7.28 Optic ischemia

Did you know that Johann Sebastian Bach (1685-1750; portrait on a stamp, mit one of the Brandenburg Concertos, see above) was blinded by acute angle-closure glaucoma a few months before he died? Also, Messrs Jose Feliciano, Stevie Wonder, and the late Ray Charles all suffered from congenital glaucoma? And former Minnesota Twins baseball all-star, the Hall-of-Famer, Kirby Puckett (1960-2006) was blinded by glaucoma in his right eye?

What kind of damages you ask? Well, the definition of glaucoma especially that of OAG (open-angle glaucoma) keeps changing. It is a sign of progress; although, the answer to "what is glaucoma?" is no longer straightforward. Perhaps in the next few years, we'll know the whole story. For now, we can only work with what we have.

We'll narrow down the discussion a bit to only open-angle glaucoma: OAG has traditionally been regarded as a topical (as opposed to a systemic) issue. In other words, if the intraocular pressure (IOP) is high, then the eye may suffer pressure-induced damages to the retina and the optic nerve, in the form of ischemia. The treatment is then to normalize the pressure using pharmaceuticals. The problem is in some cases, medicine alone seems ineffective, the disease process continues nonetheless. In low-tension glaucoma, the IOP is actually normal, yet the glaucoma-related ocular damages still occur. So, something else apparently is going on, but what is it? Is it associated with systemic circulation? Shall we now institue systemic neuro-protection? And to complicate the situation even further: It also should be noted that a high IOP does not always lead to OAG.

Even more basic: How do we know optic ischemia is involved? Or more accurately, how do we measure the oxygen level in the optic nerve under high IOP? Short of inserting an oxygen-sensing electrode into the optic nerve itself, there isn't really any good way. One can opt to study animal models or examine post-mortal glaucomatous eyes. However, to perform the measurement in the humans in vivo, a special technique is needed. This is known as T2*(pronounced T2-star)-weighted or BOLD (Blood Oxygen Level Dependent) MRI - used in functional MRI of the brain. This technique takes advantage of de-oxygenated hemoglobin being a paramagnetic which disturbs the homogeneity of a magnetic field. And an increase in oxyhemoglobin, i.e., blood oxygenation, reduces this paramagnetic effect, hence an increase in the MR signal intensity.

We have invited some volunteers for a BOLD-MRI study. Using a home-made surface coil for the eye/orbit and T2* MRI performed before and after a bolus injection of Diamox, a vasodilator via its pH lowering effect. The change in MR signals in the optic nerve near the optic disc is then determined. The results are tabulated below:

Change in image intensity in the optic nerve of normal and glaucomatous patients

Diagnosis	Time after Dx	IOP (mmHg) at MRI	Treatment history	Residual Visual Field	Optic Nerve (% change)
Normal	--	15-16	none	--	+12.1 ± 2.2 (N=4)
POAG atypical, unilateral (IOP=48 at time of Dx)	2 years	17-27	0.25% Timolol	Upper temporal quadrant	+10.6
POAG	3 years	23-29	0.5% Timolol	Lower temporal quadrant	+0.0
POAG	18 years	20	0.5% Timolol	Cetral 10° +lower temporal quadrant	-10.5
POAG Secondary to trauma?	23 years	20	argon laser trabeculotomy + 0.5% Timolol	Central 5-10°	-14.9

Note: The 4 normal volunteers are all ultra-dedicated ophthalmology residents. And the study has been approved by the IRB.

Just look at the last column. Intriguing results, we might add. They essentially confirm that in the optic nerve of the living humans, as the glaucoma advances, blood oxygen level decreases. In other words, ischemia!!

Granted this is a small study. A large scale study will have to await further developments in MRI technology: (1) even higher magnetic fields (e.g., > 1.5 Tesla) to increase the signal intensity and shorten the scan time; and (2) much reduced scanning costs to justify the utilization of MRI of the eye/orbit. There has been a recent proposal that the glaucomatous changes go beyond the eye, all the way through the optic track, the LGN, ultimately to the visual cortex. Then T2* MRI will prove the only practical means for assessing ischemic changes in the whole visual pathway.

Note: For those interested, the seminal paper on fMRI (i.e., Echo-planar BOLD-MRI) is this one:

Kwong KK, Belliveau JW, Chesler DA, Goldberg IE, Weisskoff RM, Poncelet BP, Kennedy DN, Hoppel BE, Cohen MS, Turner R, Cheng HM, Brady TJ, Rosen BR: Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci (USA) 1992;89:5675-5679.