Corneal Endothelial Damage Rate in Middle-Aged and Elderly Japanese. Hideki Fukuoka, MD, PhD1,2, Chikako Tange, PhD3, Rei Otsuka, PhD3, Fujiko Ando, MD, PhD3,4 , Hiroshi Shimokata, MD, PhD3,5   1) Department of Advanced Medicine, National Center for Geriatrics and Gerontology, Obu, Japan.  2) Shiley Eye Institute, University of California, San Diego, San Diego, CA, United States. 3) Section of NILS-LSA, National Center for Geriatrics and Gerontology, Obu, Japan.  4) Sports and Health Sciences, Aichi Shukutoku Univ, Nagakute, Japan.  5) Graduate School of Nutritional Sciences, Nagoya Univ of Arts and Sciences, Kitanagoya, Japan. All authors have no financial interests to disclose. World Cornea Congress VII 2015 San Diego

Introduction The reported rate of human corneal endothelial cell (CEC) loss is about 0.3-1% per year throughout adult life. Factors such as ophthalmic surgery can increase the rate of endothelial cell loss, which can lead to bullous keratopathy. The rate of naturally occurring human corneal endothelial loss by epidemiological research has not been fully explored.

Objective Primary: To investigate the rate of corneal endothelial cell loss in middle-aged and elderly Japanese subjects with no history of ophthalmic surgery using the severity grading system established by the Japanese Corneal Society. Secondary: To assess the relationship between corneal endothelial cell loss in the right versus left eye in subjects with no history of ophthalmic surgery.

Subjects 2nd National Institute for Longevity Sciences – Longitudinal Study of Aging (NILS-LSA). (2000–2002) 2,259 participants (1,178 males, 1,107 females, average age 59.8±11.4 y/o) ▪Presence of CEC density data from right eye. ▪ Primary objective selection criteria and ▪No surgical history of OD eye. 1,919 participants (997 males, 922 females, average age 59±11.1 y/o) ▪Secondary objective selection criteria ▪No surgical history of OS eye. 1,762 participants (905 males, 857 females, average age 58.7±11.1 y/o)

What is NILS-LSA? The National Institute for Longevity Sciences – Longitudinal Study of Aging (NILS-LSA) is a population-based study consisting of 2,267 randomly-selected males and females aged 40 to 79 years. The research area included Obu city (population 79,000) and Higashiura town (population 48,000). Those areas are located in the south of Nagoya. They contain suburban and industrial areas, but also have many orchards and farms. Thus, the study locations possess both urban and rural characteristics. Unlike the colder climate of Northern Japan and the warmer climate of Southern Japan, the climate in this study area is mild. Obu city Higashiura town ★ NILS Obu city and Higashiura town. Each area is about 12 square miles and is located close to Nagoya city. 5 mile Nagoya city JAPAN

Methods CEC density was assessed using a specular microscope (SP-2000; Topcon), and classified by severity grading for corneal endothelial damage. Data obtained from the OD eye were classified by the patient’s age group (40’s, 50’s, 60’s, 70’s, 80’s) and sex (male, female). Statistical analysis was conducted using the Statistical Analysis System (SAS9.6, SAS Institute, Cary, NC, USA). In multivariable analysis, CEC density was set in a general linear model (GLM) as the outcome variable. Predictor covariates included sex and age group. Trend analysis was performed to assess change in CEC density across age groups. We also performed correlation analysis to investigate relationships of CEC density between OD and OS eyes. ■Severity grading for corneal endothelial damage Severity grade Range of CEC density Normal CEC density≥2,000 cells/mm2 Grade 1 2,000 cells/mm2>CEC density≥1,000 cells/mm2 Grade 2 1,000 cells/mm2>CEC density≥500 cells/mm2 Grade 3 500 cells/mm2>CEC density Grade 4 Could not measure due to presence of bullous keratopathy ●Kinoshita S, Amano S, Inoue Y, et al. Grading for corneal endothelial damage. Nihon Ganka Gakkai Zasshi.;118:81-3,2014

Results Age (years old), mean±SD 59.0 ± 11.1 Sex, decades, n (%) Male 　　Female 59.0 ± 11.1 total 997 252 (25.3) 262 (26.3) 251 (25.2) 222 (22.3) 10 (1.0) total 922 224 (22.6) 259 (26.1) 229 (23.1) 199 (12.0) 11 (1.1) Participants in the second wave of NILS-LSA　

Results * CEC density was significantly higher in men than in women (cells/mm2) Corneal endothelial cell density CEC density was significantly higher in men than in women (F=10.35, *p=0.0013).

Results Male Female Proportion of subjects by severity grade Age group Age group The proportion of participants with normal CEC density decreased with age, but remained ≥90% in both sexes. In contrast, the proportion of participants with Grade 1 CEC density increased with age. The proportion of participants with Grade 2-4 CEC density was relatively low across all age groups.

Results (cells/mm2) Corneal endothelial cell density Trend analysis revealed that CEC density decreased significantly with age (F=6.14, p=0.0133).

Results CEC density; OD 2,681±332.2 OS 2,687±330.1 (cells/mm2) CEC density of the OD eye is strongly correlated (r=0.83) with that of the OS eye in patients with no history of ophthalmic surgery.

Conclusion In every age group, almost all study subjects had either normal or Grade 1 CEC densities. There is a strong positive correlation between endothelial cell density of the right and left eye in subjects with no history of ophthalmic surgery. The sharp reduction of corneal endothelial density might be caused by ophthalmic surgery or eye disorder with an onset rate less than detection-limit (0.3% within the 95% confidence limit).