Difference between corneal graft failure & corneal graft rejection . T

Difference between corneal graft failure & corneal graft rejection . Take reference from zia , khurana & kanski

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Corneal Graft Failure vs. Corneal Graft Rejection

Note: The medical library contains Kanski's Clinical Ophthalmology (10th ed.) and the Wills Eye Manual. Neither Khurana's Comprehensive Ophthalmology nor a "Zia" ophthalmology text are in the available library. The content below is drawn from Kanski with supplementary information from Wills Eye Manual and general ophthalmological knowledge consistent with standard references.

Overview

These two terms are often confused but are distinct entities:

Feature	Corneal Graft Rejection	Corneal Graft Failure
Definition	Active immune-mediated attack on donor corneal tissue	Loss of corneal clarity/function regardless of cause
Mechanism	Immunological (T-cell mediated, type IV hypersensitivity)	Immunological or non-immunological
Timing	Days to years after keratoplasty	May be primary (never cleared) or late
Reversibility	Often reversible with early aggressive treatment	Often irreversible
Inflammation	Present — ciliary injection, AC cells/flare	Absent in pure failure
Relationship	A type of insult that can cause failure	The endpoint — the graft never functions or loses function

Corneal Graft Rejection

"If the host becomes sensitized to histocompatibility antigens present in the donor cornea, rejection may result." — Kanski's Clinical Ophthalmology, p. 294

Immunological Basis

Any layer of the cornea can be immunologically rejected
Rejection of separate layers (endothelial, stromal, epithelial) can occur in isolation but typically a combination is present
Mediated by HLA-mismatched donor antigens; HLA matching has a small beneficial effect on graft survival
Gender incompatibility is an important risk factor — a male donor cornea should not be allocated to a female recipient

Risk Factors

Host stromal vascularization (most important)
Eccentric or large grafts (>8 mm diameter)
Herpetic infection
Glaucoma
Previous failed keratoplasty
Male donor → female recipient mismatch

Types & Clinical Signs

Type	Timing	Features
Epithelial	~3 months avg	Elevated, irregular epithelial rejection line in a quiet/mildly inflamed eye
Subepithelial	Weeks–months	Subepithelial infiltrates — "Krachmer spots" (similar to adenoviral keratitis)
Stromal	Variable	Deeper haze; can be chronic or hyperacute (often with endothelial rejection)
Endothelial	Most serious	Khodadoust line — linear keratic precipitates on endothelium, advancing from periphery; stromal edema if endothelium fails

Symptoms: Blurred vision, redness, photophobia, pain — but many cases are asymptomatic until rejection is established.

Treatment (Kanski, p. 295)

Preservative-free topical steroids hourly × 24 hours → taper gradually over weeks (mainstay)
Topical cycloplegia (homatropine 2% or atropine 1%)
Topical ciclosporin 0.05–2%
Systemic prednisolone 1 mg/kg/day × 1–2 weeks; or IV methylprednisolone 500 mg/day × 3 days if within 8 days of onset (most effective)
Subconjunctival dexamethasone
Other immunosuppressants: ciclosporin, tacrolimus, azathioprine
IOP monitoring is critical throughout

TIP (Kanski): "In a patient with acute corneal graft rejection, early intensive treatment greatly improves the likelihood of reversing the rejection."

Corneal Graft Failure

"Simple graft failure can occur in the absence of rejection, although rejection is a common contributory factor." — Kanski's Clinical Ophthalmology, p. 294

Types

1. Primary Graft Failure

The graft never clears from the outset
Due to pre-existing donor endothelial dysfunction or surgical trauma
Not immune-mediated

2. Secondary (Late) Graft Failure

Graft clears initially, then fails
Causes:
- Immunological: Rejection episode(s) leading to irreversible endothelial loss
- Non-immunological:
  - Progressive endothelial cell loss (normal aging + surgical trauma)
  - Recurrence of underlying disease (e.g., herpes keratitis, corneal dystrophy)
  - Glaucoma-related
  - Retro-corneal membrane formation

From Robbins Pathology: "Nonimmunologic graft failure (associated with loss of endothelial cells and subsequent corneal edema) is seen more commonly than immunologic graft rejection."

Signs

Corneal oedema, hazing, opacification
No inflammation (distinguishes it from rejection)
Stromal oedema indicates endothelial failure

(Wills Eye Manual: "Other causes of graft failure: Non-immune-mediated late corneal graft endothelial decompensation or recurrent disease in the graft.")

Epidemiology

From Tintinalli's Emergency Medicine, the causes of graft failure in order of frequency:

Corneal graft rejection — 30.9%
Corneal endothelial cell failure (non-immune) — 21.0%
Glaucoma — 8.5%
Other causes — 26.2%

Key Differentiating Points at a Glance

Parameter	Rejection	Failure
Cause	Immune-mediated (HLA sensitization)	Immune or non-immune
Inflammation	Yes — ciliary injection, AC cells	No (in non-immune failure)
Khodadoust line	Present (endothelial rejection)	Absent
Krachmer spots	Present (subepithelial rejection)	Absent
Reversibility	Reversible if treated early	Irreversible (usually)
Treatment	Intensive steroids + immunosuppression	Re-grafting (repeat keratoplasty)
Outcome if untreated	Progresses to graft failure	End-stage — re-grafting required

Practical Mnemonics

Rejection = Reversible + Red eye (inflammation) + Responds to steroids
Failure = Final endpoint + No flames (no inflammation in non-immune type) + Fix with re-graft

Sources: Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed., pp. 294–295; Wills Eye Manual, Chapter 4.28; Robbins, Cotran & Kumar — Pathologic Basis of Disease.

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