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

2. 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

3. Introduction n Penetrating keratoplasty (PK) is the most common human organ transplant n During 2000-01, 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

4. 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

5. 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

6. Materials and Methods Design of Study: Descriptive- cohort Inclusion Criteria: n PK performed during years 1998-1999 n Referral: Sequential, non-randomized n No previous H/O Immunosuppressive use use

7. 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

8. 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

9. 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

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

11. 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)

12. 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%)

13. 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%)

14. 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%

15. 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)

16. Risk factors of rejection factor Rejection P. value clear failure presence rate graft presence rate graft (%) (%) 1- Age < 40y/o 62 28.4 0.095 > 40y/o 38 37.8 > 40y/o 38 37.8 2- Corneal vasularization Mild 6.1 38.9 0.015 77.8 Mild 6.1 38.9 0.015 77.8 Moderate 9.8 48.3 62.1 13.8 Moderate 9.8 48.3 62.1 13.8 Severe 13.2 38.5 30.8 P<0.001 Severe 13.2 38.5 30.8 P<0.001 Avascular 70.9 27.8 78.9 4.8 Avascular 70.9 27.8 78.9 4.8 3- Regraft 12.5 48 0.025 47 18.8 first graft 87.5 29.5 73.8 P<0.001 first graft 87.5 29.5 73.8 P<0.001 4.6 4.6 Results...cont.(5)

17. Results......cont.(6) Risk factors of rejection factor Rejection P. value clear failure presence rate graft presence rate graft (%) (%) 4- Bilateral graft 17.5 27.5 0.035 98 - unilateral 82.5 32.8 65.2 7.4 unilateral 82.5 32.8 65.2 7.4 P<0.001 P<0.001 5- Donor size > 8mm 29.8 30-50 0.3 73.7 6.3 < 8mm 67.9 29.8 69.5 6 < 8mm 67.9 29.8 69.5 6 6- Iridocorneal 6.50 64.7 <0.001 44.1 49.2 Adhesion Adhesion 7- Irritating suture 7.8 78.3 0.001 8- Active intraocular 10.1 36.7 0.035 30 20 inflammation < 0.001 inflammation < 0.001 9- Secondary anterior 10.2 50 0.022 57.1 segment surgery segment surgery

18. Results....cont.(7) Risk factors of rejection factor Rejection P value clear failure presence rate graft presence rate graft (%) (%) 10- Eccentric graft 3.1 66.7 0.038 11- Trauma scar 3.7 63.6 0.02 28.6 14.3 <0.001 12- Poor controlled IOP 5.1 60 0.02 15.4 7.7 0.1(N.S) 13- Previous rejection 4.4 69.2 0.002 69.2 15.4 0.001 14- Graft ulcer 1.7 40 0.021 60 20 0.001 15- HSK recurrence 3.1 66.7 0.021

19. 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

20. 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

21. 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