The vitreous: Orphan of the eye

February 15, 2014

Ongoing research at the University of Washington-St. Louis suggests that degeneration of the vitreous is implicated, not only in retinal conditions, but in cataract and glaucoma as well.


Ongoing research at the University of Washington-St. Louis suggests that degeneration of the vitreous is implicated, not only in retinal conditions, but in cataract and glaucoma as well.

Dr. Beebe

Eye on Research By David C. Beebe, PhD, Special to Ophthalmology Times

The vitreous body, the clear, jelly-like substance that fills the posterior segment, is a rather neglected segment of the eye. It is discarded after vitrectomy and considered of little interest in a healthy eye. Few researchers have studied it directly. We know that the vitreous is a non-regenerative tissue that undergoes slow liquefaction with age. At the advanced stages of this degeneration, the risk of retinal tears, retinal detachment, and macular holes is increased.

Ongoing research in my lab at the University of Washington-St. Louis suggests that degeneration of the vitreous is implicated, not only in these retinal conditions, but in cataract and glaucoma as well. We’ve come to this recognition through a combination of eye bank tissue research and collaborations with observant clinicians who have provided access to human subjects undergoing vitreoretinal surgery.

The lens and the vitreous

With age, the human crystalline lens nucleus hardens and the rate of nutrient diffusion to the proteins in the center of the lens slows down dramatically. As cataract surgeons know, that harder nucleus is typically surrounded by a softer outer cortex. The cortex is full of viable cells with high levels of the protective antioxidant glutathione. But in the center of the aged lens, there is much less glutathione overall, and what is there is more likely to be the oxidized form rather than the protective reduced form of glutathione. These changes in the lens nucleus are responsible for presbyopia and nuclear cataracts, and likely play a role in the development of cortical cataracts, as well.

Yet, we understand little about what triggers this process.

A series of clues led us to suspect vitreous degeneration as the key to lens changes. The first clue was the discovery, while I was doing some research into lens development, that the genes expressed in 6-day-old chicken embryo lenses were characteristic of cells under hypoxic conditions.

Then, clinicians in Sweden observed that patients undergoing intensive hyperbaric oxygen therapy for systemic conditions such as artherosclerosis over a period of 1 year or more had some interesting ophthalmic side effects. All of the subjects became more myopic, with increased nuclear opacity, and about half developed frank nuclear cataracts.1

This suggests that oxygen, if it gets to high enough concentrations on the lens, becomes toxic and can somehow push the lens toward nuclear cataracts. (Figure 1)

It is also well known that patients undergoing vitrectomy for retinal surgery will generally develop nuclear cataracts within 2 years.

Based on all these clues-hypoxic chick embryo lenses and the rapid onset of nuclear cataract in eyes exposed to hyperbaric oxygen or vitrectomy-we proposed that the vitreous body keeps the lens in the hypoxic environment it needs to remain healthy.'


Testing the hypothesis

To test this theory, my associates and I collaborated with Nancy Holekamp, MD, a vitreoretinal surgeon in our department. Using a fiber optic device, we measured oxygen levels adjacent to the lens and in the mid-vitreous in patients undergoing retinal surgery. Measures were obtained before and after vitrectomy. We found that the lenses in the post-vitrectomy eyes were exposed to significantly more oxygen.2 (Figure 2)

The increased exposure to oxygen occurs as a result of removing the vitreous and is independent of the gauge of vitrectomy instrumentation.3

Next, we examined the state of the vitreous in eye bank globes. The eyes were graded by the percentage of vitreous liquefaction and degree of lens opacity. It turns out that the state of the vitreous is an even better predictor of nuclear cataract than age in eyes of donors between 50 to 70 years old.4

As the vitreous liquefies with age, I believe it gradually exposes the lens to more oxygen and that this exposure is largely responsible for the development of age-related nuclear cataract. It is still not clear why the vitreous degenerates earlier and more rapidly in some eyes and less rapidly in others, but it appears that the latter category of people are protected against nuclear cataracts until later in life.

In subsequent studies we noted that diabetics had lower levels of oxygen around the lens and in the vitreous, which could be protective if oxygen is the culprit in the development of nuclear cataract.5

It also turns out that diabetic eyes with ischemic retinopathy-clear evidence that the retina is hypoxic-show no significant progression of nuclear opacification for up to one year after vitrectomy.6

Nondiabetic and nonischemic diabetic eyes progress to cataract at the same rates, but the intraocular environment in the ischemic retinopathy eyes continues to be hypoxic even after vitrectomy.

Beyond the lens

Loss of the vitreous may also affect the trabecular meshwork. Stanley Chang, MD, noticed that his patients had a higher risk of primary open-angle glaucoma after vitrectomy and cataract surgery. We were able to show that he was right: Oxygen levels in the posterior chamber, anterior to the IOL, and in the anterior chamber angle were much higher in patients who had had both vitrectomy and cataract surgery.7

We also found some important racial differences in oxygen levels in the anterior segment. Prior to ocular surgery, African Americans have much higher intraocular oxygen levels, on average, than European Americans.8

This could be expected to increase oxidative damage to the outflow system over their lifetime. We don’t know whether the higher oxygen in African American eyes is due to genetic or environmental factors, but it could partly explain the large racial discrepancies in glaucoma incidence and risk.



Challenges ahead

These are fascinating studies, but there is much more to be done. Donor eyes and lenses will be a critical resource in the future, as we examine whether vitreous and lens changes can be prevented or reversed.

For example, we are now investigating whether specific compounds can be injected into the vitreous to restore its structure as a gel. The first clinical application for such compounds would likely be in cases where a very limited vitrectomy is being performed, but ideally, it could be injected even before there is separation from and damage to the retina. Initial feasibility studies are being conducted in animal eyes, but in order to translate this into human clinical trials, we’ll need to test the compound in donor eyes, as well.

We also hope to compare proteomic analysis of the structural components of the aged vitreous to that of vitreous from very young eyes to better understand how the vitreous body changes over time.

Much of our work to date has been done with local donor eyes not suitable for transplant. As we begin to require more specialized tissue (such as the very young eyes), there may be opportunities to work with the Lions Eye Institute for Transplant and Research (LEITR), which provides extensive resources for ocular tissue research and actively works to facilitate collaboration among scientists, clinicians, and industry. (See “About this series”)

Certainly, there are challenges inherent in dealing with ocular tissue or with patients in a clinical setting. The variability in human eyes is disconcerting to basic scientists who are used to tightly controlling variables. But we also learn a great deal from this variability about real-world applications.

Furthermore, our experience demonstrates how much we all have to gain from collaboration with one another. So often, observant clinicians have provided the key insights that sparked new areas of inquiry for our laboratory. In return, the basic science work that we do with eye bank tissue helps to move new therapies closer to clinical reality.

David C. Beebe, PhD, is the Janet and Bernard Becker Professor of Ophthalmology and Cell Biology at Washington University of St. Louis, MO. Readers may contact him at 314/362-1621 or



About this series

Eye on Research is a quarterly series of articles highlighting cutting-edge ophthalmic research with the potential to have significant impact on vision and ocular health worldwide. The series is supported by the Lions Eye Institute for Transplant and Research Inc. (LEITR), a nonprofit organization dedicated to the recovery, evaluation and distribution of eye tissue for transplantation, research and education. Located in Tampa, FL, LEITR is the only combined eye bank and ocular research center in the world. LEITR provides fresh donor globes, corneas, lenses, trabecular meshwork, and other tissues from diseased and healthy human eyes, often within 4 to 6 hours of death, to researchers for immediate use in their own labs or in its on-site research facility. For more information, contact or visit


(Figure 1) Color Scheimpflug photo of a nuclear cataract.

(Figure 2) Diagram of oxygen distribution in the eye before (left) and after (right) vitrectomy. (Images courtesy of David C. Beebe, PhD)



1. Palmquist BM, Philipson B, Barr PO. Nuclear cataract and myopia during hyperbaric oxygen therapy. Br J Ophthalmol. 1984;68:113-117.

2. Holekamp NM, Shui YB, Beebe DC. Vitrectomy surgery increases oxygen exposure to the lens: a possible mechanism for nuclear cataract formation. Am J Ophthalmol. 2005;139:302-310.

3. Almony A, Holekamp NM, Bai F, et al. Small-gauge vitrectomy does not protect against nuclear sclerotic cataract. Retina. 2012;32:499-505.

4. Harocopos GJ, Shui YB, McKinnon M, et al. Importance of vitreous liquefaction in age-related cataract. Invest Ophthalmol Vis Sci. 2004;45:77-85.

5. Holekamp NM, Shui YB, Beebe D. Lower intraocular oxygen tension in diabetic patients: possible contribution to decreased incidence of nuclear sclerotic cataract. Am J Ophthalmol. 2006;141:1027-1032.

6. Holekamp NM, Bai F, Shui YB, et al. Ischemic diabetic retinopathy may protect against nuclear sclerotic cataract. Am J Ophthalmol. 2010;150:543-550.

7. Siegfried CJ, Shui YB, Holekamp NM, et al. Oxygen distribution in the human eye: relevance to the etiology of open-angle glaucoma after vitrectomy. Invest Ophthalmol Vis Sci. 2010;51:5731-5738.

8. Siegfried CJ, Shui YB, Holekamp NM, et al. Racial differences in ocular oxidative metabolism: implications for ocular disease. Am J Ophthalmol. 2011;129:849-854.



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