Neuro-ophthalmology


Dr. Satya Karna
Associate Director, Ophthalmology,
Jaypee Hospital, Noida

High-field MRI scanning
Siemens won FDA clearance to introduce its 7 Tesla MRI scanner, the MAGNETOM Terra, last year. The device won European regulatory approval in August 2017, kicking off an age of high-field MRI scanning that produces imaging details previously unavailable in a clinical setting. The first such machine has been installed at the Mayo Clinic, Rochester in the US. This new MRI scanner could revolutionize diagnosis and treatment of brain tumors, stroke, demyelination and infective lesions of the brain.

An example is the case published in the Journal of Neurosurgery in March 2018, of a young doctor diagnosed with Cushing’s disease. At 1.5T and 3T MRI, her pituitary gland looked normal. At 7T, a low signal on the right side indicated the presence of a tumor. This non invasive technique helped the neurosurgeon define the exact location and size of the tumor and that helped in selective resection of the tumor, sparing other pituitary functions.

The MAGNETOM Terra is able to distinguish between the white and gray matter of the brain, a fact that can be useful when deciding on treatment options. For people with multiple sclerosis, the device can help identify lesions within the gray matter. Its ultrafine 0.2 mm in-plane anatomical resolution potentially enables visualization of previously unseen anatomical structures, as in the images below.

Advances in Optical Coherence Tomography (OCT)
A recent development in OCT that might help to understand the pathogenesis of visual loss in papilledema due to ischemia is phase contrast OCT. This technology allows to visualize capillaries and to quantify flow within a capillary bed.

OCT has been included in the most recent Multiple Sclerosis (MS) clinical trials1, and now is considered essential for assessing noninvasively, effectiveness of therapies that reduce axonal and neuronal loss by neuroprotective or myelin repair mechanisms. Developments that could improve understanding of MS in the future include OCT angiography, polarization-sensitive OCT (PS-OCT), and fluorescence labeling.

Progressive RNFL and ganglion cell- inner plexiform layer (GCIPL) thinning occurs as a function of time in patients with MS, even in the absence of Optic Neuritis, and is associated with clinically significant visual loss.

Lately, several studies have assessed the value of enhanced depth imaging optical coherence tomography (EDI-OCT) in diagnosing and evaluating Optic Nerve Head Drusen (ONHD). Deeper-penetration OCT imaging demonstrated the internal characteristics of optic disk drusen and their relationship with the lamina cribrosa in vivo. OHND appear as ovoid regions of lower reflectivity bordered by hyperreflective material. Both the larger the drusen are and the more area of the optic canal is occupied by drusen, the greater RNFL abnormalities are associated.

Optic nerve regeneration
Retinal projections are topographically arranged and orderly reconnection of axons with their central target is required. Whether mature axons can regenerate into the brain at their full length, navigate to appropriate target areas and restore visual function is being further investigated.

Recently, some degree of experimental optic nerve regeneration has been achieved by factors associated with inducing intraocular inflammation, providing exogenous neurotrophic factors, reactivating intrinsic growth capacity of mature retinal ganglion cells, or by modifying the extrinsic growth-inhibitory environment of the optic nerve.

Studies show that application of calcium channel inhibitors attenuated acute axonal degeneration3 and improved axonal regeneration after optic nerve crush, and suggest that clinical evidence of administration of calcium channel inhibitors could be future therapeutic interventions in traumatic and degenerative CNS disorders.

Advanced Technological Research
With rapid progress in medical research, a few of the not so unreal developments we could expect in the next decade:
• Intravitreal injection within 6 hours of onset for ischemic optic neuropathy to decompress the optic disc and prevent permanent damage. The novel drug QPI007 is under multicentric trial all over the world currently4.
• “Remyelinator” drugs to cure optic neuritis and traumatic optic neuropathy. Remyelination in MS is not impossible as research has shown today.
• “Microstents” to drain the CSF in idiopathic intracranial hypertension. The Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) studied patients with idiopathic intracranial hypertension and mild visual field loss. IIHTT confirmed that acetazolamide (500 mg BID, increasing to a maximum dose of 4 grams daily) was superior to placebo
treatment when combined with a supervised weight loss program, resulting in improved visual field loss, papilledema grade, weight reduction, lumbar puncture opening pressure, and quality of life.

Ongoing research efforts are nvestigating treatments for Leber hereditary optic neuropathy, nonarteritic ischemic optic neuropathy, thyroid eye disease, rehabilitation for post-stroke homonymous hemianopia and giant cell arteritis in adults, and idiopathic intracranial hypertension and optic nerve gliomas in children. The next decade will likely transform the field of neuroophthalmology as we better understand the molecular and genetic basis of neuro-ophthalmic disorders. We can anticipate significant therapeutic advancements, and perhaps cures, for individuals with severe, sight-impairing, neuroophthalmic conditions.

References
1. OCT: New perspectives in neuroophthalmology. Gema Rebolleda et al, Saudi J Ophthalmol. 2015 Jan-Mar; 29(1): 9–25.
2 The progress in optic nerve regeneration, where are we? Jennifer Wei Huen Shum, Kai Liu, Kwok-fai So, Neural Regeneration Research, January 2016,Volume 11,Issue 1.
3. Advances in experimental optic nerve regeneration. Bo Young Chuna, and Dean M. Cestari, Curr Opin Ophthalmol 2017, 28.
4. Phase 2/3, Randomized, Double- Masked, Sham-Controlled Trial of QPI-1007 in Subjects With Acute Nonarteritic Anterior Ischemic Optic Neuropathy (NAION), https://clinicaltrials.gov/ct2/ show/NCT02341560.
5. NORDIC Idiopathic Intracranial Hypertension Study Group Writing Committee. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss. JAMA. 2014;311(16):1641-1651.