Giorgio Bianciardi1*, Maria Eugenia Latronico2 and Claudio Traversi2
1Department of Medical Biotechnologies, University of Siena, Siena, Italy
2Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
Received: 30 January, 2016; Accepted: 03 March, 2016; Published: 07 March, 2016
Bianciardi Giorgio, MS, MD, PhD, Department of Medical Biotechnologies, University of Siena, Siena, Italy, E-mail:
Bianciardi G, Latronico ME, Traversi C (2016) Mass Dimension Evaluation of the Optic Nerve Head Microvascularity in Non-Glaucomatous Optic Neuropathies. Int J Oral Craniofac Sci 2(1): 006-010. DOI: 10.17352/2455-4634.000012
© 2016 Bianciardi G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Mass dimension; Fractal analysis; Optic neuritis; Nonarteritic anterior ischemic optic neuropathy; Differential diagnosis
In several diseases, fractal analysis has been proven useful to give contribution in diagnosis and prognosis of the patient and to improve treatments. In the present work we have evaluated the mass dimension of the vascular pattern of optic nerve head in non-glaucomatous optic neuropathic patients and healthy controls. Static fluorescein angiogram was performed and the images of the early venous phase were saved. A manual outline of the trajectories of the two-dimensional vascular network was performed down to vessels of 20 micron diameter, processed to threshold the vessel network without background interference and converted into an outline of single pixels and then the fractal analysis was performed. Mass dimension evaluation of the optic nerve head microvascularity was able to differentiate health condition vs. non-glaucomatous neuropathies (p<0.01), as well optic neuritis vs. nonarteritic anterior ischemic optic neuropathy (p<0.01), with high sensitivity and specificity (p<0.0001; p<0.0001). Mass dimension index shows a significantly increased vascular complexity of the optic nerve head in cases compared with controls, also permitting to distinguish between patients affected by optic neuritis vs. nonarteritic anterior ischemic optic neuropathy. This new, fast, unexpensive, methodology may be used in helping the clinician to perform the differential diagnosis between the pathologies and to study the effect of therapies during the follow up of the patient.
Fractal analysis is a very useful tool in the understanding of many phenomena in various fields, such as astrophysics, economics, biology and medicine. Interesting results have also been achieved in bacteriology, medical imaging and ophthalmology (e.g. diabetic retinopathy) [1-6].
Retinal vascular network in healthy subjects has a value of fractal dimension , close to the value of a Diffusion-Limited Aggregation (DLA) process (D≈1.70) , while in pathologic condition that value changes deeply. We can recall papers by Cavallari et al. , that showed a reduction in complexity of retinal vessels, reflecting the alteration of the brain microvessels in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ) and the ones by Doubal et al. , that found a low value of retinal vessels fractal dimension associated to the lacunar stroke and by Ţalu et al. that, recently, showed that fractal analysis is able to characterize the human non-proliferative diabetic retinopathy . In these works, fractal analysis has been demonstrated a sensitive tool to assess changes of retinal vessel branching, able to reflect the early microvessel alterations in human pathology. Moreover, the retina vessels network, described by generalized dimensions and singularity spectrum, has a multifractal structure (an object having different fractal properties in its different region) . These multifractal approaches were able to characterize the retinal vascular architecture disorder in several diseases [11,13,14].
At initial presentation, the differential diagnosis between optic neuritis (ON) and nonarteritic anterior ischemic optic neuropathy (NAION) is difficult to be performed on clinical grounds, both giving overlapping clinical profiles . However, it is fundamental to establish an early differential diagnosis, having the ON patient a clear tendency to develop multiple sclerosis, a disease where therapies should be performed as early as possible . In order to verify whether the fractal analysis of the optic nerve head microvascularity could help in the differential diagnosis between ON and NAION, we have evaluated the mass dimension of the optic nerve head vascular pattern, as revealed by fluorescein angiography.
Patients with unilateral NAION or unilateral idiopathic ON were recruited from the Department of Ophthalmology of the University of Siena. Each patient underwent a complete neuro-ophthalmic examination, including assessment of visual acuity, colour vision, papillary reaction, slit-lamp examination, applanation tonometry, Goldman visual field testing, visual evoked potentials, dilated fundoscopy and fluorescein angiogram.
The criteria for patients’ admittance with NAION to the study were: unilateral disc swelling with clinical features consistent with NAION , no recovery of visual function in the first month of follow up, exclusion of arteritic anterior ischemic optic neuropathy either on clinical grounds or following a negative temporal artery biopsy, negative magnetic resonance imaging of the brain and orbits, no other ocular pathology, no neurological diseases that might influence or explain the patient’s visual symptoms. The patient admittance criteria with ON for the present research were: unilateral visual impairment associated with impaired colour vision and visual-field loss, presence of disc oedema, young age (≤ 35 years), ocular pain associated with eye movements, recovery of visual function in the first month of follow up, no other ocular pathology, no neurological diseases that might influence or explain the patient’s visual symptoms; history or detection of multiple sclerosis confirmed the diagnosis .
Nine cases of NAION and nine cases of ON with presence of optic disc oedema were enrolled without any selection. The unaffected eye of the patient was used as control (n=10). All patients were examined using a fluorescein angiogram within the first two weeks after they reported the first symptoms and before treatments; all patients gave informed consent. The protocol for this research project was approved by the Ethics Committee of the University of Siena and it conforms to the provisions of the Declaration of Helsinki, 1955 (as revised, Edinburgh, 2000).
Static fluorescein angiogram was performed (IMAGEnet 2000,v.2.0, Topcon). The early, intermediate and late phases of the angiogram were studied. Images of the early venous phase of the angiogram (around 20 seconds) gave the best visualization of the optic disc vessels and were saved. The same magnification was used for every patient.
A manual outline of the trajectories of the two-dimensional microvascular network was performed down to microvessels of 20 micron of diameter, processed to threshold the vessel network without background interference and converted into an outline of one pixel by means of Jmicrovision, http://www.jmicrovision.com, and Image Analyzer, http://www.fosshub.com/Image-Analyzer.html, softwares.
Mass Dimension (Dm)
The images were represented on a graphic window of 500 x 500 pixels (1 pixel = 4 μm). To evaluate the mass dimension of the pattern, the set was covered with circles of radius r, (from 20 to 200 pixels), and the amount of pixels (ni) inside the circles was evaluated . A log-log plot was performed. The plot of the logarithm of ni against the logarithm of r produced a straight line with a slope equal to Dm.
The methodology was implemented using Benoit 1.3 software (TruSoft Int’l Inc, http://trusoft-international.com/.html) and validated measuring computer generated Euclidean and fractal shapes of known mass dimensions. Inter- and intra-observers errors were < 3%.
Mann-Whitney’s U test was used in order to compare the mass dimension indexes and to ascertain the significance among the groups; regression analysis was used to ascertain the log-log plot linearity. Receiver Operator Characteristic (ROC) were obtained with XLSTAT software (www.xlstat.com). Variance analysis was used in order to ascertain the dipendence of the fractal index by age or gender.
Images of the early venous phase of the angiogram (around 20 seconds) gave the best visualization of the optic disc vessels (Figure 1).