Penetrating and Endothelial Keratoplasty: An Overview
Corneal allograft is one of the most successful forms of solid organ transplantation. Normally, HLA typing and systemic immunosuppressive drugs are not utilized, yet 90 % of corneal allografts survive [1, 2]. The better acceptance of corneal allografts compared to other categories of allografts is due to the unique immunological property of cornea, coined by Medawar as immune privilege. This immune privilege is abolished in conditions such as inflammation, neovascularization, or trauma to cornea.
KeywordsAnterior Chamber Corneal Graft Immune Privilege Anterior Segment Optical Coherence Tomography Deep Anterior Lamellar Keratoplasty
3.1 Cornea Immune System
Corneal allograft is one of the most successful forms of solid organ transplantation. Though HLA typing and systemic immunosuppressive drugs are not utilized, yet 90 % of corneal allografts survive [1, 2]. The better acceptance of corneal allografts compared to other categories of allografts is due to the unique immunological property of cornea, coined by Medawar as immune privilege. This immune privilege is abolished in conditions such as inflammation, neovascularization, or trauma to cornea.
3.1.1 Mechanisms of Immune Privilege
Immune privilege of corneal allografts is sustained by one or more of the following: (1) blocking the induction of immune responses, (2) deviating immune responses down a tolerogenic pathway, or (3) blockade of immune effector elements [1, 2].
18.104.22.168 Blocking the Induction of Immune Responses
The most widely accepted explanation for corneal allograft survival is the absence of blood and lymph vessels in the non-inflamed cornea and graft bed. Earlier the concept was that absence of blood vessels is more important for immune privilege. However, recent study suggests that absence of lymph vessels is primarily responsible for immune privilege. It has recently been reported that corneal epithelial and stromal cells secrete a soluble form of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2), which blocks and inhibits lymphangiogenesis in the cornea .
22.214.171.124 Role of Immune Deviation and T Regulatory Cells
Antigens introduced into the anterior chamber (AC) induce a unique spectrum of systemic immune responses that are characterized by the antigen-specific suppression of delayed-type hypersensitivity responses and the preferential production of non-complement-fixing antibody isotypes (i.e., IgG1) and the exclusion of complement-fixing antibodies [1, 2, 4]. This form of immune deviation is termed as anterior chamber-associated immune deviation (ACAID). After surgery, corneal endothelial cells are sloughed from corneal allografts and enter the AC, where they induce ACAID. The aqueous humor also contains numerous anti-inflammatory and immunosuppressive molecules which in turn, suppresses alloimmune responses and promotes corneal allograft survival.
126.96.36.199 Blockade of Immune Effector Elements
The cornea expresses a number of cell membrane-bound molecules that neutralize immune response. FasL (CD95L) is expressed on the cell membranes on many cells within the eye, including the corneal endothelium, and induces apoptosis of neutrophils and lymphocytes that encounter the cornea during inflammation. Programmed death ligand-1 (PD-L1) is expressed on the cornea and when it engages its receptor (PD-1) on lymphocytes, it inhibits T-lymphocyte proliferation, induces T-lymphocyte apoptosis, and prevents T-lymphocyte production of interferon-γ (IFN-γ). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expressed on the corneal endothelium and induces apoptosis of activated T cells expressing its receptor (TRAIL-R2). Cell membrane-bound complement regulatory proteins (CRP) expressed on corneal epithelial cells and the soluble CRP present in the aqueous humor buffers the capacity of complement-fixing antibodies to produce corneal allograft rejection. Macrophage migration inhibitory factor (MIF) and transforming growth factor-β (TGF-β) are present in the aqueous humor at concentrations that are known to produce profound inhibition of NK cell-mediated cytolysis.
Thus, the cornea and the underlying aqueous humor have the capacity to not only block, but also eliminate immune effector elements from both the adaptive and innate immune systems. This “sword and shield” strategy provides immune privilege to the corneal allograft.
3.1.2 Loss of Immune Privilege
188.8.131.52 Posttransplant Local Events
These events are a loose suture, suture-associated infection, or herpetic infection recurrence. These lead to recruitment of alloreactive cells, angiogenesis, lymphangiogenesis, and upregulation of MHC molecules on the graft cells.
184.108.40.206 Vascularization of the Graft Recipient Bed
220.127.116.11 Rejected Previous Transplant
18.104.22.168 Inflammation at the Time of Transplant
A high antigen-presenting cell (APC) count is seen in excised recipient cornea in inflamed eyes. Cornea transplantation is avoided in actively inflamed eyes, and every attempt is made to obtain the best possible control of corneal inflammation before transplantation.
Perioperative or sustained local conjunctival or corneal inflammation can increase the allograft rejection risk by breaching the immune privilege.
3.2 Eye Banking and Donor Cornea
Slit-lamp evaluation of donor cornea in preservation medium as per cornea donor study
Specular count (cells/mm2)
Defects of 50 % or less
Haze: none to more than moderate
Exposure: none to no more than moderate
Edema: none to no more than mild
Arcus: ≥ 8 mm clear zone
Snail tracks: none to more than mild centrally
Guttae: no true guttae
Haze: moderate to severe
Edema: mild to moderate
Moderate to severe folds
NSFS: not suitable for surgery
3.3 Types of Corneal Transplantation
3.3.1 Depending Upon Indication
22.214.171.124 Optical Keratoplasty
126.96.36.199 Therapeutic Keratoplasty
188.8.131.52 Tectonic Keratoplasty
In this, keratoplasty is performed to enhance corneal strength, e.g., crescentic lamellar keratoplasty performed for advanced cases of pellucid marginal degeneration.
3.3.2 Depending Upon Technique
184.108.40.206 Lamellar Keratoplasty
This refers to selective transplantation of anterior or posterior layers of the cornea.
220.127.116.11 Penetrating Keratoplasty
This refers to transplantation of all the layers of the cornea.
3.4 Lamellar Keratoplasty
Lamellar keratoplasty (LK) is the partial replacement of host cornea with lamella of a healthy donor cornea [6, 7, 8]. In this, only a part of donor cornea is transplanted instead of the full-thickness graft. It can be classified into two broad categories
3.4.1 Anterior Lamellar Keratoplasty (ALK)
Indications for anterior lamellar keratoplasty (ALK)
Keratoconus, keratoglobus, pellucid marginal degeneration, Terrien’s marginal degeneration, post LASIK ectasias
Superficial corneal scar
Post-trauma, corneal ulcer, post-surgical injury, post-chemical injury
Salzmann’s nodular degeneration, spheroidal degeneration, band-shaped keratopathy
Ocular surface diseases
Stevens–Johnson syndrome, ocular cicatricial pemphigoid, chemical/thermal burns and vernal keratoconjunctivitis (VKC) with stromal opacity
Infectious keratitis where infectious process has not progressed beyond DM or descemetocele
Bacterial, fungal, or Acanthamoeba keratitis, non-perforated microsporidial, post-LASIK mycobacterial and gonococcal keratitis 
Where endothelium is healthy
Post-LASIK ectasia, persistent folds in the LASIK flap, intracorneal ring segment complications
To provide strength to the globe using corneal patch graft
Pellucid marginal degeneration and Terrien’s marginal degeneration
Peripheral corneal ulcers related to autoimmune disorders
Following dermoid and some tumor excision
ALK includes the following procedures:
18.104.22.168 Superficial Anterior Lamellar Keratoplasty
Where epithelium-basement membrane and a part of anterior stroma are replaced. Dissection depth is less than one-third or 160 μm.
22.214.171.124 Deep Anterior Lamellar Keratoplasty
126.96.36.199 Tuck-in Lamellar Keratoplasty
3.4.2 Posterior Lamellar Keratoplasty (Endothelial Keratoplasty)
188.8.131.52 Descemet’s Stripping Endothelial Keratoplasty (DSEK)
Where in Descemet’s endothelium complex along with a part of deeper stroma of variable thickness is transplanted and the graft preparation is done manually.
184.108.40.206 Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)
It is similar to DSEK, the difference being the use of a microkeratome for donor preparation.
220.127.116.11 Descemet’s Membrane Endothelial Keratoplasty (DMEK)
18.104.22.168 Pre-Descemet’s Endothelial Keratoplasty
The pre-Descemet’s layer, Descemet’s membrane, and the endothelium are transplanted.
22.214.171.124 Assisting Techniques
E-DMEK/E-PDEK and air-pump-assisted PDEK (Fig. 3.10b–d)
126.96.36.199 Hybrid Techniques
Which consists of a combination of two or more techniques, e.g., central DMEK and peripheral DSAEK.
Indications for posterior lamellar keratoplasty (PLK)
Fuchs endothelial dystrophy (FED)
Posterior polymorphous corneal dystrophy (PMCD)
Congenital hereditary endothelial dystrophy (CHED)
Iridocorneal endothelial syndrome (ICE)
Pseudophakic or aphakic bullous keratopathy
Endothelial decompensation from trauma
Post-glaucoma surgery or other intraocular surgery
Aniridia with corneal decompensation
Any corneal scar which involves the anterior corneal stroma along with endothelial involvement should not be considered for the posterior lamellar keratoplasty. In presence of high astigmatism (≥6D), EK is better avoided. In such cases, penetrating keratoplasty should be considered.
188.8.131.52 Preoperative Investigations
- (i)Visual potential assessment: Preoperative evaluation of visual potential is important before proceeding for surgery. This is important in decision making as well as explaining the prognosis to the patient.
Refraction and contact lens-corrected visual acuity: Best-corrected visual acuity with spectacles or with contact lenses often can give an idea about the visual potential. However, in presence of corneal opacity, these are not reliable.
Laser interferometer (LI): It uses the coherent white light or helium neon-generated interference stripes or fringes projected on retina through some clearer portion within the corneal opacity. The ability of the patient to identify the orientation of fringes gives an idea about the visual potential.
Potential acuity meter (PAM): PAM is a simple visual test where a tiny beam of light is directed through the patient’s pupil onto the retina. This light beam actually contains a visual acuity chart with letters for the patient to read.
- (d)Visually evoked response (VER): VER measures the electrical potential generated in response to visual stimulus. It represents the integrity of visual pathway from retina to occipital lobe, but it cannot differentiate between macula, optic nerve, and occipital lobe pathology. The amplitude and latency of the visual stimulus is recorded. Decreases in amplitude or increases in latency of stimulus suggest poor visual potential. VER is an invaluable tool in visual potential assessment of pediatric patients (Fig. 3.11).
Ocular surface evaluation: Evaluation of ocular surface is essential before LK. Tear breakup time (TBUT) and Schirmer test are usually done to assess the tear film status. A poor ocular surface or presence of dry eye predisposes to postoperative persistent epithelial defect. Hence, ocular surface must be stabilized before proceeding for LK.
Endothelial function: Specular microscopy is used for evaluation of endothelial function.
Anterior segment optical coherence tomography (ASOCT): ASOCT is a new imaging system that gives high-resolution cross-sectional images of the cornea and anterior chamber. ASOCT is an invaluable tool and provides much useful information such as corneal thickness, anterior chamber details, etc.
Ultrasonography (USG): The role of ultrasonography (USG) is important in cases where posterior segment visualization is difficult. USG can help to rule out conditions like retinal detachment, vitreous hemorrhage, or glaucomatous optic atrophy.
Pachymetry: Corneal thickness can be measured with ultrasonic pachymeter or instruments based on optical principle such as Orbscan, Pentacam, and specular microscopy. While ultrasonic method is the gold standard, Pentacam provides the most accurate values. Corneal thickness has got both diagnostic and therapeutic value. Prior to any LK, it provides the surgeon important information about the thinnest point on the cornea.
Corneal topography: Videokeratography, Orbscan, or Pentacam can be used for corneal topography. In the presence of high astigmatism, a PK may be preferred to an EK.
Confocal scanning: When severe corneal edema is present, it can give information about endothelial cells.
3.5 Penetrating Keratoplasty
Penetrating keratoplasty (PKP) is the operative procedure where full-thickness host cornea is replaced with a full-thickness donor corneal graft [5, 23, 24]. With the advent of lamellar keratoplasty, the preference for PKP has come down dramatically. However, in inexperienced hands and where the facilities for LK are lacking, PKP is still the most commonly performed procedure.
Indications for penetrating keratoplasty (ALK)
Pseudophakic corneal edema
Aphakic corneal edema
Keratoconus and corneal ectasias
Chemical injury sequelae
3.5.2 Preoperative Investigations
Preoperative indications include ocular surface evaluation, visual potential assessment, and evaluation of posterior segment as described under lamellar keratoplasty. However, more sophisticated investigations like specular microscopy, ASOCT, and confocal scanning are not routinely done.
3.5.3 Surgical Procedure
Surgical steps vary among surgeons, but three fundamental goals are mandatory in penetrating keratoplasty (1) obtain good wound alignment with minimal astigmatism, (2) avoid endothelial cell damage, and (3) avoid complications associated with vitreous upthrust . Achieving preoperative hypotony with mannitol (1 g/kg) is a must to avoid serious complications like expulsive hemorrhage.
184.108.40.206 Insertion of Lid Speculum
The lid speculum is sized and positioned to minimize pressure against the eye, either from the speculum itself or indirectly from the lids. A lateral canthotomy may be helpful to reduce pressure in case of narrow palpebral aperture.
220.127.116.11 Placement of Scleral Fixation Ring
18.104.22.168 Marking of Host Cornea
The donor graft is usually centered on the host cornea or over the pupillary axis.
22.214.171.124 Host Trephination
Sizing of the host trephine depends on several factors, including host corneal size, pathology, and risk of rejection. The host cornea is trephined using a handheld disposable trephine held perpendicular to the cornea. Minimal pressure is exerted against the cornea as the trephine is progressively rotated, allowing its sharp edges to penetrate gently to pre-Descemet’s membrane or until the anterior chamber is entered. For patients with a larger-than-average corneal horizontal diameter (limbal white-to-white measurement ≥12.5 mm), an 8.25 or 8.5 mm host trephine is often used, and for patients with a smaller-than-average corneal diameter (white-to-white measurement ≤11.5 mm), a 7.5 or 7.75 mm trephine is often used .
126.96.36.199 Trephination of Donor Cornea
The donor cornea is trephined with the endothelial side facing up using a sharp disposable blade in a Teflon block apparatus. The donor trephine is routinely sized 0.25 mm larger than the host trephine because, using current techniques, donor corneal tissue cut with a trephine from the endothelial surface measures approximately 0.25 mm less in diameter than host corneal tissue cut with the same diameter trephine from the epithelial surface.
188.8.131.52 Placement of Viscoelastic Material in the Anterior Chamber
The anterior chamber is filled with a viscoelastic. This helps maintain donor button orientation for accurate suture placement and provides inexpensive endothelial protection.
184.108.40.206 Placement of the Donor Corneal Tissue in the Host Bed
The tissue is gently grasped with fine-toothed forceps at the junction of the epithelium and stroma and transferred on to the recipient bed, where it rests on viscoelastic material.
220.127.116.11 Placement of Four Cardinal Sutures
18.104.22.168 Complete Suturing
Twelve additional radial interrupted 10/0 nylon sutures are placed snugly to ensure adequate tissue apposition. The anterior chamber is reformed with balanced salt solution as needed. A variety of suturing techniques exist: interrupted sutures only, running suture only, combined interrupted and running sutures, and double running sutures, all of which are valid approaches to wound closure (Fig. 3.13c, d).
At the end of the procedure, subconjunctival dexamethasone, 4 mg; subconjunctival gentamicin, 20 mg; and subconjunctival cefazolin, 25 mg; or another suitable antibiotic are injected. Penetrating keratoplasty may be combined with cataract surgery, secondary intraocular lens implantation, glaucoma surgery, strabismus surgery, and retinal surgery.
3.5.4 Postoperative Medications
A pressure patch and shield should be placed. Treatment of postoperative pain should be undertaken with acetaminophen and oral nonsteroidal anti-inflammatory medications and, in more severe cases, with narcotic medication . Antibiotics should be given to prevent infection. The newer generation of fluoroquinolone, moxifloxacin 0.5 %, or gatifloxacin 0.3 % is preferred. Topical steroid treatment is initiated with prednisolone acetate 1 % or prednisolone sodium phosphate 1 % drops. These are administered at a dosage of four to every hour depending upon the grade of inflammation. Prophylactic antiglaucoma medications should be given if simultaneous cataract surgery, vitrectomy, or lysis of synechiae has been done, and in cases with preoperative inflammation, glaucoma, and use of larger amounts of viscoelastic material .
22.214.171.124 Intraoperative Complications
If the trephines are inadvertently reversed and the donor button is smaller than the recipient site, it may be difficult to suture the button in place and secure a watertight wound.
Improper, eccentric placement of the trephine can result in large amounts of postoperative astigmatism and increased risk of graft rejection.
Damaged donor button
Donor corneas must be handled with extreme care to prevent damage to the endothelium.
Retained Descemet’s membrane
Retained Descemet’s membrane is often difficult to see. It should be gently picked up and identified with forceps, or trypan blue staining can delineate the retained Descemet’s membrane. Also viscoelastic placed behind retained Descemet’s membrane will elevate it from the iris and facilitate removal.
Posterior capsule tear
During combined keratoplasty and cataract extraction, the posterior capsule may be torn. Small tears without vitreous loss are usually of little significance, and careful placement of a posterior chamber intraocular lens with sulcus or in-the-bag fixation is possible. A large tear needs proper anterior vitrectomy.
Expulsive choroidal hemorrhage
The incidence of expulsive hemorrhage has been reported from 0.47 %  to 3.3 %.
126.96.36.199 Postoperative Complications
During the early postoperative period, low intraocular pressure and/or the presence of a shallow or flat anterior chamber suggests the possibility of a wound or suture track leak. Seidel’s test is useful for detecting an area of leakage. If the anterior chamber is flat and a wound or suture track leak is present, immediate surgical repair is indicated. If the anterior chamber remains formed despite the wound or suture track leak, a pressure patch may be used to re-appose the wound and seal the leak. If nonsurgical attempts fail to seal the leak after 24–48 h, surgical repair is recommended.
Persistent epithelial defectsDuring the early postoperative course of penetrating keratoplasty, re-epithelialization and the maintenance of an intact epithelium are critical for postoperative wound healing, improved visual acuity, graft transparency, graft survival, and protection of the stroma against infection and melting. Normally, it takes 5–7 days for complete re-epithelialization (Fig. 3.15a, b).Risk factors are given in Table 3.5.Table 3.5
Risk factors for persistent epithelial defect
Lid or lash abnormalities such as trichiasis, ectropion, entropion, and lagophthalmos
Ocular surface disease secondary to dry eye, alkali burn, Stevens–Johnson syndrome, ocular cicatricial pemphigoid
Decreased preoperative corneal sensation
Longer donor storage time
Increased recipient age
Systemic diseases, diabetes, chronic liver disease, malnutrition
Management: Postoperative medications should be modified to minimize epithelial toxicity. Since topical corticosteroids inhibit corneal epithelial wound healing, their use should be kept to a minimum. Preservative-free lubricants should be prescribed. Pressure patching avoids trauma from the eyelid motion over the healing surface. Bandage soft contact lenses have also been used to prevent and treat postoperative epithelial defects. If all these measures fail, a temporary tarsorrhaphy is done. Amniotic membrane transplantation is also an effective treatment modality. The possibility of active herpes virus infection must always be considered when an epithelial defect does not respond to treatment.
Filaments consist of abnormal collections of mucus and epithelial cells on the corneal surface. Patients with minimal symptoms should be treated with hypotonic artificial tears and with severe symptoms; the filaments should be carefully removed with a forceps followed by treatment with hypotonic tears and/or topical acetylcysteine, which has a mucolytic action.
- (iv)Suture-related complications
When suture knot or tip exposure occurs, suture rotation should be attempted at the slit lamp. If rotation is not possible, removal of the exposed suture should be performed as early as wound healing permits. Any suture that is broken, loose, or associated with stromal vascularization across the wound, however, should be removed immediately.
Exposed sutures are often associated with the accumulation of mucus and debris that may act as a nidus for microbial colonization. The suture must be removed and sent for culture. Broad-spectrum fortified antibiotics should be initiated until an organism is identified and antibiotic sensitivities are known. The use of topical corticosteroids should be temporarily discontinued in the early stages of treatment. During this period, systemic corticosteroids may be used in order to protect against an associated rejection episode. Once the infection is controlled, topical corticosteroids may be cautiously resumed (Fig. 3.15c).
Suture-related immune infiltrates
Suture-related immune infiltrates may also occur in the early postoperative period. The frequency of topical corticosteroids should be increased to at least every 2 h, and the addition of a corticosteroid ointment at bedtime should be considered.
The dots are found primarily in the depressed zone central to the swollen donor cornea edge. Their formation may be a nonspecific response of the epithelium to an area of tissue angulation.
Elevated intraocular pressure
The measurement of intraocular pressure in the early postoperative period is important. Pressure readings obtained by Goldmann applanation tonometry are inaccurate. The use of a pneumotonometer or an electronic tonometer is recommended.
The presence of a flat or shallow anterior chamber and a securely closed wound suggests the presence of pupillary block. Medical management includes the repeated application of mydriatic and cycloplegic agents in a vigorous attempt to dilate the pupil. Peripheral iridectomy should be performed if there is no response to medical treatment.
Postoperative inflammation can usually be controlled with topical corticosteroids. If fibrin membrane forms, hourly topical corticosteroids and mydriatics should be used to prevent the development of posterior synechiae and pupillary block. If the condition fails to improve, the use of periocular and/or systemic corticosteroids is recommended.
Although rare, it can occur if extensive synechiolysis, iridoplasty, or iridectomy has been performed. If the hemorrhage fails to clear spontaneously, irrigation/aspiration, aspiration with vitrectomy, or manual expression of the clot through a limbal incision can be done.
Fixed dilated pupilThe development of a fixed, dilated pupil following penetrating keratoplasty for keratoconus has been observed as part of a syndrome associated with iris atrophy, scattered pigment on the lens capsule and corneal endothelium, and secondary glaucoma with posterior synechia (Fig. 3.16).
Bacterial or fungal keratitis in the early postoperative period may result from contamination of donor material, incomplete excision of an infected host cornea, or acquisition of microorganisms from the environment. Graft infection usually manifests within 24–48 h with ciliary injection, graft edema, mucopurulent discharge, and occasionally an infiltrate in the graft or around a suture. Gram stain and culture with sensitivities should be performed. Broad-spectrum topical antibiotics should be initiated until culture results are obtained. Should a graft become extensively involved with infection, it should be replaced to prevent the development of endophthalmitis.
Primary donor failurePrimary donor failure results in irreversible edema of the corneal graft in the immediate postoperative period. It is due to inadequate endothelial cell function of an unhealthy donor endothelium, inadequate tissue preservation, or surgical trauma. Once a diagnosis of primary donor failure is made, regrafting may be performed as soon as the eye is no longer inflamed. Cases of suspected primary graft failure should be observed for at least 3 weeks for signs of graft clearing prior to regrafting (Fig. 3.17).
Postkeratoplasty astigmatismVisual acuity, binocular visual function, and patient satisfaction can be severely limited by postoperative astigmatism and anisometropia. Average postkeratoplasty astigmatism has been cited to be in the range of 4–6 diopters . Various factors that contribute include corneal thinning, eccentric trephination of the donor or host tissue, and failure to excise peripheral pathology in keratoconus or pellucid marginal degeneration, quality of wound healing, and the tension, length, depth, and configuration of corneal suture placement. Corneal topography provides the most useful and complete information regarding corneal shape (Fig. 3.18). Management of postkeratoplasty astigmatism includes spectacles or contact lens wear, selective suture removal, relaxing incisions, compression sutures, wedge resection, laser vision correction, and toric lens implantation. Repeat keratoplasty can be done when these measures fail.
Corneal allograft rejection
Corneal allograft rejection is the leading cause of corneal graft failure. Collaborative corneal transplantation studies (CCTS) has shown that failed graft and more than two quadrants of deep stromal vascularization are the major risk factors of graft rejection. Other risk factors include young recipient age (less than 40 years), large-diameter corneal grafts, eccentric graft, loose sutures in the graft, presence of preexisting inflammation in the eye, recent anterior segment surgery, preexisting glaucoma, and anterior synechiae.
Appreciation of the clinical features of corneal allograft rejection is critical to early recognition of rejection and is the first step toward effective therapy. Symptoms of redness of the eye, decreased vision, light sensitivity, or discomfort in the eye that lasts longer than a few hours require evaluation to exclude an episode of graft rejection.
Clinical signs of graft rejection include ciliary congestion (often the earliest sign of rejection), anterior chamber flare, anterior chamber cells, discrete subepithelial infiltrates, Krachmer’s lines, and endothelial keratic precipitates. Linear deposit of keratic precipitates on endothelium, referred to as the Khodadoust line, is the hallmark of corneal allograft rejection. Often, there is associated graft edema overlying the area that has been traversed by the advancing keratic precipitates, while the rest of the graft is clear, known as differential edema. Ultrasonic corneal pachymetry showing an isolated increase in corneal thickness can be a sign of allograft rejection. Elevated intraocular pressure or sudden onset of an epithelial defect in a previously healed corneal graft can also be manifestations of corneal allograft rejection.
Graft rejection can be three types: epithelial rejection, stromal rejection, and endothelial rejection. Endothelial rejection is the most common of the three types, with reported rates of from 8 to 37 % of cases undergoing rejection.An episode of rejection can be confused with herpes simplex keratouveitis. The clue to differentiate is the observation that the endothelial keratic precipitates in herpetic inflammation are not confined to the graft but involve as well the peripheral host endothelium. When epithelial downgrowth presents with inflammatory response, the differentiation becomes difficult. Steroid therapy will ultimately differentiate the conditions, since the epithelial downgrowth will not respond to steroid therapy. A low-grade corneal infection can masquerade as corneal allograft rejection.
Treatment of corneal allograft rejection
Fortunately, most episodes of corneal allograft rejection reaction can be reversed if therapy is initiated early and aggressively. Corticosteroid therapy by topical, periocular, or systemic administration is the treatment of choice for acute corneal allograft rejection reaction. Intravenous methylprednisolone pulse therapy [3–5 mg/kg IV push] may be considered in severe graft rejection. Immunosuppression by long-term corticosteroid therapy is associated with unacceptable ocular and systemic side effects. The immunosuppressive agents such as cyclosporine, tacrolimus, and mycophenolate mofetil can be used as steroid-sparing agent.
A corneal graft is considered failed if it fails to serve the purpose for which it was done. It may be primarily due to progressive endothelial loss, or it may be secondary to graft infection, recurrence of the disease, or repeated graft rejection episodes. Repeated graft rejection is the most common cause of graft failure. Management of graft failure is by repeat corneal graft. In cases where the graft failure is only due to endothelial failure, endothelial keratoplasty is a better alternative than a full-thickness graft.
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