Corneal graft failure and rejection are the nightmares for an Ophthalmologist. Here is an overview on Rejection vs Failure, identification of risk factors, prevention and Mx of a failure

1. CORNEAL GRAFT REJECTION
Dr Harsha Prathapasinghe

2. • Leading cause for secondary graft failure
• Progression from rejection to failure is 49%
• Dx made in grafts which remained clear for at least 2/52 after Sx
• Rarely before 1M
• Highest in first year
• Can occur even after 20 yrs

3. • An uncomplicated, “Low risk” PKP has 95% survival rate at 5 yrs
due to immune previlaged status of cornea
• In “High risk” pts, failure rate is 35% at 3 yrs

4. What are the factors contributing to corneal
immune privilege?
• Avascularity
• Absence of lymphatics
• Expression of FAS ligands which induce apoptosis of stimulated T
cells
• Low expression of MHC Ag
• Unique spectrum of immunomodulatory factors in aquous that
inhibit T cells and complement activation
• Anterior chamber mediated immune deviation

5. Pathogenesis of corneal graft rejection
HLA on donor tissue
interact with recipient
cytotoxic T cells
Local
inflammation
Cellular
destruction
Rejection

6. Rejection vs Failure
Primary failure
• Oedema NEVER clears from immediate post
op period
• Non immune mediated
• Due to;
– Inherent deficiency in corneal graft
– Improperly stored tissue
– Sx trauma
• Rejection failure
• Post op clear cornea at least 2 wks
• Maximally treated for at least 2 months

7. 4 forms can be identified. May occur either singly or in
combination
Epithelial rejection
• 2-10%
• In early post op period
(1-13M)
• Begin as a linear ridge
(Epithelial rejection
line) located near an
engorged limbal vessel
• Then migrate across
G-H interface and
advanced centripedally
• Stain with fluorescence
• Typically self limiting
Sub epithelial rejection
• Focal infiltrates similar
to adenovirus keratitis
Stromal rejection
• Stromal infiltrates
similar HSV keratitis
• Neovascularization
• Stromal necrosis in
severe form
Endothelial rejection
• Most common form
(37-50%)
• Most severe form
• KP begins inferiorly at
G-H junction.
• Clumps aggrevate to
form Khodadoust line.
• Then march superiorly
• AC cells
• Epithelial and stromal
oedema

9. Clinical features (From most common to least
common)
• Corneal oedema
• KP (On graft cornea. But not on peripheral recipient cornea)
• Corneal vascularization
• Stromal infiltrates
• Khodadust line
• Epithelial rejection line
• Sub epithelial infiltrates

10. DD
• Herpetic (HSV/HZ) keratouveitis
• Indolent microbial keratitis
• Epithelial downgrowth
– Mimic endothelial rejection line
• Endothelial decompensation secondary to low ECC
• Graft failure
– Not responding to topical steroid

11. Risk factors
• Prev graft failure
• Previous ocular Sx
• Glaucoma, AGT
• Ocular surface diseases, Tear film deficiencies
• Hx of uveitis/ Active uveitis
• Active keratitis
• DM
• African American ethnicity
• Young

12. Risk factors ct……
• Large/ Eccentric grafts
• Corneal neovascularization
• PAS extending to graft margin
• Broken sutures
• Suture knots at scleral side
• Suture infiltrates

13. Prevention of graft rejection
• DALK, DSEK, DMEK instead of PKP
• Patient education
– Importance of compliance and close follow up
– Symptoms which represent worsening of disease
• Long term steroid or other immunosuppressants
– Cyclosporin 0.5%
– In steroid responders, graft done for recent fungal keratitis
– Tacrolimus
– Topical (0.06%) tds for 6M shows superior to steroid in preventing rejection (100%
vs 84%) in “Low risk” pts
– Systemic (2-12mg/d) in “High risk” pts

14. Prevention of graft rejection ct…..
• Prophylactic antivirals in pts with PHx of herpetic keratouveitis
• Prevent/ early attention to infections
• Mx IOP
• Mx Neovacularization

15. How to manage?
• Symptomatic management
• Mx risk factors
• Mx graft rejection
• Mx steroid related complications
– IOP
– Cataract
– Reactivation of herpetic keratitis
– Impaired wound healing
• Visual rehabilitation

16. Mx graft rejection
• Frequent steroid (1%) eye drops
– Hourly in Endo rejection
– Less Fq in Epi/ subepithelial rejection
• Periocular steroid
– In severe rejection, Non complient
• Systemic steroid
– Oral
– IV 1 dose of 1g OR 3 doses of daily 500mg

17. References
AAO 2016-17
EyeWiki
Practicing Ophthalmologist’s
curriculum 2017-19