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Show OUP UNCORRECTED PROOF – REVISES, 09/24/12, NEWGEN 8 summary and conclusions One of the most important functions in science is to reward those who disprove our most closely held beliefs. —Carl Sagan (1934–1996) IN THIS text, we have presented a synopsis of the past 50 years of our and many others’ ocular motor research relevant to the diagnosis and treatment of infants, children, and adults with infantile nystagmus syndrome (INS) and other benign types of nystagmus of infancy. Analogous to the assessment of afferent visual system function with the use of the electroretinogram (retinal level) and visual evoked potential (prechiasmal and postchiasmal levels), defi nitive diagnostic ocular motility criteria have now been established for all types of nystagmus appearing in infancy. The purely clinical signs of these types of nystagmus, albeit indispensable, are often ambiguous and reliance on them for fi nal diagnosis and treatment without quantitative motility data will continue to cause diagnostic errors that may be compounded by poor or inaccurate choices for therapeutic intervention. In many cases, both afferent and efferent visual function can be improved by the correct therapy applied in a timely manner. Unfortunately, only in selected centers of ophthalmological or neuro-ophthalmological research are ocular motility recordings now routinely available as part of the evaluation of nystagmus patients. Decades ago, cardiologists realized that they could not rely solely on their fi ngers and ears to accurately diagnose complex disorders of cardiac function. Clinical observation alone is no longer a valid or reliable way to evaluate ocular motor disorders. To paraphrase the magician, “the (patient’s) eye is quicker than the (physician’s) eye.” Recently discovered peripheral afferent neuroanatomy with its central ocular motor connections may be the mechanism by which peripheral disruptions initiate central changes. Plasticity following peripheral nerve transection has been demonstrated throughout the neuroaxis in animal models of nerve injury. Human brain imaging studies have corroborated the fi ndings from animal models with the identification of altered functional magnetic resonance imaging activation maps due to spinal cord injury, amputation, toe-to-thumb transfer, and in patients with carpel tunnel syndrome. There is functional plasticity in several cortical areas following upper limb peripheral nerve transection and surgical repair. Until recently, most neuroscientists believed that the adult brain is hard-wired and largely incapable of reorganization. The only areas of the brain where some reorganization might occur would be those involved in learning and skill acquisition. However, over the past two decades, it has been conclusively established that even primary sensory areas of the brain are capable of reorganization in response to injuries or changes in patterns of peripheral stimulation. The mechanisms that facilitate functional plasticity are thought to include the immediate unmasking of preexisting projections from adjacent cortical and subcortical levels, and long-term sprouting of • 08_Hertle_Ch08.indd 253 253 9/24/2012 1:32:03 PM OUP UNCORRECTED PROOF – REVISES, 09/24/12, NEWGEN axons at multiple levels of the neuroaxis, including the primary somatosensory cortex. There is accumulating evidence that EOM proprioceptive afferent signals are not only available to ocular motor and visual control structures, but they influence the processing of information in these structures and may be involved in modifying visuomotor behavior after eye-muscle surgery as well as oral and topical medications. The patient’s complete diagnosis must include the motility diagnosis in addition to the afferent-system diagnosis, as must the therapeutic plan. No longer can visual scientists or clinicians ignore the complex interrelationship of the developing visual afferent and visual motor systems and, as a consequence, need to evaluate both if there is a developmental disorder in either. Most, if not all, of the technologies for evaluation of the afferent visual system are feasible for clinical use. Th is includes behavioral testing of acuity in infants, visual evoked responses, electroretinography, color, contrast sensitivity, and visual field testing. There is now also important information to be obtained from optical coherence tomography. The complex combination of structural and developmental visual sensory and visual motor abnormalities in infants and children with nystagmus results in varied and multiple effects on visual system functioning; these include decreased spatial acuity, contrast sensitivity, color, motion perception, dark adaptation, functional visual field/space, visual recognition time, and a high incidence of ametropia, binocular dysfunction, and amblyopia. There may be a form of amblyopia unique to the developing visual system of eyes in constant motion we have labeled “motion amblyopia,” the complete visual consequences of which are yet to be described. The importance of how treating the developing system affects both the afferent and efferent systems was shown in an animal model of developmental retinal disease, with associated infantile nystagmus, when, after treating the sensory system with gene-transfer therapy, the ocular motor system was also improved. The addition of eye-movement recordings in the clinical setting to augment tests of the afferent visual sensory system is now a clinical necessity. Also, best-corrected binocular visual acuity must be 254 measured in at least five gaze angles to document the sharpness of the off-peak, pretherapy decrement of visual acuity and its broadening after therapy; therein lies the most important measure of improved visual function. Also, a broader range of highest acuity will diminish the need for an anomalous head position and make up for slight errors in surgical corrections. After therapy, peak acuity may not improve significantly and nystagmus amplitude or frequency may not decline; the latter factors affect cosmesis but are not tightly correlated to visual function. The strides made in the understanding, diagnoses, analyses, and treatment of the nystagmus found in infants and children began in the 1960s and are based on accurate eyemovement data and application of the control-system approach to understanding the relevant ocular motor system mechanisms. In the ensuing fi ve decades, the key observations and hypotheses that followed were as follows: (1) the recognition that IN does not cause the eyes to oscillate across the target (as the medical texts claimed) but rather they move away from and back to the target with each cycle; (2) as the eyes approach the target, they slow down and maintain foveation for an extended period of time; (3) the resulting foveation periods can be very accurate from one cycle to the next despite variations in the nystagmus waveforms and direction; (4) the IN waveform characteristics that determine visual acuity are the duration of the foveation periods and their position and velocity variations—all other portions of the IN waveform are essentially noncontributory; (5) there are a range of secondary therapeutic benefits to extraocular muscle surgery for INS—broadening the range of gaze angles with highest acuity and improving visual recognition time; (6) in INS patients with neither gaze-angle or convergence “nulls,” simply performing a tenotomy and reatt achment (T&R) of each of the four horizontal rectus muscles duplicates the broadening benefits and improves visual function significantly; (7) a mathematical function applied to eye-movement data that was based on only the statistics of foveation periods (e.g., the eXpanded Nystagmus Acuity Function—NAFX) provides a measure of the • SUM M A RY A ND CONCLUSIONS 08_Hertle_Ch08.indd 254 9/24/2012 1:32:03 PM OUP UNCORRECTED PROOF – REVISES, 09/24/12, NEWGEN motor component (independent of the sensory component) of best-corrected visual acuity; (8) eye-movement data provide the most accurate and unbiased (i.e., not under the patient’s control, as is anomalous head position) method of determining the amount of surgical correction necessary; (9) when the NAFX is combined with measured, best-corrected visual acuity, it provides, for the fi rst time, a pretherapeutic estimate of the amount of visual function improvement that would result from the proposed therapy; and (10) the use of computer modeling to encapsulate top-down hypotheses, in the form of behavioral ocular motor system models, is of paramount importance in understanding the underlying mechanisms of different types of nystagmus present in infancy and in predicting the effects of therapy on target acquisition time for stationary and moving targets. Additionally, the development and use of the “Eyeballs 3D” program to illustrate in real time the motion of the eyes and the waveforms producing that motion has been of immense pedagogical value, both to us and to others. Th is body of ocular motor research into INS has resulted in new approaches to its diagnosis and therapy. They are presented in Chapters 5–7 and include clinical guidelines to examination and diagnosis as well as the development of surgical techniques (e.g., the nine operations) and other therapies (e.g., contact lenses or base-out prisms) based on our eye-movement fi ndings. The net result is a level of accuracy and predictability that supercedes past practices, which were based on clinical examination alone and mistaken premises; the net results are greater improvement for more patients and a higher degree of patient satisfaction. As pointed out in Chapter 2, the roots of the word nystagmus are Greek, which may partially explain the extensive mythology that had been built up around this eye sign (see Appendix B, Section B.5). Early in our research, the absence of accurate, quantitative eye-movement data was recognized as the main reason for the misstatements of fact and contradictions present in the literature as well as the simplistic presumptions regarding the possible causes and underlying mechanisms of the different types of nystagmus appearing in infancy. Unfortunately, the Greek origin of the word may also be related to the “tragedy” that still exists today—the failure to adequately treat patients and improve their visual function despite the proven therapies presented in this volume. Th is failure on the part of the medical community has relegated many children and adults with INS to a second-class life, unable to realize their full potential, professionally or personally. Fortunately for future patients, the overwhelming amount and veracity of the data gathered and analyzed in the twentieth century are slowly bringing the field of pediatric vision care out of the nineteenth and into the twenty-fi rst century, where diagnosis, therapy, and measured outcomes are data driven. We have striven to cite all relevant, scientifically sound research in the various chapters and hope that those studies cited (and the citations that each contain) have not left many we unintentionally omitted. The serious student of INS should also read the many excellent papers emanating from the laboratories of Richard Abadi and Harold Bedell; there is a wealth of relevant psychophysics in that literature. Unfortunately, because of the persistence of the ophthalmic mythology surrounding nystagmus, the literature (past and present) contains many studies that are not of the same quality of those we cited. As pointed out in Chapter 2, many of them have been reviewed as part of six literature reviews of nystagmus and saccadic intrusions and oscillations published during 1980–1991 and were not included in this volume. Finally, a small number of papers have made it into the literature despite the false and plagiarized material they contained, and the unethical behavior of some of their authors. That is an unfortunate and irreversible pollution of the literature. To cite such papers would denigrate the honest, objective science that comprises the majority of research in this area; therefore, they were not cited herein. In Appendix A, we have provided eye-movement recording methodology, analysis methodology, calibration techniques; in Appendix B, clinical examination forms, clinical pearls, and ophthalmological myths and facts; in Appendix C, illustrative cases and treatment; and in Nystagmus in Infancy and Childhood • 255 08_Hertle_Ch08.indd 255 9/24/2012 1:32:03 PM OUP UNCORRECTED PROOF – REVISES, 09/24/12, NEWGEN Appendix D, diagnosis and treatment flowcharts and graphs useful for INS analysis. On Companion Website, we provided in Appendix E, “Eyeballs 3D,” canine, and patient videos and in Appendix F, OMLAB reports, patient handouts, physician/scientist worksheets, analysis soft ware, and modeling soft ware. In the fi nal analysis, we must answer this question, “Can nystagmus patients be diagnosed 256 and treated without eye-movement data?” The answer is, “Yes, but not always correctly or optimally and only with variable or unpredictable outcomes.” Difficult, and some not-so-difficult, cases require eye-movement data to avoid problematic outcomes; the less difficult cases will also benefit from the more accurate and repeatable diagnoses and predictable, measurable therapeutic improvements based on eye-movement data. • SUM M A RY A ND CONCLUSIONS 08_Hertle_Ch08.indd 256 9/24/2012 1:32:03 PM |
