Reduced Field-of-view DTI In The Optic Nerve Of Patients With Retinitis Pigmentosa

Background and purpose Retinitis pigmentosa(RP) is a common refractory visual disease, and accounts for a large proportion of hereditary visual impairment. It is characterized by the progressive death of rod and cone photoreceptors, which leads to corresponding visual field(VF) defects. As a heterogeneous group of inherited retinal degenerative diseases, RP displays extreme genetic heterogeneity. More than 80 disease genes have been identified so far, 58 of which correspond to non-syndromic RP. Clinical features of RP include night blindness, progressive loss of peripheral VFs, reduced or non-detectable electroretinogram amplitudes, and characteristic pigmentary degenerative changes of the retina. Several studies had observed that the retinal nerve fiber layer, formed by expansion of optic nerve(ON) fibers, is significantly thinner in RP patients using optical coherence tomography, which reflects the changes of the ON in RP. Furthermore, the occurrence of optic neuropathy in RP was confirmed by a postmortem study that showed that total axon counts of the ON were significantly decreased in end-stage RP patients compared to normal controls. However, in vivo diagnosis of optic neuropathy in RP patients remains challenging as conventional MR imaging and ophthalmological exams often fail to detect ON disease. Recently, DTI has emerged as a noninvasive imaging method with great potential to investigate the morphology and function of ON in vivo. However, there has been no study of DTI in optic neuropathy of RP to date, especially reduced filed-of-view DTI(r FOV-DTI) at 3T that has the potential advantages of improved signal-to-noise ratio(SNR) and reduced susceptibility related artifacts over conventional DTI. This study set out to investigate the potential clinical utility of r FOV-DTI in diagnosing optic neuropathy in RP at 3T. In specific, we hypothesized that quantitative r FOV-DTI might be able to reveal the injury to the ON of RP, which may be related to visual functions including both VF and visual acuity(VA).Materials and methods Thirty-eight patients(24 men, 14 women; 37±15 years; range, 6–62 years) and thirty-five healthy controls(22 men, 13 women; 36±14 years; range, 9–60 years) were enrolled in this study, with both eyes of each participant involved. Routine MR imaging of the brain and orbits was performed to exclude intracranial and intraorbital diseases on a 3T scanner(Discovery MR 750, GE Healthcare, Waukesha, WI; 50 m T/m maximum gradient strength and 200 m T/m/s maximum slew rate) with a 8-channel head coil. A r FOV-DTI sequence with 2D-RF was used to derive fractional anisotropy(FA), mean diffusivity(MD), principal eigenvalue(λ//), and orthogonal eigenvalue(λ⊥) of the individual ONs. Mean FA, MD, and eigenvector maps were obtained for quantitative analysis. In addition, measures of visual field(VF) and visual acuity(VA) were also performed on all subjects. Humphrey Field Analyzer(HFA) was used to measure mean deviation of visual field(MDVF). The best corrected VA was converted to the logarithm of the minimal angle of resolution(log MAR) units. Quantitative MDVF and VA were also obtained for quantitative analysis. For DTI measurement, Differences between patients and controls and differences between right and left eyes of patients were evaluated by using independent-samples t test and paired t test respectively. Meanwhile, spearman correlations of all DTI parameter values of optic nerves with the MDVF, as well as the VA, were calculated.Results 1. No morphological and signal intensity abnormality of the ONs in RP patients was observed on rutine orbital MR imaging. 2. The ONs of RP patients as compared with control subjects, showed significantly higher MD, λ//, λ⊥ and significantly lower FA(P<0.01); while no significant difference between right and left optic nerves in patient group(P>0.05) were seen. 3. For patients with RP, MDVF of ON was significantly correlated to mean FA(r=0.364, P=0.001) and λ⊥(r=-0.254, P=0.029), but not correlated to mean MD(P=0.154) and λ//(P=0.337). Moreover, no correlation between any DTI parameter and VA in RP patients was observed(P>0.05).Conclusion 1. The present study demonstrated that r FOV-DTI measurements of the ON may reflect pathological conditions in RP patients and may serve as a biomarker of axonal and myelin damage in the optic neuropathy of RP. 2. The use of r FOV-DTI in optic neuropathy of RP may allow early assessment of the status of the ON in this patient group. 3. The alterations of ON reflected in r FOV-DTI measurements would also be valuable for assessing treatment trials in RP patients.