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International Outcomes of theBoston Type I Keratoprosthesis in Stevens-Johnson Syndrome

April 15-17, 2015World Cornea Congress VIISan Diego, California

Jamie K. Alexander, M.D.Samar K. Basak, M.D.Ma. Dominga B. Padilla, M.D.Fei Yu, Ph.D.Anthony J. Aldave, M.D.

The authors have no relevant financial interests to disclose.

Stevens-Johnson syndrome (SJS) can devastate the ocular surface. There is currently no reliable, sustainable method for restoring sight in these patients.

While initial studies of the Boston type I keratoprosthesis (KPro) indicated that its results were poorest in patients with SJS, advances in KPro design and post-operative management have improved outcomes, including those in SJS.

Using international data and the world’s most widely used keratoprosthesis, we present the largest study to date of the KPro in SJS. We compare the device’s outcomes in SJS to those of patients without SJS and seek to determine the factors influencing outcomes of the KPro in SJS.

Purpose

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• Retrospective, interventional, comparative case series

• Study approval: Institutional Review Board at UCLA Ethics Committee at Disha Eye Hospitals Institutional Ethics Review Committee at St. Luke’s Medical

Center

• Data was collected from 3 international academic medical centers on all patients undergoing KPro surgery, including preoperative characteristics, intraoperative data, and postoperative outcomes:

• Statistical Analysis: SAS software version 9.4 (SAS, Inc., Cary, NC) (p=0.05)

Stein Eye InstituteLos Angeles, CaliforniaMay 2004 – Jul 2013

Disha Eye HospitalsKolkata, IndiaMar 2009 – Jan 2014

St. Luke’s Medical Center Global CityManila, PhilippinesMar 2009 – Jan 2014

Methods

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*Comparing <1 to >2 previous corneal transplants

  SJS Non-SJS P valueNo. of procedures 40 194  No. of eyes 27 182  No. of patients 26 175  Gender (female; male) 14; 12 75; 100 0.3Mean age (range), yrs 50 (26-72) 60 (3-95) <0.001 Follow-up (mos)      

Mean (median) 17.6 (12.5) 29.3 (23.5)  0.001Standard deviation (range) 16.2 (0.5-73.1) 22.8 (0.8-106.5)  

Indication for keratoprosthesis      Failed corneal transplant -- 109 (56%)  Stevens-Johnson syndrome 27 (68%) --  Limbal stem cell deficiency -- 24 (12%)  Chemical injury -- 18 (9%)  Repeat keratoprosthesis 13 (33%) 15 (8%) <0.001Corneal vascularization -- 11 (6%)  Mucous membrane pemphigoid

-- 4 (2%)  

Aniridia -- 4 (2%)  Thermal Burn -- 3 (2%)  AKC -- 2 (1%)  Other -- 4 (2%)  

Glaucoma 7 (26%) 130 (71%) <0.001Previous glaucoma surgery 4 (15%) 45 (25%) 0.334

Previous corneal transplant(s)      0 18 (67%) 42 (23%) <0.001*1 5 (19%) 32 (18%)  2 2 (7%) 54 (30%)  3 0 33 (18.1%)  > 4 2 (7.4%) 21 (11.5%)  

Results: Preoperative Characteristics

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  Baseline 6 Months 1 Year 2 Years 3 Years 4 Years 5 Years At last follow-up

No. of eyesSJS 27 23 18 9 3 1 0 22

Non-SJS 182 169 142 99 68 43 25 16220/20-20/50

SJS 0 (0%) 14 (61%) 7 (39%) 5 (56%) 1 (33%) 1 (100%) -- 9 (41%)Non-SJS 1 (1%) 53 (31%) 45 (32%) 31 (31%) 21 (31%) 15 (35%) 9 (36%) 49 (30%)

20/60-20/100SJS 0 (0%) 5 (22%) 7 (39%) 3 (33%) 2 (67%) 0 (0%) -- 8 (36%)

Non-SJS 0 (0%) 49 (29%) 34 (24%) 18 (18%) 9 (13%) 5 (12%) 2 (8%) 33 (20%)20/125-20/200

SJS 0 (0%) 3 (13%) 4 (22%) 1 (11%) 0 (0%) 0 (0%) -- 4 (18%)Non-SJS 9 (5%) 18 (11%) 16 (11%) 18 (18%) 13 (19%) 5 (12%) 4 (16%) 20 (12%)

20/250-20/400SJS 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) -- 0 (0%)

Non-SJS 7 (4%) 9 (5%) 6 (4%) 4 (4%) 3 (4%) 4 (9%) 0 (0%) 12 (7%)CF

SJS 8 (30%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) -- 0 (0%)Non-SJS 53 (29%) 27 (16%) 21 (15%) 11 (11%) 6 (9%) 3 (7%) 4 (16%) 19 (12%)

HMSJS 9 (33%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) -- 1 (5%)

Non-SJS 61 (34%) 7 (4%) 8 (6%) 12 (12%) 10 (15%) 9 (21%) 1 (4%) 11 (7%)LP

SJS 10 (37%) 1 (4%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) -- 0 (0%)Non-SJS 51 (28%) 4 (2%) 7 (5%) 2 (2%) 3 (4%) 1 (2%) 4 (16%) 9 (6%)

NLPSJS 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) -- 0 (0%)

Non-SJS 0 (0%) 2 (1%) 5 (4%) 3 (3%) 3 (4%) 1 (2%) 1 (4%) 9 (6%)

>20/200SJS 0 (0%) 22 (96%) 18 (100%) 9 (100%) 3 (100%) 1 (100%) -- 21 (96%)

Non-SJS 10 (6%) 120 (71%) 95 (66.9%) 67 (68%) 43 (63%) 25 (58%) 15 (60%) 102 (63%)

p-value 0.367 0.01 0.002 0.055 0.547 1 -- 0.001

Results: CDVA for Most Recent KPro

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  SJS Non-SJS p-value

No. of eyes with >1 mo of follow-up 27 181  

Retroprosthetic membrane 10 (37%) 89 (49%) 0.30YAG laser membranotomy 9 (33%) 68 (38%) 0.83Surgical membranectomy 1 (4%) 13 (7%) 1

Sterile corneal stromal necrosis 16 (59%) 25 (8%) <0.001Keratoprosthesis replacement 9 (33%) 8 (4%) <0.001

Elevated IOP (>25 mmHg) 5 (189%) 32 (18%) 1Glaucoma surgery 1 (4%) 11 (6%) 1

Corneal infiltrate 8 (30%) 18 (10%) 0.009Persistent epithelial defect 16 (59%) 44 (24%) <0.001

Tarsorrhaphy 14 (52%) 22 (12%) <0.001Infectious endophthalmitis 0 4 (2%) 1

Vitreous tap and injections 0 4 (2%) 1Retinal detachment 3 (11%) 21 (12%) 1

Repair of retinal detachment 1 (4%) 14 (8%) 0.70Sterile vitreitis 0 15 (8%) 0.23

Vitreous tap and injection 0 9 (5%) 0.61Cystoid macular edema 2 (7%) 23 (13%) 0.75

Intravitreal injection 1 (4%) 17 (9%) 0.48

Results: Complications and Secondary Surgical Procedures

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  SJS Non-SJS p-value

Mean follow-up of all procedures in mos (range)* 17.6 (0.5-73.1) 29.3 (0.8-106.5)  0.001  

Retention failure      

Keratoprostheses removed (eyes) 14 of 27 (51.9%) 28 of 182 (15.4%) <0.001

Keratoprostheses removed (procedures) 18 of 40 (45.0%) 32 of 194 (16.5%) <0.001

Retention failure rate (procedures)**18 per 58.75 eye-years,

0.306/eye-year32 per 472.91 eye-years,

0.068/eye-year<0.001 

Time to failure in mos (mean, range)* 14.1 (0.5-73.1) 19.9 (3.6-82.6) 0.011 

Retention success      

Keratoprostheses retained (eyes) 22 of 27 (81.5%) 162 of 182 (89.0%) 0.335

Keratoprostheses retained (procedures) 22 of 40 (55.0%) 162 of 194 (83.5%) <0.001

Mean follow-up of retained procedures in mos (range)* 20.5 (5.8-59.5) 31.1 (0.8-106.5)  0.084

*Kruskall-Wallis test** Log-rank test

Results: Keratoprosthesis Retention Rate

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Results: Kaplan-Meier Survival of Last KPro

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 Keratoprostheses

RetainedKeratoprostheses

Removedp-value

Number (eyes; procedures) 13; 22 14; 18  

Pre-operative characteristics (eyes)      

Time from SJS to initial procedure (yrs) 13.72 12.02 0.91

Perforation at or before time of KPro 4 (31%) 7 (50%) 0.44

Bulbar conjunctival keratinization 1 (8%) 6 (43%) 0.08

Lid malpositioning* 3 (23%) 4 (29%) 1

Peri-operative characteristics (procedures)      

Tarsorrhaphy at time of keratoprosthesis 7 (32%) 5 (28%) 1

Preoperative immunosuppression 3 (13%) 2 (11%) 1

Postoperative immunosuppression 13 (59%) 8 (44%) 0.53

Indication for removal (procedure)      

Sterile corneal necrosis - 14  

Infectious corneal necrosis** - 4  

*requiring previous, concurrent or subsequent oculoplastics procedures**organisms including: mixed (1), Candida (2), budding yeast without speciation (1) 

Results: Characteristics of Patients with SJS Associated with KPro Retention and Failure

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Slit lamp photomicrograph of a 67 year-old man with SJS. Donor corneal necrosis developed 5 months following KPro surgery, necessitating replacement of the KPro. At the time of the second surgery, the donor cornea was covered with mobilized bulbar conjunctiva and extensive medial and lateral tarsorrhaphies were performed. Two years later, the donor cornea remains covered by conjunctiva and the patient maintains 20/20 CDVA.

Results: Repeat KPro Results in SJS (example)

Pre-op CDVA

# KprosTime Kpro retained (mos)

Procedure(s) Performed Following Removal of Last Type I Kpro

Follow-up After Removal of Last Type I KPro (mos)

Current CDVA

HM 2 2.2 Boston type II Keratoprosthesis 99.7 20/40

LP 1 6 Penetrating keratoplasty 4.9 LP

LP 1 5.8 Penetrating keratoplasty (x 2) 42 LP

LP 1 7.7Penetrating keratoplasty(repeat keratoprosthesis planned)

1.1 CF

HM 1 5.7Penetrating keratoplasty(repeat keratoprosthesis planned)

2 CF

Results: SJS Patients in which KPro Not Retained

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The Boston type I keratoprosthesis is the most commonly used device of its kind world-wide. This study retrospectively analyzed the international outcomes of 40 KPro procedures performed in 27 eyes of 26 patients with SJS in comparison to those of 194 procedures performed in 182 eyes of 175 patients without SJS.

DemographicsPatients undergoing KPro for SJS are more likely to be younger and less likely to have a preoperative diagnosis of glaucoma or a history of multiple previous corneal transplants compared to patients undergoing KPro for other indications. KPro procedures performed in SJS patients are significantly more likely to be performed as repeat implantations of the device (33% vs. 8%, p<0.001).

Visual OutcomesNearly all eyes undergoing KPro with SJS have a final CDVA > 20/200 when the KPro is retained (96%). - This is significantly higher than that of eyes without SJS (63%, p=0.001) - This is likely due a significantly lower incidence of preoperative glaucoma.

Conclusions

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ComplicationsSeveral post-operative complications are more common in SJS patients following KPro: sterile corneal stromal necrosis, persistent epithelial defect, and corneal infiltrate.

- No sight-threatening complications are more common.

- No endophthalmitis was encountered in SJS patients in this study.

RetentionAlthough retention failure is higher in SJS (relative risk 4.5), eyes with SJS are no less likely to ultimately retain KPro following repeat implantation (82 vs. 89%, p=0.34).

Characteristics Affecting KPro Failure/Success in SJSBased on available data, there are no identifiable pre- or postoperative characteristics that lead to KPro failure or success in SJS. - This may be due to the heterogeneous nature of the manifestations of SJS.

The Boston type I keratoprosthesis is an effective means to restore vision to patients blinded by Stevens-Johnson syndrome.

Conclusions

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