Intravenous single shot of steroids to prevent post-operative inflammatory reaction in pediatric cataract surgery.

1. Intravenous single shot of steroids to prevent post-operative inflammatory reaction in pediatric cataract surgery.   Arun K Jain MD, Jaspreet Sukhija MD, Ira Berry MD. Department of Ophthalmology Post Graduate Institute Of Medical Education and Research Chandigarh India 160012

2. Control of Postoperative Inflammation after Pediatric Cataract Surgery Quest for Quality of Vision After Pediatric Cataract Surgery ?

3. Pediatric cataract surgery Challenging- because • Small eye – IOL Power calculations • Challenging surgery- more skillful • More post operative inflammation • Post operative visual rehabilitation • Amblyopia therapy

4. More Inflammation after Pediatric cataract surgery Causes • Greater postoperative inflammatory response- tissue reactivity • Surgical trauma • Type, material, placement of IOL • Compliance with medication

5. 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.

6. Reported incidence of postoperative fibrinous uveitis in pediatric cataracts - 19% to 81.8% • Increased fibrinous uveitis – 57.5% Pandey et al . Boston , MA. May 2000.

7. Increased inflammation leads to • Fibrinous membrane formation • Pigment deposits on the IOL • Posterior Synechiae formation. • Eccentric/ irregular/immobile/fixed pupil • Poor visual outcome

8. Complications following pediatric cataract surgery continue to be a major concern. Increased inflammatory reaction is seen following pediatric intraocular surgery. Fibrinous uveitis is the most common early postoperative complication which usually becomes manifest in the first 24 hours • Burke et al 1 reported an incidence of 50% fibrinous uveitis in traumatic and infantile cataract surgeries. • Gimbel et al 2 showed that a child’s eye manifested more inflammation as compared to adult’s eye.

9. Introduction • Zwaan et al 3 reported the occurrence of iritis in all of their patients and fibrinous exudates in the anterior chamber in 13% of pediatric cataract surgeries (56.7% traumatic, 14.9% congenital, 22% developmental). • Sequelae of this exuberant reaction lead to poor visual outcome due to formation of updrawn pupil, posterior synechiae, pigmentary deposits on the intraocular lens (IOL) surface, eccentric/ immobile/ fixed pupil and decentration of the IOL. • Sharma et al 4 in their study, including congenital (43.6%), traumatic (28.2%) and developmental (28.2%) cataracts, had updrawn pupil (38.5%), decentered intraocular lens (33.3%) and pupillary capture (30.8%). • Pandey et al 5-6 reported the incidence of postoperative fibrinous anterior uveitis ranging from 19-81.8% in congenital and traumatic cataract surgeries.

10. Introduction • Various management strategies have been evaluated to control this increased postoperative inflammation with variable results. • Gimbel 2 and Cassidy 7 showed that full atropinization and frequent steroid drops postoperatively were usually enough to control the inflammation. • Raina et al 8-9 treated their patients of congenital and developmental cataract with depot steroids (subtenon triamcinolone 20 mg) at end of surgery and oral steroids (1 to 2mg/kg of prednisolone acetate) postoperatively for 2 weeks along with topical steroids with good results.10 • Use of heparin in irrigating solution has been studied by Brady 10 and Bayramlar 11 in pediatric cataract surgeries.

11. Klais et al 12 documented the safe use of intraocular recombinant tPA in pediatric cataract surgery. • Mechanical discission of inflammatory pupillary membranes has been described by Leung et al 13. • Axial organised fibrin plaque, adherent to the intraocular lens may defeat the surgical goal of maintaining a clear visual axis to prevent amblyopia. • Bound down, irregular,and decentered/eccentric pupil has been shown to interfere with quality of vision and modulation transfer function.14-16

12. Intravenous bolus of 500mg of hydrocortisone along with injection of 20 mg of methylprednisolone in the retrobulbar space, on completion of the surgical procedure, has been safely used by BenEzra et al 17 in cataract surgery in children with chronic uveitis. • We evaluated one time single shot of intravenous hydrocortisone (5 mg/kg of body weight) and dexamethasone (0.1 mg/kg of body weight) at the end of the cataract surgery to prevent exaggerated inflammatory reaction and formation of postoperative fibrinous membrane in children.

13. MATERIAL AND METHODS • Twenty two eyes of 15 children with congenital or development cataract that underwent surgery at the Ophthalmology department of Post Graduate Institute of Medical Education and Research (Chandigarh, India) were prospectively enrolled. Informed consent was acquired from the parents.

14. Complete systemic evaluation to rule out any syndromic abnormality was carried out. • Ophthalmic examination included atropine retinoscopy, fundus examination with indirect ophthalmoscopy and slit lamp examination wherever the child was cooperative. • Ultrasound examination for posterior segment was carried out in eyes with complete cataract and for measurement of the axial length of the eye. • Dahn’s or SRK formula was used for IOL power calculations • Only congenital and developmental cataracts were included in the study.

15. Mydriasis was achieved with 0.5% cyclopentolate and 2.5-5.0% phenylephrine drops. • Preoperatively topical tobramycin eye drops 0.3 % were instilled 3 times/ day for 3 days.

16. All surgeries were performed by a single surgeon (AKJ). • Under aseptic conditions, the eye was draped and superior rectus muscle bridled. A fornix based conjunctival flap was created superiorly and bipolar wet field cautery done. A partial thickness scleral groove was made 1.5-2.0 mm behind the surgical limbus and fashioned into a scleral tunnel with a crescent blade upto 1.5 mm inside the corneal tissue. The anterior chamber was entered with side ports and 1.4% sodium hyaluronate (Healon GV) injected. A 3.2 mm keratome was used to open the scleral tunnel into the anterior chamber. Anterior continuous curvilinear capsulorhexis (ACCC) was made and hydrodissection done. Cataractous lens was removed with phacoaspiration. Cortical matter aspiration and polishing was done with bi-manual irrigation-aspiration. The bag was filled with viscoelastic and posterior continuous curvilinear capsulorhexis (PCCC) done. Limited anterior vitrectomy (AV) was done and intraocular lens implanted (foldable or rigid after section enlargement) in the bag or in the sulcus. The anterior chamber was cleared of all viscoelastic and a single 10-0 nylon cross suture applied .

17. Phacoaspiration with ACCC and in the bag IOL was done in 6 eyes. These eyes developed posterior capsule opacification from a period of 1 month to 2.5 years post primary surgery for which pars plana membranectomy was done. • Phacoaspiration with ACCC with PCCC with AV and in the bag IOL was done in 16 eyes. • Nineteen eyes were implanted with HSM PMMA IOL (811C Pharmacia), 3 eyes with foldable acrylic lens (AcrySof, Alcon)

18. At the end of surgery, subconjunctival injection of gentamicin 20mg and dexamethasone 2mg was given. • A single intravenous shot of hydrocortisone 5mg/kg and dexamethasone 0.1mg/kg was given. • Postoperatively, topical cyclopentolate 2/ day, dexamethasone and antibiotic drops 6/ day alongwith combination of steroid and antibiotic ointment at night was given [tapered over period of two months]. • Patients were followed up on days 1, 2, 5, weekly for 3 weeks , every two weeks for one month and then at intervals appropriate for the individual.

19. Postoperatively anterior chamber reaction was assessed according to the following grades as slit lamp examination was not possible in all cases. • It was based on the visibility of iris and lens details (Hogan et al 18) as given in table 1.

20. Table 1: Gradation system for assessment of postoperative anterior chamber reaction. (Hogan et al 18)

21. Post operative anterior chamber reaction assessment • Grade 0 – Crystal clear iris details • Grade 1 - Minimal reaction • Grade 2 – Mild reaction • Grade 3 – Moderate reaction • Grade 4 – Severe reaction

22. Outcome measures • Postoperative inflammation • Posterior synechiae • Mobility of pupil • Centration of pupil • Endophthalmitis

23. Results • 22 eyes of 15 children with congenital or developmental cataract • 7 had bilateral cataracts • 3 months to 11 years • Average age was 4.26 years • The demographic data and the details of the surgical procedure performed are presented in Table 2 [microsoft word].

24. Results • All eyes except one eye had Grade 1 or less reaction in the anterior chamber on the first postoperative day. [Fig I] • None of the eyes had fibrinous reaction postoperatively except for one eye , which developed fibrin reaction in pupillary area on third post operative day, because of noncompliance with topical steroids. [Fig II] It was controlled with extensive topical dexamethasone eye drops • Pupil round and mobile [Fig III] in all cases except one [4.5%] in which it was slightly peaked • One eye developed minimal peaking of pupil resulting from pinpoint posterior synechia with capsulorhexis edge . • Six eyes without primary PCCC subsequently underwent pars plana posterior capsulotomy with anterior vitrectomy. • All the eyes eventually maintained clear visual axes with regular mobile pupils. • None of the eyes developed endophthalmitis.

25. Figure I First post operative day , less than garde I anterior chamber reaction

26. Figure II Fibrin on IOL in Pupillary area

27. Figure II Five year follow up – central, regular, mobile pupil- undilated and dilated

28. Discussion • Optimal results of a pediatric cataract surgery provide a clear visual axis with a round and mobile pupil to prevent amblyopia or give proper treatment, if it is present. • A child’s eye is known to exhibit increased reaction postoperatively. The cause of this fibrinoid uveitis is unknown, but it is characterized by presence of intracameral fibrin strands across the pupil which eventually lead to posterior synechiae, pigment deposition over the IOL, distortion of pupil and secondary membranes. This reaction is usually seen in the first 2 – 5 days.

29. The antiinflammatory activity of heparin is by inhibition of P – selectin, which is responsible for the initial attachment of leukocytes to the vessel wall. • This explains the effectiveness of heparin surface modified IOLs , heparinized irrigating solution , intracameral heparin and intravenous heparin. • Bleeding as a consequence of use of heparin in the irrigating solution has been reported • but now with the advent of purified low molecular weight heparin this complication is less. • Promising results have been shown by Bayramlar et al 19 in pediatric ocular surgery.

30. Fibrinolytic agents like streptokinase and tPA can be used once the fibrin has formed in the anterior chamber. • Streptokinase is an enzyme produced by a strain of beta-hemolytic streptococci belonging to Lancefield group C. It is considerably cheaper than tPA which is a serine protease and converts clot specific fibrin bound plasminogen into plasmin. • Adverse effects like toxicity to the corneal endothelium leading to corneal opacification has been reported with doses of 15000 – 30000 units. • Mullaney 20 have reported successful use of intracameral streptokinase in adults and children without any adverse effect with doses ranging from 500 to 1000 IU. • Mullaney 20 injected between 500 to 1000 IU of streptokinase in 8 children in whom intraocular fibrin formed from 1 to 4 days after cataract surgery despite topical steroid drops.

31. Klais et al 12 have used tPA in children and have also highlighted possible complications of incomplete resolution, recurrence of membranes and corneal band keratopathy. • Mechanical discission of membranes 13 and intraocular steroid delivery system have also been described. • The procedures requiring an injection in the eye or mechanical discission after the fibrin has formed are plagued by risks of repeated general anesthesia exposure to the child. • There are increased risks of infection and endophthalmitis after an injection of streptokinase or tPA in case the preparations are contaminated or a second surgery.

32. Steroids have been used before systemically to prevent excess inflammatory reaction in patients of uveitis undergoing cataract surgery. 17 • BenEzra et al 17 used 20 mg of methyl prednisolone and 30 mg gentamicin in retrobulbar space alongwith intravenous bolus of 500 mg hydrocortisone and 1000 mg of cefazolin in pediatric cataract surgeries. • High doses of intravenous steroids have been used in children for ocular (bilateral optic neuritis uveitis ) and non-ocular conditions (rheumatic diseases , asthma , transverse myelopathy , nephrotic syndrome ).

33. The importance of a round mobile pupil cannot be more stressed upon. It has been shown in various studies that ocular optical quality is pupil size, shape and centration dependent and shows loss in visual sensitivity with a decentered small pupil at low and intermediate spatial frequencies.14-16 • It has been known that when the pupil is made eccentric, spherical aberrations cause coma.21

34. Retinal information capacity and the function of pupilLaughlin SB. Ophthalmic Phsiol Opt.1992.161-4 Conclusion of the Study • When the pupil is opened to increase sensitivity there is a loss of image sharpness due to aberrations • At each luminance there is a diameter [broad range] that maximizes the information capacity • Primary function of pupillary light reflex is to maximize acuity over a wide range of luminances

35. Modulation transfer functions in children: pupil size dependence and meridional anisotropy.Carkeet A et al.Invest Ophthalmol Vis Sci. 2003;44:3248-56. Conclusion of the study : Ocular optical quality is pupil dependent, shows slight meridional anisotropy

36. Changes of higher order aberration with various pupil sizes in the myopic eye.Wang Yet al. J Refract Surg. 2003;19:S270-4 • Coma-like aberrations increased less with pupil dilation. • Spherical-like aberration showed only a small increase from 4 mm to 5 mm pupil size, but a larger increase from 5 mm to 6 mm pupil size

37. Optical modulation transfer and contrast sensitivity with decentered small pupils in the human eye.Artal Pet al. Vision Res. 1996 3575-86. Conclusion of the study The combination of the ocular transverse chromatic aberration and monochromatic aberrations accounts for the loss in visual sensitivity found with a decentered small pupil at low and intermediate spatial frequencies.

38. Although we have implanted acrylic IOLs in only three out of twenty three eyes, we did not observe any increased inflammation in these eyes as compared to heparin surface modified PMMA IOLs (811C ). • Safety of acrylic intraocular lens has been documented by Raina et al 9 and Vasavada et al 22 in pediatric eyes.

39. Heparin-surface-modified intraocular lenses in pediatric cataract surgery: Prospective randomized studyBasti et al, JCRS, 1999, 782-787 • Lower incidence of inflammatory cell deposit formation in eyes with HSM PMMA IOLs • Eleven eyes out of 68 had a coagulum over the anterior IOL surface • None had greater than grade II anterior chamber inflammation co-existing with the coagulum. • Acute anterior uveitis (≥ grade II) during the 1 week postoperative evaluation was 8.5%.

40. 40 eyes included in study IOL with a 5.25 mm optic (Slimplant LX 10 BD®) Posterior synechias formed in 10 eyes (71.4%) in the optic-capture group and 9 (34.6%) in the no-capture group (P = .04) In the optic-capture group, most synechias formed between the iris and posterior capsule over the IOL Posterior synechia formation occurred in 12 eyes (41.4%) with bag-fixated haptics and in 7 (63.3%) with sulcus-fixated haptics (P = .46). Posterior synechias formed in all eyes with sulcus-fixated haptics and optic capture through the posterior capsulorhexis (n = 4). Role of optic capture in congenital cataract and intraocular lens surgery in children.Vasavada AR. JCRS 2000, 824-831

41. Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy.Raina UK et al. JPOS.2002:278-287 • 28 children, 1.5 to 12 year • Per operative – Sub conj. Genta. 20mg, dexa. 2mg, subtenon triamcinolone 20mg • Post operatively – oral 1to2 mg /kg of prednisolone acetate – 2weeks • Fibrinous membrane- 4eyes [13%] • Posterior synechiae – 4eyes

42. Functional outcomes of acrylic intraocular lenses in pediatric cataract surgery. Raina UK. JCRS. 2004, 1082-1091 A higher incidence of inflammatory response and posterior capsule opacification (PCO) continues to be a major obstacle to early visual rehabilitation after pediatric cataract surgery Postoperative therapy • Systemic antibiotics for 5 days • Systemic steroids (1 to 2 mg/kg body weight) tapered over 4 to 6 weeks. • All patients were prescribed topical antibiotics and full-strength topical steroids every 4 hours. • Postoperative dilation was achieved intermittently using tropicamide alone or in combination with phenylephrine to prevent posterior synechia formation.

43. Functional outcomes of acrylic intraocular lenses in pediatric cataract surgery. Raina UK. JCRS. 2004, 1082-1091 Conclusion of the Study • The formation of posterior synechias for less than 3 clock hours occurred in 5 eyes (10.6%) and subsequently released in 3 eyes with rigorous mydriatic therapy. • Conclusion; The use of depot steroids and systemic steroids in the immediate postoperative period may be the reason, why the rate of postoperative inflammation was lower in the study than in others.

44. We report the use of one time intravenous bolus of hydrocortisone 5 mg/ kg of body weight with dexamethasone 0.1 mg/ kg of body weight at the end of surgery. • The rationale of using a combination of hydrocortisone and dexamethasone is based on their pharmacokinetics and pharmacodynamics. Hydrocortisone has a short duration of action where as dexamethasone has a longer duration of action.

45. Only 1 of 22 eyes (4.5%) showed a fibrinous reaction which was then treated with extensive topical steroids. • All patients had mobile and round , central pupil except one which had slight peaking of the pupil. • The visual axis was clear in all of them, 6 eyes where primary posterior capsulotomy was not done, required pars plana membranectomy and anterior vitrectomy after which a clear axis was achieved. • None of the cases developed endophthalmitis.

46. Conclusion • Single intravenous bolus of dexamethasone and hydrocortisone, at the end of surgery is effective in controlling post operative inflammation and fibrinoid reactions effectively. • It also helps to maintain pupillary shape, position,and its mobility . • Further studies should be done to assess the quality of vision [contrast sensitivity and higher order aberrations] in eyes with regular, round and mobile pupils versus peaked , irregular , eccentric or bound down pupils following pediatric catarct surgery with IOL implantation

47. References • Burke JP, Willshaw HE, Young JDH. Intraocular lens implant for uniocular cataracts in childhood. Br J Ophthalmol 1989; 73: 860-864. • Gimbel HV, Ferenzowicz M, Raanan M, et al. Implantation in children. J Pediatr Ophthalmol Strabismus 1993; 30: 69-79. • Zwaan J, Mullaney PB, Awad A, et al. Pediatric intraocular lens implantation. Ophthalmology 1998; 105: 112-119. • Sharma N, Pushkar N, Dada T, et al. Complications of pediatric cataract surgery and intraocular lens implantation. J Cataract Refract Surg 1999; 25: 1585-1588. • Pandey SK, Ram J, Werner L, et al. Visual results and postoperative complications of capsular bag versus ciliary sulcus fixation of posterior chamber intraocular lenses for traumatic cataract in children. J Cataract Refract Surg 1999; 25: 1576-1584. • Pandey SK, Wilson ME, Trivedi RH, et al. Pediatric cataract surgery and intraocular lens implantation : current techniques, complications and management. Int Ophthalmol Clin 2001; 41: 175-96. • Cassidy L, Rahi J, Nischal K, et al. Outcome of lens aspiration and intraocular lens implantation. J Cataract Refract Surg 1999; 25: 1585-1588. • Raina UK, Gupta V, Arora R, et al. Posterior continuous curvilinear capsulorhexis with and without optic capture of the posterior chamber intraocular lens in the absence of vitrectomy. J Pediatr Ophthalmol Strabismus 2002; 39: 278-287. • Raina UK, Mehta DK, Monga S, et al. Functional outcome of acrylic intraocular lenses in pediatric cataract surgery. J Cataract Refract Surg 2004; 30: 1082-1091.

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50. Thank you