even in patients with no known history of HSV keratitis. One study reported on the common signs and symptoms seen in their patient population with HSV keratitis recurring in the graft [1]. A geographic ulcer or nonhealing epithelial defect was seen in 57% of patients [1]. Fortythree percent of patients had a classic dendrite [1]. Of these patients with epithelial involvement, 36% had involvement of both the host and donor corneas [1]. Seventy-nine percent of patients were symptomatic at the time of diagnosis with 36% reporting pain or discomfort, 29% with visual complaints, and 14% with both discomfort and visual complaints [1].

Herpetic infection can involve not only the epithelium but also the endothelium and stroma as well [22]. Transmission electron microscopy has demonstrated viral particles in the keratocytes and endothelial cells of corneal grafts with postoperative necrotizing stromal keratitis [1].

The diagnosis of ocular HSV is usually clinical and the classiÞcation should be based on the one proposed by Holland and Schwartz [22]. Brießy, epithelial disease is infectious and related to active viral replication. Epithelial disease presents as grouped vesicles, geographic ulcers, or a classic HSV dendrite. Stromal disease can be infectious as in necrotizing stromal keratitis, or noninfectious as in immune stromal keratitis which is solely inßammatory and not related to active viral replication. Endothelial disease, or endotheliitis, is usually inßammatory as well. The diagnosis of recurrent ocular HSV after a PK must always be kept in mind because of the difÞculty in distinguishing recurrent HSV from a graft rejection episode.

Prophylactic antiviral therapy has been used to prevent the recurrence and relapse of herpetic keratitis after corneal transplantation. Systemic or topical acyclovir therapy used prophylactically over a period of 1 year has been found to effectively decrease the recurrence rate of HSV keratitis and improve the graft survival rate [23]. The dose of 400 mg given twice daily is typically prescribed. The efÞcacy of systemic and topical acyclovir as a prophylactic agent was Þrst studied for herpetic genital and labial infections where it was found to reduce the frequency and severity of recurrences of HSV infections [23]. Although acyclovir cannot prevent recurrent episodes completely, it does prolong the recurrence-free interval and reduces the duration of herpetic disease [23]. A recurrence rate of 15% has been reported in a cohort of patients taking systemic acyclovir [23]. A study compared oral acyclovir to oral valacyclovir in the prevention of recurrent

HSV keratitis and found them comparable [23]. Oral valacyclovir has a more comfortable dosing regimen.

The cornea surgeon performing cornea transplantation must be vigilant regarding the diagnosis of a possible herpetic keratitis in patients with a history of HSV keratitis as well as patients without a remarkable history of it. In patients that have a history of HSV disease, prophylactic antiviral therapy in the form of acyclovir or valacyclovir should be used for a minimum of 1 year post-PK and possibly for the patientÕs lifetime. We prefer systemic agents to topical ones in order to limit medication toxicity on the donor epithelium. Patients with a history of viral keratitis should not undergo cornea transplantation until the eye has been recurrence free for a minimum of 6 months to 1 year.

4.1.12 Treatment of Allograft Rejection

For an endothelial rejection, the patient is placed on topical prednisolone every 1 h while awake along with oral prednisone (1 mg/kg/day). This dosing regimen is maintained for 1 week and if the rejection episode has been treated successfully, the topical steroid dose is tapered very slowly to four times per day and then maintained at this dosage over a 3Ð4-month period before tapering it down to a maintenance dose of one more drop per day than what the patient had been using when the rejection episode occurred. If the patient had been on topical loteprednol (Lotemax, Bausch and Lomb) at the time of the rejection episode, a switch is made to topical prednisolone and dosed as outlined above. When the patient has demonstrated adequate resolution of the rejection episode, and following the slow taper of prednisolone, the surgeon may choose to switch the patient back to loteprednol at a higher dosing frequency than was being used prior to development of the rejection episode. Topical loteprednol has advantages over prednisolone in a phakic patient in that it has not been cited in the literature to cause cataract. Loteprednol also has an associated lower incidence of an IOP rise. Holland has demonstrated an 8% risk of an IOP increase in known steroid responders using prednisolone following cornea transplantation compared to a less than 1% increase in those known steroid responders using loteprednol [24].

For stromal involvement, treatment is the same as outlined for endothelial rejection. If an epithelial rejection line is present, without stromal or endothelial

involvement, the patient is placed on topical prednisolone every 1 h without the oral agent.

4.1.13Large Diameter Penetrating Keratoplasty

As mentioned above, the authors prefer a large diameter technique. LDPKs have been avoided by other cornea surgeons due to the concern that these grafts have a higher incidence of graft failure. Our study did not Þnd this to be true. The potential advantages of

Table 4.2 Results of LDPKs in 35 Patients

LDPK include the excision of the inciting pathology that may be located in the periphery, and reduced postoperative astigmatism.

In cases of corneal ectasia (PMD and some cases of KCN), the pathology extends in the far peripheral cornea. Smaller central grafts fail to excise the peripheral pathology and result in poor outcomes. Therefore in these cases, LDPKs may be the preferred procedure.

Retrospective chart reviews of our patients that have undergone LDPK have demonstrated superior astigmatism results with improved best corrected (BCVA) and UCVA postoperatively. The preoperative average BCVA was 20/100 (range 20/25 Ð HM, Table 4.2), and

the postoperative BCVA was 20/32 (range 20/20 to 20/125, Fig. 4.11). Postoperatively, 43% of patients had 20/40 or better UCVA (Fig. 4.12). Average postoperative manifest cylinder was + 2.19D (range 0 to +4.75D, Fig. 4.13) with 77% of patients having less than + 3.00D of cylinder. Our results did not indicate a higher rate of graft failure (Fig. 4.14)

4.1.14 Summary

Proper patient education and follow through preand postoperatively is important to maintaining a healthy transplant. Patients must be instructed to call with any of the warning signs of a graft rejection. These include redness, irritation or pain, decreased vision, and

Fig. 4.11 Preoperative best corrected visual acuities of patients that underwent LDPK

Fig. 4.12 Postoperative UCVA following LDPK

Preoperative BCVA

20%

Final UCVA

MRx Cylinder

Fig. 4.13 Postoperative manifest cylinder following LDPK

Fig. 4.14 LDPK with partial suture removal. Photo courtesy of Edward J. Holland

sensitivity to light. Patients must also be informed of the importance in medication use as prescribed and in keeping all follow-up visits. As mentioned, these discussions should be made preoperatively so that proper decision can be made by both the surgeon and the patient on whether to proceed with cornea transplantation. Cornea transplantation can be a very rewarding procedure if the surgeon and the patient are meticulous with respect to follow-up care and medication use. With practice, a good cornea transplant surgeon can obtain great visual results improving the quality of their patientÕs vision, as well as the quality of their lives [25].

References

1.Krachmer JH, Mannis MJ, Holland EJ (2005) Cornea. Elsevier Mosby, Philadelphia

2.Carones F, Vigo L, Scandola E et al (2002) Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after photorefractive keratectomy. J Cataract Refract Surg 28:2088Ð2095

3.Panda A, Vanathi M, Kumar A et al (2007) Corneal graft rejection. Surv of Ophthalmol 52:375Ð396

4.Javadi M, Naderi M, Zare M et al (2006) Comparison of the effect of three suturing techniques on postkeratoplasty astigmatism in keratoconus. Cornea 25:1029Ð1033

5.Dada T, Aggarwal A, Vanathi M et al (2008) Post-penetrating keratoplasty glaucoma. Indian J Ophthalmol 56:269Ð277

6.Raiskup-Wolf F, Hoyer A, Spoerl E et al (2008) Collagen cross-linking with riboßavin and ultraviolet-A light in keratoconus: long-term results. J Cataract Refract Surg 34: 796Ð801

7.Donnenfeld E, Kornstein H, Amin A et al (1999) Laser in situ keratomileusis for correction of myopia and astigmatism after penetrating keratoplasty. Ophthalmology 106: 1966Ð1974

8.Malecha MA, Holland EJ (2002) Correction of myopia and astigmatism after penetrating keratoplasty with laser in situ keratomileusis. Cornea 21:564Ð569

9.Niederkorn JY (2007) Immune mechanisms of corneal allograft rejection. Current Eye Res 32:1005Ð1016

10.Maumenee A (1951) The inßuence of donor-recipient sensitization on corneal grafts. Am J Ophthalmol 34:142Ð152

11.Khodadoust AA, Silverstein AM (1969) Transplantation and rejection of individual cell layers of the cornea. Invest Ophthalmol 8:180Ð195

12.CCTS Research Group (1992) The collaborative corneal transplantation studies. Arch Ophthalmol 110:1392Ð1403

13.Mader T, Stulting D (1991) The high-risk penetrating keratoplasty. Ophthalmol Clin North Am 4:411Ð422

14.Cowden J, Copeland R, Schneider M (1989) Large diameter therapeutic penetrating keratoplasties. J Refract Corneal Surg 5:244Ð248

15.Cherry PMH, Pashby RC, Tadros ML et al (1979) An analysis of corneal transplantation. Ann Ophthalmol 11:461Ð469

16.Tuberville AW, Foster CS, Wood TO (1983) The effect of donor cornea epithelium removal on the incidence of allograft rejection reactions. Ophthalmology 90:1351Ð1356

17.Settee R, Korean M, Anand D et al (2008) Intakes in advanced keratoconus. Cornea 27:1022Ð1029

18.Ghosh S, Jhanji E, Taylor H et al (2008) Acyclovir therapy in prevention of recurrent herpetic keratitis following penetrating keratoplasty. Am J Ophthalmol 145:198Ð202

19.Branco B, Gaudio P, Margolis T 2004) Epidemiology and molecular analysis of herpes simplex keratitis requiring primary penetrating keratoplasty. Br J Ophthalmol 88: 1285Ð1288

20.Reinhardt T, Kalgan C, Cetin A (1997) The inßuence of glaucoma history on graft survival after penetrating keratoplasty. Greases Arch Clin Exp Ophthalmol 235:553Ð557

21.Borderie V, Meritet J, Chaumeil C et al (2004) Cultureproven herpetic keratitis after penetrating keratoplasty in patients with no previous history of herpes disease. Cornea 23:118Ð124

22.Holland EJ, Schwartz GS (1999) Herpes simplex virus keratitis classiÞcation and treatment. Clinical Signs Ophthalmol 14:1Ð19

23.Goldblum D, Bachmann C, Tappeiner C et al (2008) Comparison of oral antiviral therapy with valacyclovir or acyclovir after penetrating keratoplasty for herpetic keratitis. Br J Ophthalmol 92:1201Ð1205

24.Holland EJ (2003) In post-keratoplasty patients: a safer alternative to prednisolone? Data on Þle, Bausch & Lomb pharmaceuticals

4.2Descemet’s Stripping Endothelial Keratoplasty

4.2.1 Introduction

Endothelial cornea dysfunction has previously been treated with full thickness cornea transplantation. Fuchs endothelial dystrophy, pseudophakic bullous and aphakic bullous keratopathy are conditions that are the results of endothelial dysfunction.

Pseudophakic bullous keratopathy remains the leading indication for keratoplasty [1, 2]. Fuchs endothelial dystrophy is a very common indication for cornea transplant as well, with an incidence falling just behind regraft and keratoconus [1]. Fuchs endothelial dystrophy demonstrates clinical signs that range from asymptomatic cornea guttata to a decompensated cornea with stromal edema, subepithelial Þbrosis, and epithelial bullae. Onset of the condition is typically after the age of 50 and there is a female preponderance. Some cases may be sporadic but others demonstrate autosomal dominant transmission [3].

Histopathological analysis of excised corneal buttons of patients with clinically diagnosed Fuchs dystrophy demonstrates thickening of DescemetÕs membrane, multiple guttata of varying size and shape, and attenuation of the corneal endothelium [4]. Guttata are focal excrescences of altered basement membrane material synthesized by abnormal endothelial cells [5]. The histopathological changes are noted in the central cornea and underlay areas of clinical edema. The peripheral cornea is usually clear clinically and shows little histologic change [4].

Clinically, Fuchs dystrophy progresses slowly over a period of 20 or more years with the patient Þrst developing asymptomatic cornea guttata and later developing corneal edema with decreased vision and pain [6]. Symptoms usually do not appear until middle age but some pathologic studies have suggested abnormalities in endothelial function occurring early in life [6].

Traditionally, PK was the only surgical procedure available for the correction of endothelial dysfunction. Full-thickness keratoplasty for endothelial dysfunction is complicated by the same issues that complicate PK. High astigmatism, suture-related problems, and ineffective wound healing are some of these [7]. When only the posterior layers of the cornea are diseased, it