Journal of Neuro-Ophthalmology, September 2015, Volume 35, Issue 3

Should Visual Restoration Therapy be Used in Patients With Visual Field Loss?

Should Visual Restoration Therapy be Used in Patients With Visual Field Loss? Neil R. Miller, MD, Prem S. Subramanian, MD, PhD Visual field loss, and homonymous hemianopia in particular, results in major morbidity by causing impaired mobility and reading (1). Treatment options are limited, and few if any such therapies are supported by high-quality evidence. Visual restoration therapy is thought to expand the impaired hemi-field and result in functional recovery, but the reputed benefit is controversial. Two experts debate the use of vision resto-ration therapy in patients with visual field loss. Pro: Visual Restoration Therapy: Prem S. Subramanian, MD Vision restoration therapy is designed to improve or restore function in the damaged hemifield through stimulation of remaining viable neuronal tissue in the affected cerebral cortex (2), redirection of the visual processing through alter-nate pathways that arise through neuroplasticity (3), or a com-bination of these processes. Evidence for neuroplasticity has been obtained from animal studies showing recovery of visual field loss after visual deprivation in young (4) and adult animals (5-7), and these experiments, in part, generated ini-tial and continuing interest in human visual field restoration. Using a suprathreshold flickering threshold, Sabel and col-leagues devised a computer-based method to map and then stimulate the border zone of visual field defects, where improvement through retraining was most likely to occur. They published the first clinical study of vision restoration therapy in patients with either optic nerve-based or retrochias-mal visual field loss (8). This initial report demonstrated some effectiveness (30% of patients improving) for the retrochiasmal lesions but even greater improvement in patients with optic nerve disease (72% improved). Their work led to development of a commercially available vision restoration therapy system (NovaVision, Boca Raton, FL), and many practitioners adopted the technology to treat a cohort of patients in whom options were generally limited to compensatory strategies rather than methods to improve lost function. This training was time consuming and often expensive for patients because costs were not covered by U.S. health insurance. Nonetheless, promising results were reported in published case series, and the majority of patients reported subjective improvement after therapy (9-11). Controversy then arose over the use of vision restoration therapy because of concerns that binocular training and testing may induce fixation arti-facts or vergence movements that could be perceived as visual field improvement. Indeed, small case series of patients trea-ted with various flickering stimulus regimens seemed to show that responses in the nonseeing field were not improved when fixation was monitored by methods different from those used in NovaVision vision restoration therapy (12). Despite these findings, researchers continued to explore the possibilities for restorative rather than compensatory training, and techniques that combine 2 or more stimulation modalities have shown therapeutic promise. Das and Huxlin (13) used a combined method of static and kinetic stimuli in patients with homonymous field defects and have reported more accurate and reproducible target detection in patients treated with dual stimulation rather than a static target alone. Research continues into determining the precise pathway by which this recovery is mediated (restored function within the damaged visual cortex vs recruitment of extrastriate visual pathways implicated in "blindsight"). Similarly, vision restoration therapy combined with transcranial direct cur-rent stimulation (tDCS) was found to be superior to vision restoration therapy alone, with changes on functional mag-netic resonance imaging correlating with the clinically mea-sured visual field recovery (14), and the improvement was more likely to persist after the training was concluded when compared with sham tDCS and vision restoration therapy. Application of vision restoration therapy to prechiasmal disease also has shown renewed promise with a randomized controlled trial conducted in a cohort of glaucoma patients who underwent monocular vision restoration therapy or placebo stimulation in the intact field daily for 3 months (15). The vision restoration therapy group showed signifi-cant improvement on high-resolution perimetry with gaze tracking to control for fixation, and health-related quality of life improved in this group as well. Patients with visual field deficits face potential loss of occupation, mobility, and social interaction. Because they Departments of Ophthalmology, Neurology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. The authors report no conflicts of interest. Address correspondence to Neil R. Miller, MD, Woods 458, Wilmer Eye Institute, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287; E-mail: [e-mail] Miller and Subramanian: J Neuro-Ophthalmol 2015; 35: 319-322 319 Point Counter-Point Section Editors: Andrew G. Lee, MD Gregory Van Stavern, MD Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. may not have other physical disabilities, they may not receive the same societal recognition of their disability, and even eye care professionals may not appreciate the impact of visual field loss in patients who retain good Snellen visual acuity. Compensatory training, while important and often beneficial, is not intended to take advantage of the potential visual function that may be present in our patients. The value of early and aggressive rehabilitative therapy in motor stroke is well proven, and to deny our patients, the opportunity to recover visual function from damaged but viable areas of cortex would not seem appropriate. Con: Visual Restoration Therapy Should Not Be Used In Patients With Visual Field Loss: Neil R. Miller, MD Vision restoration therapy is based on the belief that there is some degree of plasticity in the central nervous system, even in adults. The theory is that visual neurons in the brain (e.g., in the occipital lobe) adjacent to an area of damage (e.g., from stroke, trauma) that are alive but not functioning normally may be induced to function normally again or may take over the role of the dead adjacent neurons. Although several publications have suggested that vision restoration therapy can improve the visual field in patients with homonymous hemianopia and, in doing so, improve a patient's ability to perform his/her daily activities and qual-ity of life (9,16-18), there are a number of issues that should make one question these claims. First, some of the patients were assessed shortly after the onset of their visual field loss. Zhang et al (19) showed that many patients with homony-mous field defects improve, usually within 3 months from onset. Thus, patients who begin vision restoration therapy shortly after developing a homonymous field defect and sub-sequently show definite improvement may have improved without vision restoration therapy. Second, it is bothersome that patient reports of subjective improvement in daily activ-ities after a 6-month course of vision restoration therapy do not correlate with visual field improvement. Some patients with apparent improvement in their visual field report no improvement in any daily activities, whereas others with no improvement in their visual field report improvement in one or more daily activities. Third, there is compelling evidence from Reinhard et al (12) that the apparent improvement in the field of patients with homonymous hemianopias who undergo vision restoration therapy is due not to expansion of the field but to micro eye movements. These investigators assessed 17 patients with homonymous hemianopia before and after vision restoration therapy using a scanning laser ophthalmoscope to monitor fixation. They found that no patients with steady fixation showed clear-cut visual field expansion. Finally, Roth et al (20) performed a randomized controlled study comparing objective and subjective results before and after flicker training (FT). These investigators used software that generated flickering letters in areas on either side of the vertical midline with equal times in blind and seeing hemifields. The patients were instructed to fixate centrally on a vertically aligned panel with letters and had to click the mouse within 10 seconds on the panel letter that was flickering. They found that FT produced no objective or subjective effects on the visual fields of any subjects tested. In the final analysis, vision restoration therapy is not harmful to a patient with an homonymous field defect, and if it were free or the cost were minimal, it would not be an unreasonable therapy as it might very well improve visual attention or, at the very least, provide a positive placebo effect; however, the cost of vision restoration therapy would seem to be excessive for what it provides to the patient. I believe that straight-forward techniques to improve visual attention and use of the patient's existing field are preferable to vision restoration therapy. Rebuttal: Prem S. Subramanian, MD Dr. Miller raises 2 major criticisms of vision restoration therapy. He suggests that it is not appropriate to start vision restoration therapy at an early time point because some individuals may recover function spontaneously in the first 6 months after vision loss. He also describes a number of alternative methods for helping patients with visual field loss, all of which rely on compensatory strategies and make no effort to improve detection of stimuli within the damaged visual field, and states that they are effective and less expensive than vision restoration therapy. Ideally, a randomized, double-masked, placebo-controlled prospec-tive clinical trial of vision restoration therapy might establish early intervention as the preferred method. Significant barriers including cost and difficulty in obtaining a matched subject population across multiple centers make such a trial challenging. In the absence of these data, we must rely on findings from other neurological syndromes and what is known about treatment. In reviewing the stroke literature, it becomes evident that if neurological function is to be restored and not just compensated for, then the treatment regimen must be instituted early. Animal models have 320 Miller and Subramanian: J Neuro-Ophthalmol 2015; 35: 319-322 Point Counter-Point Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. shown that early intervention leads both to reorganization of function in the intact uninjured cortex and to improved preservation and recovery of function in the injured brain. Rats exposed to a stimulating environment and reach training were found to upregulate expression of FosB/FosB, a marker of use-dependent neuronal activity in perilesional cortex (21). Uninjured animals had no change in gene expression when provided with identical treatment, nor did animals exposed only to either the enriched environ-ment or reach training alone. These data provide additional support for the development of strategies that combine com-plementary rehabilitation methods and may explain in part the seemingly modest and sometimes insignificant improve-ment observed with single intervention methodology. While it is true that some patients with homonymous hemianopia will experience spontaneous visual field recovery within the first 6 months, it is precisely during that period that the maximal potential for interventional treatment exists. The AVERT (A Very Early Rehabilitation Trial) protocol, which is designed to investigate return of motor function in hospitalized acute stroke patients, engages patients in active therapy within 24 hours of symptom onset. Even patients treated with thrombolytic agents are eligible. The study is currently in Phase III, but Phase II data demonstrated a statistically significant improvement in return to walking in the treated group when compared with standard stroke rehabilitation therapy (22). A large randomized trial in China of patients with hemorrhagic stroke, where outcomes are usually poor, showed that active rehabilitation within 48 hours was associated with markedly reduced mortality at 6 months (a 4-fold difference between the groups) and improved quality of life in survivors compared with patients who underwent standard therapy (23). Compensatory training including saccadic tasks, reading guides, high-power monocular or binocular sector prisms, and even patient-directed natural recovery all do result in improved visual and overall functioning. However, by definition, they are designed to help those patients in whom recovery of visual field is not expected. This is a laudable goal, and I do not take issue with the benefit of such methods. That does not mean that we cannot and should not also develop alternate treatment strategies for our patients. We must be willing to identify and enroll patients in well-designed clinical trials that provide early intervention and overcome our tendency to wait for spontaneous recovery and then rehabilitate only the patients who continue to have visual deficits. The data from our stroke patients and their counterparts in the laboratory are compelling, and we must not allow our patients to be captives of the natural history of their debilitating disease. Rebuttal: Neil R. Miller, MD I agree with Dr. Subramanian that, in general, the earlier one intervenes after an acute neurological deficit, the more likely it is that the patient will recover at least some function. In addition, there certainly is no physical or mental harm in early intervention, even if the patient would have improved without it. I also agree that, at least by functional imaging, the adult brain is, to some degree, capable of rewiring. Finally, I agree that our goal should be to expand the nonseeing field in patients with homonymous hemianopia. Having said this, I think he and I would agree that the perfect treatment for patients with homonymous hemianopia does not yet exist and that there are alternatives to vision restoration therapy that are far less expensive. They mainly relate to improving use of the existing field. First, many patients with homonymous hemianopia learn to use their remaining visual field quite effectively on their own. Unless the patient has associated visual inattention or other neurological deficits, he or she may be able to perform most daily activities without intervention. For patients with left homonymous hemianopia, a "reading screen" can be used. This is a black screen with an adjustable opening that helps patients find the beginning of each line. The same benefit can be achieved with a ruler or other straight-edged object posi-tioned under each line of text or placing a finger at the left edge of text (24) and using proprioception to determine where the next line of text begins. For patients with right homonymous hemianopia, there is an "inversion telescope" that enables patients to read from right to left rather than left to right (25), although the same benefit can be achieved by having the patient place a finger at the right edge of text, again using proprioception to determine where the text ends. As far as improving use of the existing field is concerned, it has been shown by several investigators that saccadic visual search training can be useful (20,24). In particular, Roth et al (20) assessed the usefulness of explorative saccade training (EST). These investigators used a laptop computer with a software program that generated a random array of digits (0-9, 12-point Arial font) that were distributed with equal probability on blind and seeing sides. The patient had to move the cursor over a predefined digit. Once the cursor passed over the correct digit, the program generated a sound ("beep") and the digit turned to a red "$." These investi-gators found that EST improved saccadic behavior, natural search, and scene exploration on the blind side associated with subjective improvement in activities of daily living. Finally, Fresnel prisms have been used to expand the exist-ing field. There are several options. Option 1 is to place a 30-prism diopter prism base out on the outside half of a spectacle lens on the side of the hemianopia. This is difficult for patients because the prism has no effect in Miller and Subramanian: J Neuro-Ophthalmol 2015; 35: 319-322 321 Point Counter-Point Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. primary gaze or when gaze is shifted toward the seeing hemifield. The prism induces pericentral field loss (apical scotoma) when gaze is shifted into it. The second option is for 15- or 20-prism diopter prisms to be placed base out on the spectacle lens on the side of the hemianopia and base in on the contralateral lens. These prisms have an effect only when gaze is directed into prism and may cause apical scotoma, diplopia, or both. The final option, which is the best as far as I am concerned, is to use monocular sector prisms. These prisms are effective at all gaze angles (26,27). In summary, I am hopeful that someday, we will have a method of expanding the hemianopic field that not only truly is useful but also is inexpensive. Until then, we are stuck with our current techniques, imperfect as they are. CONCLUSIONS Vision restoration therapy may be effective for select patients, but identifying patients who might benefit remains challenging, particularly given the time and expense of treatment. The treatments available for visual field loss are supported by studies that are often hampered by the lack of a control group and reliance on subjective end points that may or may not translate into real-world visual function. A large placebo-controlled treatment trial with objective clinical end points would provide greater support for routine use of vision restoration therapy in this patient population. For the time being, vision restoration therapy will likely remain one choice among many for patients with visual field loss. REFERENCES 1. Goodwin D. 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