Risk Factors for Graft Rejectionin

Penetrating Keratoplasty

Risk Factors for Graft Rejectionin

Penetrating Keratoplasty

Labbafinejad Medical CenterLabbafinejad Medical Center

Department of OphthalmologyDepartment of Ophthalmology

20022002

Farid Karimian, MDFarid Karimian, MD Mohammad Ali Javadi, MDMohammad Ali Javadi, MD Mohammad Reza Jafari-Nasab, MDMohammad Reza Jafari-Nasab, MD Seyed Mojtaba Hosseini, MDSeyed Mojtaba Hosseini, MD Arash Anisian, MDArash Anisian, MD

Department of Ophthalmology,Department of Ophthalmology, Labbafinejad Medical Center Labbafinejad Medical Center Ophthalmic Research Center Ophthalmic Research Center

IntroductionIntroduction Penetrating keratoplasty (PK) is the most Penetrating keratoplasty (PK) is the most

common human organ transplantcommon human organ transplant During 2000-01, 2108 PK’s were performed During 2000-01, 2108 PK’s were performed

in Iranin Iran The most common cause of graft failure is The most common cause of graft failure is

“Immunologic Rejection”“Immunologic Rejection” 30% of PK’s have at least one episode of 30% of PK’s have at least one episode of

rejectionrejection 50-70% of graft rejection is treated with 50-70% of graft rejection is treated with

corticosteroidscorticosteroids

Defined Risk Factors for Graft Rejection

Defined Risk Factors for Graft Rejection

Recipient corneal Recipient corneal bed vascularizationbed vascularization

loose and irritating loose and irritating suturesuture

RegraftRegraft Bilateral graftBilateral graft Iridocorneal Iridocorneal

adhesionadhesion Intraocular and Intraocular and

corneal inflammationcorneal inflammation

Recipient young Recipient young ageage

Donor graft sizeDonor graft size Eccentric graftEccentric graft Glaucoma, poor Glaucoma, poor

controlled IOPcontrolled IOP YAG-capsulotomyYAG-capsulotomy

Purpose: Purpose:

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

Materials and MethodsMaterials and Methods

Design of Study:Design of Study: Descriptive-Descriptive-cohortcohort

Inclusion Criteria:Inclusion Criteria: PK performed during years 1998-1999PK performed during years 1998-1999 Referral: Sequential, non-randomizedReferral: Sequential, non-randomized No previous H/O ImmunosuppressiveNo previous H/O Immunosuppressive

useuse

Surgical TechniqueSurgical Technique Donor Cornea: cut from whole globe Donor Cornea: cut from whole globe

or preserved in mediaor preserved in media Trephination: Barron-Hessburg Trephination: Barron-Hessburg

VacuumVacuum Donor cornea endothelial punchDonor cornea endothelial punch Suturing technique: 4 cardinal, later Suturing technique: 4 cardinal, later

interrupted, running or combinedinterrupted, running or combined

Definitions for Graft Rejection

Definitions for Graft Rejection

Clear graft for at least first 10 days PostopClear graft for at least first 10 days Postop Epithelial RejectionEpithelial Rejection Subepithelial infiltrates (SEI)Subepithelial infiltrates (SEI) Endothelial Rejection: 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

edemaedema

Treatment and RejectionTreatment and Rejection

Epithelial and SEI: Topical Epithelial and SEI: Topical Betamethasone 0.1%Betamethasone 0.1%

Localized ER: Frequent topical Localized ER: Frequent topical Betamethasone + Systemic Betamethasone + Systemic PrednisolonePrednisolone

Diffuse ER: Topical and Systemic Diffuse ER: Topical and Systemic steroids + subtenon methyl-steroids + subtenon methyl-prednisoloneprednisolone

Statistical AnalysisStatistical Analysis

Tests: Chi-squareTests: Chi-square

T-testT-test

Multivariate Regression AnalysisMultivariate Regression Analysis

ResultsResults 295 PK in 286 patients evaluated295 PK in 286 patients evaluated Male 61.4%, Female 38.6%Male 61.4%, Female 38.6% Age: 37 ± 20 years (40 days-90 Age: 37 ± 20 years (40 days-90

years)years) Follow-up: 20 ± 10 months (24-43 mo)Follow-up: 20 ± 10 months (24-43 mo)

Results… cont Indications for Penetrating Keratoplasty

Results… cont Indications for Penetrating Keratoplasty

Keratoconus (31.9%)Keratoconus (31.9%) Regraft (13.9%)Regraft (13.9%) Corneal ulcer (perforated or non-Corneal ulcer (perforated or non-

perforated) (12.6%)perforated) (12.6%) Traumatic scars (7%)Traumatic scars (7%) Corneal chemical burn (2%)Corneal chemical burn (2%)

Prognosis according to Indications for PK:

Percentage of clear graft

Prognosis according to Indications for PK:

Percentage of clear graft

Keratoconus Keratoconus (97.8%)(97.8%)

Corneal Corneal dystrophies dystrophies (96.3%)(96.3%)

PBK (66.7%)PBK (66.7%) ABK (61.5%)ABK (61.5%)

Vascularized Vascularized scars (60%)scars (60%)

Regraft (47%)Regraft (47%) Trauma (28.6%)Trauma (28.6%) Chemical burn Chemical burn

(16.7%)(16.7%)

Results cont.…(3)

Results cont.…(3) Graft Rejection DataGraft Rejection Data

-- Total no. of rejections:Total no. of rejections: 94 (31.8%) 94 (31.8%)

- - Frequency of rejections:Frequency of rejections: Once: 20.8%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:Onset of Rejection: Ave: 7.3 ± 6 mo (20 Ave: 7.3 ± 6 mo (20 days-39mo)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: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:Graft Clarity:

-Clear: 70.6%-Clear: 70.6%

-Non-clear: 29.4% Rejection cause: -Non-clear: 29.4% Rejection cause: 6.1%6.1%

Time of Rejection:Time of Rejection:

- April: 4.1% > July and Sept.: 3.4%- April: 4.1% > July and Sept.: 3.4%

Results.....cont.(4) Results.....cont.(4)

Risk factors of rejectionRisk factors of rejection factor Rejection P. value clear failure factor Rejection P. value clear failure

presence rate graft presence rate graft

(%)(%)

1- Age < 40y/o 62 28.4 1- Age < 40y/o 62 28.4 0.0950.095

> 40y/o 38 37.8> 40y/o 38 37.8

2- Corneal vasularization2- Corneal vasularization

Mild 6.1 38.9 0.015 77.8Mild 6.1 38.9 0.015 77.8

Moderate 9.8 48.3 62.1 13.8Moderate 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 4.8Avascular 70.9 27.8 78.9 4.8

3- Regraft 12.5 48 0.025 47 18.83- 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

4.64.6

Results...cont.(5)Results...cont.(5)

Results......cont.(6)Results......cont.(6)Risk factors of rejectionRisk factors of rejection factor Rejection P. value clear failure factor Rejection P. value clear failure

presence rate graft presence rate graft

(%)(%)

4- Bilateral graft 17.5 27.5 0.035 98 - 4- Bilateral graft 17.5 27.5 0.035 98 -

unilateral 82.5 32.8 65.2 7.4unilateral 82.5 32.8 65.2 7.4

P<0.001P<0.001

5- Donor size > 8mm 29.8 30-50 5- Donor size > 8mm 29.8 30-50 0.30.3 73.7 6.3 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 49.26- Iridocorneal 6.50 64.7 <0.001 44.1 49.2

Adhesion Adhesion

7- Irritating suture 7.8 78.3 0.0017- Irritating suture 7.8 78.3 0.001

8- Active intraocular 10.1 36.7 0.035 30 20 8- Active intraocular 10.1 36.7 0.035 30 20

inflammation < 0.001inflammation < 0.001

9- Secondary anterior 10.2 50 0.022 57.1 9- Secondary anterior 10.2 50 0.022 57.1

segment surgery segment surgery

Results....cont.(7)Results....cont.(7)

Risk factors of rejection factor Rejection P value clear failureRisk factors of rejection factor Rejection P value clear failure

presence rate graft presence rate graft

(%)(%)

10- Eccentric graft 3.1 66.7 0.038 10- Eccentric graft 3.1 66.7 0.038

11- Trauma scar 3.7 63.6 0.02 28.6 14.3 11- Trauma scar 3.7 63.6 0.02 28.6 14.3 <0.001<0.001

12- Poor controlled IOP 5.1 60 0.02 15.4 7.7 12- Poor controlled IOP 5.1 60 0.02 15.4 7.7 0.1(N.S)0.1(N.S)

13- Previous rejection 4.4 69.2 0.002 69.2 15.4 13- Previous rejection 4.4 69.2 0.002 69.2 15.4 0.0010.001

14- Graft ulcer 1.7 40 0.021 60 20 14- Graft ulcer 1.7 40 0.021 60 20 0.0010.001

15- HSK recurrence 3.1 66.7 0.02115- HSK recurrence 3.1 66.7 0.021

Discussion and ConclusionsDiscussion and Conclusions The most common causes of PK at LMC are The most common causes of PK at LMC are

different from Western reports (Kerataconus different from Western reports (Kerataconus vs ABK-PBK)vs ABK-PBK)

The most common type of Rejection isThe most common type of Rejection is EndothelialEndothelial

Age (>40 vs <40 years) was not a risk factor Age (>40 vs <40 years) was not a risk factor for rejectionfor rejection

Severity of vascularization increases rate of Severity of vascularization increases rate of rejection and graft failurerejection and graft failure

Discussion and Conclusions…. Cont.(1)

Discussion and Conclusions…. Cont.(1)

RegraftRegraft increases risk of rejection increases risk of rejection Bilateral graftBilateral graft (vs unilateral) was (vs unilateral) was notnot

a risk factor (controversial in a risk factor (controversial in previous reports) probably due to previous reports) probably due to main primary indications for PKmain primary indications for PK

There was There was nono significant difference significant difference in in graft sizegraft size (>8 vs <8 mm) as risk (>8 vs <8 mm) as risk factorfactor

Discussion and Conclusions… cont. (2)

Discussion and Conclusions… cont. (2)

Iridocorneal adhesions, irritating Iridocorneal adhesions, irritating sutures, active intraocular inflammation, sutures, active intraocular inflammation, secondary intraocular surgeries, secondary intraocular surgeries, eccentricity of graft, poor controlled IOP, eccentricity of graft, poor controlled IOP, presence of graft ulcer and recurrence of presence of graft ulcer and recurrence of Herpes:Herpes:IncreaseIncrease risk of risk of rejectionrejection and and consequently graft consequently graft failurefailure