Eye-movement-based assessment of visual function in patients with infantile nystagmus syndrome.

The Daroff-Dell'Osso Ocular Motility Laboratory, Louis Stokes Cleveland Department of Veterans Affairs Medical Center and CASE Medical School, Cleveland, Ohio 44106, USA.
Optometry and vision science: official publication of the American Academy of Optometry (Impact Factor: 2.04). 09/2009; 86(8):988-95. DOI: 10.1097/OPX.0b013e3181b2f2ee
Source: PubMed

ABSTRACT Infantile Nystagmus Syndrome (INS) is an ocular motor system dysfunction characterized by the rhythmic to-and-fro oscillations of the eyes. Traditionally, the assessment of INS visual function solely focused on null- or primary-position visual acuity. Our purpose is to use the past four decades of INS research to introduce a more complete assessment of visual function in patients with INS.
All eye-movement data were obtained using high-speed digital video, infrared reflection, or scleral search coil systems.
We have introduced four important aspects of a more complete INS visual function assessment: the eXpanded Nystagmus Acuity Function and visual acuity measurements in primary position; broadness of the eXpanded Nystagmus Acuity Function peak and high-acuity field; target acquisition time; and gaze-maintenance capability.
Visual function in patients with INS is multifactorial and the simple assessment of primary position visual acuity is both inadequate and may not be the most important characteristic in overall visual function. A more complete visual function assessment should also include primary and lateral gaze eye-movement and visual acuity examinations, target acquisition time and gaze holding.


Available from: Louis Frank Dell'Osso, Aug 26, 2014
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    ABSTRACT: Investigative Ophthalmology & Visual Science doi: 10.1167/iovs.14-14756 Invest. Ophthalmol. Vis. Sci. August 8, 2014 vol. 55 no. 8 4952-4954 Grating Visual Acuity in Infantile Nystagmus in the Absence of Image Motion Louis F. Dell'Osso1 Author Affiliations E-mail: I read with great interest the paper, “Grating Visual Acuity in Infantile Nystagmus in the Absence of Image Motion” by Dunn et al.1 It concluded, “Treatments and therapies that seek to modify and/or reduce eye movements may therefore be fundamentally limited in any improvement that can be achieved with respect to VA [visual acuity].” Such an overreaching conclusion is not only counterintuitive (as the authors acknowledged in a previous publication2), but also—fortunately for patients—contradicted by published data and posttherapy patient observations. Its possible use, by those unfamiliar with the ocular motor research of the past 50 years, to deny effective treatment to nystagmus patients makes such a conclusion extremely problematic. During the conduct of scientific experiments, when data analysis suggests a conclusion that is counterintuitive, a red flag should immediately go up and a critical analysis of the methods and assumptions underlying them should be undertaken. If, as is the case here, that conclusion is also contradicted by published data, a similar analysis of the data in the literature should uncover errors before such a conclusion could be drawn; the former may not have been done and the latter does not appear in the paper. In my opinion, the methodology leading to the published conclusions linking various infantile nystagmus syndrome (INS) therapies to clear improvements in visual acuity (VA; and in other measures of visual function) in all patients with low expanded nystagmus acuity function (NAFX: !0.6) or longest foveation domain (LFD: !25°) values is solid. They are not only intuitively satisfying but, more importantly, conform to the laws of physics. Therefore, I shall concentrate on possible methodological errors that may have led to such a demonstrably false conclusion in this paper. The Introduction cited papers showing a strong intersubject correlation between nystagmus waveform foveation quality and VA, but failed to report (not even in the papers that were cited3,4) that these and other published studies demonstrating how therapies that improved the foveation quality in specific INS patients (i.e., intrasubject) also improved their NAFX/VA.5"""–9 The increase in peak NAFX value is directly proportional to the VA increase in each patient.10,11 In 1953, long before foveation periods were even identified, Anderson,12 in describing the results of muscle-recession surgery to center INS nulls, stated: “It has been found that such operation not only may greatly lessen torticollis, but may also improve vision by lessening the nystagmus itself.” In 1968, I observed that base-out prisms markedly improved my measured VA (0.5–0.8 or 60%)13 and suddenly opened up a world of detail previously hidden from me. Then, in 1979, we demonstrated that the Kestenbaum surgery reduced the infantile nystagmus over a broad range of gaze angles in other INS patients and improved their VA.14 That latter study led me to hypothesize that a simple tenotomy and reattachment of the four horizontal extraocular muscles would accomplish the same improvements in VA and could be applied to the population of INS patients who did not exhibit a “null” angle or whose null was in primary position.15 The rest is history—history that, oddly, this paper apparently attempts to deny or rewrite. Clearly, much published data and many INS patients treated optically and surgically contradict the paper's conclusion that therapy could not improve VA in Page 1 of 5 Grating Visual Acuity in Infantile Nystagmus in the Absence of Image Motion 8/20/14 10:33 AM a specific INS patient. It was measured improvements (e.g., NAFX and LFD) in individual INS patients (intrapatient) that produced the NAFX and LFD curves currently used to make pretherapy estimates of the posttherapy visual function improvements in subsequent patients (interpatient).5 Also, the “cart-before-the- horse” speculation that “poor VA may result in the development of a waveform with less accurate, briefer foveations” (i.e., lower NAFX) fails to explain the many INS patients with associated afferent deficits and low VA who conversely have high NAFX waveforms, and all with INS from birth. Such a speculation may be true for some individuals, but obviously is not for many others with INS nor can it be a fundamental, generalizable mechanism. The fact that short flashes of light are perceived despite the time of occurrence in the INS cycle is used as a foundation for the tachistoscopic presentation method used in the study. However, the perception of a flash of light at all times is unrelated to the perception of high-spatial frequency detail in a target; the latter can only take place during foveation periods, as the published (and cited) data from normals demonstrated and simple physics dictates. The INS patient does not perceive the variable quality image (due to both distances from the fovea and high-image velocities) that is available throughout each cycle. Rather, the perception of a clear world is maintained from one INS cycle to the next and reinforced during each foveation period. Thus, as has been described before, in INS the high-acuity perception is similar to, but not equal to, a sample-data system (i.e., it is not the “on/off” of vision but rather, the “sample and hold” of a high-VA percept). Perhaps the paper's conclusion was just poorly expressed and the authors meant to say that for patients with high (>0.6) peak NAFX values, no improvement in peak VA should be expected, but that has already been reported, as have the measured improvements in individuals from both unassociated (i.e., isolated) and associated INS-patient populations.3,5,16 Thus, there was no need to arbitrarily exclude the latter from this study. It is also unfortunate that the antiquated and fundamentally inaccurate misnomer “idiopathic” was used to describe the subpopulation of unassociated INS patients reported in this paper. This brings us to the Methods, which were in some ways ingenious in their attempts to justify using a tachistoscopic presentation to INS patients or to incorrectly imply that such stimulation was equivalent in those with INS and normals. One possible fault in that methodology is that no mention was made of the NAFX values of the included subjects or if those with high NAFX values were excluded, as they should have been since little/no improvement in their VA would be possible, either after waveform-improving therapy or under tachistoscopic target presentation. Another is the possible source of error (and poorer than normal acuity when tested monocularly) resulting from the inclusion of some patients with INS with a latent component (or even fusion maldevelopment nystagmus syndrome); perhaps both such instances were precluded by using waveform analysis rather than clinical signs to definitively diagnose INS. Although the methodology attempted to account for the position changes inherent in an unsynchronized tachistoscopic presentation, it did not address, nor did it account for, the cortical “sampling” (see above) of high-VA data utilized by INS patients. In fact, such lack of synchrony, vis-à-vis foveation periods, would be expected to confound the elegant mechanisms already in place in individuals with INS that simultaneously suppress oscillopsia and maintain a clear and stable (from INS cycle to cycle) perceived image/world. This is possibly the major fault responsible for the lack of improvement found. The use of 75-ms flashes was a little low, as 100-ms flashes would have allowed a maximal (20/20 = 1.0) acuity. The well-known poorer acuity for vertical gratings in the Results (and the perceptual horizontal image shrinkage experienced) in predominantly horizontal INS supports the role of eye motion in limiting VA. For the above reasons, I disagree with the statement in the Discussion that the negative findings during tachistoscopic target presentation imply that eye motion, and its reduction during foveation periods, is not the limiting factor in VA of unassociated INS patients; indeed, there is a wealth of published data that identify it as the major factor in most patients, including associated INS. The Page 2 of 5 Grating Visual Acuity in Infantile Nystagmus in the Absence of Image Motion 8/20/14 10:33 AM paragraph on inter- versus intrasubject correlation simply ignores the scores of individual patients (including this author) whose peak VA immediately and permanently improved with either prism or surgical therapy; clearly their/my VA was not fixed as some low level just because they/I had INS. The authors should read the description (in the Epilogue of our recent book) by Kaila Uniacke of how her visual world improved postsurgery and how life changing it was17; it has been even more life changing to many patients with severe associated afferent limitations to their VA. Real-world, objectively measured improvements can neither be ignored nor supplanted simply because contrived experiments claiming to accurately duplicate reality failed to do either. The statement at the end of the penultimate paragraph that treatments designed to reduce INS velocity “rarely elicit improvements in VA” is unsupported by two of the cited papers (Hertle et al.,3 in which there was improvement in all low-NAFX patients in whom improvement could be expected and Kumar et al.,18 which concluded, “The procedures used mainly for correction of AHP [anomalous head posture] in INS do yield significant improvement in the visual acuity”). The third (McLean et al.,19 a clinical trial of memantine and gabapentin) failed to apply NAFX-based exclusion criteria to prevent false negatives; unfortunately, similar false negatives were also probably present in some uncited papers that showed improvements. The statement is also contradicted by the many patients exhibiting improvement (including 14 of 15 with INS plus albinism20), not only in peak VA but more importantly in the huge increases in VA at gaze angles lateral to that peak.4,9 The final paragraph contains several misstatements of fact or unsubstantiated conclusions. For the reasons given above, the first conclusion is unjustified and is contradicted by published data. The speculation about causation being reversed (poor VA casing poor NAFX) cannot explain all those patients in whom therapy has improved both their NAFX and their VA at all gaze angles. Primary outcome measures for therapies aimed solely at improving INS waveforms should be those direct objective outcomes of the therapies (e.g., peak NAFX, gaze-angle NAFX, target acquisition times, etc.) and not desired/derived and inadequate medical outcomes like peak VA alone; at the very least, clinically determined gaze-angle VAs (not merely peak VA) should be measured as a secondary outcome measure to document the important and larger improvements in VA at lateral gaze angles. The broadening of the VA versus gaze angle curve is solely a result of the foveation improvements in the INS waveforms and unaffected by any static afferent visual deficit that might be present. To summarize: (1) improving the foveation quality (i.e., the NAFX) of INS patients results in improved VA by an amount based on the pretherapy NAFX, least at the peak gaze angle and greatest at gaze angles lateral to the peak angle—that is a fact, already demonstrated in hundreds of patients. (2) The foveation quality of INS waveforms may either improve in infancy or already be high at birth—that is a fact, observed over the past 5 decades of ocular motor studies of over a thousand patients. (3) The direct cause of INS in all patients (unassociated and associated) is the failure of the damping control of smooth pursuit to calibrate properly—that is a hypothesis that is consistent with the above facts and the known instability of the normal smooth pursuit system. Its veracity has been strongly supported over a decade by a behavioral ocular motor model that has not only reproduced all the complex pendular and jerk waveforms of INS, their foveation characteristics, and responses to common static and moving stimuli, but also produced emergent properties that duplicated patient data and predicted the NAFX/VA improvements resulting from therapy. Rather than continuing to try to “prove” their paper's counterintuitive hypothetical construct (an impossible task), a more scientifically valid approach would be for these authors to conduct experiments designed to disprove it (a possible task). If such an attempt succeeds, it will have advanced our knowledge and the authors will also experience, as this author has several times, the satisfaction of having been the one to disprove one's own hypothesis. If those attempts repeatedly fail, they will have provided some support for that hypothesis; at present, none exists. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. References Page 3 of 5  
    Investigative Ophthalmology &amp Visual Science 08/2014; 55(8):4952-4954. DOI:10.1167/iovs.14-14756 · 3.66 Impact Factor
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    ABSTRACT: Objective To perform the first randomized controlled trial comparing soft contact lens (SCL) with rigid gas-permeable lens (RGPL) wearing in infantile nystagmus (IN), using spectacle wear as a baseline. Design Randomized, controlled cross-over trial with an intention-to-treat design. Participants and Controls A total of 24 participants with IN (12 idiopathic, 12 with albinism). Methods Participants were randomized into 1 of 2 treatment arms receiving the following sequence of treatments (2–3 weeks for each treatment): (A) spectacles, SCL, RGPL, and spectacle wear; or (B) spectacles, RGPL, SCL, and spectacle wear. Main Outcome Measures The main outcome measure was mean intensity of nystagmus at the null region viewing at 1.2 m. Secondary outcome measures included the same measure at 0.4 m viewing and across the horizontal meridian (measured over a ±30° range at 3° intervals) for distance and near. The nystagmus foveation characteristics were similarly assessed over ±30° and at the null region at 1.2 m and 0.4 m viewing. Visual outcome measures included best-corrected visual acuity (BCVA) at 4 m and 0.4 m, gaze-dependent visual acuity (GDVA) (i.e., visual acuity when maintaining gaze angles over a ±30° range at 10° intervals) at 4 m, and reading performance at 0.4 m derived from the Radner reading chart. Results There were no significant differences between SCL and RGPL wearing for any nystagmus characteristics or compared with spectacle wearing. The BCVA, reading acuity, and critical print size were significantly worse for SCL wearing compared with RGPL and baseline spectacle wear (P<0.05), although mean differences were less than 1 logarithm of the minimum angle of resolution (logMAR) line. Conclusions Nystagmus was not significantly different during SCL and RGPL wearing in IN, and contact lens wearing does not significantly reduce nystagmus compared with baseline spectacle wearing. The wearing of SCL leads to a small but statistically significant deterioration in visual function compared with both RGPL and spectacle wearing at baseline, although mean effect sizes were not clinically relevant.
    Ophthalmology 09/2014; 121(9). DOI:10.1016/j.ophtha.2014.03.007 · 6.17 Impact Factor
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    ABSTRACT: Purpose: Infantile nystagmus (IN) consists of largely horizontal oscillations of the eyes that usually begin shortly after birth. The condition is almost always associated with lower than normal visual acuity (VA). This is assumed to be at least partially due to motion blur induced by the eye movements. Here, we investigated the effect of image motion on VA. Methods: Grating stimuli were presented, illuminated by either multiple tachistoscopic flashes (0.76 ms) to circumvent retinal image motion, or under constant illumination to subjects with horizontal idiopathic IN and controls. A staircase procedure was used to estimate VA (by judging direction of tilt) under each condition. Orientation-specific effects were investigated by testing gratings oriented about both the horizontal and vertical axes. Results: Nystagmats had poorer VA than controls under both constant and tachistoscopic illumination. Neither group showed a significant difference in VA between illumination conditions. Nystagmats performed worse for vertically-oriented gratings, even under tachistoscopic conditions (p < 0.05), but there was no significant effect of orientation in controls. Conclusions: The fact that VA was not significantly affected by either illumination condition strongly suggests that the eye movements themselves do not significantly degrade VA in adults with IN. Treatments and therapies that seek to modify and/or reduce eye movements may therefore be fundamentally limited in any improvement that can be achieved with respect to VA.
    Investigative ophthalmology & visual science 03/2014; 55(8):4955-4957. DOI:10.1167/iovs.14-15070 · 3.66 Impact Factor