Penetrating Keratoplasty for Keratoconus With and Without Resolved Corneal Hydrops: Long-term Results JAY J. MEYER, AKILESH GOKUL, ALEXANDRA Z. CRAWFORD, AND CHARLES N.J. MCGHEE PURPOSE: To evaluate the long-term risk of endothelial hydrops is frequently seen in eyes with keratoconus and rejection, graft survival, and associated factors following has been reported to occur in approximately 3% of patients penetrating keratoplasty (PK) for keratoconus, with and with this condition, but also occurs in other ectatic condi- without prior resolved corneal hydrops. tions such as pellucid marginal degeneration and keratoglo- 1,2 DESIGN: Retrospective cohort study. bus. The natural course of hydrops typically involves the METHODS: Primary outcome measures were endothelial spontaneous resolution of corneal edema over 2– rejection–free survival and failure-free survival. Secondary 4 months.3,4 Upon resolution of the edema, patients may outcome measures were corneal neovascularization have minimal to severe vision loss depending on the following hydrops and complications following PK. degree of residual scarring. RESULTS: A total of 245 eyes underwent PK for kera- Following resolution of hydrops, up to 60% of eyes may toconus with mean follow-up of 5.6 ± 3.6 years. Eyes require keratoplasty for visual rehabilitation.1 Although with prior hydrops (n [ 74) had lower endothelial rejec- penetrating keratoplasty (PK) performed for keratoconus tion–free survival rates compared with eyes without prior carries a favorable overall prognosis, endothelial graft hydrops: 86.5% ± 4.0% vs 86.5% ± 2.6% at 1 year, rejection may result in graft failure.5 Numerous studies 61.0% ± 6.2% vs 76.9% ± 3.3% at 5 years, and 45.8% have reported the long-term outcomes of PK for keratoco- ± 10.1% vs 70.9% ± 4.3% at 10 years, respectively nus and factors associated with increased risk of rejection (P [ .023). Multivariate analysis identified factors asso- and/or failure.5–19 However, only a few studies have ciated with endothelial rejection as age £25 years (P [ specifically assessed the outcomes of PK for eyes with .017), corneal neovascularization (P [ .001), donor prior resolved hydrops, with conflicting results.1,20,21 A trephination size >8mm(P [ .017), and poor clinic study by Tuft and associates1 found a higher risk of endo- attendance (P [ .015). There was no difference in the thelial rejection following PK in 87 eyes with prior failure-free survival rates with and without prior resolved hydrops, although other associated and poten- hydrops: 98.6% ± 1.3% vs 97.1% ± 1.3% at 1 year, tially confounding factors were not evaluated. Basu and 97.3% ± 1.9% vs 95.1% ± 1.9% at 5 years, and 97.3% associates20 also found a higher rate of endothelial rejec- ± 1.9% vs 92.2% ± 2.7% at 10 years, respectively tion in their study of 32 eyes with prior hydrops and (P [ .42). Corneal neovascularization was present at subanalysis identified longer duration of corneal hydrops the time of PK in 44.6% of eyes with prior hydrops and (>3 months) and ocular allergies as significant factors. 7.6% without prior hydrops (P < .001). However, Akova and associates21 did not find an CONCLUSIONS: Corneal neovascularization, a frequent increased rate of endothelial rejection in 35 eyes with complication of corneal hydrops, was associated with prior hydrops. increased risk of endothelial rejection following PK. The current study assessed the long-term outcomes of However, allograft survival was similar in eyes with and penetrating keratoplasty for keratoconus in a large series without prior hydrops. (Am J Ophthalmol 2016;169: of eyes with and without prior resolved corneal hydrops 282–289. Ó 2016 Elsevier Inc. All rights reserved.) to evaluate the long-term risk of endothelial rejection, graft survival, and associated factors. CUTE CORNEAL HYDROPS IS THE DEVELOPMENT OF marked corneal edema owing to a break in the A Descemet membrane what allows aqueous humor to enter the corneal stroma and epithelium. Corneal METHODS WE CONDUCTED A RETROSPECTIVE COHORT STUDY OF ALL Accepted for publication Jul 1, 2016. From the Department of Ophthalmology, New Zealand National Eye patients who underwent PK for keratoconus between Centre, Faculty of Medical and Health Sciences, University of January 2000 and June 2013 in the Ophthalmology Depart- Auckland, Auckland, New Zealand. ment, Greenlane Clinical Centre, Auckland, which is the Inquiries to Jay J. Meyer, Department of Ophthalmology, Private Bag 92019, University of Auckland, Auckland, New Zealand; e-mail: major tertiary center for corneal transplantation in New [email protected] Zealand. The study was approved by the University of 282 © 2016 ELSEVIER INC.ALL RIGHTS RESERVED. 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2016.07.001 Auckland Ethics Committee (#013907) and followed the required for each transplant procedure. Corneal neovascu- tenets of the Declaration of Helsinki. larization was recorded as the number of quadrants of Exclusion criteria included post-PK follow-up of less neovascularization present and the number of quadrants than 2 years, repeat PK, prior hydrops of unknown duration of neovascularization crossing the trephination. or treatment, hydrops complicated by microbial keratitis, Endothelial rejection was defined clinically as the acute PK performed for nonoptical reasons, and PK performed onset of anterior uveitis with overlying graft edema. Endo- before clinical resolution of hydrops. thelial rejection episodes were all initially treated with topical corticosteroids (prednisolone acetate 1%) every DATA COLLECTION: The medical records of all eligible hour. Patients treated with intravenous (IV) methylpred- patients were reviewed by 1 experienced clinical investi- nisolone received 500–1000 mg daily for 1–3 days. Graft gator (J.M.). Acute corneal hydrops was defined clinically failure was defined clinically as the loss of transparency as the onset of corneal edema in eyes with keratoconus for at least 3 months with associated decline in vision. with or without an identifiable break in Descemet mem- Compliance with clinic appointments was calculated as brane and without signs of an alternative diagnosis. The the number of appointments attended divided by the num- duration of hydrops was calculated as the date of onset of ber of appointments scheduled, during the first 2 years symptoms to the date of complete disappearance of corneal following PK. edema by slit-lamp examination. Atopy (nonocular) was defined as a history of asthma, ANALYSIS: The primary outcome measures were (1) atopic dermatitis/eczema, or allergic rhinitis and was self- endothelial rejection–free allograft survival and (2) reported by the patient and/or was identified by review of pa- failure-free allograft survival. The rejection-free survival tients’ nonophthalmologic electronic medical record or elec- time was calculated as the date of the PK to the date of tronic pharmacy records for medications used to treat these the first episode of endothelial rejection. Secondary ana- conditions. Ocular allergy was diagnosed based on a history lyses were degree of corneal neovascularization in eyes of symptoms of ocular itching and ocular findings of a papil- with prior hydrops and complications in all eyes following lary reaction or hyperemia of the conjunctiva, or if topical PK. medications for allergic conjunctivitis were prescribed. All statistical analyses were performed using SPSS 19.0 The treatments of episodes of hydrops were recorded, for Windows (SPSS; IBM, Chicago, Illinois, USA). Preop- including type, frequency, and duration of topical cortico- erative features were compared using the x2 test. Primary steroid, if prescribed. All episodes of acute corneal hydrops analyses involved Kaplan-Meier survival analysis to esti- were treated with topical medications at the discretion of mate the cumulative probability (reported as percentage the clinician. with standard error) of endothelial rejection–free allograft All PK procedures were performed using standard survival and failure-free allograft survival; univariate anal- techniques under general anesthesia. Donor corneas were ysis of potential risk factors for endothelial rejection, stored at 34 C in New Zealand Eye Bank organ culture me- performed using the log-rank test; and multivariate analysis dium. The donor corneal button was typically oversized by of factors with significant univariate associations, 0.25 mm and sutured using 10-0 nylon in an interrupted, performed using a Cox proportional hazards model to esti- continuous, or combined interrupted and continuous mate the relative effect of variables on allograft survival. fashion. Patients were examined 1 day, 1 week, 1 month, Secondary analyses were focused on potential risk fac- and 3 months postoperatively, and then scheduled for exam- tors for endothelial rejection specific to eyes with prior inations approximately every 3 months. All patients received hydrops only, and on risk factors for the development a topical antibiotic (chloramphenicol 0.5% or ciprofloxacin of corneal neovascularization prior to undergoing PK. 0.3%) 3–4 times daily and corticosteroid (prednisolone ace- Univariate associations were determined using the x2 tate 1%) every 1–2 hours for the first week. Thereafter, the test, log-rank test, and independent samples t test. A P corticosteroid was typically reduced to 4 times daily and value of less than .05 was considered statistically signifi- tapered by 1 drop every 3 months to 1 drop daily and was cant. continued until suture removal. Loose or broken sutures were removed upon presentation. Intact sutures were routinely removed in one sitting in the operating theatre at 18–24 months post-PK using aseptic technique, followed RESULTS by topical antibiotic coverage for 2 weeks and topical corticosteroid with g. prednisolone acetate 1% 4 times a OF THE 410 EYES THAT UNDERWENT PK FOR KERATOCONUS day for 1 month and discontinued thereafter if no previous in the study period, 245 were included in the study (74 rejection or significant risk factors for rejection. with prior hydrops, 171 without prior hydrops), with a Corneal neovascularization was recorded by the surgeon mean follow-up of 5.6 6 3.6 years.