Descemet stripping with automated endothelial keratoplasty: A comparative study of outcome in patients with preexisting glaucoma

Abstract

Purpose

To compare postoperative complications after Descemet stripping with automated endothelial keratoplasty (DSAEK) in patients with and without glaucoma.

Methods

For this retrospective study a series of 298 DSAEK cases performed at the Doheny Eye Institute were taken, we compared postoperative complications in eyes with glaucoma on medication (55) or with previous glaucoma surgeries (64) with a time-matched group of all other DSAEK cases (179, control).

Results

With a mean follow-up of 1.85 ± 1.12 years, the complication rates were 12.8%, 11.1%, and 26.8% for postoperative graft detachment, graft failure, and IOP elevation, respectively. Graft detachment was an independent risk factor for graft failure (odds ratio OR = 12.35, 95% confidence interval CI [5.46–27.90], P < 0.001). Graft detachment was not associated with either history of glaucoma or glaucoma surgery (P > 0.05). Glaucoma on medication had no increased risks of graft failure compared to normal eyes (P = 0.38). However, increased risk of failure was seen in eyes with prior incisional glaucoma surgeries (OR = 4.26, 95% CI [1.87–9.71], P < 0.001). Medically managed glaucoma has increased risks of postoperative IOP elevation (OR = 2.39, 95% CI [1.25–4.57], P = 0.013), whereas surgically managed glaucoma has no significant elevation (P = 0.23). Elevation of IOP was not significantly correlated with graft failure (P = 0.21).

Conclusion

DSAEK is the preferred treatment for corneal endothelial dystrophy. We observed that having glaucoma or glaucoma surgery is not associated with graft detachment. A history of glaucoma surgery and postoperative graft detachment appeared to be important risk factors for graft failure. And more studies are indicated to study long-term IOP evolution in post-DSAEK patients and its association with graft survival.

Introduction

Endothelial keratoplasty (EK) has become the preferred surgical remedy for corneal endothelial diseases, due to the remarkably expeditious visual rehabilitation and favorable complication profiles, compared to those achieved with penetrating keratoplasty (PKP).^1–6 Among the repertoire of EK procedures, Descemet stripping with automated endothelial keratoplasty (DSAEK) emerges as the procedure of choice for many corneal surgeons.⁷ Commonly reported postoperative complications of DSAEK are graft detachment (1.5–82%), iatrogenic primary graft failure (0–45%), induced glaucoma (0–15%), pupillary block (0–2%), and rarely, epithelial ingrowth and retinal detachment.^6,8–20 Most complications are related to surgical technique, and recent surgical innovations effectively reduce the incidence of complications.^{8,10,12,20–23}

Despite its immense popularity, DSAEK is still a relatively new procedure, and the effects of glaucoma or a history of glaucoma surgery on postoperative complications have not been fully investigated. The reportedly high rates of intraocular pressure (IOP) elevation after DSAEK are particularly concerning, especially when the identified risk factors include a history of ocular hypertension, preexisting glaucoma, or previous glaucoma surgery.^15,16,18 Another salient finding is the association between preexisting glaucoma or steroid-responsive ocular hypertension and the increased risk of graft rejection.¹⁹ A similar correlation between glaucoma and PKP graft failure has been reported.²⁴

Given the risks of graft rejection and development of glaucomatous optic neuropathy in DSAEK patients, it is essential to characterize surgical outcomes in these patients. Accordingly, we evaluated the incidence of graft detachment, graft failure, and IOP elevation in three groups of DSAEK patients: those with no history of glaucoma; those receiving medication(s) for glaucoma; and those with a history of glaucoma procedures. Subsequently, we compared the long-term course of IOP changes in these groups.

Methods

This retrospective study included all patients who underwent DSAEK for corneal endothelial failure at the Doheny Eye Institute; all surgeries were performed by the corneal specialists (SCY, JCS, MH). A total of 316 DSAEK cases, treated from April 2006 to August 2010, were evaluated in this study. All preoperative evaluations and DSAEK procedures were performed at the Doheny Eye Institute. The study was approved by the Institutional Review Board at the University of Southern California and was in accordance with the tenets set forth in the Declaration of Helsinki. All procedures and data management conformed to the Health Insurance Portability and Accountability Act of 1996.

Classification

Patients were classified as the medical glaucoma (MG) group if they met any of the following criteria: a documented history of glaucoma, preoperative use of ocular antihypertensive medications, or evidence of glaucomatous optic neuropathy on preoperative evaluation or on subsequent examination if the initial view was suboptimal. The presence of a narrow angle or a history of prophylactic laser iridotomy was not classified as medical glaucoma unless the aforementioned criteria were met. A history of glaucoma filtering procedure and/or glaucoma drainage device implant was the inclusion criterion for classification as surgical glaucoma (SG). The remaining patients were designated non-glaucoma (N).

IOP elevation

The study criteria for postoperative IOP elevation were IOP ⩾ 24 mmHg or a relative increase ⩾ 10 mmHg from preoperative value. The criteria were selected for consistency with prior studies.^15,25 At any subsequent visit, IOP measurements which satisfied the study criteria would be categorized as postoperative IOP elevation. The IOP measurements were obtained by either a trained ophthalmic technician or an ophthalmologist using a calibrated TonoPen® XL tonometer (Medtronics, Jacksonville, FL). Only readings with a confidence limit of 5% were used. Average of three measurements was recorded.

Graft detachment or graft failure

Terry and colleagues⁹ defined posterior graft dislocation as complete separation of the donor tissue from the recipient bed by a layer of interfacial fluid, requiring postoperative intervention. In contrast, Suh et al.¹³ described detachment as partial or complete detachment or dislocation, regardless of whether patients required postoperative surgical intervention. Since DSAEK may be more technically challenging in eyes with prior surgery, particularly glaucoma drainage device placement, we defined graft detachment to include any interfacial separation, which may or may not require postoperative surgical intervention. Similarly, we expanded graft failure to include persistent corneal edema lasting longer than 6 weeks after transplantation, including failure after dislocation or detachment, despite proper apposition of the DSAEK lenticule.

Statistical analysis

Statistical analyses were performed by GraphPad InStat version 3.05 for Windows (GraphPad Software, San Diego, CA; www.graphpad.com). Descriptive statistics were reported as mean ± standard deviation, unless otherwise stated. We defined statistical significance at P-values < 0.05. The odds ratios (OR)) of complications, 95% confidence interval (95% CI), and P values were calculated using the two-tailed Fisher exact test. We excluded patients having less than 90-day follow-up. Mean IOP values were compared using the one-way ANOVA tests because the data followed a Gaussian distribution according to the method of Kolmogorov and Smirnov.

Results

Of the 316 transplants reviewed, 18 were excluded because of inadequate follow-up (<90 days); a total of 298 were included for analysis. Mean follow-up period was 1.85 ± 1.12 years, with a range of 90–1649 days. The overall mean patient age was 74.0 ± 11.8 years (range = 28–97 years). The age breakdown for the three groups, non-glaucoma (N), medical glaucoma (MG), and surgical glaucoma (SG), was 75.3 ± 10.8, 72.4 ± 10.7, and 73.1 ± 14.8 years, respectively. Females constituted 60.7% of the overall group. The most common medical comorbidity was hypertension, followed by diabetes and arthritis. Many of our patients had ocular comorbidities that contributed to poor visual rehabilitation Table 1. The complexity of the past medical and ocular histories of our patients reflected the fact that our institute is a tertiary referral center.

Table 1.

Demographics.

Medical comorbidity	% of patients
Hypertension	45.8
Arthritis	18.3
Diabetes	17.6
Cardiac diseases	15.3
Dyslipidemia	5.0
Thyroid disease	3.8
Malignancies	3.4
Asthma	2.3
Ocular comorbidity
Glaucoma	40
Diabetic retinopathy	8.4
Age-related macular degeneration	5.7
Epiretinal membrane	3.1
Cystoid macular edema	4.6
History of retinal detachment	3.4
History of retinal vein occlusion	0.8
Band keratopathy	1.1
Giant cell arteritis	0.4
Amblyopia	1.5
Wet AMD	1.1
Past ocular surgery
Cataract extraction/intraocular lens insertion (CE/IOL) only	41.6
CE/IOL & glaucoma surgery	13.1
CE/IOL & corneal surgery	6.7
CE/IOL & vitreoretinal surgery	4.0
Corneal surgery	2.0
Vitreoretinal surgery	0.0
Glaucoma surgery	0.7
Three or more types of intraocular surgeries	8.7
Diagnosis of corneal edema
PBK	41.9
FED	22.8
FED + PBK	16.8
Failed DSEK	8.1
Failed PK	3.7
APK	1.0
Corneal decompensation	5.7

Note: Findings are for ipsilateral eye. Here, vitreoretinal surgery was defined as intraocular vitreoretinal surgery; cryocoagulation, photocoagulation, or intravitreal injections were excluded. Similarly, intraocular glaucoma surgery encompassed glaucoma drainage device implant or trabeculectomy; laser iridotomy or trabeculoplasty were excluded. DSEK: Descemet’s stripping and endothelial keratoplasty; PKP: penetrating keratoplasty; FED: Fuchs endothelial dystrophy; PBK: pseudophakic bullous keratopathy; APK: aphakic keratopathy.

229 (76.8%) had undergone prior intraocular surgery, including cataract extraction (212 or 71.1%). Accordingly, pseudophakic bullous keratopathy (PBK) accounted for a majority of the cases (125 or 41.9%), followed by Fuchs’ endothelial dystrophy (FED, 68 or 22.8%), combined FED and PBK (50 or 16.8%), and others Table 1. Forty percent of the recipients (119) had preexisting glaucoma; of those, 55 were only on medication with no prior incisional glaucoma surgery (MG group) and 64 had prior incisional glaucoma surgeries (SG group). The SG group was composed of 18 eyes with history of trabeculectomy and mitomycin C, 35 eyes with glaucoma drainage device placements, and 11 eyes with both. 179 eyes with no history of glaucoma comprised the N group.

The overall rates of complication were as follows: graft detachment (12.8%), graft failure (11.1%), and IOP elevation (26.8%). Forty eyes had graft detachment, and 40% of these detachments (18/40) progressed to develop graft failure despite refloating and/or suture placement, ultimately requiring repeat DSAEK (12) and PKP (6). Twenty grafts (20/40) remained clear after refloating and/or suture placement. Two detachments (2/40) spontaneously reattached.

As expected, graft detachment was associated with a significant risk of graft failure (OR = 12.35, 95% CI [5.46–27.90], P < 0.0001). Detachment rate was highest in patients who have had prior incisional glaucoma surgeries (18.2%), followed by patients who were only on ocular antihypertensive eyedrops (12.7%), and lowest in non-glaucoma patients (11.1%), Fig. 1. Within the SG group, 3/18 patients with prior trabeculectomy/MMC, 6/35 of patients with only glaucoma drainage device implants, and 2/11 of patients with both trabeculectomy/MMC and glaucoma drainage implant placements had detachment Fig. 1. Compared to group N, however, the association was not statistically significant (P > 0.05).

Figure 1.

Complication distribution among the normal (N), medical glaucoma (MG) and surgical glaucoma (SG).

Over this follow-up period, the overall incidence of IOP elevation in this series was 80 eyes (26.8%). Incidence of IOP elevation was highest in the MG group (22/55, 40%), followed by SG (19/64, 29.7%) and N groups (39/179, 21.8%). 12/80 (15%) of the eyes with IOP elevation developed graft failure compared to 21/221 (9.5%) with normal IOP. This correlation did not reach statistical significance (OR = 1.42, 95% CI [0.86–2.33], P = 0.21). Here, postoperative IOP elevation was associated with the MG (OR = 2.39, 95% CI [1.25–4.57], P = 0.013), but not the SG group (OR = 1.52, 95% CI [0.80–2.88], P = 0.23). We did not discern a significant correlation between IOP elevation and graft failure.

Having prior incisional glaucoma surgery appeared to increase the risks of graft failure (OR = 4.26, 95%CI [1.87–9.81], P < 0.001). Breaking down SG into subgroups suggested that having both glaucoma filtering procedure and glaucoma drainage device implant had the highest risk (OR = 5.22, P = 0.045), followed by drainage device implant only (OR = 4.82, P = 0.002); filtering procedure had non-significant risk (OR = 2.78, P = 0.14). In contrast, no increased risk of failure was observed in the MG group (P = 0.38).

Risk analysis substantiated the increased risk of graft failure in patients with a priori glaucoma. Cumulatively, DSAEK recipients with glaucoma had a higher risk of graft failure compared to those without glaucoma, (OR = 2.98, 95% CI [1.41–6.33], and P = 0.004). This risk increased further in the group SG, compared to group N with no a priori diagnosis of glaucoma (OR = 4.26, 95% CI [1.87–9.71], P < 0.001). Breaking down SG into subgroups suggested that having both glaucoma filtering procedure and glaucoma drainage device implant had the highest risk (OR = 5.22, P = 0.045), followed by drainage device implant only (OR = 4.82, P = 0.002); filtering procedure had non-significant risk (OR = 2.78, P = 0.14). In contrast, no increased risk of failure was observed in the MG group (P = 0.38).

Discussion

Descemet stripping with endothelial keratoplasty has become the surgical modality of choice for management of endothelial disorders because of its excellent visual outcomes and favorable complication profiles compared to PKP. Five-year data from Price et al.²⁶ showed similar cumulative 5-year survival rates between DSAEK and full-thickness corneal transplant for FED (95% vs. 93%) and pseudophakic or aphakic corneal edema (76% vs. 73%). Innovations in surgical techniques continue to improve surgical outcomes and patient satisfaction.^{10,12,20–23} Concerns remain, however, regarding graft failure and post-endothelial keratoplasty glaucoma. This retrospective study aimed to offer insights into these postoperative complications and recipient predispositions.

Recent data from a smaller series also found no statistical significance between the detachment rate in the surgical glaucoma and control groups (22.2 vs. 24.1%, Aldave A, Yu F, 2009 Annual Meeting of the American Association of Cataract and Refractive Surgery, unpublished data). These conclusions were corroborated by Phillips et al.²⁷ and Shah et al.,²⁸ although their rates were much lower than in the present series. Our definition of detachment was similar to that of Suh et al.,¹³ which was more inclusive than that of Terry and colleagues; Suh et al reported a detachment rate of 23%. We found an overall detachment rate of 12.8%. Similarly, our analyses showed no significant correlation between prior incisional glaucoma procedures and DSAEK graft detachment.

Since DSAEK is an emerging and widely adopted procedure, the true incidence of induced glaucoma after DSAEK has not been clearly established. Earlier reports suggested an incidence of zero to 18%.¹⁷ Vajaranant et al.¹⁵ reported a relatively high incidence of IOP elevation after DSAEK in 35% of patients with no prior glaucoma, 45% of patients with prior glaucoma, and 43% of patients with preexisting glaucoma surgery. Lee et al.¹⁴ reported an IOP rise to greater than 30 mmHg during the first 6 months following DSAEK surgery in 13%. The importance of post-endothelial keratoplasty glaucoma cannot be overemphasized; unfortunately, preoperative assessment of glaucoma in undiagnosed patients is a difficult task, especially at a tertiary referral center. Comparison of pre- and postoperative optic nerve findings and visual field progression may be hindered by media opacity at presentation or by the decision of some patients to return to their referring physician after receiving surgery. For PKP, IOP elevation, with or without associated visual field loss or changes of the optic nerve, continues to be a commonly used indicator of postkeratoplasty glaucoma; yet the criteria for IOP elevation has been inconsistent in the literature.^15,29–31 Here, our study criteria were similar to those defined by Vajaranant et al.:¹⁵ postoperative IOP elevation where IOP ⩾ 24 mmHg or relative increase ⩾ 10 mmHg in IOP from preoperative value. We found that 26.7% of the cohort met these criteria for IOP elevation over a mean follow-up of 1.85 years. Interestingly, we noted that medically managed glaucoma patients had the highest incidence of IOP elevation and up to 22% of patients with no previous diagnosis of glaucoma also had IOP elevation. These numbers were slightly lower than those reported by Vajaranant et al.¹⁵ The disparity may be due in part to different patient constituency in the two studies (16% vs. 18.5% in the MG group and 5% vs. 21.5% in the SG group). The patients in their series predominantly had FED. A larger proportion (71.1%) of our series was pseudophakic. Proposed mechanisms for post-DSAEK glaucoma include pupillary block, closed angle from peripheral anterior synechiae, distortion of angle from long or tight suture, and steroid response.^14,15,17,32 The observation that IOP elevation began near postop month one in the MG group lends some evidence to hypothesis of steroid response contribution in post-DSAEK glaucoma.

It is difficult to isolate each factor as an individual risk for graft failure; undoubtedly, the causality is multifactorial. In our series, graft detachment appeared to be the most significant contributor to graft failure (P-value < 0.001). Accordingly, an effective way to further reduce the risk of graft failure is continued innovations of surgical techniques to minimize graft detachment.^{10,12,20–23}

Glaucoma has been documented in the PKP literature²⁴ as a significant risk factor for graft failure and, more recently, has been proposed as a risk factor for DSAEK¹⁹ as well. Overall, we found that IOP elevation by itself may not increase the risk (P > 0.05); however, having had a history of glaucoma, particularly glaucoma drainage device implant, significantly increases predisposition to failure (P < 0.001). Our findings corroborate data from the literature. Price et al.^19,26 reported a 5-year survival rate of 40% in patients with prior glaucoma shunt or trabeculectomy surgery compared to 95% of those without, and the hazard ratio was calculated to be 2. This trend was also observed in PKP patients where pseudophakia, aphakia, and prior glaucoma surgery substantially increased the risks of graft failure.^24,33 Recently, Hollander et al.³⁴ reported a 3-year failure rate of 59.1% in PKP patients with Ahmed valves. Our data suggest that preexisting glaucoma is associated with graft failure.

The findings that medically treated glaucoma was associated with increased IOP but not graft failure, whereas surgically treated glaucoma was associated with graft failure but not increased IOP, maybe consistent with the existing literature suggesting possible post-GDI breach in blood–aqueous barrier or chronic trauma producing elevated levels of aqueous humor oxidative and inflammatory products that may precipitate corneal endothelial damage.³⁵ Given that DSAEK patients have a higher incidence of prior glaucoma shunt and trabeculectomy surgeries compared to PKP in a series by Price et al.,²⁶ more investigations are recommended to elucidate the mechanism, natural progression, and methods to improve outcome, either by further innovation in surgical techniques or by optimization of pre- and postoperative management.

Caution is needed when interpreting these findings, as the many limitations inherent in a retrospective study were clearly recognized here and may prevent generalization of our results. This series captured cumulative data over a mean follow-up period of 2 years, which is both an advantage and disadvantage. It allows inclusion of a larger database. However, the heterogeneous patient population may confound the analysis; and the evolution of surgical techniques among the four corneal surgeons may have influence on the surgical outcomes. We acknowledge that IOP measurement using Tonopen is an important flaw, as it has been reported to provide inadequate measurement for the management of glaucoma and ocular hypertension.^36,37 In this series, the Tonopen measurement was only used as a screening parameter and not for IOP management. Nevertheless, the results of this series add to a growing body of literature that aims to address the long-term IOP management in DSAEK patients. The association between graft failure and history of glaucoma surgery, as well as the high incidence of postoperative IOP elevation in this series and others, should prompt the surgeon to focus on preoperative risk assessment and postoperative management to reduce the risks of graft failure and glaucoma.

Acknowledgments/disclosure

• a.Financial support: NEI core grant EY03040 and an unrestricted grant from Research to Prevent Blindness. Pho Nguyen is supported by the Heed Ophthalmic Foundation and the Fletcher Jones Foundation.
• b.Financial disclosure: The authors have no financial interests in the topic of this manuscript.

  No conflicting relationship exists for any author.

• c.Contributions of authors: per Contributions form
• d.Statement about conformity: The research was approved by the Institutional Review Board at the University of Southern California and was in accordance with the tenets set forth in the Declaration of Helsinki. All procedures and data management conformed to the Health Insurance Portability and Accountability Act of 1996.