Corneal blindness is a major cause of blindness worldwide and in India. There are approximately 11 lakh people in India suffering from corneal blindness. However, only 25,000 corneal transplants are performed annually, while the need is over 1,00,000 per year. Key reasons for this gap include insufficient eye donation and viable eye banks. Corneal graft rejection remains a challenge, with risk factors including donor-recipient antigen mismatch, technical issues, and post-operative infections. New techniques such as lamellar keratoplasty and treatments including immunosuppressants aim to reduce rejection rates.

3. Causes of Blindness
1) Cataract
2) Injuries
3) Diabetic Retinopathy
4) Glaucoma
5) Refractive errors
6) Hereditary diseases of eye
7) ARMD
8) Corneal blindness

4. Human Resources
1) Total Ophthalmologists in India (approximately) :
a) Registered : 26,700
b) Unregistered : 12,000
2) New addition of Ophthalmologists every year: 1,500
3) Total No. of eye banks : 764 (In India)
4) Viable eye banks : 420

5. Corneal blindness is one of the leading causes of blindness
in the world.
World Health Organization (WHO) reports estimate that
approximately 5% of the world’s population is blind due to
corneal diseases alone.

6. In India, approximately 68 lakh people suffer from corneal
blindness in at least one eye; of these, 11 lakh people are
blind in both their eyes.
On an average 40-50 percent donated eyes/corneas are
utilized for corneal transplantation annually.

7. More than 1,00,000 corneal transplants are required
annually in India.
25 to 30 thousand eyes are collected every year.

8. Current annual transplant number is 25,000.
around 11 lakh people are suffering from corneal blindness
in India and 30,000 new cases are being added each year,
whereas, only 25,000 corneal transplants are conducted
every year in India.

9. Important Corneal Blindness causes
1) Corneal opacities
2) Corneal dystrophies
3) Corneal injuries
4) Vitamin A deficiency
5) ABK, PBK, BSK
6) Congenital corneal blindness

10. Definition of Corneal Graft Rejection
1) Graft rejection is an active phenomena, where in there
will be immunological reaction from host antigens
against donor corneal tissue and the grafted cornea
should be clear for at least 10 to 15 days after
transplantation. This graft rejection is different from
graft failure.

11. Graft Rejection v/s Graft Failure
What is the difference…?

12. If there is corneal graft rejection, it may lead to graft failure
or it may (cornea) turn back to normal clear cornea with
timely prompt and timely treatment.
If the graft is failed, it is failed forever.

13. Primary Graft failure
Primary donor graft failure is defined as cornea edema
that never clears from the immediate postoperative
period secondary to inherent deficiencies in the donor
graft, surgical trauma, or improperly stored tissue.

14. History of organ transplantation:
Examples in mythology
Lord Ganesha’s head replaced with Elephant head
Bhakhta kanappa (eye donation/transplant)

16. • Autograft -within same individual
•Isograft --- From genetically identical twins
•Allograft- From genetically different
member of the same species.
•Xenograft- From different species
•Future grafts-transgenic species
TYPES OF GRAFTS:

17. • Heart
• Lung
• Kidney
• Liver
• Skin
• Blood & components
• Pancreas
• Bone
• Tendon
• Muscle
• Cornea
• Intestine
Human organs that can be transplanted:

18. Human organ transplant Act

19. HOTA Act (1994) & its amendments:
• Ethical aspects
• Social aspects
• Financial aspects
• Humanitarian aspects
Jeevandan Program, Government of Andhra Pradesh

20. •The Transplantation of Human Organs Act, 1994 was
enacted by the Parliament during 1994 and came into
force on February 4, 1995 in the States of Goa, Himachal
Pradesh and Maharashtra and all the Union Territories.
Thereafter it was adopted by all States except the States of
Jammu & Kashmir and Andhra Pradesh, which have their
own legislations to regulate transplantation of Human
Organs

21. Types of Keratoplasty:
• Full thickness Penetrating Keratoplasty
• Lamellar Keratoplasty
• Grafting of Superficial layers (including stroma)
• Endothelial Graft(s)
• DALK(Deep anterior Lamellar Keratoplasty)
• DSEK(Descemet Stripping Endothelial Keratoplasty)
• DMEK(Descemet Membrane Endothelial Keratoplasty)

22. History of evolution of
corneal surgeries

23. History of corneal surgeries
• Galen 130–200 Idea of restoring transparency of an opaque cornea.
• Darwin in 1760 idea of removal of opaque cornea by trephination.
• Bigger 1837 First successful transplant in animals.
• Von Hippel 1886 First lamellar transplant in 30 patients.
• Zirm1905 Penetrating transplant with permanent success
• Filatov1935 First eye bank (Odessa, Russia)
• Paton1945 First US eye bank (New York).

24. • Maumanee1941 Graft rejection recognized as a clinical en
• 1961Eye Bank Association of America.
• 1974McCarey-Kaufmann donor preservation.
• 1989First idea of use of laser for trephination. Jones1998 Endothelial
lamellar keratoplasty
• Terry2001 Deep lamellar endothelial keratoplasty
• Anwar2002 Big-bubble technique of DAL.
• Price2005 Descemet’s stripping endothelial keratoplasty
.

26. Classification of corneal Graft Rejection:
Epithelial
Chronic Stromal
Hyperacute stromal
Chronic Focal/ Endothelial
Combined stromal and
endothelial

43. Causes for corneal graft rejection:
• Donor Factors
• Host Factors
• Technical Factors
• Post operative infection(s)

44. Pre-operative causes
Per-operative causes
Post-operative causes

45. Pre-operative causes
1) Donor factors
a) Antigen load of donor
b) HLA / ABO incompatibility
c) Duration of tissues storage
d) Technique of corneal button cutting
e) Vaccination of Flu, Covid-19

46. Pre-operative causes
2) Host corneal factors
a) Vascularization
b) Failed graft and regraft
c) Ocular surface disease like Dry eye, chemical
injury, Lime injury, SJ syndrome, Pemphigoid,
facial palsy, surface infection, viral keratitis
d) ABO incompatibility
e) Post excimer laser

47. Pre-operative causes
2) Host corneal factors
f) Pilocarpine and other drugs
g) PAS
h) Un controlled glaucoma
i) Young aged recipient
j) Large graft
k) Interstitial keratitis

48. Per-operative causes
1) Large graft
2) Eccentric graft
3) PAS
4) Bilateral graft
5) Loose sutures
6) Previous anterior segment surgeries

49. Post-operative causes
1) Loose sutures
2) Exposed suture edges
3) Blepharitis
4) Entropion
5) Trichiasis
6) PAS
7) Posterior Synechiae
8) Vascularization

54. Symptoms of Graft Rejection
• Redness
• Pain
• Photophobia
• Diminution of vision

55. Signs of Graft Rejection
• Conjunctival Congestion
• Circumciliary Congestion
• Chemosis
• Corneal Edema
• Raised IOP
• Keratic precipitates
• Sub-Epithelial infiltrates
• Stromal infiltrates &
vascularization
• Endothelial Rejection Line
• Khodadoust Line
• Anterior Chamber Flare &
Cells

57. Immuno-Pathology Of Corneal Graft Rejection
Corneal Immune privilege systems:
1. Avascularity
2. Lack of lymphatics
3. ACAID (anterior chamber associated immune
deviations)

58. Despite of all the above-mentioned privileges, graft
rejection still occurs but at lower rates when compared to
other organ transplants, because of mismatching of
Donor to Recipient MHC/HLA antigens and rarely ABO
incompatibility can be another cause for graft rejection.

62. MECHANISM OF CORNEAL GRAFT FAILURE
•Type IV cell-mediated immune reaction.
•Role of CD-4 cells:
•Foreign MHC class II antigens act as a strong stimulus
and can be recognized by host CD4+ T cells. The host
Langerhans cells can also process foreign class I
antigen and present it in conjunction with self-class Il
molecules to host CD4 T cells. The result of either
mechanism is CD4 T-cell activation

63. Activated CD4 T cells release IL-2 and other lymphokines that
stimulate the proliferation and activation of CD4 T cells, cytotoxic T
cells, and B lymphocytes.
• Role of CD-8 cells: Host cytotoxic T cells (CD8+) can recognize foreign
class I cell-surface antigens on the surface of donor cells. They result
in lysis of the donor cells. NK activity also has a cytotoxic role.
• B Lymphocytes
• Antibody production by B cells enables opsonization, complement
binding, and facilitation antibody-dependent cell-mediated
cytotoxicity (K cell activity). Exaggerated response by induction of
donor MHC class II

73. Differential Diagnosis of Corneal Graft Rejection
1) Disciform viral keratitis
2) Infectious endophthalmitis
3) Endotheliitis
4) Epithelial down growth
5) Large graft failure
6) Posner Schlossman syndrome

74. Differential Diagnosis:
LATE GRAFT FAILURE:
•Gradual onset of
graft edema
•No inflammation or
KPs
STERILE/INFECTIOUS
ENDOPHTHALMITIS
•Severe ocular
inflammation
•Hypopyon
•Vitreous infiltrates

75. Differential Diagnosis:
EPITHELIAL DOWNGROWTH
RECURRENT HERPETIC
KERATITIS
• H/o graft in herpetic cornea
• No endothelial line in
presence of intense AC
reaction
• Response to topical Antiviral
therapy
• Clumps of cell like material in
AC
• No response to CS
• Associated raised IOP
unresponsive to medical
therapy

76. Management of Corneal Graft Rejection
1) Local and systemic steroids
 Prednisolone eye drops
 Dexamethasone eye drops
 Tablet – Prednisolone / wysolone
 IVMP pulse therapy – Dose for 3-5 days
2) Cytotoxic agents
 Azathioprine : 1 to 2mg per KG weight
 Cyclosporin ‘A’ – Topical / Systemic 0.50%
3) Combination of cytotoxic agents and steroids

77. Management of Corneal Graft Rejection
Newer Advances
4) Newer immune modulators
 Tacrolimus – FK-506 0.6mg / KG weight
5) Repamycin
 Lipophylic drug with high potency
6) Deoxy spergualin (DSG)

78. Management of Corneal Graft Rejection
Newer Advances
7) Tissue cultured corneal epithelial and
endothelial cells
8) Anti VEGF agents
9) Selective glucocorticoid receptor agonist (SEGRA)

79. Management of corneal graft rejection
Newer Advances:
• Cord Blood Stem cell culture for human
organ/tissue
• Cryo banking
• Bionic organs

81. Prevention of Corneal Graft Rejection
1) Proper case selection
2) Look for pre-operative risk factors
3) Patient education
4) Paramedical staff education
5) Prompt follow-up of patients
6) Treatment compliance – patient

84. Topical CS
• Pre op instillation in high
risk graft
• To be complimented with
systemic steroid therapy in
form of pulse steroid
dosage.
• Systemic steroids are to
be continued orally after
the initial pulse therapy.
Systemic CS
• Oral CS is recommended
in a higher doses than the
routine 60-80 mg daily
• It is to be tapered off
when the graft begins to
recover and usually cured
by 6-8 weeks
IV Pulse CS
• 500 mg in 150ml IV fluid
• The dose is to be repeated
after 48 hours.
• Oral maintenance to be
continued

85. Studies related to Corneal Graft Rejection
1) Australian Corneal transplant Registry
2) Singapore Corneal transplant Registry
3) UK Corneal Corneal transplant Registry
4) Corneal transplant collaborative research study
group
5) Corneal graft rejection treatment and follow up
group

86. CONCLUSIONS

87. CONCLUSIONS
1) Recent invention of component, layer by layer corneal
lamellar Keratoplasties has revolutionized the success
rate of cornea transplantation. With corneal
component layer by layer surgery. CGR rate has come
down to 0.56%

88. CONCLUSIONS
2) UV light treatment of cornea before grafting has
reduced post-operative vascularization
3) Trails are going on with corneal epithelial and
endothelial cell transplantation which were cultured
out side (invitro), just at the starting of CGR
4) Pre and Post operative measurement of corneal
thickness (pachymetry) is useful for knowing the
prognosis of graft success

89. CONCLUSIONS
6) Recent treatment trails with tacrolimus, cyclosporin ‘A’
along with corticosteroids is found to be more
effective treatment for CGR
7) Cytotoxic agents like methotrexate and
Cyclophosphamide are also tried for the treatment of
CGR
8) Drugs like Rapamycin, DSG (Deoxy Sergualin),
Mycophenolate, SEGRA (Selective Gluco Corticoid
Receptor Agonist) are still under experimental stage.

90. CONCLUSIONS
9) Anti VEGF drugs like Bevacizumab has been tried to
prevent corneal vascularization at the starting of
corneal graft rejection

91. THANK YOU