracameral triamcinolone therapy. Severe inflammation in the immediate postoperative period occurred in 1 case, a 6-week-old infant with congenital cataract and very narrow palpebral apertures in whom ocular examination and eye drop instillation proved very difficult. This patient was managed with serial examinations under anesthesia at weekly intervals for 3 weeks. At the first examination under anesthesia (EUA), division of synechiae was performed and intracameral triamcinolone and cefuroxime injections were given. At the second EUA, the intracameral triamcinolone and cefuroxime injections were repeated. At 3 weeks, the child began to open the eye spontaneously; EUA showed good resolution of inflammation with a white eye, clear cornea, and deep and quiet anterior chamber. Intracameral triamcinolone in this case promoted rapid resolution of inflammation in a setting in which effective topical therapy was not possible; it also prevented the need for high-dose oral steroid therapy. DISCUSSION In the pediatric population, inflammation after cataract surgery is common and leads to long-term morbidity. It
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INTRACAMERAL TRIAMCINOLONE ACETONIDE AFTER PEDIATRIC CATARACT SURGERY
Table 2. Patient demographic, surgical details, and outcomes. Pt
Type of Cataract
Eye
Other Diagnoses
1
Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Posterior polar cataract Posterior polar cataract Posterior polar cataract Posterior polar cataract Congenital nuclear sclerosis Congenital nuclear sclerosis Traumatic cataract Posterior polar cataract
R
Trisomy 21
0.3
1.7
Yes
Yes
No
L
No
0.2
9.4
Yes
Yes
No
R
Trisomy 21
0.1
6.5
Yes
No
No
L
Trisomy 21
0.1
6.2
Yes
No
No
0.4
7.4
Yes
No
No
0.4
7.4
Yes
No
No
8.8 8.9 14.7 14.8 0.1
11.6 10.9 12.5 10.6 1.2
No No No No Yes
Yes Yes Yes Yes No
No No No No No No
2 3 3 4 4 5 5 6 6 7 7 8 9 10 10 11 11 12 13 14 14 15 16
Developmental cataract (posterior polar) Developmental cataract (posterior polar) Congenital cataract Congenital cataract Posterior polar cataract Posterior capsular cataract Posterior subcapsular cataract Posterior subcapsular cataract Congenital cataract Congenital nuclear sclerosis
R L R L R L R
Microphthalmia, microlissencephaly Microphthalmia, microlissencephaly No No No Trisomy 21 No No
0.2
1.0
Yes
No
L L
No No
12.1 5.6
3.3 11.8
No No
L
No
10.8
17.0
No
Yes YAG PC Yes IOL repositioning, Nd:YAG PC 6 mo postop No No
R
No
10.9
15.9
No
No
No
R L R L R
Perisylvian polymicrogyria Perisylvian polymicrogyria No No Type 1 DM
0.7 0.7 5.4 4.2 14.0
4.0 4.0 0.7 3.5 15.0
Yes Yes Yes Yes No
No No Yes Yes Yes
No No No No No
L
Type 1 DM
13.9
15.5
No
Yes
Nd:YAG PC
R R
3.2 0.1
13.4 1.4
No Yes
Yes Yes
0.1 1.0 11.4
16.4 12.7 14.8
Yes Yes No
Yes Yes Yes
10.5 0.1
3.0 13.2
No Yes
Yes No
YAG PC No
0.1
12.7
Yes
No
No
13.5 0.1
1.9 8.3
No Yes
Yes No
15.2 1.1
4.4 6.5
No Yes
Yes Yes
17 18 19
Congenital cataract Congenital cataract Traumatic cataract
R R R
20 21
Lamellar cataract Congenital nuclear sclerosis Congenital nuclear sclerosis Anterior polar cataract Congenital nuclear sclerosis Lamellar cataract Posterior lenticonus
R R L
Hypotony
22 23 24 25
Reoperation
L
Left pseudophakia Small palpebral apertures, very difficult to assess or instill drops No No Dog-mauled face and eye Left pseudophakia Hypotony
21
Age (Y) FU (Mo) PC and AV IOL
R R L L
No PHPV anterior type, microphthalmia Right pseudophakia
No EUA and intracameral triamcinolone injection at weekly intervals for 3 wk postop Surgical PC Surgical PC YAG PC
No Surgical iridotomies and PC 4 mo postop No No (continued on next page)
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Table 2 (continued ) Pt
Type of Cataract
Eye
Other Diagnoses
26
Congenital nuclear sclerosis Congenital nuclear sclerosis
R
Microphthalmia, hypotony, plagiocephaly Microphthalmia, hypotony, plagiocephaly
26
L
Age (Y) FU (Mo) PC and AV IOL
Reoperation
0.1
3.5
Yes
No
No
0.1
3.3
Yes
No
No
AV Z anterior vitrectomy; DM Z diabetes mellitus; EAU Z examination under anesthesia; IOL Z intraocular lens; Nd:YAG Z neodymium:YAG; PC Z posterior capsulotomy; PHPV Z persistent hyperplastic primary vitreous; Pt Z patient
is notoriously difficult to manage.2,4,8,9 Missed doses and noncompliance due to behavioral problems lead to subtherapeutic administration of topical antiinflammatory medication and may partly explain why outcomes are worse in children than in adults. In support of this, high-dose systemic steroid agents can provide good control of postoperative uveitis, suggesting that the condition is steroid sensitive in most cases. In addition, the immature eye is more prone to severe inflammatory reactions and the poor outcomes after pediatric cataract surgery may be related to biologic differences rather than the bioavailability of steroid therapy. The frequent administration of topical steroid therapy is especially challenging in small infants. Possible significant advantages of intracameral triamcinolone include ease of administration at the end of surgery because the crystals persist for several days in the anterior chamber, providing a prolonged antiinflammatory effect. The half-life of preservative-free triamcinolone acetonide in the nonvitrectomized eye is estimated to
Table 3. Findings at postoperative examinations. Finding Conjunctival injection O1 Day 1 Day 7 Day 14 Day 21 Anterior chamber reaction O2 Day 1 Day 7 Day 14 Corneal edema O1 Day 1 Day 7 Day 14 Day 21 Fibrin formation Posterior synechiae
Eyes (n)
1 1 1 1 1 1 1 1 1 1 1 1 1
be 18.7 G 5.7 days.10 It has been widely used in vitreoretinal surgery for the delineation of vitreous membranes and has also been used in complicated cataract surgery in adults and in children to visualize vitreous in the anterior chamber.10 It does not appear to be toxic to the corneal endothelium. Karalezli et al.11 report that the use of intracameral triamcinolone instead of postoperative steroid drops to control inflammation in adult cataract surgery appeared equally efficacious. We decided against conducting a placebocontrolled study of intracameral triamcinolone alone after pediatric surgery because withdrawal of steroid therapy in the pediatric population would be detrimental to patient care given the high incidence of severe inflammatory reactions. Moreover, we decided against intracameral injections of placebo compounds because this has risk and no potential benefit to the child. Thus, we introduced intracameral triamcinolone as an adjunct to topical steroid therapy and studied the surgical outcomes over a period of more than 1 year. None of our pediatric patients developed glaucoma, endophthalmitis, or raised IOP as the result of triamcinolone use. Karalezli et al12 and Gills and Gills13 found no change in IOP with the use of intracameral triamcinolone in adults. Other intracameral anti-inflammatory therapies have been tested in the pediatric population. Mehta and Adams14 report the results of intracameral tissue plasminogen activator (tPA) for severe postoperative fibrinous uveitis in 4 eyes in a series of 37 children who had cataract surgery. No patient in the study received oral steroids. A drawback to tPA as a therapy is the necessity for administration under a second general anesthetic. Reported postoperative adverse effects included raised IOP and persistent posterior synechiae, although these are more likely related to surgery than to the tPA. In a randomized placebo-controlled trial, Siatiri et al.7 found r-tPA was more effective than the placebo in suppressing fibrin formation in the first 2 weeks postoperatively; however, both the treatment group and the control
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group also received systemic steroids. Although intraoperative intracameral heparin infusion has also been reported to be effective in suppressing postoperative fibrinous reaction, it can cause anterior chamber hemorrhage, which has also been reported with tPA use.14–17 Another potential shortcoming is that heparin and tPA have short half-lives (approximately 6 hours and 10 hours, respectively); in contrast, the half-life of intracameral triamcinolone is 18.7 G 5.7 days. Thus, it is likely that neither heparin nor tPA would remain active in the anterior chamber for longer than 72 hours. This is not enough time for heparin or tPA to completely suppress a severe postoperative inflammatory response, which may rebound once the drug is eliminated from the anterior chamber. Another option, although currently limited by high cost, are implants that provide sustained drug delivery within the anterior chamber. They are an appealing approach to postoperative inflammatory reactions and merit further study. One such device is Surodex, a dexamethasone-delivery system. This biodegradable pellet is implanted in the anterior chamber at the time of surgery.18 The pellet contains 60 mg of dexamethasone incorporated in a polymer matrix, which controls release of the drug over 7 days, resulting in higher intraocular dexamethasone levels than topical drops. In 1 study, severe postoperative uveitis developed in only 2 (11%) of 18 eyes having pediatric cataract surgery and implantation of the dexamethasone pellet.19 This study has all the drawbacks of a retrospective design. In addition, it is difficult to accurately grade inflammation and objectively record IOP in younger children. A randomized controlled study is questionable because it may be unethical to withhold steroid therapy given the inevitable severe postoperative inflammation in these patients. It would also require multicenter participation to gain enough patients. Ideally, we would have measured IOP in every child in this study at repeated intervals. However, accurate IOP measurement in young children and infants requires EUA, and most parents in the study did not consent to this. Further evaluation of the long-term effects of suspended particles of intracameral triamcinolone on IOP, the corneal endothelium, and corneal pachymetry is necessary. In summary, we found that the use of preservativefree intracameral triamcinolone in pediatric cataract surgery resulted in quiet eyes with few inflammatory signs in most cases. We believe it is safe and of significant benefit because intensive steroid eye drop instillation is a problem in younger children, particularly in those with small palpebral apertures. Triamcinolone crystals persist for up to 5 days within the anterior chamber and may prove effective in
suppressing inflammation in the initial postoperative period. REFERENCES 1. Lloyd IC, Ashworth J, Biswas S, Abadi RV. Advances in the management of congenital and infantile cataract. Eye 2007; 21: 1301–1309 2. Knight-Nanan D, O’Keefe M, Bowell R. Outcome and complications of intraocular lenses in children with cataract. J Cataract Refract Surg 1996; 22:730–736 3. Hing S, Speedwell L, Taylor D. Lens surgery in infancy and childhood. Br J Ophthalmol 1990; 74:73–77. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1041993/pdf/brjopthal005760010.pdf. Accessed June 15, 2010 4. Keech RV, Tongue AC, Scott WE. Complications after cataract surgery for congenital and infantile cataracts. Am J Ophthalmol 1989; 108:136–141 5. Lloyd IC, Goss-Sampson M, Jeffrey BG, Kriss A, RussellEggitt I, Taylor D. Neonatal cataract: aetiology, pathogenesis and management. Eye 1992; 6:184–196 6. Malukiewicz-Wisniewska G, Kaluzny J, Lesiewska-Junk H, Eliks I. Intraocular lens implantation in children and youth. J Pediatr Ophthalmol Strabismus 1999; 36:129–133 7. Siatiri H, Beheshtnezhad AH, Asghari H, Siatiri N, Moghimi S, Piri N. Intracameral tissue plasminogen activator to prevent severe fibrinous effusion after congenital cataract surgery. Br J Ophthalmol 2005; 89:1458–1461. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1772932/pdf/bjo08901458. pdf. Accessed June 15, 2010 8. Lambert SR, Drack AV. Infantile cataracts. Surv Ophthalmol 1996; 40:427–458; correction, 1996; 41:unnumbered page before page 1 9. Sharma N, Pushker N, Dada T, Vajpayee RB, Dada VK. Complications of pediatric cataract surgery and intraocular lens implantation. J Cataract Refract Surg 1999; 25:1585–1588 10. Dyer D, Callanan D, Bochow T, Abraham P, Lambert HM, Lee SY, Schneiderman T, Potts SL, Walker TM. Clinical evaluation of the safety and efficacy of preservative-free triamcinolone (TriesenceÒ [triamcinolone acetonide injectable suspension] 40 mg/mL for visualization during pars plana vitrectomy. Retina 2009; 29:38–45 11. Karalezli A, Borazan M, Akova YA. Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification. Acta Ophthalmol (Oxf) 2008; 86:183–187. Available at: http://www3.interscience.wiley.com/ cgi-bin/fulltext/120090782/PDFSTART. Accessed June 15, 2010 12. Karalezli A, Borazan M, Kucukerdonmez C, Akman A, Akova YA. Effect of intracameral triamcinolone acetonide on postoperative intraocular pressure after cataract surgery. Eye 2010; 24:619–623 13. Gills JP, Gills P. Effect of intracameral triamcinolone to control inflammation following cataract surgery. J Cataract Refract Surg 2005; 31:1670–1671 14. Mehta JS, Adams GGS. Recombinant tissue plasminogen activator following paediatric cataract surgery. Br J Ophthalmol 2000; 84:983–986. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1723658/pdf/v084p00983.pdf. Accessed June 15, 2010 15. Wedrich A, Menapace R, Ries E, Polzer I. Intracameral tissue plasminogen activator to treat severe fibrinous effusion after cataract surgery. J Cataract Refract Surg 1997; 23:873–877 16. Bayramlar H, Totan Y, Borazan M. Heparin in the intraocular irrigating solution in pediatric cataract surgery. J Cataract Refract Surg 2004; 30:2163–2169
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17. Johnson RN, Blankenship G. A prospective, randomized, clinical trial of heparin therapy for postoperative intraocular fibrin. Ophthalmology 1988; 95:312–317 18. Chang DF, Wong V. Two clinical trials of an intraocular steroid delivery system for cataract surgery. Trans Am Ophthalmol Soc 1999; 97:261–276. discussion 276–279 Available at: http://www.ncbi.nlm.nih.gov.medlib.med.miami.edu:2048/pmc/
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articles/PMC1298264/pdf/taos00002-0284.pdf. Accessed June 15, 2010 19. Lee S-Y, Chee S-P, Balakrishnan V, Farzavandi S, Tan DTH. Surodex in paediatric cataract surgery [letter]. Br J Ophthalmol 2003; 87:1424–1426. Available at: http://www.ncbi.nlm.nih.gov/ pmc/articles/PMC1771875/pdf/bjo08701424.pdf. Accessed June 15, 2010
J CATARACT REFRACT SURG - VOL 36, OCTOBER 2010
Intracameral triamcinolone acetonide after pediatric cataract surgery Catherine A. Cleary, FRCSI, Bernadette Lanigan, MBA, Michael O’Keeffe, FRCS
PURPOSE: To assess the use of preservative-free intracameral triamcinolone as an adjunct to topical steroidal agents after pediatric cataract surgery. SETTING: Children’s University Hospital, Dublin, Ireland. DESIGN: Retrospective case series. METHODS: From the 2008 to 2009, intracameral preservative-free triamcinolone 4 mg/0.1 mL (Triesence) was used immediately after cataract surgery. Clinical indices of anterior segment inflammation were assessed at 1, 7, 14, 21 days and at 6 weeks postoperatively. RESULTS: There were no complications secondary to triamcinolone use in 36 eyes of 26 children. In all but 1 case, intracameral triamcinolone was highly effective in controlling postoperative inflammation after pediatric cataract surgery, resulting in quiet eyes with few inflammatory signs (grade 0 to 1). CONCLUSION: Intracameral triamcinolone provided a safe and useful adjunct to topical steroid drops after pediatric cataract surgery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. J Cataract Refract Surg 2010; 36:1676–1681 Q 2010 ASCRS and ESCRS
Although the pathophysiology of fibrinous uveitis after cataract surgery is not well understood, it is thought to be caused by a breakdown of the blood– ocular barrier and an imbalance in the coagulation and fibrinolytic pathways. In the pediatric population, this reaction may be exaggerated by an immature blood–ocular barrier combined with an exuberant healing response.1 Severe fibrinous reaction can lead to poor operative outcomes and long-term morbidity; it is a particular hazard in cataract surgery in infants and is especially an issue after intraocular lens (IOL) implantation.2 Postoperative fibrinous uveitis has
Submitted: March 10, 2010. Final revision submitted: April 20, 2010. Accepted: April 20, 2010. From Doheny Eye Institute (Cleary), University of Southern California, Los Angeles, California, USA; Children’s University Hospital (Lanigan, O’Keeffe), Dublin, Ireland. Corresponding author: Michael O’Keeffe, FRCS, The Eye Clinic, The Children’s University Hospital, Temple Street, Dublin 7, Ireland. E-mail: [email protected].
1676
Q 2010 ASCRS and ESCRS Published by Elsevier Inc.
been reported in up to 100% of pediatric patients having cataract surgery.3–5 At present, topical and systemic corticosteroid agents are the mainstay of therapy. Moreover, many cases of postoperative uveitis remain poorly controlled despite systemic steroid treatment, leading to clinically significant complications. Complications include secondary membrane formation requiring surgical intervention in up to 27% of children6; this compares with a 3% incidence of severe postoperative fibrinous uveitis in adult populations.7 In this paper, we describe the outcomes in children who received intracameral preservative-free triamcinolone as an adjunct to topical steroid therapy after cataract surgery. PATIENTS AND METHODS Between August 2008 and December 2009, consecutive patients who had pediatric cataract surgery at the Children’s University Hospital, Dublin, received intracameral preservative-free triamcinolone acetonide 4 mg/0.1 mL (Triesence) and intracameral cefuroxime 1 mg/0.1 mL at the end of surgery. In all cases, the parents provided written informed consent. 0886-3350/$dsee front matter doi:10.1016/j.jcrs.2010.04.038
1677
INTRACAMERAL TRIAMCINOLONE ACETONIDE AFTER PEDIATRIC CATARACT SURGERY
Surgical Technique After general anesthesia was administered and sterile preparation and draping were performed in the usual way, a clear corneal incision was made and an ophthalmic viscosurgical device (OVD) (sodium hyaluronate 1% [Healon]) injected into the anterior chamber. Next, a continuous curvilinear capsulorhexis was created using an Orbit universal diathermy unit (Oertli Instruments AG). The lens nucleus and cortex were aspirated using a bimanual technique. In children younger than 4 years in whom the eye was left aphakic, OVD was injected to deepen the capsular bag and a cystotome used to make an opening in the posterior capsule. A vitrector was inserted through the opening to perform a posterior capsulotomy and anterior vitrectomy. In cases in which an IOL was used, the IOL was first placed in the capsular bag, after which posterior capsulotomy and anterior vitrectomy were performed using the vitrector via a pars plicata sclerotomy located 2.5 mm from the limbus. Corneal wounds were sutured with 10-0 polyglactin (Vicryl), and sclerotomies were sutured using 7-0 glycolide–lactide copolymer sutures (Polysorb). At the end of surgery, all patients received an intracameral injection of cefuroxime 1 mg/0.1 mL and preservative-free triamcinolone 4 mg/0.1 mL using a Rycroft cannula.
Table 1. Grading system used to assess anterior segment inflammation. Score Conjunctival injection Grade 0 Grade 1 Grade 2 Grade 3 Anterior chamber reaction* Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Corneal clarity Grade 0 Grade 1 Grade 2 Grade 3
Postoperative Protocol Postoperatively, all patients were prescribed topical prednisolone acetate 1% (Pred Forte) drops every 2 hours for 1 week followed by every 4 hours for 2 weeks and then 4 times daily for 4 weeks. Patients also received topical chloramphenicol (Chloromycetin) drops every 6 hours for 2 weeks and topical atropine 1% once daily for 1 month. No patient received oral or subconjunctival steroid agents. All patients were examined postoperatively at 1, 7, 14, 21, 28 days and 6 weeks, and monthly thereafter. All examinations were performed using a portable or fixed slitlamp. Table 1 shows the grading system used to assess anterior chamber inflammation. Ten of the children in the study had postoperative intraocular pressure (IOP) measurement under anesthesia, 5 at 3 months and 5 at 6 months.
RESULTS The study comprised 36 eyes of 26 children (10 boys) with a mean age of 5 years (range 6 weeks to 15 years). The mean postoperative follow-up was 8 months (range 3 weeks to 16 months). Table 2 shows the patients’ characteristics, surgical details, outcomes, and complications. Triamcinolone crystals persisted within the anterior chamber for up to 5 days postoperatively. No complications were associated with its use. One eye developed significant postoperative inflammation (Table 3). The mean IOP in 5 eyes at 3 months was 11.8 mm Hg (range 8 to 17 mm Hg) and in 5 eyes at 6 months was 12.0 mm Hg (range 5 to 17 mm Hg). There were no cases of increased IOP. Four patients had a neodymium:YAG posterior capsulotomy. Two patients required surgical capsulotomy to clear the visual axis. In 1 patient with persistent hyperplasia of the primary vitreous and microphthalmos,
Description
White eye Mild conjunctival injection Moderate conjunctival injection Severe conjunctival injection
!5 cells 5–10 cells 10–20 cells 20–30 cells Cells too numerous to count; hypopyon formation Clear cornea; no edema Descemet membrane folds Stromal edema and haze Microcystoid epithelial edema or subepithelial bullae
*Anterior chamber cells were measured with a slit beam 3.0 mm high and 1.0 mm wide at a 45- to 60-degree angle
surgical iridotomies and a surgical capsulotomy were required 4 months after the initial cataract surgery for the treatment of acute iris bombe secondary to adhesions between the iris and the lens capsule and anterior hyaloid. These complications were thought to be due to surgery rather than intracameral triamcinolone therapy. Severe inflammation in the immediate postoperative period occurred in 1 case, a 6-week-old infant with congenital cataract and very narrow palpebral apertures in whom ocular examination and eye drop instillation proved very difficult. This patient was managed with serial examinations under anesthesia at weekly intervals for 3 weeks. At the first examination under anesthesia (EUA), division of synechiae was performed and intracameral triamcinolone and cefuroxime injections were given. At the second EUA, the intracameral triamcinolone and cefuroxime injections were repeated. At 3 weeks, the child began to open the eye spontaneously; EUA showed good resolution of inflammation with a white eye, clear cornea, and deep and quiet anterior chamber. Intracameral triamcinolone in this case promoted rapid resolution of inflammation in a setting in which effective topical therapy was not possible; it also prevented the need for high-dose oral steroid therapy. DISCUSSION In the pediatric population, inflammation after cataract surgery is common and leads to long-term morbidity. It
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INTRACAMERAL TRIAMCINOLONE ACETONIDE AFTER PEDIATRIC CATARACT SURGERY
Table 2. Patient demographic, surgical details, and outcomes. Pt
Type of Cataract
Eye
Other Diagnoses
1
Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Congenital nuclear sclerosis Posterior polar cataract Posterior polar cataract Posterior polar cataract Posterior polar cataract Congenital nuclear sclerosis Congenital nuclear sclerosis Traumatic cataract Posterior polar cataract
R
Trisomy 21
0.3
1.7
Yes
Yes
No
L
No
0.2
9.4
Yes
Yes
No
R
Trisomy 21
0.1
6.5
Yes
No
No
L
Trisomy 21
0.1
6.2
Yes
No
No
0.4
7.4
Yes
No
No
0.4
7.4
Yes
No
No
8.8 8.9 14.7 14.8 0.1
11.6 10.9 12.5 10.6 1.2
No No No No Yes
Yes Yes Yes Yes No
No No No No No No
2 3 3 4 4 5 5 6 6 7 7 8 9 10 10 11 11 12 13 14 14 15 16
Developmental cataract (posterior polar) Developmental cataract (posterior polar) Congenital cataract Congenital cataract Posterior polar cataract Posterior capsular cataract Posterior subcapsular cataract Posterior subcapsular cataract Congenital cataract Congenital nuclear sclerosis
R L R L R L R
Microphthalmia, microlissencephaly Microphthalmia, microlissencephaly No No No Trisomy 21 No No
0.2
1.0
Yes
No
L L
No No
12.1 5.6
3.3 11.8
No No
L
No
10.8
17.0
No
Yes YAG PC Yes IOL repositioning, Nd:YAG PC 6 mo postop No No
R
No
10.9
15.9
No
No
No
R L R L R
Perisylvian polymicrogyria Perisylvian polymicrogyria No No Type 1 DM
0.7 0.7 5.4 4.2 14.0
4.0 4.0 0.7 3.5 15.0
Yes Yes Yes Yes No
No No Yes Yes Yes
No No No No No
L
Type 1 DM
13.9
15.5
No
Yes
Nd:YAG PC
R R
3.2 0.1
13.4 1.4
No Yes
Yes Yes
0.1 1.0 11.4
16.4 12.7 14.8
Yes Yes No
Yes Yes Yes
10.5 0.1
3.0 13.2
No Yes
Yes No
YAG PC No
0.1
12.7
Yes
No
No
13.5 0.1
1.9 8.3
No Yes
Yes No
15.2 1.1
4.4 6.5
No Yes
Yes Yes
17 18 19
Congenital cataract Congenital cataract Traumatic cataract
R R R
20 21
Lamellar cataract Congenital nuclear sclerosis Congenital nuclear sclerosis Anterior polar cataract Congenital nuclear sclerosis Lamellar cataract Posterior lenticonus
R R L
Hypotony
22 23 24 25
Reoperation
L
Left pseudophakia Small palpebral apertures, very difficult to assess or instill drops No No Dog-mauled face and eye Left pseudophakia Hypotony
21
Age (Y) FU (Mo) PC and AV IOL
R R L L
No PHPV anterior type, microphthalmia Right pseudophakia
No EUA and intracameral triamcinolone injection at weekly intervals for 3 wk postop Surgical PC Surgical PC YAG PC
No Surgical iridotomies and PC 4 mo postop No No (continued on next page)
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Table 2 (continued ) Pt
Type of Cataract
Eye
Other Diagnoses
26
Congenital nuclear sclerosis Congenital nuclear sclerosis
R
Microphthalmia, hypotony, plagiocephaly Microphthalmia, hypotony, plagiocephaly
26
L
Age (Y) FU (Mo) PC and AV IOL
Reoperation
0.1
3.5
Yes
No
No
0.1
3.3
Yes
No
No
AV Z anterior vitrectomy; DM Z diabetes mellitus; EAU Z examination under anesthesia; IOL Z intraocular lens; Nd:YAG Z neodymium:YAG; PC Z posterior capsulotomy; PHPV Z persistent hyperplastic primary vitreous; Pt Z patient
is notoriously difficult to manage.2,4,8,9 Missed doses and noncompliance due to behavioral problems lead to subtherapeutic administration of topical antiinflammatory medication and may partly explain why outcomes are worse in children than in adults. In support of this, high-dose systemic steroid agents can provide good control of postoperative uveitis, suggesting that the condition is steroid sensitive in most cases. In addition, the immature eye is more prone to severe inflammatory reactions and the poor outcomes after pediatric cataract surgery may be related to biologic differences rather than the bioavailability of steroid therapy. The frequent administration of topical steroid therapy is especially challenging in small infants. Possible significant advantages of intracameral triamcinolone include ease of administration at the end of surgery because the crystals persist for several days in the anterior chamber, providing a prolonged antiinflammatory effect. The half-life of preservative-free triamcinolone acetonide in the nonvitrectomized eye is estimated to
Table 3. Findings at postoperative examinations. Finding Conjunctival injection O1 Day 1 Day 7 Day 14 Day 21 Anterior chamber reaction O2 Day 1 Day 7 Day 14 Corneal edema O1 Day 1 Day 7 Day 14 Day 21 Fibrin formation Posterior synechiae
Eyes (n)
1 1 1 1 1 1 1 1 1 1 1 1 1
be 18.7 G 5.7 days.10 It has been widely used in vitreoretinal surgery for the delineation of vitreous membranes and has also been used in complicated cataract surgery in adults and in children to visualize vitreous in the anterior chamber.10 It does not appear to be toxic to the corneal endothelium. Karalezli et al.11 report that the use of intracameral triamcinolone instead of postoperative steroid drops to control inflammation in adult cataract surgery appeared equally efficacious. We decided against conducting a placebocontrolled study of intracameral triamcinolone alone after pediatric surgery because withdrawal of steroid therapy in the pediatric population would be detrimental to patient care given the high incidence of severe inflammatory reactions. Moreover, we decided against intracameral injections of placebo compounds because this has risk and no potential benefit to the child. Thus, we introduced intracameral triamcinolone as an adjunct to topical steroid therapy and studied the surgical outcomes over a period of more than 1 year. None of our pediatric patients developed glaucoma, endophthalmitis, or raised IOP as the result of triamcinolone use. Karalezli et al12 and Gills and Gills13 found no change in IOP with the use of intracameral triamcinolone in adults. Other intracameral anti-inflammatory therapies have been tested in the pediatric population. Mehta and Adams14 report the results of intracameral tissue plasminogen activator (tPA) for severe postoperative fibrinous uveitis in 4 eyes in a series of 37 children who had cataract surgery. No patient in the study received oral steroids. A drawback to tPA as a therapy is the necessity for administration under a second general anesthetic. Reported postoperative adverse effects included raised IOP and persistent posterior synechiae, although these are more likely related to surgery than to the tPA. In a randomized placebo-controlled trial, Siatiri et al.7 found r-tPA was more effective than the placebo in suppressing fibrin formation in the first 2 weeks postoperatively; however, both the treatment group and the control
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group also received systemic steroids. Although intraoperative intracameral heparin infusion has also been reported to be effective in suppressing postoperative fibrinous reaction, it can cause anterior chamber hemorrhage, which has also been reported with tPA use.14–17 Another potential shortcoming is that heparin and tPA have short half-lives (approximately 6 hours and 10 hours, respectively); in contrast, the half-life of intracameral triamcinolone is 18.7 G 5.7 days. Thus, it is likely that neither heparin nor tPA would remain active in the anterior chamber for longer than 72 hours. This is not enough time for heparin or tPA to completely suppress a severe postoperative inflammatory response, which may rebound once the drug is eliminated from the anterior chamber. Another option, although currently limited by high cost, are implants that provide sustained drug delivery within the anterior chamber. They are an appealing approach to postoperative inflammatory reactions and merit further study. One such device is Surodex, a dexamethasone-delivery system. This biodegradable pellet is implanted in the anterior chamber at the time of surgery.18 The pellet contains 60 mg of dexamethasone incorporated in a polymer matrix, which controls release of the drug over 7 days, resulting in higher intraocular dexamethasone levels than topical drops. In 1 study, severe postoperative uveitis developed in only 2 (11%) of 18 eyes having pediatric cataract surgery and implantation of the dexamethasone pellet.19 This study has all the drawbacks of a retrospective design. In addition, it is difficult to accurately grade inflammation and objectively record IOP in younger children. A randomized controlled study is questionable because it may be unethical to withhold steroid therapy given the inevitable severe postoperative inflammation in these patients. It would also require multicenter participation to gain enough patients. Ideally, we would have measured IOP in every child in this study at repeated intervals. However, accurate IOP measurement in young children and infants requires EUA, and most parents in the study did not consent to this. Further evaluation of the long-term effects of suspended particles of intracameral triamcinolone on IOP, the corneal endothelium, and corneal pachymetry is necessary. In summary, we found that the use of preservativefree intracameral triamcinolone in pediatric cataract surgery resulted in quiet eyes with few inflammatory signs in most cases. We believe it is safe and of significant benefit because intensive steroid eye drop instillation is a problem in younger children, particularly in those with small palpebral apertures. Triamcinolone crystals persist for up to 5 days within the anterior chamber and may prove effective in
suppressing inflammation in the initial postoperative period. REFERENCES 1. Lloyd IC, Ashworth J, Biswas S, Abadi RV. Advances in the management of congenital and infantile cataract. Eye 2007; 21: 1301–1309 2. Knight-Nanan D, O’Keefe M, Bowell R. Outcome and complications of intraocular lenses in children with cataract. J Cataract Refract Surg 1996; 22:730–736 3. Hing S, Speedwell L, Taylor D. Lens surgery in infancy and childhood. Br J Ophthalmol 1990; 74:73–77. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1041993/pdf/brjopthal005760010.pdf. Accessed June 15, 2010 4. Keech RV, Tongue AC, Scott WE. Complications after cataract surgery for congenital and infantile cataracts. Am J Ophthalmol 1989; 108:136–141 5. Lloyd IC, Goss-Sampson M, Jeffrey BG, Kriss A, RussellEggitt I, Taylor D. Neonatal cataract: aetiology, pathogenesis and management. Eye 1992; 6:184–196 6. Malukiewicz-Wisniewska G, Kaluzny J, Lesiewska-Junk H, Eliks I. Intraocular lens implantation in children and youth. J Pediatr Ophthalmol Strabismus 1999; 36:129–133 7. Siatiri H, Beheshtnezhad AH, Asghari H, Siatiri N, Moghimi S, Piri N. Intracameral tissue plasminogen activator to prevent severe fibrinous effusion after congenital cataract surgery. Br J Ophthalmol 2005; 89:1458–1461. Available at: http://www. ncbi.nlm.nih.gov/pmc/articles/PMC1772932/pdf/bjo08901458. pdf. Accessed June 15, 2010 8. Lambert SR, Drack AV. Infantile cataracts. Surv Ophthalmol 1996; 40:427–458; correction, 1996; 41:unnumbered page before page 1 9. Sharma N, Pushker N, Dada T, Vajpayee RB, Dada VK. Complications of pediatric cataract surgery and intraocular lens implantation. J Cataract Refract Surg 1999; 25:1585–1588 10. Dyer D, Callanan D, Bochow T, Abraham P, Lambert HM, Lee SY, Schneiderman T, Potts SL, Walker TM. Clinical evaluation of the safety and efficacy of preservative-free triamcinolone (TriesenceÒ [triamcinolone acetonide injectable suspension] 40 mg/mL for visualization during pars plana vitrectomy. Retina 2009; 29:38–45 11. Karalezli A, Borazan M, Akova YA. Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification. Acta Ophthalmol (Oxf) 2008; 86:183–187. Available at: http://www3.interscience.wiley.com/ cgi-bin/fulltext/120090782/PDFSTART. Accessed June 15, 2010 12. Karalezli A, Borazan M, Kucukerdonmez C, Akman A, Akova YA. Effect of intracameral triamcinolone acetonide on postoperative intraocular pressure after cataract surgery. Eye 2010; 24:619–623 13. Gills JP, Gills P. Effect of intracameral triamcinolone to control inflammation following cataract surgery. J Cataract Refract Surg 2005; 31:1670–1671 14. Mehta JS, Adams GGS. Recombinant tissue plasminogen activator following paediatric cataract surgery. Br J Ophthalmol 2000; 84:983–986. Available at: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1723658/pdf/v084p00983.pdf. Accessed June 15, 2010 15. Wedrich A, Menapace R, Ries E, Polzer I. Intracameral tissue plasminogen activator to treat severe fibrinous effusion after cataract surgery. J Cataract Refract Surg 1997; 23:873–877 16. Bayramlar H, Totan Y, Borazan M. Heparin in the intraocular irrigating solution in pediatric cataract surgery. J Cataract Refract Surg 2004; 30:2163–2169
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17. Johnson RN, Blankenship G. A prospective, randomized, clinical trial of heparin therapy for postoperative intraocular fibrin. Ophthalmology 1988; 95:312–317 18. Chang DF, Wong V. Two clinical trials of an intraocular steroid delivery system for cataract surgery. Trans Am Ophthalmol Soc 1999; 97:261–276. discussion 276–279 Available at: http://www.ncbi.nlm.nih.gov.medlib.med.miami.edu:2048/pmc/
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