Boston type 1 keratoprosthesis outcomes in ... - Wiley Online Library

Acta Ophthalmologica 2013

Boston type 1 keratoprosthesis outcomes in ocular burns Fernanda Pedreira Magalha˜es, Flavio Eduardo Hirai, Luciene Barbosa de Sousa and Lauro Augusto de Oliveira Department of Ophthalmology, Federal University of Saõ Paulo, Saõ Paulo ⁄ SP, Brazil

ABSTRACT. Purpose: To report the outcomes of Boston type I keratoprosthesis (BKPro) in the management of ocular burn injuries. Methods: This was a prospective study including all cases of BKPro implantation for ocular burns at the External Diseases and Cornea Service of the Federal University of Saõ Paulo, between February 2008 and February 2010. Ten patients (10 eyes) were enrolled. Procedures performed to manage ocular injury were identified, and data were collected regarding patients’ ocular history, surgical procedure(s) performed, and postoperative outcomes, including visual acuity, retention, complications and required surgical procedures. Results: A total of 11 Type 1 BKPro were implanted in 10 eyes of 10 patients. The mean follow-up period was 25.7 ± 10.8 months. Preoperative best-corrected visual acuity (BCVA) ranged from count fingers to light perception. Postoperative BCVA was better than 20 ⁄ 200 in 90% of the patients and better than 20 ⁄ 60 in 60% of the patients. The overall BKPro retention rate was 90%. The most common complications were retroprosthetic membrane formation (50%) and persistent corneal epithelial defect evolving to corneal melting (40%). Patients who underwent ocular surface procedures such as limbal transplantation prior to BKPRo implantation had a lower incidence of corneal melting ⁄ thinning (p = 0.07), although this was not statistically significant. Conclusion: The anatomical and functional results identified in this study support the use of BKPro in managing bilateral limbal stem cell deficiency secondary to ocular burns. Key words: chemical burn – keratoprosthesis – ocular injury

Acta Ophthalmol. 2013: 91: e432–e436 ª 2013 The Authors Acta Ophthalmologica ª 2013 Acta Ophthalmologica Scandinavica Foundation. Published by Blackwell Publishing Ltd.

doi: 10.1111/aos.12083

Introduction Chemical and thermal burns have the potential to cause devastating eye injuries (Tuft & Shortt 2009). Consequences of ocular burns can be severe, and their management can be particularly challenging (Fish & Davidson

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2010). The goal of treatment is to restore the ocular surface and corneal clarity with visual acuity improvement. Surgical options for ocular surface reconstruction have been based on symblepharon correction and limbal stem cell transplantation (LSCT) (Shortt et al. 2007). Corneal trans-

plants may be necessary to clear the visual axis. However, keratoplasties in end-stage dry eye and limbal stem cell deficiency may have poor prognoses. In the most compromised cases, implantation of a keratoprosthesis (KPro) might be the only option to improve vision (Dohlman & Doane 1994). Therefore, KPro surgeries are usually reserved for eyes with advanced disease that have undergone multiple procedures (Barnes et al. 2007). KPro surgery has been attempted for more than two centuries. However, only in the past two decades have improvements in the technique and KPro design led to promising results in its use for treatment of complicated corneal disease (Sayegh et al. 2008). Improved outcomes with Boston type 1 KPro (BKPro) are likely secondary to recent modifications in its model and in postoperative management (Aldave et al. 2009). BKPro has become a viable option for highrisk patients for corneal transplantation, such as those with repeated graft failure and ⁄ or with severe ocular surface disease. Recently, its use in patients with corneal blindness with a poor prognosis if submitted to conventional penetrating keratoplasty has been described in the literature with good anatomical and functional results (Ma et al. 2005; Zerbe et al. 2006; Bradley et al. 2009; Dunlap et al. 2010). Although several BKPro case series have been reported, including analyses of chemical burn cases (Yaghouti et al. 2001; Harissi-Dagher & Dohlman


2008; Sejpal et al. 2011), data on specific results in patients with ocular burns have not been published. The purpose of this study was to report the use of BKPro in ocular burn injuries and to describe intraoperative and postoperative characteristics, visual outcomes and complications.

Materials and methods This was a prospective study conducted at the External Diseases and Cornea Service of the Federal University of Saõ Paulo. After obtaining approval from the institution’s Investigational Review Board, 10 patients (10 eyes) with a previous diagnosis of ocular burn were enrolled in this study for type 1 BKPro implantation (February 2008–February 2010). Informed consent was obtained from all subjects, and the research followed the tenets of the Declaration of Helsinki. The study included patients with bilateral severe corneal opacification due to ocular burns with prior ocular surface reconstruction as needed (correction of lid deformity, symblepharon and trichiasis and LSCT). Nine patients were previously diagnosed with alkali burn, and one patient was a victim of thermal burn (hot oil). Exclusion criteria were patients younger than 18 years or those with persistent epithelial defects, end-stage glaucoma or retinal detachment. Individuals with preserved vision in one eye were also excluded from the study. Patients were examined at 1 day, 1 week and every month after surgery. Visual acuity, slit-lamp examination, fundoscopy and intraocular digital pressure measurement were performed at each visit. Regular visual fields and retinography data were obtained from all patients (when transparency allowed). Data regarding complications were recorded. Surgical technique

Placement of the Type 1 BKPro device was performed following a previously reported technique (Dohlman et al. 2002) using a donor corneal button oversized by 0.5 mm. To improve BKPro centration, the standard technique was modified slightly: the 3-mm central trephination was performed

before the outer diameter punch was used (Khalifa & Moshirfar 2010). Postoperative management

Postoperative care included the use of a disposable soft contact lens over the keratoprosthesis in all patients for an indefinite time (replaced at every visit) and a prophylactic regimen of daily topical 0.5% moxifloxacin (one drop twice a day) and 5% povidone-iodine at every regular visit (one drop monthly). In the initial postoperative period, topical prednisolone acetate (1% suspension) eye drops were prescribed depending on the severity of the inflammation; the drops were tapered until discontinuation. Statistical analysis

A Kaplan–Meier survival analysis was used to evaluate the anatomical retention of the device. Mean visual acuity was compared between baseline and postoperative values (3, 6, 12, 18 and 24 months) using the Wilcoxon test. Categorical data were compared with Fisher’s exact test. A p value of < 0.05 was considered statistically significant. The analysis was performed with Stata v.10 (College Park, TX, USA).

Results A total of 11 Type 1 BKPro were implanted in 10 eyes of 10 patients (one patient underwent a second implantation after keratoprosthesis extrusion secondary to extensive corneal melting). The mean follow-up period was 25.7 ± 10.8 months (range, 13–41 months). Nine patients were male and one was female, with a mean age of 41.5 ± 13.3 years (range, 27–58 years). The mean duration of disease was 15 ± 9.7 years (range, 2– 30 years). Primary causes of ocular burn were alkali burn (nine patients) and thermal injury (hot oil; one patient). Four patients had undergone LSCT, one had undergone oral mucous membrane grafting (OMMG) for symblepharon correction, and two had undergone both procedures. The stem cell transplants were generated from living-related donors HLA-compatible in five eyes. In one patient, autologous stem cells were cultivated and expanded ex vivo on amniotic

membrane. LSCT procedures were performed at least 3 years before keratoprosthesis implantation. None of the patients were in use of immunosuppression therapy at the time of BKPro surgery. Seven eyes had previously failed penetrating keratoplasties. Preoperative visual acuity ranged from count fingers to light perception. The average baseline Schirmer’s test value was 15.5 ± 10.2 (range, 4–30 mm). Table 1 lists patients’ preoperative and postoperative characteristics, visual acuity outcomes and complications. Intraoperative variables

The pseudophakic Type 1 BKPro was used in six procedures, and the aphakic model was used in four. The recipient and donor trephine sizes were 8.5 and 9.0 mm, respectively, in all patients. Concomitant procedures included cataract extraction with intraocular lens implantation (one case), cataract extraction without intraocular lens implantation (two cases), tarsorrhaphy (two cases) and tube shunt implantation associated with pars plana vitrectomy (one case). Visual acuity variables

Postoperatively, the keratoprosthesis improved visual acuity in the majority of patients (Table 1). Final postoperative vision was improved compared with preoperative vision in 9 of 10 eyes and was unchanged in only one eye (this patient had vision of light perception at baseline and evolved to hand motions). All patients were followed for at least 1 year, and at this point, nine eyes (90%) achieved a best-corrected visual acuity of 20 ⁄ 200 or better, with four eyes (40%) achieving vision of 20 ⁄ 60 or better (Fig. 1). The anatomical retention rate of the initial keratoprosthesis was 90% (9 ⁄ 10) after 24 months of follow-up. One patient developed extensive sterile corneal melting with BKPro extrusion at 1 year of follow-up, requiring keratoprosthesis replacement. The final visual acuity of this patient, after the second procedure, was 20 ⁄ 60. Glaucoma and keratoprosthesis

Considering that all patients had opaque ocular media at baseline, suspicion of preoperative glaucoma was

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Table 1. Preoperative and postoperative variables. Type of ocular burn

Previous surface surgery

1

Alkali

2 3

Alkali Alkali

4

Alkali

LSCT MMG LSCT LSCT MMG –

Alkali Alkali Alkali Alkali Thermal Alkali

MMG LSCT LSCT LSCT – –

25 8 30 30 11 15

Patient No.

5 6 7 8 9 10

Schirmer’s baseline

Baseline VA

One-year VA

Two-year VA

Follow-up (months)

Complications

4 mm

LP

HM

HM

41

RPM, melting

20 mm 8 mm

HM CF

20 ⁄ 60 20 ⁄ 200

20 ⁄ 80 –

40 13

RPM, IK, melting RPM, melting, extrusion

4 mm

HM

20 ⁄ 100

20 ⁄ 400

36

LP LP CF HM HM HM

20 ⁄ 25 20 ⁄ 80 20 ⁄ 80 20 ⁄ 80 20 ⁄ 25 20 ⁄ 60

20 ⁄ 30 20 ⁄ 125 20 ⁄ 100 – – –

29 27 25 18 14 14

Glaucoma, RPM, RD, corneal thinning – RPM, melting – – – –

mm mm mm mm mm mm

CT, corneal transplantation; VA, visual acuity; LSCT, limbal stem cell transplantation; MMG, mucous membrane grafting; LP, light perception; HM, hand motions; CF, counting fingers; RPM, retroprosthetic membrane; IK, infectious keratitis; RD, retinal detachment.

Fig. 1. Box-plot showing median visual acuity over a 24-month follow-up period (values are Snellen equivalent medians).

based on ocular ultrasound findings of a suggestive increased cup-disc ratio and elevated intraocular pressure (IOP) estimated by digital palpation. Preoperatively, six eyes (60%) were suspicious for glaucoma. One patient underwent transscleral Nd:yttriumaluminium-garnet (YAG) cyclophotocoagulation before the BKPro implantation, and one eye had a prior tube shunt. Only one patient underwent concomitant BKPro–tube shunt implantation. After the BKPro was implanted, elevated IOP was present in six eyes (60%) and topical hypotensive drugs were prescribed. Of the six patients with suspected glaucoma preoperatively, five were confirmed to have glaucoma after the procedure, and three (50%) had progression of underlying glaucoma. One eye (10%) with no suspicion of glaucoma before

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BKPro developed high IOP and cupping of the optic disc requiring glaucoma surgery. Serial optic nerve head photographs and visual field tests were performed in all patients when transparency allowed. Postoperative complications and management

One of the most common complications was retroprosthetic membrane formation, which occurred in 5 ⁄ 10 cases (50%). All of these eyes were successfully treated with YAG laser membranotomy. No patients required surgical membranectomy. Other complications encountered after Type 1 BKPro implantation included persistent corneal epithelial defect (PED) evolving to corneal melting (four eyes, 40%), corneal thinning

with no epithelial defect (one eye, 10%), newly diagnosed glaucoma (one eye, 10%), progression of underling glaucoma (three eyes, 50%) and retinal detachment (one eye, 10%). One patient (10%) developed infectious keratitis caused by Staphylococcus aureus that was resistant to 0.5% moxifloxacin and 0.3% gatifloxacin with a minimal inhibitory concentration (MIC) of >32.0 but was sensitive to vancomycin (MIC = 2.0). The infection was controlled by tailored antimicrobial therapy based on sensitivity and MIC tests. There were no cases of endophthalmitis. Those who developed corneal melting (n = 4) had a baseline Schirmer’s test score of 10.0 ± 6.9 mm compared with a mean value of 19.2 ± 10.7 in those who did not develop these complications (n = 6) (p = 0.169). Patients who underwent ocular surface procedures such as limbal transplantation prior to BKPRo implantation had a lower incidence of corneal melting ⁄ thinning (p = 0.07), although this was not statistically significant. Other procedures performed after initial Type 1 BKPro implantation included keratoprosthesis replacement (one occurrence, 10%), corneal patch graft as the first treatment in the same eye that underwent BKPro extrusion (one eye, 10%), amniotic membrane transplantation (one eye, 10%), cyanoacrylate glue for corneal thinning ⁄ melting (three eyes, 30%), pars plana vitrectomy for retinal detachment (one eye, 10%) and tube shunt implantation (one eye, 10%).


Discussion Treatment of severe cases of limbal stem cell deficiency, such as that caused by ocular burns, primarily involves re-establishment of the anatomical and physiological conditions of the ocular surface by reconstruction of corneal and conjunctival epithelium (Shimazaki et al. 1997). Surgical options are a conjunctival limbal autograft in unilateral disease or a conjunctival limbal allograft, associated or not with amniotic membrane transplantation, from a living-related donor or a keratolimbal allograft from a cadaver (Santos et al. 2005; Tseng et al. 1990; Holland & Schwartz 2000). Despite the variety of surgical procedures available to restore the ocular surface, the longterm success rate of current techniques become less favourable over time (40– 80% at 1 year to 33–50% at 2 years) (Shimazaki et al. 1997; Santos et al. 2005; Tseng et al. 1998). The type 1 BKPro can provide substantial visual improvement and long-term anatomical retention in severely traumatized eyes (Harissi-Dagher & Dohlman 2008). In the present study, the overall device retention was 90%, and the vast majority of patients with severe ocular burn presented with better vision at the 1-year follow-up with mean visual acuity improvement from hand motions to 20 ⁄ 120 (0.78 logMAR). No patient had worsening of baseline visual acuity, and the only patient who developed BKPro extrusion presented with a final visual acuity of 20 ⁄ 60 (0.47 logMAR) 12 months after the second procedure. The global KPro anatomical retention rate observed in this series of ocular burns was comparable with those reported in previous BKPro studies. Aldave et al. (2009) reported a keratoprosthesis retention rate of 84% at an average follow-up of 17 months. Bradley et al. (2009) described an 83.3% retention rate of the initial keratoprosthesis at a mean follow-up of 19 months. Zerbe et al. (2006), in the Multicenter Boston Type 1 Keratoprosthesis Study, demonstrated a 95% retention rate at an average follow-up of 8.5 months. Greiner et al. (2011) in a study involving a longer follow-up, reported an 80% retention rate after 33.6 months.

The most common postoperative complications were retroprosthetic membrane formation (50%) and PED evolving to corneal melting (40%). The rate of retroprosthetic membrane formation in our study was similar to rates found in other studies: 25% (Zerbe et al. 2006), 43% (Bradley et al. 2009), 44% (Aldave et al.2009) and 55% (Greiner et al. 2011). Of all four eyes that developed corneal melting, three patients developed corneal melting around the optical stem and had aqueous leakage. One patient developed corneal necrosis at the donor button–recipient cornea junction with no leakage. Of these patients, two were successfully treated with cyanoacrylate glue, one was successfully treated with amniotic membrane transplantation and one developed KPRo extrusion despite initial treatment with cyanoacrylate adhesive and corneal patching. Preparation of the ocular surface seems to be an important step preceding keratoprosthesis implantation in severely compromised eyes. Early eyelid abnormality correction may also be beneficial because it can decrease corneal exposure, improve contact lens retention and decrease the risk of corneal graft melting (Ostheimer TA, et al. IOVS 2011;52: ARVO E-Abstract 346). Of all patients enrolled in this study, seven had been submitted to a previous ocular surface reconstruction procedure: four had undergone prior LSCT, one had undergone oral mucous membrane grafting for symblepharon correction, and two patients had undergone both procedures. The mean baseline Schirmer’s test value was 15.5 mm. The incidence of sterile corneal necrosis ⁄ corneal melting was higher in patients who did not undergo LSCT and ⁄ or OMMG prior to BKPro implantation (p = 0.07) and in patients with lower Schirmer’s measurements (p = 0.169). Although not statistically significant, probably because of the small sample size, these data suggest the importance of ocular surface reconstruction in preventing BKPro complications such as epithelial defects and sterile stromal necrosis. Further studies with a greater number of patients are required to better elucidate the correlation between ocular surface recovery techniques preoperatively and

BKPro results in patients with severe ocular surface disease. Ideally, it would be a prospective randomized study involving patients with ocular burns who undergo, or do not undergo, ocular surface repair (limbal stem cell graft) before the BKPro implantation. Glaucoma is a potential visionthreatening complication in all keratoprosthesis patients (Banitt 2011). Furthermore, patients with severe chemical and thermal injury intrinsically have a high prevalence of glaucoma (Tsai et al. 2006). In this study, six eyes (60%) had glaucoma or were suspicious for glaucoma before surgery. One patient underwent transscleral Nd:YAG cyclophotocoagulation before BKPro implantation, and one eye had a prior tube shunt. Of these six patients, only one underwent tube shunt surgery at the time of BKPro implantation. The decision to perform a single procedure in the other patients was because of severe conjunctival fibrosis. Of the six patients with suspected glaucoma preoperatively, five were confirmed to have glaucoma after the procedure and three (50%) had progression of their underlying glaucoma. One patient did not exhibit significant improvement in visual acuity because of a cupped and pale optic disc (light perception to hand motions). After the BKPro was implanted, elevated IOP was present in six eyes (60%). One patient developed glaucoma postoperatively and required a glaucoma drainage device. Considerable technical difficulties were encountered during drainage tube shunt implantation because of large areas of conjunctival fibrosis in this eye. Advanced glaucoma and retinal detachment were the major determinants of the visual outcome. In summary, the anatomical and functional results found in this study support the use of the BKPro in managing bilateral limbal stem cell deficiency secondary to ocular burns. It can be considered an alternative for visual rehabilitation in patients with ocular surface disease because a significant improvement in BCVA was achieved in the majority of patients (90%) up to 2 years after surgery. Epithelial defect formation is a common postoperative complication in eyes with limbal stem cell deficiency

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and is associated with an increased rate of sterile stromal necrosis.

Acknowledgements This study was supported by CAPES, Ministry of Education, Brazil.

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Received on June 6th, 2012. Accepted on December 4th, 2012. Correspondence: Fernanda Pedreira Magalha˜es, MD Department of Ophthalmology Federal University of Saõ Paulo Rua Botucatu, 820 Saõ Paulo, SP 04023-062 Brazil Tel: (55) (11) 5085 2010 Fax: (55) (11) 2124 1124 Email: fernandapedreiramagalhaes@ yahoo.com.br