Risk Factors for Graft Rejection in Penetrating Keratoplasty Labbafinejad Medical Center Department of Ophthalmology 2002

n Farid Karimian, MD n Mohammad Ali Javadi, MD n Mohammad Reza Jafari-Nasab, MD n Seyed Mojtaba Hosseini, MD n Arash Anisian, MD Department of Ophthalmology, Labbafinejad Medical Center Ophthalmic Research Center Department of Ophthalmology, Labbafinejad Medical Center Ophthalmic Research Center

Introduction n Penetrating keratoplasty (PK) is the most common human organ transplant n During , 2108 PKs were performed in Iran n The most common cause of graft failure is Immunologic Rejection n 30% of PKs have at least one episode of rejection n 50-70% of graft rejection is treated with corticosteroids

Defined Risk Factors for Graft Rejection n Recipient corneal bed vascularization n loose and irritating suture n Regraft n Bilateral graft n Iridocorneal adhesion n Intraocular and corneal inflammation n Recipient young age n Donor graft size n Eccentric graft n Glaucoma, poor controlled IOP n YAG-capsulotomy

Purpose: To evaluate the significance of risk factors in causing graft rejection in our corneal graft patients in Labbafinejad Medical Center To evaluate the significance of risk factors in causing graft rejection in our corneal graft patients in Labbafinejad Medical Center

Materials and Methods Design of Study: Descriptive- cohort Inclusion Criteria: n PK performed during years n Referral: Sequential, non-randomized n No previous H/O Immunosuppressive use use

Surgical Technique n Donor Cornea: cut from whole globe or preserved in media n Trephination: Barron-Hessburg Vacuum n Donor cornea endothelial punch n Suturing technique: 4 cardinal, later interrupted, running or combined

Definitions for Graft Rejection n Clear graft for at least first 10 days Postop n Epithelial Rejection n Subepithelial infiltrates (SEI) n Endothelial Rejection: - Localized: KP´s, - Localized: KP´s, - Diffuse: Endothelial Rejection Line - Diffuse: Endothelial Rejection Line (Khodadoust), diffuse KP´s, corneal (Khodadoust), diffuse KP´s, corneal edema edema

Treatment and Rejection n Epithelial and SEI: Topical Betamethasone 0.1% n Localized ER: Frequent topical Betamethasone + Systemic Prednisolone n Diffuse ER: Topical and Systemic steroids + subtenon methyl- prednisolone

Statistical Analysis Tests: Chi-square T-test Multivariate Regression Analysis

Results n 295 PK in 286 patients evaluated n Male 61.4%, Female 38.6% n Age: 37 ± 20 years (40 days-90 years) n Follow-up: 20 ± 10 months (24-43 mo)

Results… cont Indications for Penetrating Keratoplasty n Keratoconus (31.9%) n Regraft (13.9%) n Corneal ulcer (perforated or non- perforated) (12.6%) n Traumatic scars (7%) n Corneal chemical burn (2%)

Prognosis according to Indications for PK: Percentage of clear graft n Keratoconus (97.8%) n Corneal dystrophies (96.3%) n PBK (66.7%) n ABK (61.5%) n Vascularized scars (60%) n Regraft (47%) n Trauma (28.6%) n Chemical burn (16.7%)

Results cont.…(3) Graft Rejection Data - Total no. of rejections: 94 (31.8%) - Frequency of rejections: Once: 20.8% Twice: 7.8% Twice: 7.8% Three times: 2% Three times: 2% >3 times: 0.9 % >3 times: 0.9 % - Onset of Rejection: Ave: 7.3 ± 6 mo (20 days-39mo) - During first 6 mo.: 62.8% - During first 6 mo.: 62.8% - first 12 mo.: 87.2% - first 12 mo.: 87.2% - first 14 mo.: 92.6% - first 14 mo.: 92.6%

Types of Rejection: - Endothelial: 20.7% - Endothelial: 20.7% - Multi-layer: 6.1% - Multi-layer: 6.1% - SEI: 3.1% - SEI: 3.1% Graft Clarity: -Clear: 70.6% -Clear: 70.6% -Non-clear: 29.4% Rejection cause: 6.1% -Non-clear: 29.4% Rejection cause: 6.1% Time of Rejection: - April: 4.1% > July and Sept.: 3.4% - April: 4.1% > July and Sept.: 3.4% Results.....cont.(4)

Risk factors of rejection factor Rejection P. value clear failure presence rate graft presence rate graft (%) (%) 1- Age < 40y/o > 40y/o > 40y/o Corneal vasularization Mild Mild Moderate Moderate Severe P<0.001 Severe P<0.001 Avascular Avascular Regraft first graft P<0.001 first graft P< Results...cont.(5)

Results......cont.(6) Risk factors of rejection factor Rejection P. value clear failure presence rate graft presence rate graft (%) (%) 4- Bilateral graft unilateral unilateral P<0.001 P< Donor size > 8mm < 8mm < 8mm Iridocorneal < Adhesion Adhesion 7- Irritating suture Active intraocular inflammation < inflammation < Secondary anterior segment surgery segment surgery

Results....cont.(7) Risk factors of rejection factor Rejection P value clear failure presence rate graft presence rate graft (%) (%) 10- Eccentric graft Trauma scar < Poor controlled IOP (N.S) 13- Previous rejection Graft ulcer HSK recurrence

Discussion and Conclusions n The most common causes of PK at LMC are different from Western reports (Kerataconus vs ABK-PBK) n The most common type of Rejection is Endothelial n Age (>40 vs 40 vs <40 years) was not a risk factor for rejection n Severity of vascularization increases rate of rejection and graft failure

Discussion and Conclusions…. Cont.(1) n Regraft increases risk of rejection n Bilateral graft (vs unilateral) was not a risk factor (controversial in previous reports) probably due to main primary indications for PK n There was no significant difference in graft size (>8 vs 8 vs <8 mm) as risk factor

Discussion and Conclusions… cont. (2) n Iridocorneal adhesions, irritating sutures, active intraocular inflammation, secondary intraocular surgeries, eccentricity of graft, poor controlled IOP, presence of graft ulcer and recurrence of Herpes:Increase risk of rejection and consequently graft failure