Original article
Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema☆

https://doi.org/10.1016/S0002-9394(01)01269-7Get rights and content

Abstract

PURPOSE: To investigate the relationship between diabetic macular edema and the levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in aqueous humor and plasma.

DESIGN: Comparative cross-sectional study.

METHODS: Fifty-four eyes from 54 diabetic patients were used. The concentrations of VEGF and IL-6 in undiluted aqueous specimens (obtained from the eyes during cataract surgery) and in plasma were measured by an enzyme-linked immunosorbent assay. To assess blood-aqueous barrier function, the aqueous flare intensity was measured by a laser flare-cell meter as an estimate of the aqueous protein level.

RESULTS: The aqueous levels of VEGF and IL-6 were significantly correlated with the severity of macular edema (ρ = 0.628, P < .001 and ρ = 0.517, P < .01, respectively), as well as with the aqueous protein concentration (ρ = 0.618, P < .001 and ρ = 0.588, P < .001, respectively). Aqueous levels of VEGF and IL-6 were significantly higher than their respective plasma levels (both P < .001). In addition, the aqueous level of VEGF was significantly correlated with that of IL-6 (ρ = 0.537, P < .01). Furthermore, the status of the posterior vitreous significantly correlated with the severity of macular edema (ρ = 0.618, P < .0001).

CONCLUSIONS: These results suggest that both VEGF and IL-6 are produced together in the intraocular tissues, and are involved in the pathogenesis of macular edema.

Section snippets

Subjects

: We obtained undiluted aqueous humor samples and corresponding plasma samples from 54 diabetic patients (54 eyes) undergoing cataract surgery (Table 1). There were 27 men and 27 women with a mean age of 62.5 years (range, 38 to 70 years). The mean duration of diabetes was 16.9 years (range, 1 to 28 years) and the mean one-year average HbA1c value was 7.3% (range: 5.4% to 12.9%). The protocol for sample collection was approved by the institutional review board and all patients gave informed

Severity of retinopathy and macular edema

The severity of retinopathy was as follows: 14 eyes were level 10, 10 eyes were level 20, 18 eyes were level 35, 4 eyes were level 43, 4 eyes were level 47, and 4 eyes were level 53. There were 28 eyes with no macular edema, 18 eyes with focal macular edema, and 8 eyes with diffuse macular edema or CME. The average preoperative visual acuity was 20/40 (range: finger motion to 40/50). The visual acuity was 20/40 or better in 28 eyes, 20/50 to 20/100 in 22, and 20/100 or worse in 4.

Severity of macular edema and cytokine levels

: The VEGF

Discussion

The major findings of this study were as follows : (1) the aqueous levels of VEGF and IL-6 are closely correlated with the severity of macular edema, (2) VEGF and IL-6 levels in the aqueous humor are higher than the corresponding plasma levels, (3) aqueous levels of VEGF and IL-6 are strongly correlated with the aqueous protein concentration, (4) the status of the posterior vitreous is correlated with the severity of macular edema, and (5) the aqueous levels of VEGF, IL-6, and protein are

Acknowledgements

We thank Dr. Shigehiko Kitano, Dr. Yuichiro Nakanishi, Dr. Kensuke Haruyama, and Dr. Shinko Nakamura for their assistance in collecting the aqueous and plasma samples and performing the ophthalmologic examinations. We also thank Dr. Yasuhiko Iwamoto and Dr. Naoko Iwasaki for their assistance in performing the general medical examinations. Finally, we would like to thank Katsunori Shimada for conducting the statistical analysis.

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    ☆

    This study was supported by a Health Science Research Grant (#10060101, to Drs. Funatsu, Hori, and Yamashita) from the Japanese Ministry of Health and Welfare for Research on Eye and Ear Sciences, Immunology, Allergy and Organ Transplantation.

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