Clinical INS Assessment to Determine Maximally Effective Therapy:

What can the Physician Apply from the Bench to the Bedside?

L.F. Dell’Osso, Ph.D.

From the Daroff-Dell’Osso Ocular Motility Laboratory¹, Louis Stokes Cleveland DVA Medical Center and Dept. of Neurology², Case Western Reserve University, Cleveland OH, USA

¹ Director Emeritus

² Professor Emeritus

OMLAB Report #061214

Written: 06/03/14; Placed on Web Page: 06/12/14; Last Modified: 06/12/14

Downloaded from: OMLAB.ORG

Send questions, comments, and suggestions to: lfd@case.edu

Introduction

This is a tutorial intended for ophthalmologists who see and treat patients with nystagmus; it divides infantile nystagmus syndrome (INS) patients into three groups based on whether they have high, low, or mid-range measured peak visual acuity. The tutorial’s aims are to: 1) apply the results of the past 50 years of ocular motor research in the office/clinic; 2) enable more accurate diagnoses; 3) determine the most effective, patient-specific therapies to improve the visual function of their patients; and 4) identify which patients need eye-movement recordings to accomplish the above. A Key to Abbreviations used in this tutorial appears at its end; these self-explanatory terms allow concise listings of INS characteristics, therapies, and outcome measures. Finally, to enhance its pedagogical impact, the text is devoid of the hundreds of references that anchor much of the content, which is derived from published research from the laboratories of R. Abadi, H. Bedell, as well as the Daroff-Dell’Osso Ocular Motility Laboratory, accessible at http://www.omlab.org/Personnel/lfd/Jrnl_Arts/lfd3.html. These complementary bodies of work are the “ABD’s” of modern nystagmus research; their study and understanding is a prerequisite for the beginning nystagmus researcher. The significant research of others is also referenced in those papers and chapters. For a “single source” containing the above research, therapies, and literature citations, see Hertle, R. W. & Dell'Osso, L. F. (2012) Nystagmus in Infancy and Childhood. Current Concepts in Mechanisms, Diagnoses, and Management. Oxford University Press: Oxford. Pages 1-324.

Ocular motor (OM) research has demonstrated that clinical observation alone cannot reliably accomplish the difficult tasks of accurate and repeatable diagnosis of INS and its differentiation from other types of nystagmus (e.g., fusion maldevelopment nystagmus syndrome, FMNS; nystagmus blockage syndrome, NBS; spasmus nutans syndrome, SNS; acquired nystagmus, AN; etc.). The complex waveforms of INS exhibit idiopathic variation with gaze angle, convergence, fixating eye, and time; significant changes in specific waveforms or changes to other waveforms cannot be dependably identified clinically by even the most experienced observer, this author included. Thus, post-therapeutic improvements in visual function are often invisible to both the physician (BCVA may be unchanged) and family members (the nystagmus “looks the same”), leaving them unable to understand or explain either patients’ reports that they “see” better or improvements in patients’ visually guided behavior that accompany their improved visual function. The latter is often most evident in infants and children whose parents report dramatic post-therapy behavioral improvements; these can neither be simply dismissed as “placebo” effects nor their therapeutic importance be diminished just because the single, and inadequate, measurement of best-corrected visual acuity (BCVA) may not have improved significantly.

At present, reliable and repeatable measurements of important INS characteristics are only possible from analysis of OM data obtained from carefully controlled and accurately calibrated eye-movement measurement systems using small (≤0.5°), easy to see, non-anxiety-producing targets (e.g., a small laser spot). In addition to eye-movement recording and the associated calculation of OM functions (e.g., eXpanded Nystagmus Acuity Function, NAFX and Longest Foveation Domain, LFD), all INS patients should have their distance BCVA measured at different gaze angles (see below) and at near while in primary position. Visual acuity measurements should be made with both eyes open, even if only one is fixating due to strabismus. From these measurements, the key clinical measures required to assess INS patients are: 1) peak visual acuity (VApk), 2) high-acuity, gaze-angle range (HAgar), and 3) the presence or absence of strabismus. All acuities discussed in this tutorial are BCVA.

Note: The actual visual acuity within the HAgar is idiosyncratic and, in some patients, their “peak” acuity may be quite low.

Research, using eye-movement data, has documented significant improvements in several of the factors contributing to overall visual function (e.g., peak visual acuity, breadth of the high-acuity gaze-angle range, and speed of target acquisition) in most INS patients. This applies to patients with or without associated afferent visual deficits (e.g., ocular albinism, OA) and whether or not such deficits are severe (i.e., moderate or severe foveal dysplasia or aplasia). Thus, contrary to common presumption, foveal dysplasia or other visual deficits are not contraindications for INS therapy aimed at improving visual function. In summary, percentage improvements in the NAFX may be high, moderate, or low for initial NAFX values that are low, mid range, or high, respectively. Similarly, for the LFD, percentage improvements may be high, moderate, or low for initial LFD values that are low, mid range, or high, respectively. The presence, severity, or absence of sensory deficits affects only the absolute value of the NAFX outcome, not the percentage improvements of either; the latter depend solely on the resulting waveform improvements. Thus, for a given pre-therapy foveation quality in INS waveform, the post-therapy improvement percentages (e.g., in NAFX or LFD) will be equal for patients with no, little, or severe associated afferent visual sensory deficits.

What can a physician do to provide the best clinically based evaluation of an INS patient in the absence of eye-movement recordings (as is often the case)? Specifically, is there a way to use clinical data alone to estimate efficacy of various therapies, even while recognizing that such estimations may not be as accurate as those based on the NAFX and LFD? This tutorial attempts to answer those questions by providing a clinical roadmap to the evaluation of INS patients. It should be used as a supplement to the normal ocular, retinal, and physiological examinations of INS patients, which are not discussed herein. Similarly, the issue of strabismus is discussed only as it affects the potential surgical therapies of INS; the point should be made however, that both the INS and strabismus surgeries should be combined into a single procedure for cost-effectiveness and minimization to anesthesia exposure or other surgical problems. Finally, the details of specific surgical procedures are discussed in the book referenced above.

Research Foundations and Methods

Because many therapies for different types of nystagmus are specific for that type, the first, and most important, step is establishing a definitive diagnosis from the differential diagnoses of INS, FMNS, and mixtures of INS and FMNS. In addition, the NBS and SNS must be identified if present. All of these are easily distinguished using eye-movement data. However, in some cases, their clinical characteristics may suggest which is most likely. Distinguishing INS from FMNS using clinical signs alone may be done easily in some cases, with difficulty in others, and may be impossible in some (see also “Time-Varying Nystagmus”).

Patients with the NBS have INS with a variable strabismus such that INS is present when the eyes are aligned on a distant target but when the patient performs a purposive esotropia, the INS either damps or is converted to a low-amplitude FMNS. This esotropia is not true convergence since the vision in the non-fixating eye is suppressed to prevent diplopia. For either damped INS or FMNS, the nystagmus is usually minimal when the fixating eye is in adduction, resulting in a head turn toward the fixating eye.

Patients with SNS have nystagmus with variable conjugacy that may not be clinically detectable. The oscillations of the two eyes may vary within seconds to minutes from perfect conjugacy to 180° disconjugacy and the relative amplitudes of the eye oscillations may vary from equality to uniocular nystagmus. In addition, some SNS patients exhibit a purposive head shaking to simultaneously damp the nystagmus and use their intact VOR to maintain fixation and improve their acuity. To the observer, the eyes remain fixed on the target during the head oscillation (i.e., there is no nystagmus). This purposive head shaking is not the same as the involuntary head tremor sometimes seen in INS. The latter is due to the nystagmus signal itself driving the neck muscles and, to the observer, the eyes continue to have nystagmus. The involuntary head tremor of INS has no beneficial effect on either the nystagmus or visual acuity (i.e., it is not “compensatory”), again due to an intact VOR.

It is important to understand that when an INS patient’s BCVA is measured, the resulting value is dependent on two components: the presence (and amount) of a visual sensory deficit and the foveation quality of the INS waveform. Here I am presuming that any optical deficits are correctable after proper refraction. One cannot determine the relative contributions of these two components from measuring BCVA alone. However, measurement of both the foveation quality (see discussion of the NAFX below) and the BCVA allows quantification of the sensory deficit. Most INS therapies are aimed at improving foveation quality and do not affect any associated sensory deficit that may be present. Although eye-movement data provide quantitative measures of foveation quality from which therapeutic improvement may be estimated, there are instances where one can infer foveation quality from BCVA and use the latter to make estimates of therapeutic improvement with varying probabilities. For instance, INS patients with high BCVA may be reliably presumed to have little or no afferent sensory deficits and also good foveation quality in their nystagmus waveform. In these cases, the BCVA value (decimal Snellen) is equal to the NAFX and can be used to estimate therapeutic improvement in BCVA with high probability. Application of these considerations follows in the analyses of Cases 1 and 2 below.

The major deficit in most INS patients is the dramatic loss of VA as the eyes are directed laterally from the angle at which VApk occurs. Thus, the significant clinical deficit is not the less-than-normal peak visual acuity. Although VApk is determined by both afferent sensory visual deficits plus the INS waveform’s foveation characteristics, the dramatic fall-off in BCVA at gaze angles lateral to VApk is due solely to the poorer foveation across the nystagmus field; i.e., it is a dynamic motor deficit added to the static sensory deficit. Therefore, the key to a comprehensive clinical evaluation of INS patients is to document this important but clinically neglected deficit by making multiple visual acuity measurements at different gaze angles. To do this properly, the head should be stabilized by a head mount and chin cup fixed to the chair in which the patient is seated. The patient should be instructed to try to keep their head steady in the straight-ahead position and to use only their eyes to look at the eye chart. If necessary (especially for children), the head may be realigned to the straight-ahead position (vis-à-vis, the body) before each acuity measurement to ensure gaze-angle accuracy. Presentation of acuity targets at different gaze angles can be accomplished in two ways: 1) rotate the chair (and, therefore, the patient’s body and head) to known, accurately marked angles from the acuity display, which remains fixed on the wall in the original primary position or 2) project the targets to known, accurately calibrated angles while the chair and head remain stationary in primary position. Given the space limitations of most clinical offices and the ease of accomplishment, the first is the preferred method. One needs to simply have permanent marks on the floor in front of the chair at 0° (primary position), and ±10°, ±20°, and ±30°. This allows for seven acuity measurements across the 60° central range of gaze angles; for those with a sharp peak in their VA vs. Gaze Angle curve, pre-therapy VA measurements in far lateral gaze (relative to their VApk angle) may not always be possible. A primary-position acuity reading with a free head should also be taken and head angle noted to ensure that VApk is also included; the latter value may then also be plotted on the VA vs. Gaze Angle curve.

Note: A simple and effective way to obtain this curve is to use the Excel spreadsheet to plot the Snellen decimal acuity vs. gaze-angle points and fit the data with a 2^nd order polynomial trend line. This can be accomplished automatically by merely entering the measured acuities for each gaze angle into a skeleton spreadsheet set up to plot those values and trend line.

From those clinical measurements, the gaze angle (i.e., opposite to head angle) at which VApk actually occurs (see note below on head turns), and HAgar may be determined. Plots of the measured visual acuities vs. gaze angle will parallel those made from the NAFX analysis of eye-movement data (see Appendix, Figure A3) and can be used in a similar, albeit not as accurate, manner to estimate therapeutic improvements. By design, the NAFXpk ó potential VApk ≥ measured VApk; i.e., for those patients with no afferent deficits, potential acuity = measured acuity, making the latter directly equivalent to the NAFX. The HAgar can be calculated in a manner equivalent to the LFD calculation (i.e., the range of gaze angles where VA ≥ 0.9VApk). The decrease of visual acuity at gaze angles to either side of the peak acuity is due solely to the reduction of INS-waveform foveation quality and is independent of any associated sensory visual deficit. Thus, unlike the motor + sensory relationship between NAFXpk and VApk, the purely motor-determined LFD will equal the HAgar regardless of the presence or severity of afferent deficits. Based on the estimations of therapeutic improvements that have been demonstrated from NAFX and LFD data, the clinical measures of VApk and HAgar may help determine whether or not any OM therapy may be expected to improve visual function and the amount of that improvement. If both HAgar is ≤ 25° and VApk is ≤ 0.6 (20/35), INS therapy will probably improve visual function by improving both (i.e., broader HAgar and higher VApk). If HAgar is ≤ 25°, INS therapy will probably improve visual function (broader HAgar) regardless of VApk. If HAgar is > 25° and VApk is ≤ 0.6 (20/35), INS therapy will probably improve visual function (higher VApk). The amounts of improvement in these measures may be estimated using the graphs in Figure A3. Only if both HAgar is >25° and VApk is > 0.6 (20/35), is no INS therapy likely to improve visual function (see Table 1, Group 1, top section where 9 of 12 patient types should receive no OM therapy; the remaining three in that section may benefit from the strong therapeutic effects of BMR). Therapies for corrective shifting of VApk from lateral gaze angles (especially if resulting in head turns) are indicated in those cases where present.

Note: The presence of a preferred head position indicates two things: 1) there is a gaze angle at which acuity is maximal and, more importantly, 2) acuity drops off sharply at gaze angles lateral to the peak (i.e., the LFD is low). A preferred head position includes primary position; acuities lateral to 0° will fall off sharply. All preferred head positions are indications that INS therapy will improve visual function.

At best, head turns are inaccurate and inconsistent indicators under the control of the patient and therefore, subject to patient bias (e.g., the child, in an effort to please both his parents and doctor, refuses to adopt a head turn immediately after surgery whose goal was “to straighten his head;” even an adult patient may initially maintain a straight-ahead head position). The net result is a time-limited, “false-positive” result. Such a patient initially sacrifices better vision to show the “success” of the surgery in straightening the head. However, as time goes on, the patient will naturally adopt the post-surgical head turn (less than pre-surgically if the surgery was inadequate) that maximizes visual acuity. That scenario gave rise to the myth of the “returning null.” Longitudinal measurements of the actual INS “nulls” in many patients have demonstrated that the post-surgical positions are immediate, stationary over time, and remain in primary position if the surgery was adequate. Inadequate surgeries (such as those resulting from the “one-size-fits-all” approach inherent in strabismus-derived formulae for muscle recessions and resections) may be corrected by a second procedure to move the peak acuity to primary position, negating the need for any head turn.

A patient’s head turn need not be measured nor should attempts to measure it be used to determine the amount of surgery that might be necessary; head turns/tilts do, however, serve as an indication that VApk is at some gaze (or tilt) angle other than primary position. Nystagmus surgery should be aimed at, and direct therapeutic outcomes measured by, centering and improving the INS best waveforms over the greatest range of gaze angles, not correcting a head turn, which is a problematic, patient-controlled, secondary effect of the INS characteristics. When the former is achieved, the latter will automatically follow; i.e., since it is no longer beneficial, the head turn will disappear when VApk is moved from its pre-therapy lateral gaze angle to primary position.

Once it is determined whether therapy would benefit an INS patient, the more difficult determination of which therapy should provide the greatest improvements to visual function must be made. This tutorial contains summaries and discussions of illustrative types of INS patients with subtle differences in their clinical profiles along with the inferences that may (or, in certain cases, may not) be drawn in the absence of eye-movement data; when possible, estimated therapeutic outcomes are included. For simplicity and to best illustrate this approach to INS therapy, only the more common horizontal variations are presented. These may be extended to cover more complex cases with both horizontal and vertical variations of horizontal INS or even multiplanar INS. The six illustrative cases begin with the simplest (INS alone, Cases 1 and 2) and progress to the more complex INS plus associated afferent visual deficits (Cases 3 - 6). In each case, the clinical characteristics are first outlined, motor and sensory inferences listed, INS therapies with their expected improvements listed, and lastly, possible therapies are discussed. To ensure internal completeness, each case presentation includes all of the above elements despite the resulting redundancy. Thus, once the clinician identifies the case that fits a particular patient, everything needed for accurate diagnosis, therapy determination, estimation of therapeutic effectiveness, and measurements of the latter is available in one place.

Illustrative Cases

The cases in this tutorial illustrate the considerations producing the therapeutic choices listed in the Tables; Cases 1 and 2 when VApk is high (>0.6, Table 1), Cases 3 and 4, when it is low (<0.25, Table 2), and Cases 5 and 6, when it is mid range (≥0.25 to ≤0.6, Table 3). These Cases appear highlighted and superscripted in their respective Tables. In cases of either high or low VApk, the physician can make some high-probability inferences about the patient’s NAFX and LFD and use them to identify the best INS therapy; mid-range VApk values are more problematic. Pre-therapeutic, clinically based estimations of therapeutic efficacy are necessarily imprecise since, without the NAFX and LFD values specific for the INS motor contributions to visual function, accurate or repeatable estimations based on clinical data alone are not possible at this time. The purpose of the information presented herein is to provide guidelines to the many clinicians who have no access to eye-movement data and help in determining: the cases where INS therapy would be beneficial; the best therapy; and the amount of surgery required on each EOM to provide the greatest improvements in visual function. This tutorial is not meant to infer that clinical analysis alone is the best standard of care in INS. Eye-movement data and their analyses remain the only bases for accurate and repeatable diagnoses, reliable pre-therapy estimations of therapeutic efficacy, and accurate post-therapy measurements of the improvements in INS that are the direct outcomes of both surgical and non-surgical INS therapies. Therefore, specific cases in which clinical assessments alone are insufficient to make the above judgments should be referred to centers where eye-movement recordings and analyses can be performed and therapeutic suggestions offered, before proceeding to treatment.

Each INS characteristic and sensory deficit impacts on whether or not a specific therapy is indicated and to what extent that therapy might improve the patient’s visual function. Their many combinations determine which, if any, INS therapies might improve visual function and the magnitude of their effectiveness. Both VApk and HAgar may be high, low, or mid range, resulting in 9 combinations of these two variables alone. Then, VA at far could be ≥ near (although it is not likely to exceed near VA) or < near, raising the total to 18 combinations. For each of these, VApk may occur in either primary position, < ±10°, or ≥ ±10°; that yields 54 combinations. Finally, the patient may or may not have strabismus, making the final number, 108. Because, in many of these cases, the presence or absence of strabismus does not alter the nystagmus portion of the surgery, this number is effectively reduced to 81. Of all these different combinations of INS characteristics, few are unlikely to benefit from OM therapy of any kind (surgical or non-surgical). As described above, these few lie in the categories with both high VApk (in primary position) and high HAgar (see Table 1). Thus, for most INS patients, therapies exist that will improve their visual function in one or more ways whether or not they also have an associated afferent visual deficit.

Illustrative Cases (High Acuity, Table 1)

The cases below illustrate the considerations producing the therapeutic choices listed in Table 1, Cases 1 and 2; the Cases appear highlighted and superscripted in Table 1. Patients with high VApk (>0.6) either have “unassociated” (or “isolated”) INS or some minimal associated afferent deficit and allow for high-probability inferences about their NAFX and LFD that can be used to identify the best INS therapy.

Case 1. A high VApk in or near (< ±5°) primary position with a low HAgar; near acuity same as or greater than distance; ± strabismus (Table 1, Group 1, Types hlfp, hlfpS, hlnp, and hlnpS)

A. far acuity ≥ near; ± strabismus (Table 1, Group 1, Types hlfp, hlfpS)

Inferences:

OMà a high NAFXpk in or near primary position at distance (unchanged with

convergence)

a low LFD

Sensoryà little or no afferent sensory deficit (e.g., OA with little foveal dysplasia)

INS Therapies:

T&Rà little or no improvement in VApk (little-changed NAFXpk)

large broadening of the HAgar (increased LFD)

SCLà little or no improvement in VApk (little-changed NAFXpk)

possibly large broadening of the HAgar (increased LFD)

Table 1. INS Characteristics and Preferred Therapies for High Visual Acuity Patients

Group 1 Types

VApk

HAgar

VA

VApk

Strabismus

INS Therapies

h

l

m

h

l

m

f ≥ n

n > f

p

s

L

S

(Preferential Order)^1

hhfp

Y

Y

Y

Y^2

N

None,SCL,±T&R

hhfpS

Y

Y

Y

Y^2

Y

(None,SCL,±T&R)+SS

hhfs

Y

Y

Y

Y^2

N

None,A+T&R,SCL

hhfsS

Y

Y

Y

Y^2

Y

(None,A+T&R,SCL)+SS

hhfL

Y

Y

Y

Y^2

N

None,K,SCL

hhfLS

Y

Y

Y

Y^2

Y

(None,K,SCL)+SS

hhnp

Y

Y

Y

Y^2

N

BMR,BOPr,SCL,±T&R

hhnpS

Y

Y

Y

Y^2

Y

(None,SCL,±T&R)+SS

hhns

Y

Y

Y

Y^2

N

BMR+A,BMR,BOPr,SCL

hhnsS

Y

Y

Y

Y^2

Y

(None,A+T&R,SCL)+SS

hhnL

Y

Y

Y

Y^2

N

BMR+K,BOPr,SCL

hhnLS

Y

Y

Y

Y^2

Y

(None,K,SCL)+SS

hlfp^c1

Y

Y

Y

Y

N

T&R,SCL

hlfpS^c1

Y

Y

Y

Y

Y

(T&R,SCL)+SS

Hlfs^c2

Y

Y

Y

Y

N

A+T&R,SCL

hlfsS^c2

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

hlfL^c2

Y

Y

Y

Y

N

K,SCL

hlfLS^c2

Y

Y

Y

Y

Y

(K,SCL)+SS

hlnp^c1

Y

Y

Y

Y

N

BMR,BOPr,T&R,SCL

hlnpS^c1

Y

Y

Y

Y

Y

(T&R,SCL)+SS

hlns^c2

Y

Y

Y

Y

N

BMR+A,BMR,BOPr,SCL

hlnsS^c2

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

hlnL^c2

Y

Y

Y

Y

N

BMR+K,BOPr,SCL

hlnLS^c2

Y

Y

Y

Y

Y

(K,SCL)+SS

hmfp

Y

Y

Y

Y

N

T&R,SCL

hmfpS

Y

Y

Y

Y

Y

(T&R,SCL)+SS

hmfs

Y

Y

Y

Y

N

A+T&R,SCL

hmfsS

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

hmfL

Y

Y

Y

Y

N

K,SCL

hmfLS

Y

Y

Y

Y

Y

(K,SCL)+SS

hmnp

Y

Y

Y

Y

N

BMR,BOPr,T&R,SCL

hmnpS

Y

Y

Y

Y

Y

(T&R,SCL)+SS

hmns

Y

Y

Y

Y

N

BMR+A,BMR,BOPr,SCL

hmnsS

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

hmnL

Y

Y

Y

Y

N

BMR+K,BOPr,SCL

hmnLS

Y

Y

Y

Y

Y

(K,SCL)+SS

VApk = peak visual acuity; HAgar = high-acuity gaze-angle range; h = high (>25°); l = low (≤10°);

m = mid range (10° < mid ≤ 25°); f = far; n = near; p = primary position; s = small lateral angle (<10°);

L = large lateral angle (≥10°); S = strabismus; None = no therapy likely to make significant improvements;

N = no; Y = yes; SCL = soft contact lenses; T&R = tenotomy and reattachment;

SS = strabismus surgery; A = Anderson; K = Kestenbaum; BMR = bimedial recession; BOPr = base-out prisms

¹ Based on the probability of highest percentage improvements

² Depending on the breadth of HAgar, no peak may be discernable

Group identification letters simply reflect the “Y” responses in each column

^c1 Case 1 (see text); ^c2 Case 2 (see text)

B. near acuity > far; ± strabismus* (Table 1, Group 1, Types hlnp, hlnpS)

Inferences:

OMà a high NAFXpk in or near primary position at distance (improved with

convergence)

a low LFD

Sensoryà little or no afferent sensory deficit (e.g., OA with little foveal dysplasia)

INS Therapies:

BMR*à improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

BOPr**à improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

* if strabismus, BMR is not an option and BOPr is usually not an option

** with -1.00 S added OU to refraction for pre-presbyopic patients and removed

when the patient becomes presbyopic

T&Rà little or no improvement in VApk (little-changed NAFXpk)

large broadening of the HAgar (increased LFD)

SCLà little or no improvement in VApk (little-changed NAFXpk)

possibly large broadening of the HAgar (increased LFD)

Discussion:

Case 1 patients have isolated, unassociated INS with no significant afferent deficits; there may or may not be strabismus and measured acuity may or may not improve at near. The high peak acuity that falls off quickly in lateral gaze means that eye-movement data would show a high NAFXpk in or near primary position and a low LFD. Because of a good afferent visual system, the INS alone limits visual acuity and improvements in the foveation quality of INS waveforms will be translated directly into improvements in visual function.

Two types of INS therapy are possible for Case 1A.

1. Surgically, the 4-muscle T&R procedure may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) with little or no improvement in peak acuity (VApk=NAFXpk) since acuity is already high and further improvement in foveation quality has a diminishing effect. If strabismus is present, it should be corrected at the same time as the T&R procedure by suitable recessions and/or resections.

2. Soft contact lenses may have the same positive effects on visual function. In this, and all cases, soft contact lenses may also be used in addition to other therapies.

Note: A good way to identify those INS patients in whom contact lenses would have a beneficial effect is to gently rub or scratch the forehead above one eye and observe the nystagmus. If this afferent stimulation of the ophthalmic division of the trigeminal nerve damps the nystagmus, contact lenses should also.

Four types of INS therapy are possible for Case 1B (if strabismus is present, this is reduced to two, “3” and “4”).

1. Surgically, the BMR procedure may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) and provide improvement in peak acuity (VApk=NAFXpk).

2. Non-surgically, base-out prisms (7 PD) in both eyes with -1.00 S added OU to the patient’s refractive correction (if pre-presbyopic) would have similar effects.

3. Surgically, the 4-muscle T&R procedure may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) but not to improve peak acuity (VApk=NAFXpk).

4. Soft contact lenses may have some positive effects on visual function.

Note: Initially, based on the 4-muscle data from the Kestenbaum procedure, we recommended that the 2-muscle BMR be accompanied by a 2-muscle T&R of the lateral rectus muscles. However, subsequent data from studies of the effects of convergence and prisms on INS demonstrated that convergence alone maximally damps INS; therefore, the addition of the T&R of the lateral rectus muscles is neither required nor recommended. Thus, the BMR is the only 2-muscle procedure recommended to damp INS.

Figure 1 illustrates the expected improvements in VApk and HAgar resulting from either the T&R (for patients without convergence damping or with strabismus) or BMR (or BOPr) (for binocular patients) therapies. Because VApk is high, VA measurements are equal to NAFX values. The initial low VAgar value (≤10°) may be expected to increase post-therapy to approximately 30° for the T&R and >40° for the BMR. For those patients without strabismus whose INS damps with convergence, BMR or BOPr may be expected to improve VApk and HAgar to a greater extent then the T&R. This patient should improve from someone who is effectively blind when looking laterally to VApk to one who substantially has their highest VApk across a wider range of gaze angles.

INS Therapy is indicated because broadening of the range of gaze angles where the patient has the highest acuity is the single most important improvement to better visual function in most daily activities and especially in sports, where reduced target acquisition time will also improve visual function and allow both participation in, and enjoyment of, many sports (see Summary, Observations, and Conclusions).

Figure 1. Measured VA vs. Gaze Angle plots for Case-1 patients with high VApk = NAFXpk in or near primary position and low Hagar = LFD including: VAf = VAn, ± strabismus [Case 1A] and VAf < VAn, no strabismus [Case 1B]. In Figure legends 1 – 6, f = far, and n = near. Solid = pre-therapy curve, and dashed and dot-dashed = post-therapy T&R [Case 1A] and BMR/BOPr [Case 1B] curves respectively. Because they include different possible combinations of INS characteristics, Figures 2 – 6 are more complex than the simple plot from an individual patient, which, like Figure 1, would only contain that patient’s personal pre- and post-therapy acuities.

Case 2. A high VApk in lateral gaze with a low HAgar

A. far acuity ≥ near; ± strabismus (Table 1, Group 1, Types hlfs, hlfsS, hlfL, hlfLS)

i) VApk @ < ±10° lateral gaze (Table 1, Group 1, Types hlfs, hlfsS)

Inferences:

OMà a high NAFXpk in lateral gaze angle at distance (unchanged with convergence)

a low LFD

Sensoryà little or no afferent sensory deficit (e.g., OA with little foveal dysplasia)

INS Therapies:

A+T&Rà VApk shifted to primary position (also NAFXpk)

little or no improvement in VApk (little-changed NAFXpk)

large broadening of the HAgar (increased LFD)

SCLà no shifting of, and little or no improvement in, VApk (little-changed

NAFXpk)

possibly large broadening of the HAgar (increased LFD)

ii) VApk @ ≥ ±10° lateral gaze (Table 1, Group 1, Types hlfL, hlfLS)

Inferences:

OMà a high NAFXpk in lateral gaze angle at distance (unchanged with convergence)

a low LFD

Sensoryà little or no afferent sensory deficit (e.g., OA with little foveal dysplasia)

INS Therapies:

Kà VApk shifted to primary position (also NAFXpk)

little or no improvement in VApk (little-changed NAFXpk)

large broadening of the HAgar (increased LFD)

SCLà no shifting of, and little or no improvement in, VApk (little-changed

NAFXpk)

possibly large broadening of the HAgar (increased LFD)

B. near acuity > far; ± strabismus* (Table 1, Group 1, Types hlns, hlnsS*, hlnL, hlnLS*)

i) VApk @ < ±10° lateral gaze (Table 1, Group 1, Types hlns, hlnsS*)

Inferences:

OMà a high NAFXpk in small lateral gaze at distance and higher with

convergence

a low LFD

Sensoryà little or no afferent sensory deficit (e.g., OA with little foveal dysplasia)

INS Therapies:

BMR*+ à VApk shifted to primary position (also NAFXpk)

A+T&R improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

BMR*à improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

BOPr**à improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

* if strabismus, BMR is not an option and BOPr is usually not an option

** with -1.00 S added OU to refraction for pre-presbyopic patients and removed

when the patient becomes presbyopic

SCLà little or no improvement in VApk (little-changed NAFXpk)

possibly large broadening of the HAgar (increased LFD)

ii) VApk @ ≥ ±10° lateral gaze (Table 1, Group 1, Types hlnL, hlnLS*)

BMR*+Kà VApk shifted to primary position (also NAFXpk)

improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

BOPr**à improvement in VApk (increased NAFXpk)

large broadening of the HAgar (increased LFD)

* if strabismus, BMR is not an option and BOPr is usually not an option

** with -1.00 S added OU to refraction for pre-presbyopic patients and removed

when the patient becomes presbyopic

SCLà no shifting of, and little or no improvement in, VApk (little-changed

NAFXpk)

possibly large broadening of the HAgar (increased LFD)

Discussion:

Case 2A is similar to Case 1, with isolated, unassociated INS and no significant afferent deficits; there may or may not be strabismus and measured acuity does not improve at near. The high peak acuity that falls off quickly in gaze to either side of the lateral peak means that eye-movement data would show a high NAFXpk at a specific lateral gaze position (i.e., the INS “null”) and a low LFD. Because of a good afferent visual system, the INS alone limits visual acuity and improvements in the foveation quality of INS waveforms will translate directly into improvements in measured visual acuity.

Note: Although INS patients with afferent deficits will have lower pre- and post-therapy measured visual acuities than indicated by their NAFX values, the percent improvements in foveation quality still translate directly into percent improvements in visual function.

Two types of INS therapy are possible for Case 2A i).

1. Surgically, a 2-muscle Anderson recession procedure combined with a T&R of the remaining 2 horizontal muscles will achieve similar improvements to the 4-muscle Kestenbaum procedure. That is, it may be expected to broaden the high-acuity and gaze-angle region (HAgar=LFD) with little or no improvement in peak acuity (VApk=NAFXpk) since it is already high and further improvement in foveation quality has a diminishing effect on acuity. However, peak acuity would be shifted from the prior lateral gaze angle to primary position. If strabismus is present, it should be corrected at the same time as the surgical procedure by suitable recessions and/or resections.

Note: There are no NAFX analyses demonstrating that a 2-muscle Anderson procedure by itself (i.e., without the additional T&R) would have equivalent beneficial effects on visual function (e.g., HAgar broadening). Therefore, an Anderson procedure, by itself, is not currently recommended for INS.

2. Soft contact lenses may have the same positive effects on visual function but will not shift the peak-acuity gaze angle to primary position.

Two types of INS therapy are possible for Case 2A ii).

1. Surgically, the 4-muscle Kestenbaum procedure may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) with little or no improvement in peak acuity (VApk=NAFXpk) since it is already high and further improvement in foveation quality has a diminishing effect on acuity. However, peak acuity would be shifted from the prior lateral gaze angle to primary position. If the peak-acuity gaze angle is large, the 4-muscle Kestenbaum procedure is the surgery of choice. If strabismus is present, it should be corrected at the same time as the surgical procedure by suitable recessions and/or resections.

2. Soft contact lenses may have the same positive effects on visual function but will not shift the peak-acuity gaze angle to primary position.

Note: For the Kestenbaum and Anderson procedures, the actual amounts of recessions and resections should be determined from the graph in Figure 7 of Dell’Osso and Flynn, Arch Ophthalmol 97:462-469, 1979 by using the gaze angle at which peak acuity was measured, and not from the various strabismus formulae which are neither applicable to nystagmus surgery nor patient-specific to their exact gaze angle for peak acuity. Using equal of amounts of recessions and resections maintains homeostasis by equalizing the surgical repositioning. [A usable worksheet from this Figure may be found in Figure D.4 of Hertle, R. W. & Dell'Osso, L. F. (2012) Nystagmus in Infancy and Childhood. Current Concepts in Mechanisms, Diagnoses, and Management. Oxford University Press: Oxford and is downloadable as Figure F.3.1 from http://www.oup.com/us/nystagmus.]

Figure 2 illustrates the expected improvements in VApk and HAgar resulting from either the A+T&R or K (for patients without convergence damping or with strabismus) or BMR+A+T&R (or BOPr) or BMR+K (for binocular patients) therapies. Because VApk is high, VA measurements are equal to NAFX values. The initial low VAgar values (≤10°) may be expected to increase post-therapy to approximately 30° for the A+T&R or K and >40° for the BMR+A+T&R or BMR+K. For those patients without strabismus whose INS damps with convergence, BMR or BOPr may be expected to improve VApk and HAgar to a greater extent then the T&R. They should improve from being effectively blind when looking lateral to VApk to patients who substantially have their highest VApk across a wider range of gaze angles. Note that the expected results are the same regardless of the lateral extent of VApk and are equal to those in Figure 1, for a primary-position VApk.

INS Therapy is indicated in Case 2A i) and ii) because of the broadening of the range of gaze angles where the patient has the highest acuity. The shifting of the gaze angle with the highest acuity to primary position has both visual function and orthopedic benefits, making the two surgical therapies preferable.

Again, Case 2B i) is similar to Case 1, with unassociated INS and no significant afferent deficits; however, there is no strabismus and measured acuity does improve at near. The high peak acuity that falls off quickly in gaze to either side of the small lateral peak means that eye-movement data would show a high NAFXpk at a specific lateral gaze position (i.e., the INS “null”) and a low LFD; convergence would increase both the NAFXpk and LFD values. Because of a good afferent visual system, the INS alone limits visual acuity and improvements in the foveation quality of INS waveforms will translate directly into improvements in visual acuity.

Four types of INS therapy are possible for Case 2B i).

1. Surgically, a 2-muscle Anderson plus 2-muscle T&R combined with a BMR procedure may be expected to shift and broaden the high-acuity, gaze-angle region (HAgar=LFD) and provide improvement in peak acuity (VApk=NAFXpk). Because of the Anderson portion of the procedure, peak acuity would also be shifted from the prior lateral gaze angle to primary position. If there is strabismus, the BMR is contraindicated leaving a 2-muscle Anderson plus 2-muscle T&R. Because of the Anderson portion of the procedure, peak acuity would also be shifted from the prior lateral gaze angle to primary position.

Figure 2. Measured VA vs. Gaze Angle plots for Case-2 patients with high VApk = NAFXpk at a small [i) VApk @ < 10°] or large [ii) VApk @ ≥ 10°] lateral gaze angle, and low Hagar = LFD including: VAf = VAn, ± strabismus [Case 2A] or VAf < VAn, no strabismus [Case 2B]. Solid = possible pre-therapy curves, and dashed and dot-dashed = post-therapy A+T&R [Case 2A i)] or K [Case 2A ii)] and BMR* = BMR±(A+T&R)/BOPr [Case 2B i)] or BMR* = BMR+K [Case 2B ii)] curves respectively. Consistent with the Tables, s = small lateral angle (<10°) and L = large lateral angle (≥10°).

2. The BMR procedure alone may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) and provide improvement in peak acuity (VApk=NAFXpk). Also, if a small amount of lateral gaze is required for peak acuity and there is sufficient broadening of the resulting high-acuity, gaze-angle region (HAgar=LFD), peak acuity could shift from the prior lateral gaze angle, closer to primary position. If there is strabismus, the BMR is contraindicated.

3. Non-surgically, base-out prisms (7 PD) in both eyes with -1.00 S added OU to the patient’s refractive correction (if pre-presbyopic) would have similar effects. If there is strabismus, the use of base-out prisms is contraindicated.

4. Soft contact lenses may have the same positive effects on the breadth of the high-acuity, gaze-angle region (HAgar=LFD) but will neither shift the peak-acuity gaze angle to primary position nor raise peak acuity appreciably.

Note: The amount of BOPr used therapeutically is based on the convergence necessary to damp the INS for distant targets while still allowing the patient to further converge on near targets; it is not determined by the convergence that produces maximal INS damping. The same applies for the magnitude of the recessions in the BMR procedure.

Note: After refracting each eye individually, once you add the BOPr OU, the final refraction (to determine the amount of additional –S required to cancel the vergence-induced accommodation) must be done binocularly. That is, you add small amounts of negative spheres in equal pairs to determine the final spherical correction needed for BCVA at distance. Do not occlude either eye or convergence will cease, INS will increase, and the monocular acuity obtained will be for adduction of the non-occluded eye.

INS Therapy is indicated in Case 2B i) because of the broadening of the range of gaze angles where the patient has the highest acuity. The additional improvement in the highest acuity makes the surgical and prismatic therapies preferable, with the above caveats in cases with strabismus.

Case 2B ii) is similar to the Case 2B i), with unassociated INS and no significant afferent deficits; there is no strabismus but measured acuity does improve at near; occasionally acuity improves at near even in the presence of strabismus. The peak acuity occurs at a larger lateral gaze angle. The high peak acuity that falls off quickly in gaze to either side of the lateral peak means that eye-movement data would show a high NAFXpk at a specific lateral gaze position (i.e., the “null”) and a low LFD; convergence would increase both the NAFXpk and LFD values. Because of a good afferent visual system, the INS alone limits visual acuity and improvements in the foveation quality of INS waveforms will translate directly into improvements in visual acuity.

Three types of INS therapy are possible for Case 2B ii).

1. Surgically, a 4-muscle Kestenbaum combined with a BMR procedure may be expected to broaden the high-acuity, gaze-angle region (HAgar=LFD) and provide improvement in peak acuity (VApk=NAFXpk). If there is strabismus, the BMR is contraindicated leaving a 4-muscle Kestenbaum procedure. Because of the Kestenbaum procedure, peak acuity would also be shifted from the prior lateral gaze angle to primary position.

2. Non-surgically, base-out prisms (7 PD) in both eyes with -1.00 S added OU to the patient’s refractive correction (if pre-presbyopic) will have similar effects on the high-acuity, gaze-angle region (HAgar=LFD) but a residual shift would remain at the gaze angle at which peak acuity is found. If there is strabismus, the use of base-out prisms is contraindicated.

3. Soft contact lenses may have the same positive effects on the breadth of the high-acuity, gaze-angle region (HAgar=LFD) but will neither shift the peak-acuity gaze angle to primary position nor raise peak acuity appreciably.

INS Therapy is indicated in Case 2B ii) because of the broadening of the range of gaze angles where the patient has the highest acuity. The additional improvement of shifting the highest acuity point to primary position makes the surgical therapy the best and the broadening plus rising of peak acuity makes the prismatic therapy preferable to the soft contact lenses.

Illustrative Cases (Low Acuity, Table 2)

The cases below illustrate the considerations producing the therapeutic choices listed in Table 2, Cases 3 and 4; the Cases appear highlighted and superscripted in Table 2. In cases of low VApk (<0.25), we can make some high-probability inferences about the patient’s NAFX and LFD and use them to identify the best INS therapy.

Table 2. INS Characteristics and Preferred Therapies for Low Visual Acuity Patients

Group 2 Types

VApk

HAgar

VA

VApk

Strabismus

INS Therapies

h

l

m

h

l

m

f ≥ n

n > f

p

s

L

S

(Preferential Order)^1

lhfp

Y

Y

Y

Y^2

N

SCL,±T&R

lhfpS

Y

Y

Y

Y^2

Y

(SCL,±T&R)+SS

lhfs

Y

Y

Y

Y^2

N

A+T&R,SCL

lhfsS

Y

Y

Y

Y^2

Y

(A+T&R,SCL)+SS

lhfL

Y

Y

Y

Y^2

N

K,SCL

lhfLS

Y

Y

Y

Y^2

Y

(K,SCL)+SS

lhnp

Y

Y

Y

Y^2

N

BMR,BOPr,SCL,±T&R

lhnpS

Y

Y

Y

Y^2

Y

(SCL,±T&R)+SS

lhns

Y

Y

Y

Y^2

N

BMR+A,BMR,BOPr,SCL

lhnsS

Y

Y

Y

Y^2

Y

(A+T&R,SCL)+SS

lhnL

Y

Y

Y

Y^2

N

BMR+K,BOPr,SCL

lhnLS

Y

Y

Y

Y^2

Y

(K,SCL)+SS

llfp^c3

Y

Y

Y

Y

N

T&R,SCL

llfpS^c3

Y

Y

Y

Y

Y

(T&R,SCL)+SS

llfs

Y

Y

Y

Y

N

A+T&R,SCL

llfsS

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

llfL

Y

Y

Y

Y

N

K,SCL

llfLS

Y

Y

Y

Y

Y

(K,SCL)+SS

llnp

Y

Y

Y

Y

N

BMR,BOPr,T&R,SCL

llnpS

Y

Y

Y

Y

Y

(T&R,SCL)+SS

llns

Y

Y

Y

Y

N

BMR+A,BMR,BOPr,SCL

llnsS

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

llnL

Y

Y

Y

Y

N

BMR+K,BOPr,SCL

llnLS

Y

Y

Y

Y

Y

(K,SCL)+SS

lmfp

Y

Y

Y

Y

N

T&R,SCL

lmfpS

Y

Y

Y

Y

Y

(T&R,SCL)+SS

lmfs^c4

Y

Y

Y

Y

N

A+T&R,SCL

lmfsS^c4

Y

Y

Y

Y

Y

(A+T&R,SCL)+SS

lmfL^c4

Y

Y

Y

Y

N

K,SCL

lmfLS^c4

Y

Y

Y

Y

Y

(K,SCL)+SS

lmnp

Y

Y

Y

Y

N

BMR,BOPr,T&R,SCL

lmnpS

Y

Y

Y

Y

Y

(T&R,SCL)+SS

lmns^c4

Y

Y

Y

Y

N