ASSOCIATION OF FUNCTIONAL VISION AND ORTHOPTIC TESTING WITH HIGH RESOLUTION OCT FINDINGS IN PATIENT WITH NEURODEGENERATIVE DISORDES

This project aims to explore the associations between clinical, retinal imaging, and functional vision testing in patients with neurological diseases, focusing on Multiple Sclerosis (MS). The primary objective is to identify potential biomarkers and establish a framework for monitoring treatment responses. Specifically, we investigate abnormality in Visual Evoked Potential (VEP), Visual Field (VF), Contrast Sensitivity (CS), and Color Vision in patients affected by clinically and radiologically typical MS, as well as those MS patients presenting with "red flags," indicating atypical signs for MS (MS-plus group). Our ultimate goal is to establish a relationship between functional testing and Optical Coherence Tomography (OCT) in the early diagnosis and follow-up of neurological disorders. BACKGROUND: Neurological diseases, such as Multiple Sclerosis (MS), pose significant diagnostic and management challenges. Identifying reliable biomarkers and developing effective methods for monitoring treatment responses are critical for improving patient outcomes.. MS is an autoimmune condition primarily affecting the central nervous system, leading to inflammation and damage to the nervous tissue. It is a complex disease influenced by various genetic and environmental factors, with an onset typically between the ages of 15 and 45, more commonly affecting females. Given the complexity of MS, it is crucial to identify reliable biomarkers for early diagnosis and effective treatment monitoring. METHODS: Patient Selection: Patients referred from the Neurology Department to the Eye Clinic at AOU Careggi, Florence, Italy, between October 2022 and June 2023 were evaluated using functional tests. Inclusion criteria included patients with relapsing-remitting MS (RRMS) exhibiting typical clinical and radiological features, as well as a subgroup referred to as "MS-plus," who met predefined criteria. Exclusion criteria consisted of contraindications for MRI scans, specific ophthalmological conditions, and a history of ocular surgery or trauma. Diagnostic Evaluations: All patients underwent neurological evaluations, with MRI using T2 FLAIR sequences performed by an experienced neurologist. MRI assessed white matter lesions (WML) in the central nervous system. Patients were categorized based on the presence of the central vein sign (CVS) in more or less than 50% of perivenular lesions (PVLs). Functional Testing: 1. Visual Field Testing: Visual Field was performed for all patients using Zeiss Humprey 740 Visual Field Analyzer. The central 30 degrees field of the retina was analyzed, and parameters such as Mean Deviation (MD) and Pattern Standard Deviation (PSD) were recorded. 2. Contrast Sensitivity (CS): CS was assessed using the CSO – Vision Chart in monocular vision. This test evaluated contrast sensitivity at different spatial frequencies (SF) using sine-wave gratings. 3. Color Vision: A pseudochromatic Vision Chart Plate Test CSO assessed color vision using specially designed pseudo colors. The test aimed to identify color vision deficiencies (Protan, Deutan, Tritan plates). 4. Visual Evoked Potential (VEP): Pattern reversal VEPs were recorded using the CSO RETIMAX system. The stimuli were black and white checks presented at 15 and 60 degrees. Parameters recorded included latencies of N75, P100, and N135, as well as amplitude N75–P100. Results: A total of 27 patients (54 eyes) were evaluated in the study. In the MS group (defined as Typical), nine patients exhibited typical clinical features of MS. In the MS-plus group, 18 patients met specific criteria, with 10 in MS+0 (less than 50% PVLs) and eight in MS+1 (more than 50% PVLs). Notably, patients with a history of monolateral optic neuritis were included in both groups. A comparison of patients with and without prior optic neuritis manifestations revealed no significant differences in the visual parameters. Color Vision: The study found a prevalent Tritan deficit in all three MS groups, with no significant differences in the number of missed plates for each type of color vision defect. Contrast Sensitivity: Patients in the MS+0 group (less than 50% CVS in WML) showed worse contrast sensitivity on all spatial frequencies compared to MS+1 and MS Typical, although the differences were not clinically significant. Visual Field: The MS+0 group exhibited worse MD and PSD values compared to MS+1 and MS Typical. However, the correlation was not statistically significant, except for a borderline trend in PSD values. Visual Evoked Potential: The results showed no significant difference between ON and NON eyes, with small sample sizes limiting the analysis. Amplitude and latency variations in VEPs were observed, but their clinical significance was unclear. A comparison of the three MS groups indicated no significant differences in visual functional parameters. However, the small sample size of the MS+0 group could potentially affect the statistical significance of the results. Conclusion: This preliminary research project aimed to investigate the potential of various functional tests, as biomarkers in neurological diseases like MS. The study focused on both typical MS cases and MS-plus cases presenting with atypical signs, particularly assessing the presence of the central vein sign in white matter lesions (WML). The findings suggest that certain trends exist within these functional tests, although the sample size was limited. The study found color vision deficits, with a prevalent Tritan deficiency among the tested patients. Contrast sensitivity appeared to be worse in patients with less than 50% central vein sign in their WML, although the differences were not statistically significant. Visual field parameters were more affected in the MS+0 group than in the MS+1 and MS groups, but once again, statistical significance was not achieved. Visual Evoked Potentials showed variations in amplitude and latency, but clinical significance remained unclear. The limitations of the study primarily revolve around the small sample size, which could hinder the detection of statistically significant differences. Additionally, the results indicated trends rather than definitive conclusions, which emphasizes the exploratory nature of this research. Further investigations with larger sample sizes and more comprehensive data collection are needed to confirm and extend these findings. Future studies should explore correlations between functional vision testing and retinal imaging, particularly Optical Coherence Tomography (OCT), as a potential avenue for identifying robust biomarkers. Establishing a clear relationship between functional testing and retinal imaging may lead to more accurate and timely diagnosis, as well as improved monitoring of treatment responses in neurological diseases like MS.