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  • 2020–2021 BCSC Basic and Clinical Science Course™

    Go to Academy Store Learn more and Purchase.

    8 External Disease and Cornea

    Chapter 15: Clinical Approach to Corneal Transplantation

    Penetrating Keratoplasty

    Postoperative Care and Complications

    The long-term success of a PK depends on appropriate postoperative management and conscientious patient adherence. Routine postsurgical care includes short-term use of topical antibiotics and a prolonged, perhaps indefinite, course of topical steroids (prednisolone, difluprednate ophthalmic emulsion 0.05%, fluorometholone 0.25% or 0.1%). (See “Prevention of graft rejection,” later in the chapter.) Frequent office visits are necessary to facilitate rapid vision rehabilitation and early recognition of the many complications that can occur after PK. The following sections review some common postsurgical complications.

    Section 3, Penetrating Keratoplasty: Postoperative Management. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 2. 4th ed. Philadelphia: Elsevier; 2017:1289–1354.

    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.)

    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 occurs in a minority of patients experiencing rejection and is usually seen early in the postoperative period (1–13 months). It may be asymptomatic; however, blurred vision can occur if the epithelial ridge is near the visual axis.

    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.)

    Stromal rejection

    Isolated stromal rejection is not common after PK; it is seen more commonly after DALK. It may present as stromal infiltrates, neovascularization, or, typically, noninfiltrative keratolysis within the graft–host interface that does not extend into the peripheral recipient stroma. In severe or prolonged episodes of graft rejection, the stroma can become necrotic.

    Endothelial rejection

    The most common and serious form of graft rejection is endothelial 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 underlying or in some cases outlining the area of corneal edema (Khodadoust line; Fig 15-11). Inflammatory cells are usually seen in the anterior chamber as well, but anterior uveitis is usually mild. As endothelial function is lost, the corneal stroma thickens with the development of posterior folds, and microcystic or bullous epithelial edema can occur. Patients have symptoms related to inflammation and corneal edema, such as photophobia, redness, irritation, halos around lights, or fogginess of vision.

    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).

    Prevention of graft rejection

    Surgical techniques that avoid proximity to the peripheral cornea and early attention to loosening sutures and infections will minimize the risk of rejection.

    According to a survey of members of the Cornea Society conducted in 2011, prednisolone is the topical steroid of choice for prophylaxis against graft rejection; however, some surgeons prefer dexamethasone instead. In low-risk cases, the dosage is typically 4 times per day for at least 3 months; it is then tapered by 1 drop either each month or every 2 months until it has been reduced to once per day. Notably, 13% of respondents reported using difluprednate in high-risk eyes for the first 6 months. In patients with a steroid response causing ocular hypertension, respondents reported substituting loteprednol etabonate ophthalmic suspension or fluorometholone. The phakic patient may be tapered off steroids or maintained on one of low-concentration to minimize the risk of cataract. The pseudophakic patient is typically kept on a once-daily steroid regimen. Patients using steroids should continue to be followed for IOP elevation, which can occur many months or even years after treatment.

    Long-term immunosuppressive agents such as topical cyclosporine have been used to prevent graft rejection, but in general, cyclosporine is not as effective as topical steroids. In high-risk cases, the use of various immunosuppressive agents, including oral cyclosporine, tacrolimus, and mycophenolate mofetil, has been reported, but these medications require very careful follow-up because of their narrow therapeutic index. Topical tacrolimus has also been advocated for use in high-risk patients.

    Kharod-Dholakia B, Randleman JB, Bromley JG, Stulting RD. Prevention and treatment of corneal graft rejection: current practice patterns of the Cornea Society (2011). Cornea. 2015; 34(6):609–614.

    Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.

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    2022-2023 Basic and Clinical Science Course, Residency Print Set
    2022-2023 Basic and Clinical Science Course, Residency eBook Set
    2022-2023 Basic and Clinical Science Course Complete Set
    2022-2023 Basic and Clinical Science Course Residency Set
    2022-2023 Basic and Clinical Science Course, Section 01: Update on General Medicine
    2022-2023 Basic and Clinical Science Course, Section 02: Fundamentals and Principles of Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 03: Clinical Optics and Vision Rehabilitation
    2022-2023 Basic and Clinical Science Course, Section 04: Ophthalmic Pathology and Intraocular Tumors
    2022-2023 Basic and Clinical Science Course, Section 05: Neuro-Ophthalmology
    2022-2023 Basic and Clinical Science Course, Section 06: Pediatric Ophthalmology and Strabismus
    2022-2023 Basic and Clinical Science Course, Section 07: Oculofacial Plastic and Orbital Surgery
    2022-2023 Basic and Clinical Science Course, Section 08: External Disease and Cornea
    2022-2023 Basic and Clinical Science Course, Section 09: Uveitis and Ocular Inflammation
    2022-2023 Basic and Clinical Science Course, Section 10: Glaucoma
    2022-2023 Basic and Clinical Science Course, Section 11: Lens and Cataract
    2022-2023 Basic and Clinical Science Course, Section 12: Retina and Vitreous
    2022-2023 Basic and Clinical Science Course, Section 13: Refractive Surgery
    The Technician Point System: How to Improve Practice Accountability and Bottom Line (Free Member Webinar)
    Transitioning Your Practice: Retiring, Selling or Buying a Practice (Free Member Webinar)
    2022 IRIS Registry (Intelligent Research in Sight) Preparation Kit
    Advances in Medical and Surgical Management: The 2022 Update on Glaucoma
    Presbyopia-Correcting IOLs
    2022 Codequest - Multistate (Recorded March 29)
    2022 Codequest Virtual (Multistate)
    Retina Patient Education Video Collection
    Cataract and Refractive Surgery Patient Education Video Collection
    Glaucoma Patient Education Video Collection
 
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