Intravenous Dexamethasone Vs Methylprednisolone Pulse Therapy
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Eye (2009) 23, 635–639 & 2009 Macmillan Publishers Limited All rights reserved 0950-222X/09 $32.00 www.nature.com/eye 1 1 1 1 Intravenous R Tandon , K Verma , B Chawla , N Sharma , CLINICAL STUDY JS Titiyal1, M Kalaivani2 and RB Vajpayee1,3 dexamethasone vs methylprednisolone pulse therapy in the treatment of acute endothelial graft rejection Abstract both groups, with significantly lower final pachymetry in the dexamethasone group Purpose To study the outcome of therapy for (P ¼ 0.017). No adverse effects were observed. acute endothelial graft rejection with an Conclusion I.v. pulse therapy with 1Cornea and Refractive intravenous (i.v.) pulse of dexamethasone dexamethasone may be used as an effective Surgery Services, vs methylprednisolone, in addition to topical alternative to methylprednisolone in reversing Dr Rajendra Prasad Centre corticosteroids. for Ophthalmic Sciences, All acute endothelial graft rejection. India Institute of Medical Records of 98 eyes of 99 patients Methods Eye (2009) 23, 635–639; doi:10.1038/eye.2008.25; Sciences, New Delhi, India treated for endothelial graft rejection with a published online 22 February 2008 single i.v. pulse of dexamethasone or 2Department of Biostatistics, methylprednisolone in addition to topical Keywords: endothelial graft rejection; All India Institute of Medical Sciences, New Delhi, India steroids, between January 1999 and June 2004, intravenous pulse therapy; methylprednisolone; were retrospectively reviewed. Baseline dexamethasone; topical steroids 3 characteristics such as surgery-rejection Centre for Eye Research Australia, University of interval, time taken to consult after onset of Melbourne, Melbourne, symptoms, history of failed grafts, extent of Australia stromal vascularization, best-corrected visual Introduction acuity (BCVA) and corneal thickness at the Correspondence: R Tandon, time of presentation were noted. Main Corneal graft rejection remains an important Professor of Ophthalmology, outcome measures following treatment for cause of graft failure all over the world.1 Cornea and Refractive Surgery Services, rejection included improvement in BCVA, Corticosteroids are the mainstay of treatment Dr Rajendra Prasad Centre change in corneal thickness, and reversal of for successful reversal of graft rejection, but for Ophthalmic Sciences, graft rejection. there are wide variations in the choice All India Institute of Medical Results Fifty-one patients were treated with of steroid, route of administration, and dosage.2–5 Sciences, i.v. methylprednisolone and 47 with i.v. Evidence available so far suggests a beneficial New Delhi-110029, India. Tel: þ 91 11 2659 3145; dexamethasone, in addition to topical steroids. role of intravenous (i.v.) methylprednisolone Fax: þ 91 11 2658 8626. Both groups were found to be comparable when combined with topical steroids over E-mail: radhika_tan@ with respect to baseline parameters, that is, frequent topical steroids alone,6 and also over yahoo.com time taken to present, history of failed grafts, oral steroids in combination with topical extent of stromal vascularization, BCVA, and steroids,7 in selected cases. In addition, pulse Received: 17 September graft thickness. Graft rejection could be therapy also carries the advantage of avoiding 2007 Accepted in revised form: successfully reversed in 72.3% cases in the the potential side-effects of prolonged oral 21 January 2008 7 dexamethasone group and 49% in the medication. In our clinical experience, frequent Published online: 22 methylprednisolone group (P ¼ 0.018). A topical steroids alone have been inadequate in February 2008 significant improvement in visual acuity was successfully reversing corneal endothelial recorded following treatment in both groups, rejection, necessitating the use of pulse therapy. This article was presented in part as a poster at the World with a better outcome in the dexamethasone Since i.v. methylprednisolone is an expensive Cornea Congress, group (P ¼ 0.012). Post-treatment pachymetry drug, it is not within the reach of many patients Washington DC, USA in values were lower than pretreatment values in in this part of the world. In clinical situations, March 2005. Pulse therapy in endothelial graft rejection R Tandon et al 636 where therapy with i.v. methylprednisolone is not response. At every follow-up visit, a complete possible, i.v. dexamethasone has been successfully used ophthalmological examination was carried out including as a substitute.8–10 The purpose of this study is to report recording of visual acuity, slit-lamp examination, our experience on the outcome of therapy with a single tonometry, and ultrasonic pachymetry. i.v. pulse of dexamethasone as compared to i.v. Primary outcome measures included improvement in methylprednisolone, in addition to topical steroids, in BCVA, change in corneal thickness as evident by serial reversing corneal endothelial graft rejection. ultrasonic pachymetry measurement and reversal of graft rejection following treatment as evident by slit-lamp biomicroscopy. Reversal of graft rejection was Materials and methods defined as a point where there were no cells in the The study was a retrospective, non-randomized, anterior chamber and graft oedema had completely interventional case series. The medical records of resolved. patients treated for acute endothelial graft rejection with BCVA and pachymetry values at the end of first month i.v. pulse therapy between January 1999 and June 2004 at following treatment were noted from the records and the Cornea and Refractive Surgery Services of our centre were used for the purpose of statistical analysis. were retrospectively reviewed. Ninety-eight eyes of 98 Before commencing treatment, an informed consent consecutive patients were identified. had been obtained from the subjects and they were made Data were collected by chart review. Demographic aware of the various treatment options available to them. data such as age, sex, and primary diagnosis of the We certify that all institutional regulations concerning the patients were noted. Baseline characteristics recorded at ethical use of human volunteers were followed during the time of presentation including the surgery-rejection this research. interval, time taken by the patient to reach the hospital after the onset of symptoms, extent of stromal Statistical analysis vascularization, history of failed grafts, best-corrected visual acuity (BCVA), corneal thickness determined by Statistical analysis was performed using STATA 9.0. ultrasonic pachymetry (Sonomed Inc., NY, USA), and (College Station, TX, USA). Data were presented as either intraocular pressure measured by Goldman applanation number (%) or mean±SD as appropriate. Continuous tonometry were noted. baseline characteristics (such as age, BCVA, and corneal Endothelial graft rejection was defined as an eye with a thickness) and post-treatment BCVA and pachymetry previously clear graft that developed stromal oedema values were compared between two treatment groups and aqueous cells associated with an endothelial using an independent t-test, whereas categorical baseline rejection line and/or presence of keratic precipitates on characteristics (such as failed graft, surgery-rejection the corneal endothelium. Treatment of corneal interval, time taken to present after onset of symptoms, endothelial graft rejection consisted of administering stromal vascularization and the outcome variable of graft either 100 mg dexamethasone or 500 mg of rejection) were compared using w2-test. Wilcoxon rank methylprednisolone in 150 ml of 5% dextrose solution as test was used to compare the difference in the medians of a slow i.v. infusion over 1–2 h as a single-pulse therapy. surgery-rejection interval between the two treatment The choice of pulse therapy was determined by groups since the data was non-normal. Unadjusted and affordability of the drug by each patient. Patients were adjusted odds ratio (adjusted for surgery-rejection monitored for haemodynamic stability during i.v. interval) for treatment were calculated for the outcome infusion. Topical prednisolone acetate 1% eyedrops were variable of graft rejection. A P-value less than 0.05 was administered in addition to i.v. pulse therapy in all the considered statistically significant. cases. Initially, the eyedrops were recommended at hourly intervals during the day for 1 week, two hourly Results for the next week, and tapered off thereafter depending on the clinical response and signs of graft rejection Out of 98 patients who were identified as having been reversal. Supportive therapy in the form of topical treated with pulse therapy for acute endothelial rejection chloramphenicol (0.3%) four times a day, homatropine during the study period, 51 were treated with i.v. hydrobromide (2%) three times a day, timolol maleate methylprednisolone and 47 with i.v. dexamethasone, (0.5%) twice a day, and lubricating eyedrops was along with topical steroids. There were 78 males and 20 prescribed. No follow-up oral corticosteroids were females with a mean age of 45.2±19.7 years. Both groups administered in either group. were comparable with respect to baseline parameters, Patients were followed-up at regular intervals as was that is, mean age (P ¼ 0.417), time taken to present after considered necessary depending on their clinical the onset of symptoms (P ¼ 0.553), failed grafts Eye Pulse therapy in endothelial graft rejection R Tandon et al 637 (P ¼ 0.306), stromal vascularization (P ¼ 0.726), visual interval and found that there was no significant