Figure 15-7 Infectious crystalline keratopathy after PK.

Late nonimmune 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. Alternatively, progressive loss of endothelial cells could occur secondary to a poorly placed anterior chamber lens, which may cause endothelial damage; this warrants removal of the IOL. Tube shunts have also been associated with nonimmune graft failure.

Control of Postoperative Corneal Astigmatism and Refractive Error

A corneal transplant was once considered successful merely if the graft remained clear. However, today success also depends on the refractive outcome. Severe astigmatism may be associated with decreased visual acuity, anisometropia, aniseikonia, image distortion, and monocular diplopia, rendering an otherwise successful operation ineffective. Many methods have been used to reduce astigmatism, including

variation of suture techniques

intraoperative adjustments with qualitative keratometry

improvement of trephines and use of new technology, such as the femtosecond laser, to better match donor and host

selective suture removal or adjustment of the continuous suture using computerized

videokeratography and wavefront analysis for postoperative management

The primary method of minimizing astigmatism postoperatively is to readjust or remove the sutures. If a single continuous suture technique has been used, the surgeon may redistribute the suture tension at 1 month postoperatively using corneal topography as a guide. Alternatively, if there is a combination of continuous and interrupted sutures, the interrupted sutures can be removed starting at 1 month. If the patient has only interrupted sutures, suture removal should begin at a later stage to avoid wound slippage or dehiscence. Clinicians must be especially careful with older patients placed on long-term topical corticosteroid therapy, as the wound healing is often slower in these patients.

Prior to removal of the sutures, the most critical step is to identify the steep axis using corneal topography, handheld keratoscopy, photokeratoscopy, or manual keratometry. For example, in Figure 15-8 the simulated keratometry readings show the steep axis of 49.93 at 11 and the flat axis of 44.06 at 101. The photokeratoscopy shows clear rings that are ovalized, with the shorter axis horizontally corresponding to the steep axis. The presence of distinct rings demonstrates the smooth surface indicative of regular astigmatism. When the rings are very irregular or indistinct, it may indicate irregular astigmatism, and in that case suture removal is not recommended until clear and stable measurements can be obtained.

Figure 15-8 Corneal topography with a Nidek OPD showing astigmatism after corneal transplantation. (Courtesy of Robert W.

Weisenthal, MD.)

Manifest refraction is helpful to confirm the steep axis (plus cylinder). The autorefraction in Figure 15-8 is –9.00 +6.75 at 4°. The manifest refraction is –7.00 +5.00 at 4°, providing 20/25 acuity; the good visual acuity confirms the presence of regular astigmatism. Removing the interrupted sutures at the 4° meridian or adjusting the continuous suture will compensate for the induced astigmatism. After manipulation or removal of the sutures, the patient is placed on a topical antibiotic

for 4 days and scheduled for a follow-up visit in 1 month for repeated corneal topography and manifest refraction.

Relaxing incisions are used to reduce astigmatism if a large amount of residual astigmatism is present after all sutures have been removed. Incisions are placed either in the donor cornea anterior to the graft–host junction or in the graft–host interface at the steep (plus cylinder) meridian in an arcuate manner, for maximum effect (astigmatic keratotomy). The effect can be augmented by suture placement at the flat meridian. LASIK, photorefractive astigmatic keratectomy, and femtosecond laser–assisted astigmatic keratoplasty have also been used to manage astigmatism (see BCSC Section 13, Refractive Surgery).

All of these procedures are associated with the potential for microperforation and macroperforation, infection, rejection, undercorrections and overcorrections, chronic epithelial defects, and worsening of irregular astigmatism.

If the patient has a visually significant cataract associated with anisometropia following PK, cataract extraction with appropriate IOL power selection will reduce the asymmetry in refraction. If the patient has significant regular, stable astigmatism and a healthy endothelial cell count, a toric IOL is an excellent option. However, if the endothelial cell count is borderline (creating a risk for future graft failure), it may be better to implant a nontoric IOL. If the patient has intolerable anisometropia or significant astigmatism and a clear lens, a contact lens is helpful; in some cases, the surgeon may elect to place a phakic IOL.

Diagnosis and Management of Graft Rejection

Corneal allograft rejection rarely occurs within the first month, and it may occur as late as 20 years after PK. Fortunately, most episodes of graft rejection do not cause irreversible graft failure if recognized early and treated aggressively with corticosteroids. Corneal transplant rejection takes 4 clinical forms, which may occur either singly or in combination. (See Chapter 6 for further discussion on the immunology of graft rejection.)

Forms of corneal transplant rejection

Epithelial rejection The immune response may be directed entirely at the donor epithelium (Fig 15-9). Lymphocytes cause an elevated, linear epithelial ridge that advances centripetally. Because host cells replace lost donor epithelium, this form of rejection is problematic only in that it may herald the onset of endothelial rejection. Epithelial rejection has been reported at a rate of 10% of patients experiencing rejection; it is usually seen early in the postoperative period (1–13 months).

Figure 15-9 An epithelial rejection line (arrow) with subepithelial infiltrates (arrowhead) after PK. (Courtesy of Robert W. Weisenthal,

MD.)

Subepithelial rejection Corneal transplant rejection may also present as subepithelial infiltrates (Fig 15-10). Alone, they may cause no symptoms. It is not known whether these lymphocytic cells are directed at donor keratocytes or at donor epithelial cells. 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 light. They resemble infiltrates of adenoviral keratitis. Subepithelial graft rejection leaves no sequelae if treated, but it may presage the more severe endothelial graft rejection.

Figure 15-10 Corneal graft rejection manifested by subepithelial infiltrates. (Courtesy of Charles S. Bouchard, MD.)

Stromal rejection Isolated stromal rejection is not common but may present as stromal infiltrates, neovascularization, or typically noninfiltrative keratolysis within the graft–host interface not extending into the peripheral recipient stroma. In very aggressive severe or prolonged bouts of graft rejection, the stroma can become necrotic.

Endothelial rejection The most common form of graft rejection is endothelial rejection, with reported rates of 8%–37%. It is also the most serious form of corneal transplant rejection, because loss of a significant number of endothelial cells leads to graft failure. Inflammatory precipitates are seen on the endothelial surface in fine precipitates, in random clumps, or in linear form under an area of corneal edema (Khodadoust line; Fig 15-11). Inflammatory cells are usually seen in the anterior chamber as well. As endothelial function is lost, the corneal stroma thickens and the epithelium becomes edematous. Patients have symptoms related to inflammation and corneal edema, such as photophobia, redness, irritation, halos around lights, and fogginess of vision.

Figure 15-11 Corneal endothelial graft rejection with stromal and epithelial edema. Note the Khodadoust line (arrow). (Courtesy

of Robert W. Weisenthal, MD.)

Treatment

Frequent administration of corticosteroid eyedrops is the mainstay of therapy for corneal allograft rejection. Either dexamethasone 0.1% or prednisolone 1.0% 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, with less frequency in dosage; however, close follow-up to monitor for increased IOP is recommended. Although topical corticosteroid ointment may be used on occasion, the bioavailability of topical ointment is not as beneficial as that of frequently applied eyedrops.

Corticosteroids may be given by periocular injection (triamcinolone acetonide 40 mg) for severe rejection episodes or noncompliant patients. In particularly fulminant cases, systemic corticosteroids may be administered either orally (40–60 mg per day, tapered as the graft rejection responds) or intravenously (a 1-time dose of 125–500 mg methylprednisolone).

Prevention

Attention to surgical techniques to avoid the peripheral cornea and early attention to loosening sutures and infections will minimize rejection. Long-term use of topical corticosteroids or immunosuppressive agents such as cyclosporine may reduce episodes of rejection as well. In highrisk cases, the use of various immunosuppressive agents, including oral cyclosporine, tacrolimus, and mycophenolate mofetil has been reported, but these require very careful follow-up because of the narrow therapeutic index of these medications. Topical tacrolimus has also been advocated for use in