Author Affiliations: Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Smith-Kettlewell Eye Research Institute, San Francisco, California. Dr Parsa is now with the Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin–Madison.
It has long been known that little correlation exists between visual function and tumor size with respect to optic gliomas (World Health Organization grade I juvenile pilocytic astrocytomas).1- 3 Surprisingly, however, a deterioration in visual function in those harboring such masses is still often taken as clinical evidence of tumor progression and used to justify intervention for lesions that otherwise may have failed to demonstrate any growth.4
An understanding of why deterioration of clinical function may not be a sign of tumor progression but could actually indicate glioma regression may help to better resist physician and family impulses to intervene.5
Optic gliomas are congenital in origin. Masses formed within the central nervous system in utero may influence the subsequent apoptosis of excess axons,6 in effect molding themselves in relative harmony with remaining axons to allow maximal visual function despite the presence of what may otherwise appear to be an impressive tumor. Nonetheless, following the final organization of visual pathways, subsequent growth could alter such an in utero–established arrangement. Optic gliomas are also intrinsic to the optic nerve. Thus, the hamartomatous overgrowth of glial cells with supporting tissue elements that normally surround each axon, should it occur in uniform fashion, may not necessarily impede axoplasmic flow and neuronal signaling. Neurons remain functional and viable with elevated pressures uniformly distributed.7,8 Pressure applied focally, on the other hand, particularly from tumors arising extrinsic to a nerve, can easily create pressure gradients that pinch axons and block axoplasmic flow, thus producing subsequent atrophy.8 As an analogy, just as a human can withstand high pressure evenly distributed, such as is generated by several tons of water when near the bottom of a swimming pool, it could nonetheless poorly tolerate even a fraction of such pressure were it to be applied focally, such as by an elephant resting its foot on a person's torso (Alfredo A. Sadun, MD, PhD, oral communication, February 2009).
Hence, some optic gliomas can be large congenitally or noted to continue to grow to great extents along considerable lengths of the visual axonal pathways without causing any perceptible loss of visual acuity or function.1- 3 Others much smaller but with less uniform growth may compress or kink axons focally, causing considerable visual morbidity.1- 3
It should then be of no surprise that an intrinsic lesion shrinking in nonuniform fashion could also give rise to inhomogeneities and pressure gradients causing kinking of axons and loss of function,3,8 just as an enlarging tumor might do. Such an apparently paradoxical worsening of vision is acknowledged during the medical treatment of prolactinomas. While external compression of the chiasm may produce an initial visual field loss, following successful medical involution of the pituitary tumor, the chiasm itself may herniate into an enlarged and relatively empty sella. In some cases, this may result in traction and kinking of axons with renewed loss of function.9 Likewise, although the intracranial pressure diminishes following cerebrospinal fluid leaks, deterioration of visual function can also be expected when the brain, no longer buoyed by fluid, settles onto the skull base and compresses the chiasm with pressure points between the brain and pituitary fossa.10 Keeping such alternative processes in mind, one can comprehend the futility of using functional testing such as visual evoked potentials to monitor the progression of optic gliomas.
To summarize, spontaneous regression of gliomas is not a rare occurrence and can be accompanied by loss of vision.3 Some medical practitioners misinterpret loss of function, either clinically or by means such as visual evoked potentials, as evidence of tumor progression. This can misguide them to initiate unproven treatment modalities for gliomas that are already beginning to shrink. They may subsequently attribute efficacy to a purported remedy for an eventually detected reduction of glioma size. Particularly when trying to assess the beneficial effects of future therapies in investigational trials, such errors should not be allowed to occur.
Correspondence: Dr Parsa, Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin–Madison, 2870 University Ave, Ste 206, Madison, WI 53705 (firstname.lastname@example.org).
Financial Disclosure: None reported.
Previous Presentation: This paper was presented at the 37th Annual Meeting of the European Paediatric Ophthalmology Society; October 13, 2011; Thessaloniki, Greece.
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