Intraocular Oxygen Distribution in Advanced Proliferative Diabetic Retinopathy

doi:10.1016/j.ajo.2011.02.014

American Journal of Ophthalmology

Volume 152, Issue 3, September 2011, Pages 406-412.e3

https://doi.org/10.1016/j.ajo.2011.02.014 Get rights and content

Purpose

To determine the preretinal distribution of oxygen in advanced proliferative diabetic retinopathy, and to investigate the relationship between intraocular oxygen tensions and vitreous cytokine concentrations.

Design

Comparative cross-sectional study.

Methods

Oxygen levels were measured at sites in the vitreous and at the inner retinal surface using an optical oxygen sensor in 14 control subjects and in 14 subjects with advanced proliferative diabetic retinopathy who had developed tractional retinal detachments despite previous panretinal photocoagulation. The vitreous and plasma concentrations of 42 cytokines were measured using multiplex cytokine arrays and their correlation with intraocular oxygen tension was investigated.

Results

The mean oxygen tension in the mid-vitreous in diabetic retinopathy was 46% lower than that in control subjects (P = .017). However, the mean preretinal oxygen tension at the posterior pole in diabetic retinopathy was 37% higher than in controls (P = .039). We measured significant alterations in the vitreous concentrations of 9 cytokines—eotaxin, Flt-3 ligand, growth-related oncogene (GRO), interleukin (IL)-6, IL-8, IL-9, IFN-inducible protein-10 (IP-10), macrophage-derived cytokine (MDC), and vascular endothelial growth factor (VEGF)—in advanced proliferative diabetic retinopathy, and found that oxygen tension at the posterior pole was directly correlated with vitreous VEGF concentration.

Conclusion

We identified significant intraocular oxygen gradients in proliferative diabetic retinopathy. Our findings are consistent with the hypothesis that VEGF induces the development of neovascular complexes in the posterior retina that are richly perfused but nonetheless fail to redress hypoxia in the mid-vitreous. Upregulation of vitreous VEGF may be a consequence of retinal hypoxia at unidentified sites or of chronic inflammatory processes in advanced proliferative diabetic retinopathy.

Section snippets

Study Population

We recruited 14 individuals having vitrectomy surgery for advanced proliferative diabetic retinopathy and 14 control subjects having surgery for idiopathic epiretinal membrane or full-thickness macular hole. Informed consent was obtained from all subjects prior to entering the study. Exclusion criteria were any history of previous intraocular surgery or the presence of intraocular hemorrhage or inflammation. All subjects included in this study were phakic. Because systemic hyperoxia can

Ex Vivo Assessment of Sensor Accuracy

To determine the reliability of the oxygen sensor before and after gas sterilization, we tested 6 probes in 6 sealed containers filled with a range of gas mixtures of known oxygen tensions (0-147.4 mm Hg). We identified very strong correlations between sensor readings and actual oxygen tensions, both before (Pearson correlation 0.997, P = .0001) and after gas sterilization of the probes (Pearson correlation 0.996, P = .0001). We also determined that illumination of the sensor by the

Discussion

The importance of ischemia-induced expression of retinal cytokines in the development of diabetic retinopathy is widely accepted. However, direct evidence of retinal hypoxia is weak and there have been no direct measurements of retinal oxygen in humans. In this study we tested the feasibility of measuring preretinal oxygen tension in advanced diabetic retinopathy in human subjects who had developed preretinal neovascularization and tractional retinal detachments involving the macula despite

Clemens Lange is a Clinical Research Fellow at the Institute of Ophthalmology and Moorfields Eye Hospital in London. His main focus of research is in the field of molecular oxygen-sensing, angiogenesis and retinal vascular disease.

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Original articleIntraocular Oxygen Distribution in Advanced Proliferative Diabetic Retinopathy

Purpose

Design

Methods

Results

Conclusion

Section snippets

Study Population

Ex Vivo Assessment of Sensor Accuracy

Discussion

Prog Retin Eye Res

Am J Ophthalmol

Exp Eye Res

Am J Ophthalmol

Surv Ophthalmol

Exp Cell Res

J Obstet Gynecol Neonatal Nurs

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Surv Ophthalmol

Diabetes Res Clin Pract

Blood

Retinal oxygen: fundamental and clinical aspects

Arch Ophthalmol

HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia

PLoS One

Mechanisms of retinal and choroidal neovascularization

Invest Ophthalmol Vis Sci

The retinal oxygen profile in cats

Invest Ophthalmol Vis Sci

Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia

J Gen Physiol

[Vitreous oxygen tension of proliferative diabetic retinopathy]

Nippon Ganka Gakkai Zasshi

The gel state of the vitreous and ascorbate-dependent oxygen consumption: relationship to the etiology of nuclear cataracts

Arch Ophthalmol

The effect of the retinal circulation on vitreal oxygen tension

Curr Eye Res

Effect of increased oxygen on the development of the retinal vessels; an experimental study

Br J Ophthalmol

Original article
Intraocular Oxygen Distribution in Advanced Proliferative Diabetic Retinopathy