Disclosed are devices, systems and methods for non-invasive neuromodulation system for treating inherited or acquired retinal, choroidal and optic nerve disorders caused by acute or chronic dysregulated reduced ocular blood flow (OBF) and/or energy failure by up regulation of trigemino-vascular system (TVS), trigeminal autonomic brain reflexes (TABRs) and pancreatic trigemino-vagal reflex (TVR) through stimulation of ophthalmic nerve (V1), more specifically but not limited to SP, and CGRP containing unmyelinated C nerve fibers. The invention, in some embodiments thereof, relates to the methods for enhancing SP and CGRP expression in neurovascular tissue of the retina and choroid. The invention, in some embodiments thereof, relates to SP/CGRP mediated pathways, including those involved in vasodilatation, augmentation of OBF, RPE proliferation, prevention of apoptosis, suppressing neuroinflammation, promoting migration and differentiation of vascular endothelial cells as well as mobilization of endogenous mesenchymal stem cells (EMSCs) from the bone marrow to the circulation to accelerate tissue repair. The site of stimulation of V1 nerve includes but not limited to; nasal vestibule nasal bridge, forehead, and upper eyelids. Additionally or alternatively, the subject's sympathetic nervous system (SNS) is down regulated by sympatholytic agents specifically antioxidants. The subject's TVS and autonomic nervous system (ANS) are modulated in a manner that is effective to treat the subject for retinal, choroidal and/or optic nerve disorders. In some embodiments, the devices are handheld, portable with nose supported, having one or more intra-nasal or extra-nasal application heads. The signal can include vibration, chemical, ultrasonic, optical, electrical, hybrid electro-optical or combination of two or more of these types of stimuli. The invention, in some embodiments thereof, relates to a method for decreasing vascular resistance, enhancing vasodilatation in ophthalmic artery and its branches by the release of Vasoactive intestinal peptide (VIP),substance P and CGRP thereof increasing OBF to the retina, choroid and optic nerve in subject's with acute or chronic dysregulated, reduced OBF. The invention, in some embodiments thereof, is also related to the methods for improving delivery of oxygen, glucose, vitamin A, humoral mediators, growth factors, stem cells and pharmacological agents to the targeted tissues of the retina, choroid and optic nerve. The invention, in some embodiments thereof, relates to the methods for improving pancreatic insulin secretion, thereof to enhance glucose uptake by PRs and other retinal cells. Additionally or alternatively, the invention relates to restoration of transduction of signaling in cone PRs by ONS induced glutamate release. The methods of the invention, in some embodiments thereof, include priming of the retina choroid and optic nerve thereof to enhance the efficacy of cell transplantation therapy. The methods of the invention, in some embodiments thereof, also include identifying a subject prone to or suffering from a disease or condition associated with reduced OBF. Methods of the invention, in some embodiments thereof, may also include monitoring the subject for prophylactic treatment where the patients are at pre-clinical stage of the disease. The OBF of subjects who had received neuromodulation treatment may also be monitored for re-treatment. 
     The present invention, in some embodiments thereof, relates to a method and/or device for treatment of dysregulated reduced blood (e.g. reduced ocular blood flow) and, more particularly, but not exclusively, to methods and/or devices for treatment retinal, choroidal and optic nerve disorders. Optionally, treatment may include application of an effective amount of ONS ophthalmic nerve stimulation alone and/or in combination with pen-ocular administration of substance Neuropeptides/Platelet Rich Plasma (N/PRP) and/or ascorbic acid as a sympatholytic agent