CLINICAL SCIENCE
Long-term Outcomes of Penetrating Keratoplasty for Keratoconus With Resolved Corneal Hydrops
Sayan Basu, MBBS, MS,* Jagadesh C. Reddy, MBBS, MS,* Pravin K. Vaddavalli, MBBS, MS,* Geeta K. Vemuganti, MD,† and Virender S. Sangwan, MBBS, MS*
cute corneal hydrops develops when sudden spontaneous Purpose: To address the controversial issue of whether the Arupture of the Descemet membrane (DM) leads to bullous occurrence of corneal hydrops adversely affects the fate of sub- corneal edema, in eyes with progressive keratectasia.1 It is sequent penetrating keratoplasty (PK), this study compared the long- a rare complication of keratoconus affecting only 2% to term outcomes of PK in keratoconic eyes with resolved corneal 3% of cases and is associated with severe ocular allergy.2,3 hydrops with those without prior corneal hydrops. Resolution is spontaneous and 31% to 63% of patients 2,3 Methods: This was a retrospective chart review of 102 eyes of 102 recover useful vision with contact lenses. However, poor patients with keratoconus who underwent PK. The primary outcome vision because of central corneal scarring or contact lens – intolerance necessitates a penetrating keratoplasty (PK) in measure was endothelial rejection free allograft survival and the 2–4 secondary outcomes were vision, postoperative complications, and 20% to 59% of patients. histopathologic findings of corneal buttons obtained during PK. Among the numerous studies that have reported the long-term outcomes of PK in keratoconus,5–18 only two pre- Results: The mean follow-up after PK was 5.5 ± 3.3 years. The vious studies have explored the association between corneal Kaplan–Meier endothelial rejection–free allograft survival at 1 and hydrops and allograft rejection/survival but with conflicting 5 years post-PK were 93.7% ± 4% and 82.6% ± 7%, respectively, in results.3,4 Although Tuft et al3 noted that eyes with resolved 32 eyes with hydrops and 100% and 98% ± 2%, respectively, in hydrops had significantly higher chances of endothelial 70 eyes without hydrops (P = 0.04). Multivariate analysis showed rejection episodes compared with those without hydrops that the risk of endothelial rejection episodes was greater in eyes (20% vs. 5%; P = 0.02), Akova et al4 noted fewer allograft with longer duration of corneal hydrops (P = 0.019) and coexistent rejection episodes in the hydrops group (6% vs. 11%; ocular allergy (P = 0.012). All rejection episodes were reversed P = 0.7). Tuft et al3 postulated that rejection episodes may medically and only 1 allograft failed because of postoperative be more common after hydrops because of the associated endophthalmitis. More than 90% of eyes achieved a visual acuity ocular allergy and/or vascularization; however, this associa- of better than 20/40. Common postoperative complications were tion was not tested statistically. To address this controversial cataract and graft infiltrate. Histopathology in cases of resolved issue, in this large case series, we compared the long-term hydrops after intracameral gas showed unique compression artifacts clinical outcomes of PK in keratoconic eyes with resolved like folding and burial of the broken ends of Descemet membrane corneal hydrops with those without prior corneal hydrops. in the stroma. Conclusions: Although endothelial rejection episodes are more METHODS common in eyes with resolved corneal hydrops, long-term allograft Patient Selection survival and visual results after PK in eyes with keratoconus are This study followed the tenets of the Declaration of excellent, irrespective of prior corneal hydrops. Helsinki and was approved by the Ethics Committee of the Key Words: acute corneal hydrops, keratoconus, penetrating L V Prasad Eye Institute, Hyderabad, India. This was keratoplasty, allograft rejection, allograft survival, histopathology a retrospective interventional study of patients with clinically diagnosed keratoconus who underwent corneal transplanta- (Cornea 2012;31:615–620) tion between January 1995 and December 2009. Exclusion criteria were cases in which (1) the treatment and/or duration of corneal hydrops could not be reliably ascertained, (2) lamellar keratoplasty was performed, (3) PK was performed Received for publication January 10, 2011; revision received July 10, 2011; for nonoptical indications, (4) PK was performed before accepted August 4, 2011. complete clinical resolution of corneal hydrops, and (5) From the *Cornea and Anterior Segment Service; and †Ocular Pathology post-PK follow-up was less than 1 year. Laboratory, L V Prasad Eye Institute, Hyderabad, India. Supported by the Hyderabad Eye Research Foundation. The authors state that they have no financial or conflicts of interest to disclose. Data Collection Reprints: Sayan Basu, Cornea and Anterior Segment Service, L V Prasad Eye Institute, Kallam Anji Reddy Campus, Rd No.2, Banjara Hills, All patients underwent a comprehensive ophthalmic Hyderabad, India (e-mail: [email protected]). examination at each follow-up visit. The medical records of Copyright © 2012 by Lippincott Williams & Wilkins the eligible patients were reviewed by 1 examiner (S.B.), and
Cornea Volume 31, Number 6, June 2012 www.corneajrnl.com | 615 Basu et al Cornea Volume 31, Number 6, June 2012 the relevant demographic and clinical data were collected yearly from 1 to 5 years and 10 years postoperatively. All other in predesigned spreadsheets. Acute corneal hydrops was de- postoperative complications after PK were also noted. fined clinically as sudden onset of bullous corneal edema in eyes with keratoconus with or without an identifiable break in Statistical Analysis the DM on slit-lamp examination. Duration of corneal hydrops All statistical analysis was performed using MedCalc was calculated from the date of onset of symptoms to the date version 11.3 for Windows (MedCalc Software, Mariakerke, of complete disappearance of corneal edema on slit-lamp Belgium). Means with SDs were reported for all normally examination. Associated ocular allergy was diagnosed based distributed continuous variables. Preoperative features, post- on symptoms of itching and/or eye rubbing along with clinical operative vision, and complications were compared using the signs of papillary reaction on the tarsal and/or limbal conjunc- x2 – fi test (Yates corrected). Kaplan Meier survival analysis was tiva. An endothelial rejection episode was de ned clinically as performed to estimate the cumulative probability (reported as the acute onset of anterior uveitis with keratic precipitates on the percentage with standard error) of endothelial rejection–free graft endothelium and overlying graft edema. allograft survival. Univariate (log rank test) analysis was done to identify the variables associated with allograft survival, Interventions which were subsequently fitted in a multivariate (Cox During acute corneal hydrops, all patients received proportional hazard) model to estimate their relative effect tapering doses of topical steroid (prednisolone acetate on allograft survival (after checking all the assumptions and 1%), lubricant (carboxymethyl cellulose sodium 0.5%), interactions of the model). A P value of less than 0.05 was hyperosmotic (sodium chloride 5%), and cycloplegic considered to be statistically significant. (homatropine hydrobromide 2%) eye drops until the clinical resolution of corneal edema. Some patients also received a single intracameral injection of 14% perfluor- RESULTS 2 opropane (C3F8)gas. AstandardPKprocedurewasper- Demographic and Baseline Data formed for all patients, under local or general anesthesia, Of the 442 eyes of 398 patients who underwent using donor corneas stored in McCarey Kaufman medium, corneal transplantation for keratoconus in the study period, with a 0.25 to 0.5 mm over sizing of the donor corneal 102 eyes of 102 patients were included in the study (255 eyes button and 10-0 nylon interrupted suturing. All patients with inadequate post-PK follow-up, 66 eyes undergoing were seen again on day 1, day 7, and day 30 postopera- anterior lamellar keratoplasty, 12 eyes treated elsewhere for tively. Subsequent follow-up and selective suture removal hydrops, 5 eyes operated before resolution of hydrops, and were performed according to the discretion of the treating 2 eyes undergoing therapeutic PK were excluded). The age ophthalmologist. All patients received topical steroid of the patients at PK was 20.4 ± 9.5 years. In the 32 patients fl (prednisolone acetate 1%) and antibiotic (cipro oxacin with corneal hydrops, the age at acute hydrops was 19.6 ± 0.3%) eye drops for 1 week postoperatively after which 9.3 years, duration of corneal hydrops was 4.3 ±2.6 months the antibiotic was discontinued and the steroids were (2.25 ± 1.5 months in 8 C3F8-treated eyes and 4.1 ± tapered gradually. After the initial 3 to 6 months, most 1.6 months in other 24 eyes), and the duration between patients were maintained on a once daily or twice daily resolution of hydrops and PK was 11.2 ± 7.2 months. Table 1 dosing of steroid eye drops. In the event of an endothelial shows that at the time of PK, eyes with hydrops had rejection episode, the topical steroid dosage was inten- asignificantly higher association with ocular allergy than fi si ed, starting from every 1 hourly, and tapered according others (P , 0.0001). to the response. Systemic steroids were not administered for endothelial rejection episodes. Primary Outcome The Kaplan–Meier endothelial rejection–free allograft Histopathology Findings survival rates were 98% ± 1% at 1 year, 92.9% ± 3% at The corneal buttons of all 102 cases were retrieved 5 years, and 87.3% ± 5% at 10 years (Fig. 1A). The endo- from the Ophthalmic Pathology Laboratory. The hematoxylin thelial rejection–free allograft survival rates at 1, 5, and – and eosin and periodic acid-Schiff stained sections of 10 years postoperatively were 93.7% ± 4% and 82.6% ± fi fi formalin- xed paraf n-embedded tissues were reviewed by 7%, respectively, in 32 eyes with hydrops and 100%, 98% 2 observers (G.K.V. and S.B.) and evaluated with special ± 2%, and 90.1% ± 6%, respectively, in 70 eyes without attention to the appearance of DM and endothelium. hydrops (P = 0.04; Fig. 1B). An endothelial rejection episode occurred in 7 eyes (6.8%), all of which were reversed with Outcome Measure intensive topical medication. None of the eyes had epithelial The primary outcome measure was endothelial rejection– or stromal rejection episodes. Allograft failure occurred in 1 free allograft survival. The survival time was calculated in eye after acute postoperative endophthalmitis with graft melt- months from the date of PK to the date the patient developed ing. On univariate analysis, occurrence of hydrops, duration the first episode of endothelial rejection or failure (clinically of hydrops (.3 months), coexistent ocular allergy, and cor- defined as the loss of transparency of the central cornea for at neal vascularization were found to be significantly associated least 3 months). The secondary outcome measure was best- with endothelial rejection–free allograft survival (Table 2). corrected visual acuity (BCVA), assessed at 6 time points: Multivariate analysis showed a significantly higher risk of
616 | www.corneajrnl.com 2012 Lippincott Williams & Wilkins Cornea Volume 31, Number 6, June 2012 PK for Resolved Corneal Hydrops
TABLE 1. Baseline Demographic Characteristics of Eyes That Underwent PK for Keratoconus Characteristics Total, n (%) Hydrops, n (%) No Hydrops, n (%) P Gender 102 32 70 0.67 Male 72 (70.6) 24 (75) 48 (68.6) Female 30 (29.4) 8 (25) 22 (31.4) Age at PK, yr 102 32 70 0.1 #16 47 (46.1) 19 (59.4) 28 (40) .16 55 (53.9) 13 (40.6) 42 (60) Laterality of operated eye 102 32 70 0.5 Right 54 (52.9) 15 (46.9) 39 (55.7) Left 48 (47.1) 17 (53.1) 31 (44.3) Active ocular allergy 102 32 70 ,0.0001 Present 17 (16.7) 13 (40.6) 4 (5.7) VKC 15 (14.7) 12 (37.5) 3 (4.3) Others 2 (1.9) 1(3.1) 1 (1.4) Absent 85 (83.3) 19 (59.4) 66 (94.3) Corneal vascularization 102 32 70 0.12 Present 21 (20.6) 10 (31.3) 11 (15.7) Superficial 20 (19.6) 9 (28.1) 11 (15.7) Deep 1 (0.9) 1 (3.2) 0 (0) Absent 81 (79.4) 22 (68.7) 59 (84.3) Indication for PK 102 32 70 0.14 Poor CL corrected vision 47 (46.1) 21 (65.6) 29 (41.4) CL intolerance 44 (43.1) 9 (28.1) 32 (45.7) Poor CL fitting 11 (10.8) 2 (6.3) 9 (12.9) Donor trephine size, mm 102 32 70 0.56 #8 42 (41.2) 15 (46.9) 27 (38.6) .8 60 (58.8) 17 (53.1) 43 (61.4) Donor ECD, cells/mm2 102 32 70 0.17 2150–2499 17 (16.7) 2 (6.3) 15 (21.4) 2500–3000 65 (63.7) 25 (78.1) 40 (57.1) .3000 20 (19.6) 5 (16.6) 15 (21.4)
CL, contact lens; ECD, endothelial cell density; VKC, vernal keratoconjunctivitis. Values in bold indicate statistically significant results. endothelial rejection episodes in eyes with longer duration of ceftazidime (2.25 mg) and vancomycin (1 g). The vitreous on corneal hydrops (hazard ratio, 6.1; 95% confidence intervals, culture showed significant growth of Streptococcus pneumo- 1.4–27.4; P = 0.019) and coexistent ocular allergy (hazard niae. One year postoperatively, the patient had a clear graft ratio 8.5; 95% confidence intervals, 1.6–45.3; P = 0.012). with BCVA of 20/40. Loose sutures were seen in 16 eyes (15.7%), all within 12 months of PK. Five of these eyes fi Secondary Outcome (4.9%) developed peripheral graft in ltrates caused by The visual outcomes after PK are provided in Table 3. coagulase-negative Staphylococcus species. Complete resolu- At all follow-up visits, more than 90% of patients had BCVA tion of infection and scarring was seen in all 5 eyes with intensive application of fortified cefazolin (5%) eye drops. of better than 20/40. Astigmatism was 4.3 ± 2.6 diopters (D), fi 3.4 ± 1.6 D, 3 ± 1.2 D, 2.8 ± 1.2 D, 2.6 ± 0.9 D, and 2.3 ± Visually signi cant posterior subcapsular cataract developed in 7 eyes (6.8%), and all patients underwent uneventful 0.8 D at 1 years and 2, 3, 4, 5, and 10 years, respectively. fi Corneal topography-guided selective removal of tight sutures phacoemulsi cation with posterior chamber intraocular lens was successful in treating patients with high postoperative implantation. None of the 102 eyes showed an increase in astigmatism, and no patients developed keratectasia or needed intraocular pressure or needed antiglaucoma medications additional surgical interventions. during the entire study period.
Complications Histopathology Findings One patient presented with acute postoperative endoph- All specimens showed epithelial hyperplasia, fragmen- thalmitis with graft infiltrate and melting, 5 days after PK. tation of the Bowman layer with variable scarring, and Immediate therapeutic PK with pars plana vitrectomy were thinning of the corneal stroma; these features were consistent performed along with intraocular injection of 0.1 mL each of with a clinical diagnosis of keratoconus. DM and endothelium