Medical Journal of Dr. D.Y. Patil Vidyapeeth

: 2019  |  Volume : 12  |  Issue : 4  |  Page : 376--377

Eye as a window to the brain in central nervous system diseases

Samanthila Waduthantri 
 Department of Ophthalmology, Singapore National Eye Centre, Singapore Eye Research Institute, Singapore

Correspondence Address:
Samanthila Waduthantri
Department of Ophthalmology, Singapore National Eye Centre, Singapore Eye Research Institute

How to cite this article:
Waduthantri S. Eye as a window to the brain in central nervous system diseases.Med J DY Patil Vidyapeeth 2019;12:376-377

How to cite this URL:
Waduthantri S. Eye as a window to the brain in central nervous system diseases. Med J DY Patil Vidyapeeth [serial online] 2019 [cited 2020 Jul 4 ];12:376-377
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Full Text

Anterior visual pathway, including the retina and optic nerve, is an integral part of the central nervous system (CNS), as they share similar embryologic origins, anatomic features, physiological properties, and regulatory mechanisms.[1] Therefore, it is not surprising that CNS pathologies frequently affect the eye, and ocular manifestations often precede the diagnosis of CNS disease. This implicates that ophthalmic investigations could offer a means of the early diagnosis.

In the article titled “Eye as a window for glioblastoma multiforme-case reports,” authors described three cases of glioblastoma multiforme that presented with optic disc swelling which prompted the ophthalmologist to order neuroimaging. According to the authors, there were no ocular complaints at presentation, and optic disc swelling was noted during routing ophthalmic evaluation. Although the conclusion of this article is not particularly novel, it emphasizes the importance of eye examination in patients presenting with neurological symptoms.

Ophthalmic signs and symptoms such as decreased visual acuity, visual field defects, ophthalmoplegia, papilledema, and optic atrophy may occur as initial presentation in 46.8%–88.6% of the patients diagnosed with a primary intracranial tumor due to raised intracranial pressure, compression of cranial nerves or tumor infiltration of intraocular structures, and adnexa.[2],[3],[4] It is estimated that, in up to 95% of the cases, the intracranial tumor can cause progressive loss of vision and/or visual field defects over weeks to months before the initial diagnosis of the tumor. A pituitary adenoma is the most common tumor that impairs the structures of the visual pathway, followed by craniopharyngioma, posterior fossa tumor, and meningioma.[2],[3],[4] A pituitary microadenoma accounts for approximately 96.5% of the nonfunctioning pituitary adenomas.[5] It is estimated that 67.8% of these cases present with visual field defects and the ophthalmologist may be the first person to diagnose the pituitary tumor in these patients. Changes in the visual field can be used to monitor the progression or recurrence of the tumor. Xie et al.[6] suggested that new or worsening visual field defects might indicate tumor progression in patients with glioblastoma multiforme and should prompt further investigation.

Neurological diseases such as primary CNS lymphoma and multiple sclerosis (MS) often masquerade as chronic intraocular inflammation.[1] Studies have revealed that optic neuritis provide a useful clinical model with which to couple of clinical measures of visual function with validated and objective structural and physiological correlates of MS.[7] It is estimated that 20%–40% of MS patients initially present with optic neuritis and approximately 80% of the cases develop optic neuritis at some point during the course of their disease.

Several studies have demonstrated the potential use of high-definition optical coherence tomography of peripapillary and macular retinal nerve fiber layer (RNFL) as an adjunctive diagnostic and prognostic tool in CNS diseases. Danesh-Meyer et al.[8] reported that the long-term visual recovery after surgical decompression of pituitary lesions is predicted by the preoperative RNFL thickness. Trip et al.[9] reported that RNFL thinning in MS exists independent of a history of optic neuritis. Peripapillary RNFL as well as composite ganglion cell layer–inner plexiform layer thickness inversely correlated with the intracranial volume in MS patients.[10] Another study reported that lower foveal and pericentral neuroretinal thickness was associated with damaged white matter microstructure, in terms of lower fractional anisotropy and higher mean and radial diffusivity in HIV-infected children.[11]

Small cerebral vessels and retinal microvasculature share similar anatomical and physiological features. Therefore, the changes in retinal microvasculature can be used as a biomarker marker for cerebral small-vessel diseases. Recent studies have shown that certain retinal microvascular abnormalities such as retinal fractal dimension reduction, small-caliber retinal arteriole, arteriovenous nicking, retinal hemorrhages, and microaneurysms are associated with stroke.[12] Retinal vasculature abnormalities such as narrower venular caliber, decreased arteriolar and venular fractal dimension, and increased arteriolar and venular tortuosity have been observed in patients with Alzheimer's disease.[13]

The locus coeruleus in the brainstem has a significant role in pupil response due to increased cognitive activity in the brain. Granholm et al.[14] suggested task-evoked pupillary response as a psychophysiological biomarker of early risk for Alzheimer's disease. Dysfunctions of saccadic and/or smooth pursuit eye movements have been proposed as bio markers of obsessive-compulsive disorder, schizophrenia, and autism.[15]

In conclusion, ocular features can be considered as a window through which we can detect certain CNS disorders. Published literature emphasizes the importance of eye examinations as potential screening tools for CNS diseases. Development of efficient and reliable screening tools is imperative since the diagnosis is often made in the advanced stages of the disease. Although neuro-imaging such as MRI is the current gold standard in diagnosing and monitoring of CNS diseases, visual function tests and ocular imaging may provide low-cost noninvasive alternative approach in the primary health-care settings, in particular, where resources are limited.


1London A, Benhar I, Schwartz M. The retina as a window to the brain-from eye research to CNS disorders. Nat Rev Neurol 2013;9:44-53.
2Onakpoya OH, Komolafe EO, Akintomide F, Ajite K, Komolafe MA, Adeolu AA, et al. Ophthalmic manifestations in patients with intracranial tumors. Afr J Neurol Sci 2009;28:55-60.
3Tagoe NN, Essuman VA, Fordjuor G, Akpalu J, Bankah P, Ndanu T, et al. Neuro-ophthalmic and clinical characteristics of brain tumours in a tertiary hospital in Ghana. Ghana Med J 2015;49:181-6.
4Sefi-Yurdakul N. Visual findings as primary manifestations in patients with intracranial tumors. Int J Ophthalmol 2015;8:800-3.
5Ferrante E, Ferraroni M, Castrignanò T, Menicatti L, Anagni M, Reimondo G, et al. Non-functioning pituitary adenoma database: A useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol 2006;155:823-9.
6Xie K, Liu CY, Hasso AN, Crow RW. Visual field changes as an early indicator of glioblastoma multiforme progression: Two cases of functional vision changes before MRI detection. Clin Ophthalmol 2015;9:1041-7.
7Balcer LJ. Clinical practice. Optic neuritis. N Engl J Med 2006;354:1273-80.
8Danesh-Meyer HV, Wong A, Papchenko T, Matheos K, Stylli S, Nichols A, et al. Optical coherence tomography predicts visual outcome for pituitary tumors. J Clin Neurosci 2015;22:1098-104.
9Trip SA, Schlottmann PG, Jones SJ, Li WY, Garway-Heath DF, Thompson AJ, et al. Optic nerve magnetization transfer imaging and measures of axonal loss and demyelination in optic neuritis. Mult Scler 2007;13:875-9.
10Saidha S, Sotirchos ES, Oh J, Syc SB, Seigo MA, Shiee N, et al. Relationships between retinal axonal and neuronal measures and global central nervous system pathology in multiple sclerosis. JAMA Neurol 2013;70:34-43.
11Blokhuis C, Demirkaya N, Cohen S, Wit FW, Scherpbier HJ, Reiss P, et al. The eye as a window to the brain: Neuroretinal thickness is associated with microstructural white matter injury in HIV-infected children. Invest Ophthalmol Vis Sci 2016;57:3864-71.
12Wu HQ, Wu H, Shi LL, Yu LY, Wang LY, Chen YL, et al. The association between retinal vasculature changes and stroke: A literature review and meta-analysis. Int J Ophthalmol 2017;10:109-14.
13Cheung CY, Ong YT, Ikram MK, Ong SY, Li X, Hilal S, et al. Microvascular network alterations in the retina of patients with Alzheimer's disease. Alzheimers Dement 2014;10:135-42.
14Granholm EL, Panizzon MS, Elman JA, Jak AJ, Hauger RL, Bondi MW, et al. Pupillary responses as a biomarker of early risk for Alzheimer's disease. J Alzheimers Dis 2017;56:1419-28.
15Jaafari N, Rigalleau F, Rachid F, Delamillieure P, Millet B, Olié JP, et al. A critical review of the contribution of eye movement recordings to the neuropsychology of obsessive compulsive disorder. Acta Psychiatr Scand 2011;124:87-101.