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Diffusion Tensor Imaging Detects Rarefaction of Optic Radiation in Glaucoma Patients

Rationale and Objectives

Diffusion tensor imaging (DTI) can depict rarefaction of the optical fibres. Hence, we applied DTI to assess pathological changes of the optic radiation in glaucoma patients.

Materials and Methods

Fifty glaucoma patients and 50 healthy age-matched controls were examined by a 3T high-field magnetic resonance scanner. Fiber tracts were volume rendered using a semiquantitative approach to assess rarefaction and results were correlated with the extent of optic nerve atrophy and reduced spatial-temporal contrast sensitivity of the retina using established ophthalmological examinations.

Results

Twenty-two glaucoma patients (44%) showed significant rarefaction of the optic radiation: the volume was reduced to 67 ± 16% compared with controls. Hereby, the glaucomatous optic nerve atrophy stage correlated with the presence of DTI-derived rarefied optic radiation (Kendall tau-b 0.272, P = .016). Aside, cerebral microangiopathy affecting the optic radiation was significantly higher among glaucoma patients compared to controls (10 patients compared with 2 patients, P < .05).

Conclusion

In patients with glaucomatous optic nerve atrophy, there is anterograde and—most likely because of microangiopathic lesions within the optic radiation—retrograde transneuronal rarefaction of the optic radiation that can be assessed in vivo using DTI with good correlation to established ophthalmological examinations.

Transneuronal degeneration is a process of primary neuron injury affecting the linked distal neurons. It was described for pathophysiological changes in neurological diseases such as Alzheimer disease and brain trauma . More recent studies have suggested that this damage also occurs in the development of glaucoma .

Loss of ganglion cells in the retina (first and second neuron of the visual pathway) and their axons representing the optic nerve (third neuron) and a loss of astrocytes is, because of an increased intraocular pressure, the predominant finding in glaucoma. The axons of various retinal ganglion cell subtypes, differing in specific morphology and function, exit the eye ball, and finally converge to anatomically distinguishable layers of the lateral geniculate nucleus (LGN) where a loss of neural cells has also been described for glaucoma . The LGN serves as a relay station transmitting the information via the optic radiation (fourth neuron of the visual pathway) to the primary visual cortex .

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Methods

Patient Population

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Figure 1, Woman, 68 years of age OD/OS with primary open angle glaucoma, in OS a parapapillary bleeding of the optic nerve head. (a) In both eyes (OS [left] > OD [right]) the automated perimeter showed predominantly superior visual field defects due to a loss of axons of the 3rd neuron. (b) The frequency doubling test indicated impaired spatial-temporal contrast sensitivity primarily in OS in the superior and temporal area as well as nasal near the center. (c) Typical signs of glaucomatous optic nerve atrophy were recorded by a non-mydriatic fundus camera that is in OS a small rim area, smaller inferior rim than temporal and a parapapillary bleeding (arrows). (d) DTI shows intact optic radiation in a healthy 67-year-old woman without any visual disturbances. (e) DTI reveals significant rarefication of the optic radiation compared to the age-matched control (arrows). DTI, diffusion tensor imaging; OD, right eye; OS, left eye.

Figure 2, Generalized microangiopathy was coexistent with optic nerve head damage in 30 of 49 patients. Here, 10 patients showed remarkable microangiopathic lesions within the optic radiation (8 patients with glaucomatous optic nerve atrophy and 2 patients with nonglaucomatous optic nerve atrophy, respectively) and DTI revealed rarefication of the optic radiation in 8 of these 10 patients. An example is given in (a) and (b) (T2-weighted fluid-attenuated inversion recovery [FLAIR] sequence). DTI, diffusion tensor imaging.

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Grading of Optic Nerve Head Damage

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Determination of the Frequency Doubling Test Score

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MRI

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Assessment of Microangiopathy

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Data Analysis

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Results

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Table 1

Concomitant Diseases of the Glaucoma and Control Population

Concomitant Disease Glaucoma Patients Controls Arterial hypertension 23 19 Arterial hypotension 1 0 Hypercholesterolemia 14 11 Diabetes 4 2 Brain infarction 3 2 Myocardial infarction 1 1 Peripheral arterial disease 1 2 Affections of the thyroid gland 9 6 Cancerogenic diseases including brain 7 6 Hyperuricemia 3 2 Failure of heart or cardiac valves 3 5 Surgery of carotid artery 1 2 Multiple sclerosis 1 0

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Ophthalmic Examination

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Table 2

Characterization of the Glaucoma Patients by Ophthalmologic Findings

Ophthalmologic Findings in Glaucoma Patients Mean SD Age (y) 57.3 15.9 FDT duration

(≤50 s) OD 66.7 34.8 OS 72.0 33.0 FDT score

(≤5) OD 13.5 16.4 OS 14.1 13.9 Mean defect

(≤4) OD 4.8 6.1 OS 4.3 5.3 Corrected refraction OD 0.76 0.30 OS 0.73 0.26 IOP

(<22 mm Hg) OD 14.9 4.2 OS 15.3 4.3 HRT disk area

(1.69‒2.82 mm 2 ) OD 2.326 0.596 OS 2.353 0.643 HRT cup area

(0.26‒1.27 mm 2 ) OD 1.051 0.512 OS 1.108 0.611 HRT rim area

(1.20‒1.78 mm 2 ) OD 1.276 0.511 OS 1.246 0.613 RNFL thickness

(0.18‒0.31 mm) OD 0.194 0.062 OS 0.194 0.124

OD, right eye; OS, left eye; FDT, frequency doubling test (loss of spatial-temporal contrast sensitivity: A = mild relative >95%, B = moderate relative >98%, C = severe >99%; number of fields of a maximum of 17); FDT score, sum of fields multiplied by A*1, B*2, and C*3. Mean defect, visual field defect determined by Octopus perimeter; IOP, intraocular pressure; HRT, Heidelberg retinal tomograph; RNFL, retinal nerve fiber layer.

Normal values are given in brackets.

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Table 3

Grading of Optic Nerve Atrophy in the Right/Left Eye of Glaucoma Patients

Grading of Optic Nerve Atrophy in Glaucoma Patients

Right Eye/Left Eye 0 1 2 3 4 Total 13/13 8/11 9/10 7/5 12/10 49/49

Grading 0 = normal optic nerve head, 4 = substantially advanced damage of the optic nerve head.

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MRI

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Table 4

Microangiopathy in Glaucoma Patients and Controls

Glaucoma Patients Controls Statistics MA 30 20P < .05 No MA 20 30P < .05 MA inside the optic radiation 10 2P < .05 MA outside the OR 20 18P = .87 Rarefaction of the OR with MA inside the OR 8 0P < .05 Rarefaction of the OR with MA outside the OR 9 0P < .05 Rarefaction of the OR without MA 5 0P < .05

MA, microangiopathy; OR, optic radiation.

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Correlation between Ophthalmic Examination and MRI

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Discussion

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