J. Doe IV1, M. B. Horsley2, T. John1, J. Sugar2, E. Y. Tu2, J. B. Rubenstein3, and C.S. Bouchard1 1Ophthalmology, Loyola University Medical Center, Maywood, IL

2Ophthalmology, University of Illinois at Chicago, Chicago, IL3Ophthalmology, Rush University Medical Center, Chicago, IL

Purpose: To clarify the influence of the death-to-preservation time interval (DtPT) on overall corneal graft survival as measured by central corneal thickness (CCT), best corrected visual acuity (BCVA) and rejection events after penetrating keratoplasty in keratoconus patients. Methods: We performed a retrospective chart review on 432 keratoconus patients in Chicago that received a penetrating keratoplasty (PKP) between 1993 and 2003. Inclusion criteria: at least 2 years of follow-up as well as 2 CCT measurements at the following time points: 3 months, 6 months, 1 year, 2 years and 5 years. A multivariate analysis was performed using donor age, DtPT and cell count as independent variables. CCT and best-corrected visual acuity (BCVA) at 3 months, 6 months, 1 year, 2 years and 5 years were then correlated with these indices. Results: 111 keratoconus patients fit our inclusion criteria. For the 3 month, 6 month, 1 year and 2 year time points, a higher cell count correlated more strongly with a lower CCT than either DtPT or donor age (ANOVA: p = 0.029, p = 0.054 for 3 and 6 months respectively). The adjusted R Square was 0.048, suggesting a small effect on corneal thickness. For BCVA, 5 years after PKP there was a highly negative correlation between DtPT and BCVA (Zero order correlation: -0.582, p = 0.002). Finally, rejection events occurred in 29.5% of the 111 total grafts. Conclusions: Endothelial cell count proved to have a higher correlation with a more favorable corneal thickness when compared with donor age and death to preservation interval. Although no association was present initially with BCVA, at the 5-year follow-up, a significant correlation existed between a better BCVA and a shorter DtPT. Surprisingly, no significance was shown between DtPT and the development of a graft rejection. Finally, initial data suggest that DtPT has a weak correlation with overall corneal thickness. A future study with a larger cohort of patients will allow us to further examine the extent of this relationship. .

ABSTRACT

To clarify the influence of the death-to-preservation time interval (DtPT) on overall corneal graft survival as measured by central corneal thickness (CCT), best corrected visual acuity (BCVA) and rejection events after penetrating keratoplasty in keratoconus patients.

PURPOSE

Keratoplasty (PKP) between 1993 and 2003. Inclusion criteria: at least 2 years of follow-up as well as 2 CCT measurements at the following time points: 3 months, 6 months, 1 year, 2 years and 5 years. A multivariate analysis was performed using donor age, DtPT and cell count as independent variables. CCT and best-corrected visual acuity (BCVA) at 3 months, 6 months, 1 year, 2 years and 5 years were then correlated with these indices

METHODS

Snyder C. "Alois Glogar, Karl Brauer, and Eduard Konrad Zirm." Arch Ophthalmol. 1965 Dec;74(6):871-4. Sugar A., Sugar J. “Techniques in Penetrating Keratoplasty: A Quarter Century of Development” Cornea.19 (5): 603-610.George J.T., Larkin D.F.P. “Corneal Transplantation: The Forgotten Graft.” American Journal of Transplantation. 4(5). 678. May 2004.Lois N, Kowal VO, Cohen EJ, Rapuano CJ, Gault JA, Raber IM, Laibson PR. “Indications for penetrating keratoplasty and associated procedures”, 1989-

1995. Cornea. 1997 Nov; 16(6):623-9.Harbour RC, Stern GA. “Variables in McCarey-Kaufman corneal storage. Their effect on corneal graft success.” Ophthalmology. 1983 Feb; 90(2):136-42.Lundh BL, Kallmark B. “Endothelial cell density after penetrating keratoplasty using long-time banked donor material after long distance transportation

(Denmark-Sweden).”Acta Ophthalmol (Copenh). 1986 Oct;64(5):492-8.Hu FR, Tsai AC, Wang IJ, Chang SW. “Outcomes of penetrating keratoplasty with imported donor corneas.” Cornea. 1999 Mar;18(2):182-7.Grabska-Liberek I, Szaflik J, Brix-Warzecha M. “The importance of various factors relating to the morphological quality of corneas used for PKP by the

Warsaw Eye Bank from 1996 to 2002.” Ann Transplant. 2003;8(2):26-31.Basic and Clinical Science Course. External Disease and Cornea. American Academy of Ophthalmology. Section 8, Pg. 361.Patel SV, Hodge DO, Bourne WM. “Corneal endothelium and postoperative outcomes 15 years after penetrating keratoplasty.” Am J Ophthalmol. 2005

Feb;139(2):311-318.Yo C, Ariyasu RG. “Racial differences in central corneal thickness and refraction among refractive surgery candidates.” J Refract Surg. 2005 Mar-

Apr;21(2):194-7.Aghaian E, Choe JE, Lin S, Stamper RL. “Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese in a

glaucoma clinic. Ophthalmology.” 2004 Dec;111(12):2211-9.Gherghel D, Hosking SL, Mantry S, Banerjee S, Naroo SA, Shah S. “Corneal pachymetry in normal and keratoconic eyes: Orbscan II versus ultrasound.” J

Cataract Refract Surg. 2004 Jun;30(6):1272-7.Bourne WM, Hodge DO, Nelson LR. “Corneal endothelium five years after transplantation.” Am J Ophthalmol. 1994 Aug 15; 118(2):185-96.

REFERENCES

Decreased Corneal Donor Death-to-Preservation Interval is a Prognostic Factor in Graft Survival and Final BCVA of Penetrating Keratoplasty in Keratoconus Patients

Acknowledgements: This work was supported by The Richard A. Perritt Charitable Foundation.

RESULTS

111 keratoconus patients fit our inclusion criteria. For the 3 month, 6 month, 1 year and 2 year time points, a higher cell count correlated more strongly with a lower CCT than either DtPT or donor age (ANOVA: p = 0.029, p = 0.054 for 3 and 6 months respectively). The adjusted R Square was 0.048, suggesting a small effect on corneal thickness. For BCVA, five years after PKP there was a highly negative correlation between DtPT and BCVA (Zero order correlation: -0.582, p = 0.002). Finally, rejection events occurred in 29.5% of the 111 total grafts.

SUMMARY OF RESULTS

DtPT verse s BVCA at 5 years

y = -0.0003x + 0.8927

R2 = 0.1235

.00

.10

.20

.30

.40

.50

.60

.70

.80

.90

1.00

1.10

- 120 240 360 480 600 720 840 960 1,080 1,200 1,320

Preservation Time<minutes>

BC

VA

Cornea Ratings and Final BCVA 20/30 or Better

05

101520

2530354045

good+g/vg verygood excellent+vg/e

Rating

Coun

ts

up to 20/30 (p=0.54) worse than 20/30 (p=0.46)

Cornea Ratings and Final BCVA 20/25 or Better

0

5

10

15

20

25

30

good+g/vg verygood excellent+vg/e

Rating

Coun

ts

up to 20/25 (p=2.96) worse than 20/25 (p=0.09)

DtPT: Death to preservation time; Best Corrected Visual Acuity BCVA: 1.00=20/20, .80=20/25, .67=20/30, .50=20/40, .10=20/200

Corneal Donor Rating vs Final BCVA

The goal of this project was to see if death to preservation time intervals had any real effect of the outcomes of PKPs. We wanted to control for immune rejection as much as possible as a cause for graft failure. It is well known that indications for grafts such as Fuch’s, the corneal dystrophies, trauma, corneal infection/ulceration tend to have reoccurrences in the graft and higher rates of immune rejections because of abnormal recipient beds. Graft failures are much more common for these indications than for keratoconus, which does not tend to recur in the graft, usually has a normal host bed and lacks vascular tissue in close proximity to the graft. This becomes one of the purest forms of PKP and graft rejection or failure is most likely an effect of poor corneal buttons, poor surgical technique, poor patient compliance or some confounding ocular condition. Keratoconus has the best long-term survival for penetrating keratoplasty compared with other diagnosis such as Fuch’s Endothelial Dystrophy. Keratoconus did not reoccur in any of our grafts. The PKP procedures were performed by four different surgeons, but the surgeries and management were all similar. Having controlled for immune rejections to the best of our abilities we found that DtPT did have real and surprising effects on our measured outcomes. Intuitively it made sense to us that the longer the DtPT interval the more likely the graft would suffer from either poor visual acuity, increased graft thickness (CCT), rejection events or a combination of all three. Our finding that increased DtPT correlated to increased central thickness at the 6 month, 1 and 2 year data points did not surprise us but the fact that visual acuity did not correlate with the CT at those points did. Our finding that central corneal thickness did not correlate with either BCVA or rejection events was quite surprising. This most likely represents the fact that there were so few rejection events that occurred and only one true failure.

DISCUSSION

Endothelial cell count proved to have a higher correlation with a more favorable corneal thickness when compared with donor age and death to preservation interval. Although no association was present initially with BCVA, at the 5-year follow-up, a significant correlation existed between a better BCVA and a shorter DtPT. Surprisingly, no significance was shown between DtPT and the development of a graft rejection. Finally, initial data suggest that DtPT has a weak correlation with overall corneal thickness. A future study with a larger cohort of patients will allow us to further examine the extent of this relationship.

CONCLUSIONS