The article by Robison and associates, titled “Vitreomacular Adhesion in Active and End-Stage Age-Related Macular Degeneration,” is an important one. It confirms prior findings in a larger study published by some of the authors in 2007. Both articles together strongly suggest a role of the vitreous gel in the pathogenesis of active exudative age-related macular degeneration (AMD) when the cortical vitreous is still attached to the macula. However, I find the potential mechanisms proposed by the authors to explain this striking finding to be unsatisfactory. In light of new information on a recently discovered biochemical property of the vitreous gel, I would like to propose another mechanism.

The vitreous gel has recently been found to consume molecular oxygen. In fact, the vitreous gel is an important regulator of intraocular oxygen tension. Molecular oxygen is perhaps the most potent anti-VEGF agent known. If the vitreous gel is adherent to the macula and the gel is actively lowering oxygen levels, then VEGF levels are likely to rise. It is well known that higher VEGF levels are pro-angiogenic in AMD. It is also well known that we physicians can manipulate VEGF levels in the vitreous gel to alter the course of exudative AMD, as we do routinely with therapeutic intravitreal injections of ranibizumab and bevacizumab. Perhaps the vitreous gel manipulates oxygen, and therefore VEGF, on its own.

One may ask why complete posterior vitreous detachment (PVD) appears to offer protection against exudative AMD. A plausible explanation comes from the work of Quiram and associates. They reported that PVD increases intraocular oxygen tension. Thus, in eyes with PVD, intraocular oxygen tension will be higher and VEGF levels are likely to be lower. This would create an anti-angiogenic vitreal environment surrounding the macula.

In summary, the authors report strong evidence that the vitreous gel may play a role in the development of active, exudative AMD. I concur and propose that the recently discovered ability of the vitreous gel to consume oxygen may be the mechanism by which this occurs.