Primary donor failure (primary endothelial failure)

When a graft is edematous from the first postoperative day and remains so without inflammatory signs, a deficiency of donor endothelium should be suspected (Fig 15-3). Most surgeons allow at least 4 weeks and up to 2 months for spontaneous resolution of edema before considering regrafting. The cause of the donor failure is not always clear and may be related to intraoperative handling of the tissue.

Wound misalignment or leak

The wound is always checked carefully for aqueous leakage at the end of surgery. A Seidel test can be helpful in postoperatively assessing wound integrity, particularly in patients with low intraocular pressure (IOP) and a normal or shallow anterior chamber. Small wound leaks or suture track leaks without iris incarceration often close spontaneously. Patching, therapeutic contact lenses, and use of aqueous suppressants may facilitate a watertight seal. Resuturing is advised for leaks associated with shallow anterior chambers and low pressures lasting longer than 3 days.

Figure 15-3 Slit-lamp photograph of primary donor failure after penetrating keratoplasty (PK).

Flat chamber or iris incarceration in the wound

If the IOP is low and there is a flat chamber or iris incarceration in the wound, the clinician should return the patient to surgery to reposit the iris, re-form the anterior chamber, and suture the wound. If the problem is not addressed promptly and appropriately, anterior synechiae may form, increasing the risk of graft rejection, glaucoma, or graft failure. Normal or high IOP with a shallow or flat anterior chamber may signify pupillary block or malignant glaucoma (aqueous misdirection). Initially, the surgeon should dilate the pupil to help break the pupillary block; if this is not successful, other measures are required. See BCSC Section 10, Glaucoma, for discussion of pupillary block and malignant glaucoma.

Endophthalmitis

After PK, endophthalmitis may arise owing to intraoperative contamination, contamination of the donor corneal button, or postoperative invasion by microorganisms. The incidence of endophthalmitis is considerably higher in PK patients than cataract surgery patients, particularly if the vitreous is invaded or if the donor died of infection. Immunosuppressed patients with moderate to severe eyelid inflammation are also at greater risk for infection. Early recognition and aggressive intervention can save the eye and vision in some cases. Donor rim culture may identify any potential contaminants. See also BCSC Section 9, Uveitis and Ocular Inflammation.

Chen JY, Jones MN, Srinivasan S, Neal TJ, Armitage WJ, Kaye SB; NHSBT Ocular Tissue Advisory Group and Contributing Ophthalmologists (OTAG Audit Study 18). Endophthalmitis after penetrating keratoplasty. Ophthalmology. 2015;122(1):25–30.

Persistent epithelial defect

Large epithelial defects are common after PK, but they should heal within 7–14 days. After this time, irreversible scarring and ulceration may occur. Patients who have reduced corneal sensation or decreased blink rate before surgery are at greater risk. Ocular surface disease (eg, dry eye, exposure, rosacea, blepharitis) should be identified and treated. Lubrication, patching, therapeutic contact lenses, punctal occlusion with plugs or cautery, and temporary or permanent lateral tarsorrhaphy may be helpful in difficult cases. (See the discussions of neurotrophic keratopathy and persistent epithelial defects in Chapter 4 and of tarsorrhaphy in Chapter 13.) If these measures are not successful, the diagnosis of herpetic keratitis (Fig 15-4) should be considered even if this was not the underlying reason for the graft. Oral antivirals can be used as a therapeutic trial.

Elevated intraocular pressure

High IOP may occur at any time after PK. Often, the first clinical sign is the loss of folds in the Descemet membrane. IOP elevation early in the postoperative period can be due to pupillary block, malignant glaucoma, hemorrhage or pigment blocking the trabecular meshwork, or an overly tight running suture. Elevated IOP starting a month or more after the procedure may be due to response to steroids such as topical prednisolone or difluprednate ophthalmic emulsion 0.05%. If glaucoma develops, aggressive treatment with appropriate topical medications, laser surgery, or other surgical intervention is indicated. Though uncommon, epithelial downgrowth or fibrous ingrowth can also cause postoperative pressure elevation. See also BCSC Section 10, Glaucoma.

Figure 15-4 Slit-lamp photograph showing recurrence of herpes simplex keratitis in a graft.

(Courtesy of Robert W. Weisenthal, MD.)

Recurrence of primary disease

Bacterial, fungal, viral, or amebic keratitis can recur in a graft in the early postoperative period. In recurrent infections, medical treatment directed at the causative agent is the initial form of therapy (see Chapters 9 and 10). Epithelial–stromal dystrophies such as granular or lattice dystrophy can superficially recur a year or later after the initial procedure (Fig 15-5). Visually significant lesions can be removed using phototherapeutic keratectomy (PTK); see Chapter 13.

Figure 15-5 Slit-lamp photograph showing recurrence of granular corneal dystrophy after corneal transplantation.

(Courtesy of Robert W. Weisenthal, MD.)

Suture-related problems

Postoperative problems related to sutures include the following:

• excessive tightness of the sutures, producing an irregular astigmatism or elevated IOP

• loosening (usually as a result of wound contraction, suture breakage, resolution of wound edema, or suture cheese-wiring; Fig 15-6)

• breakage of a continuous suture

• infectious abscesses (usually localized around loose, broken, or exposed sutures; Fig 15-7)

• noninfectious (toxic) suture infiltrates, often multiple and in areas of pannus, or extension of sutures beyond the limbus

• giant papillary conjunctivitis from exposed knots

• vascularization along suture tracks

Figure 15-6 Slit-lamp photograph of an eroded continuous suture after PK.

(Courtesy of Robert W. Weisenthal, MD)

Figure 15-7 Slit-lamp photograph of a suture abscess in a corneal graft.

(Courtesy of Stephen Orlin, MD.)

Loose or broken sutures do not contribute to wound stability and should be removed as soon as possible. Loose sutures stain with fluorescein because they usually have broken through the corneal epithelium. Totally buried fragments of interrupted sutures may be left. Vascularization along the suture indicates that the wound is adequately healed in the vicinity and that sutures may be removed safely. Vascularized sutures are also prone to loosening and may increase the likelihood of graft rejection. After the sutures are removed, the refractive error or astigmatism may shift dramatically, so the surgeon should see the patient in 3–4 weeks to ensure wound stability and to recheck refraction. The shift may occur even years after surgery.

Microbial keratitis

Long-term use of topical steroids, loss of corneal sensation after transplantation, uneven tear film, and suture exposure or erosion all predispose the patient to infectious keratitis, sometimes caused by unusual organisms. Culture of the infiltrate and the exposed suture is recommended, and initiation of broad-spectrum antibiotic therapy can help avoid graft failure. A peculiar form of keratitis, infectious crystalline keratopathy (Fig 15-8), is occasionally seen in grafts and other immunocompromised corneas. Branching colonies of organisms proliferate in the deep corneal stroma, with minimal or no inflammatory response. Many organisms have been implicated, but viridans streptococci are the most frequent causative organisms.

Late non–immune-mediated endothelial failure

In the absence of acute inflammation or graft rejection, visually significant corneal edema months to years after the procedure may be due to the normal loss of endothelial cells in tissue that had a marginal number of endothelial cells originally. The Cornea Donor Study showed that the 10-year cumulative probability of non–immune-mediated graft failure was higher in patients treated for pseudophakic or aphakic corneal edema than in patients treated for Fuchs endothelial corneal dystrophy. The higher failure rate may be related to the placement of a poorly designed anterior chamber lens or improper placement of the lens during previous, complex cataract surgery. Such problems may require an exchange of the IOL at the time of PK. In addition, patients with a prior diagnosis of glaucoma— especially those with a history of glaucoma surgery (particularly tube shunt implantation) and, to a lesser extent, those taking glaucoma medications—face a higher probability of graft failure than do patients who have no history of glaucoma.

Figure 15-8 Slit-lamp photograph showing infectious crystalline keratopathy after PK.

(Courtesy of Stephen Orlin, MD.)

Sugar A, Gal RL, Kollman C, et al; Writing Committee for the Cornea Donor Study Research Group. Factors associated with corneal graft survival in the Cornea Donor Study. JAMA Ophthalmol. 2015;133(3):246–254.

Graft rejection

Corneal allograft rejection rarely occurs within the first month; however, it may occur many years after PK. Fortunately, most episodes of graft rejection do not cause irreversible graft failure if recognized early and treated aggressively with steroids. Corneal transplant rejection after PK occurs in 4 distinct clinical forms, which may occur either singly or in combination. (See BCSC Section 9, Uveitis and Ocular Inflammation, and Chapter 11 in this volume for further discussion on the immunology of graft rejection.)

Subepithelial rejection

Corneal transplant rejection may also present as subepithelial infiltrates (Fig 15-10). These may be asymptomatic or may cause glare or reduced vision. It is not known whether these lymphocytic cells are directed at donor keratocytes or at donor epithelial cells. In atypical cases, a cellular anterior chamber reaction may accompany this form of rejection. Easily missed on cursory examination, subepithelial infiltrates can best be seen with broad, tangential illumination. They resemble the infiltrates associated with adenoviral keratoconjunctivitis. Subepithelial graft rejection may completely resolve if treated, but it may presage the more severe endothelial graft rejection.

Figure 15-9 Slit-lamp photograph showing an epithelial rejection line (arrow) with subepithelial infiltrates (arrowhead) after PK.

(Courtesy of Robert W. Weisenthal, MD.)

Figure 15-10 Slit-lamp photograph showing corneal graft rejection manifested by subepithelial infiltrates.

(Courtesy of Charles S. Bouchard, MD.)

Treatment

Frequent administration of steroid eyedrops is the mainstay of therapy for corneal allograft rejection. Either dexamethasone 0.1% or prednisolone 1% eyedrops are used, as often as every 15 minutes to 2 hours, depending on the severity of the episode. Difluprednate ophthalmic emulsion 0.05% can also be used, in less frequent doses; however, close follow-up to monitor for increased IOP is recommended. Although topical steroid ointment may be used on occasion, the reduced bioavailability of topical ointment is not as effective as frequently applied eyedrops.

Figure 15-11 Slit-lamp photograph showing corneal endothelial graft rejection with epithelial and stromal edema. Note the Khodadoust line (arrows).

(Courtesy of Robert W. Weisenthal, MD.)

Steroids may be given by periocular injection (triamcinolone acetonide 0.5 cc of 40 mg/mL or dexamethasone 0.5 cc of 4 mg/mL) for severe rejection episodes or nonadherent patients. Caution is advised in patients who may have steroid-induced elevation of IOP or a history of herpetic keratitis. In particularly fulminant cases, steroids may be administered either orally (80 mg per day, tapered as the graft rejection responds) or intravenously (a one-time dose of 125–500 mg methylprednisolone).