LETTER

Dear Editor:

Thank you for publishing the interesting and thought-provoking article “Vitreous Research: The Oxygen Story” (May 2012 Retinal Physician by Nancy M. Holekamp, MD). I would like to raise the following for your consideration:

► 1. Regarding the level of oxygen in the central vitreous, the article mentions a direct and inverse relationship between the concentration of ascorbate and the level of oxygen in the central vitreous. Further, it is clarified on page 21 that this phenomenon of hypoxia is maximal in cadaver vitreous in an intact gel state (indicating that only ascorbate concentration and not living vitreous was a prerequisite for the phenomenon of hypoxia) and that stirring made the cadaver vitreous lose its power to create hypoxia (indicating that the creation of hypoxia was also dependent on the physical state of the vitreous).

From this, it is evident that the phenomenon of midcavity hypoxia was best created by a vitreous gel rich in ascorbate, which was independent of whether the vitreous was in a living patient or a cadaver. Hence, it is evident that this capacity of the vitreous is clearly a chemical property (relying on ascorbate) that depends on its physical state (gel/liquefied), and it is not a biological or physiological property. However, in addition to the above, the possibility of additional oxygen depletion by the presence of any cellular components of the vitreous cannot be ruled out (which was not evaluated in the article).

► 2. Regarding the issue of hypoxia and the lens, the author’s third reference¹ clearly notes that in normal phakic patients, the oxygen concentration was lower in front of the lens in the posterior chamber than in the anterior chamber. After cataract surgery, in the presence of an intact vitreous, it was found that the concentration of oxygen was significantly higher in the posterior chamber, indicating that the lens also actively consumes oxygen (probably the anterior capsular cellular components).

Further, in the same reference, it is clarified that vitrectomy surgery increased the oxygen concentration in the posterior chamber and that vitrectomy grossly increased the concentration of oxygen in the posterior surface of the lens. This finding could have been due to the direct diffusion of oxygen from the oxygen-rich retinal and uveal tissues tracking to the posterior surface of the lens. I do not wish to debate whether this is the only direct cause of increased cataract incidence. However, I wonder whether if it is only the physical gel-like state of the vitreous that acts as a mechanical barrier for the diffusion of oxygen to the posterior lens surface, as evident from the 48% increase in concentration postvitrectomy. This fact suggests a mechanical, rather than a biochemical, protective property of the vitreous.

► 3. Further, to confirm her hypothesis, the author analyzed the oxygen concentration of the vitreous before vitrectomy surgery (3 mL). It is worth considering that vitrectomy is usually performed in diseased eyes (previous vitreoretinal pathology) and hence this analysis could be erroneous and not as relevant as analyzing standard controls would be.

► 4. Finally, I refer to the increased incidence of cataract occurring after vitrectomy surgery. If hypoxia secondary to vitrectomy is the only cause of cataracts, why is it not common across all ages, sexes, and races after vitrectomy? Shouldn’t we give due consideration to the idea that rapid fluidics, chemical changes (antibiotics/gas/oil/steroids), and possible micromechanical damage to the posterior lens surface during surgery could be additional causes of cataracts, rather than increased oxygen concentration alone?

In conclusion, a larger, multicentric, and more detailed study would shine more light into this intriguing and interesting component of the eye. Perhaps in the future, we will see vitreoretinal surgeons injecting gel into the eye to re-form the vitreous cavity after vitrectomy.

Azimuddin Azim Siraj, MD Brunei

REFERENCE

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

Response

BY NANCY M HOLEKAMP, MD

Thank you for your interest in “Vitreous Research: The Oxygen Story.” I would like to respond to a few of the points you raised.

► 1. You correctly conclude that midvitreous cavity hypoxia was best created by a vitreous gel rich in ascorbate, independent of whether the vitreous was in a living patient or a cadaver. My research colleagues and I were able to rule out the possible role of any cellular components contributing to hypoxia by boiling the vitreous. After boiling cadaver vitreous, the oxygen consumption was unchanged.

► 2. You correctly conclude that the crystalline lens also consumes oxygen. As an aside, the corneal endothelium and ciliary body epithelium also demonstrate oxygen consumption.

Further, the presence of an oxygen concentration gradient in the vitreous cavity indicates that active consumption of oxygen by the vitreous gel — and not diffusion — is creating an oxygen sink. The role of the gel nature of the vitreous is to avoid “mixing” of the oxygen in the posterior chamber so that convection currents do not flow along the retinal surface, thereby increasing available oxygen. The retina and the other vascularized tissues of the eye are the source of oxygen.

► 3. While it is true that the vitreous experiments were performed on patients undergoing retinal surgery, patients with macular holes or macular puckers do not have a diseased vitreous. It is interesting to note that vitreous oxygen consumption depended only on the physical (gel vs liquid) state of the gel and not the retinal pathology.

► 4. It is true that hyperoxia secondary to vitrectomy is the only cause of postvitrectomy nuclear sclerotic cataract. This phenomenon is seen in all sexes and races in patients older than age 50. (My research group and I have published extensively on the only exception: patients with ischemic diabetic retinopathy. The vasculature is so diseased that there is no postvitrectomy hyperoxia.) Before age 50, the lens has the capacity to consume oxygen and protects itself for many years from nuclear sclerotic cataract.

Finally, I agree with you that more research in this area is needed. Ideally, surgeons could reform the vitreous gel after vitrectomy surgery and prevent postvitrectomy nuclear sclerotic cataract.RP

Nancy M. Holekamp, MD
Pepose Vision Institute
Saint Louis, MO