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Young Eun Lee, MD 1,2 , Eui Seok Han, MD 1,2 , Mee Kum Kim, MD 1,2 , Won Ryang Wee, MD 1,2 PowerPoint PPT Presentation


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Risk factor Analysis for Long-term Outcome of Keratolimbal Allografts. Young Eun Lee, MD 1,2 , Eui Seok Han, MD 1,2 , Mee Kum Kim, MD 1,2 , Won Ryang Wee, MD 1,2. 1 Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea

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Young Eun Lee, MD 1,2 , Eui Seok Han, MD 1,2 , Mee Kum Kim, MD 1,2 , Won Ryang Wee, MD 1,2

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Young eun lee md 1 2 eui seok han md 1 2 mee kum kim md 1 2 won ryang wee md 1 2

Risk factor Analysis for

Long-term Outcome of Keratolimbal Allografts

Young Eun Lee, MD1,2, Eui Seok Han, MD1,2,

Mee Kum Kim, MD1,2, Won Ryang Wee, MD1,2

1Department of Ophthalmology, Seoul National University College of Medicine,

Seoul National University Hospital, Seoul, Korea

2Laboratory of corneal regenerative medicine and ocular immunology,

Seoul Artificial Eye Center, Seoul National University Hospital

Clinical Research Institute, Seoul, Korea

The authors have no financial interest in the subject matter of this poster


Introduction purpose

Introduction & Purpose

  • Several conditions influencing KLAL success7-11

  • Chronic conjunctival inflammation

  • Tear film deficiency

  • Symblepharon

  • Rejection

  • Keratolimbal allograft (KLAL)

  • Several successful short-term reports in the 1990s1-4

  • Long-term results were not satisfactory.5,6

  • Survival of KLAL: 23.7%/21.2% at 5 years (2002 reports)5,6

Because there have been few documented studies on a large number of KLAL patients, the important prognostic factors influencing KLAL success are unknown.

So, we retrospectively reviewed our cases to elucidate the prognostic factors for KLAL success and the long-term outcomes of KLAL in our series over 10-year period.

Pupose


Patients and methods

Patients and Methods

Corneal vascularization or

Conjunctivalization or

Persistent epithelial defect or

Goblet cell on the corneal surface

Patients

Surgical procedures


Patients and methods1

Patients and Methods

  • If rejection,

    • Oral CSA ↑ or add MMF 1g bid

    • Oral Corticosteroid ↑

    • Corticosteroid eyedrop ↑

  • Ocular care

    • Ofloxacin

    • Corticosteroid

    • Autoserum

    • Artificial tears

    • Therapeutic contact lens

  • Immunosuppression

    • Corticosteroid 30mg/day for 2weeks

    • Cyclosporin A (CSA) 2.5~5.0mg/kg for 6 months/ dose-adjustment for 100~150ng/ml trough level

    • Mycophenolate mofetil (MMF) 1g bid in high-risk

  • Delayed epithelialization: full epithelialization after 2 months postoperatively

  • Infectious keratitis: proved when culture (+)

  • Increased intraocular pressure (IOP) ≥ 21mmHg

  • Graft failure:

If, REJECTION

Corneal vascularization or

Conjunctivalization or

Persistent epithelial defect or

Goblet cell on the corneal surface

Postoperative care

Rejection care

Definition of complications


Patients and methods2

Patients and Methods

Clinical outcome evaluation

Prognostic factor evaluation


Patients and methods3

Evaluation of KLAL survival

Patients and Methods

  • Kaplan-Meier survival curve

Clinical outcome evaluation

P < 0.10

P < 0.05

Statistics of prognostic factor


Result clinical outcome

Result (Clinical outcome)

  • Delayed epithelialization: 3 eyes (5months on average)

  • Newly developed epithelial defect: 8 (33.3%)

  • Increased IOP: 9 (37.5%), 6 medically controlled.

  • Corneal melting: 2 (8.3%)

  • Bacterial keratitis: 3

  • Fungal keratitis: 1

  • Herpetic keratitis: 1

  • Patients characteristics

  • M:F (17:5), 24 eyes of 22 patients

  • Age: 39.4± 17.4 years

  • Follow-up: 47.3± 22.0 months (17-114)

  • Diagnosis

  • SJS 6

  • Chemical burn 5

  • Others 13

  • Total KLAL: 46 times (1 outside)

  • Simultaneous PKP: 11 eyes

  • KLAL failure (n=16, 66.7%)

  • Primary failure 3 (12.5%)

  • Persistent epithelial defect 8 (33.3%)

  • Conjunctivalization 4 (16.6%)

  • Corneal neovascularization 7 (29.2%)

  • PKP failure (n=7, 63.6%)

  • Corneal opacity by limbal insufficiency 5 (45.5%)

  • Irreversible rejection with opacity 2 (18.2%)

  • Reversibility of KLAL and PKP rejection

  • Only KLAL rejection: 6 eyes (all reversible)

  • Only PKP rejection: 5 eyes (all reversible)

  • KLAL+PKP rejection: 4 eyes (2 irreversible)

Patients

Causes of KLAL & PKP failure

Rejections

Complications


Result clinical outcome and survival

Result (Clinical outcome and survival)

Long-term survival (+) after KLAL once

SJS: Stevens-Johnson syndrome

CB: chemical burn

O: others

Repeated KLAL

114 months

Rapid decline until postoperative 10 months

Postoperative months


Result clinical outcome and survival1

Result (Clinical outcome and survival)

Postoperative BCVA means the BCVA at the last follow-up, which was almost the same or better than preoperative BCVA

A

B

C

KLAL success (thermal burn)

Preop

1 month

4 months

Preop

1 month

4 months

KLAL failure (Ocular cicatrical pemphigoid)

D

E

F

Postoperative months


Result prognostic factor analysis

Result(Prognostic factor analysis)

PKP = penetrating keratoplasty; BCVA = best corrected visual acuity; IOP = intraocular pressure; AMT = amniotic membrane transplantation; CSA = cyclosporine A.

aUnivariate analysis was performed using the chi-square or Mann-Whitney U test.

bVariables which were associated with risk of KLAL failure on univariate analysis (p<0.1) were analyzed in the multivariate Cox regression survival model.

c95% confidence interval:0.016-0.563.

dInitial CSA dose was 5.0mg/kg daily in usual.


Discussion

Discussion

The overall success of KLAL was 33.3% at 4 years, which is similar to two previous reports of the long-term outcome of KLAL.5-6 Our study included a relatively high portion of patients with SJS and OCP (37.5%), which are known to lead to a relatively poor outcome.11

Simultaneous PKP and KLAL were performed because of the limited availability of donor corneal tissues. The success of PKP was highly dependent on the success of KLAL, because grafted cornea often becomes opaque due to persistent epithelial defect or neovascularization following KLAL failure.

Our KLAL rejection rate was 41.7% with strong systemic immune suppression, lower than the 87.5% in eyes with CSA alone6 but higher than the 17% rate in eyes receiving mycophenolate mofetil and tacrolimus.7

All the rejection in KLAL alone was reversible, whereas concurrent rejection in both KLAL and PKP was irreversible in half cases. A more potent combination of immunosuppressants should be considered in concurrent KLAL/PKP rejection.


Discussion1

Discussion

In conclusion, KLAL has been partly successful for reconstruction of limbal stem cell deficiency, and symblepharon has been identified as a significant prognostic factor for KLAL survival

1. Thoft RA. The role of the limbus in ocular surface maintenance and repair. ActaOphthalmol Suppl. 1989;192:91-94.

2. Tsai RJ, Tseng SC. Human allograft limbal transplantation for corneal surface reconstruction. Cornea. 1994;13(5):389-400.

3. Tan DT, Ficker LA, Buckley RJ. Limbal transplantation. Ophthalmology. 1996;103(1):29-36.

4. Tsubota K, Toda I, Saito H, Shinozaki N, Shimazaki J. Reconstruction of the corneal epithelium by limbal allograft transplantation for severe ocular surface disorders. Ophthalmology. 1995;102(10):1486-1496.

5. Tsubota K, Satake Y, Ohyama M, et al. Surgical reconstruction of the ocular surface in advanced ocular cicatricialpemphigoid and Stevens-Johnson syndrome. Am J Ophthalmol. 1996;122(1):38-52.

6. Solomon A, Ellies P, Anderson DF, et al. Long-term outcome of keratolimbal allograft with or without penetrating keratoplasty for total limbal stem cell deficiency. Ophthalmology. 2002;109(6):1159-1166.

7. Ilari L, Daya SM. Long-term outcomes of keratolimbal allograft for the treatment of severe ocular surface disorders. Ophthalmology. 2002;109(7):1278-1284.

8. Liang L, Sheha H, Tseng SC. Long-term outcomes of keratolimbal allograft for total limbal stem cell deficiency using combined immunosuppressive agents and correction of ocular surface deficits. Arch Ophthalmol. 2009;127(11):1428-1434.

9. Maruyama-Hosoi F, Shimazaki J, Shimmura S, Tsubota K. Changes observed in keratolimbal allograft. Cornea. 2006;25(4):377-382.

10. Samson CM, Nduaguba C, Baltatzis S, Foster CS. Limbal stem cell transplantation in chronic inflammatory eye disease. Ophthalmology. 2002;109(5):862-868.

11. Shimazaki J, Shimmura S, Fujishima H, Tsubota K. Association of preoperative tear function with surgical outcome in severe Stevens-Johnson syndrome. Ophthalmology. 2000;107(8):1518-1523.

12. Tsubota K, Satake Y, Kaido M, et al. Treatment of severe ocular-surface disorders with corneal epithelial stem-cell transplantation. N Engl J Med. 1999;340(22):1697-1703.

  • Preoperative symblepharon is the most significant prognostic factor.

    • Forniceal contracture usually leads to frequent falling off of the contact lens, resulting in an unstable surface.

    • Combining lid entropion due to shortage of the fornix induces surface irritation and epithelial erosion..

  • Limitations

    • It is a retrospective study and has limited variable factors that could not be controlled

    • The protocol of immunosuppressant administration and the surgeon’s skill likely changed over 9 years.


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