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Hypotheses
"Not a single scientist in the meeting believed a word of what I said. Now, I know I am right."
Hermann von Helmholtz (1821-1894), upon returning to his laboratory after giving a lecture on his latest theories.
Listed and explained below are some of the major hypotheses, with the publlication citations, that resulted from research conducted at OMLAB. Many of them remain viable hypotheses, i.e., they were supported by subsequent research, whereas, some (those followed by "*") were disproved by subsequent OMLAB research.
Both the saccadic and pursuit systems function normally in CN.
An internal monitor of efference copy is necessary for CN.
CN is superimposed on both the saccadic and pursuit outputs.
(Dell'Osso, L. F. (1968). A Dual-Mode Model for the Normal Eye Tracking System and the System with Nystagmus. (Ph.D. Dissertation). University of Wyoming, Laramie.)
1970-1979
Corrective saccades require an internal monitor of efference copy.
(Weber, R. B., & Daroff, R. B. (1971). The metrics of horizontal saccadic eye movements in normal humans. Vision Res, 11, 921-928.)
Glissades are monocular corrective eye movements.
(Weber, R. B., & Daroff, R. B. (1972). Corrective movements following refixation saccades: Type and control system analysis. Vision Res, 12, 467-475.)
CN may result from a primary deficit in saccades.*
CN may be due to a high-gain instability in the smooth pursuit system.
(Dell'Osso, L. F., Gauthier, G., Liberman, G., & Stark, L. (1972). Eye movement recordings as a diagnostic tool in a case of congenital nystagmus. Am J Optom Arch Am Acad Optom, 49, 3-13.)
Smooth pursuit is ipsilaterally controlled.
(Troost, B. T., Daroff, R. B., Weber, R. B., & Dell'Osso, L. F. (1972). Hemispheric control of eye movements. II. Quantitative analysis of smooth pursuit in a hemispherectomy patient. Arch Neurol, 27, 449-452.)
CN oscillates away from and back to the intended line of fixation.
CN is caused/intensified by fixation attempt.
(Dell'Osso, L. F. (1973). Fixation characteristics in hereditary congenital nystagmus. Am J Optom Arch Am Acad Optom, 50, 85-90.)
Schizophrenics do not have a basic pursuit deficit.
(Troost, B. T., Daroff, R. B., & Dell'Osso, L. F. (1974). Eye tracking patterns in schizophrenia. Science, 184, 1202-1203.)
The OKN asymmetry in INO is due to superposition of the slow adduction saccades and the oppositely directed slow phases.
(Dell'Osso, L. F., Robinson, D. A., & Daroff, R. B. (1974). Optokinetic asymmetry in internuclear ophthalmoplegia. Arch Neurol, 31, 138-139.)
PAN is due to a time-varying neutral/null zone.
(Daroff, R. B., & Dell'Osso, L. F. (1974). Periodic alternating nystagmus and the shifting null. Can J Otolaryngol, 3, 367-371.)
There is considerable variability in saccadic velocity-amplitude relationships.
(Boghen, D., Troost, B. T., Daroff, R. B., Dell'Osso, L. F., & Birkett, J. E. (1974). Velocity characteristics of normal human saccades. Invest Ophthalmol, 13, 619-623.)
All CN is due to a motor instability.
(Dell'Osso, L. F., Flynn, J. T., & Daroff, R. B. (1974). Hereditary congenital nystagmus: An intrafamilial study. Arch Ophthalmol, 92, 366-374.)
Saccadic pulses are responsible for the abduction "nystagmus" of INO.
(Dell'Osso, L. F., Robinson, D. A., & Daroff, R. B. (1974). Optokinetic asymmetry in internuclear ophthalmoplegia. Arch Neurol, 31, 138-139.)
All saccades are generated by the same mechanism.
(Sharpe, J. A., Troost, B. T., Dell'Osso, L. F., & Daroff, R. B. (1975). Comparative velocities of different types of fast eye movements in man. Invest Ophthalmol, 14, 689-692.)
New visual information is continually available to alter the latency or cause cancellation of a saccade.
(Carlow, T., Dell'Osso, L. F., Troost, B. T., Daroff, R. B., & Birkett, J. E. (1975). Saccadic eye movement latencies to multimodal stimuli: intersubject variability and temporal efficiency. Vision Res, 15, 1257-1262.)
An internal brain stem monitor (efference copy) mediates corrective saccades.
(Dell'Osso, L. F., Troost, B. T., & Daroff, R. B. (1975). Macro square wave jerks. Neurology, 25, 975-979.)
There are 12 CN waveforms: pendular (P), asymmetric pendular (AP), pendular with foveating saccades (Pfs), jerk (J), jerk with extended foveation (Jef), pseudocycloid (PC), pseudojerk (PJ), pseudopendular (PP), pseudopendular with foveating saccades (PPfs), triangular (T), bidirectional jerk (BDJ), and dual jerk (DJ).
Most jerk CN slow phases are increasing-velocity exponentials.
The goal of individuals with CN is prolonged foveation.
Periods of extended foveation are due to the fixation mechanism.
Foveal function is indicated by bias reversals (jitter).
(Dell'Osso, L. F., & Daroff, R. B. (1975). Congenital nystagmus waveforms and foveation strategy. Doc Ophthalmol, 39, 155-182.)
"Braking" saccades may serve to brake a runaway SEM.
(Dell'Osso, L. F., & Daroff, R. B. (1976). Braking saccade--A new fast eye movement. Aviat Space Environ Med, 47, 435-437.)
There is a local, resettable neural integrator in the saccadic pulse generator that is distinct from the common, non-resettable neural integrator responsible for maintaining eye position.
The common neural integrator is controlled by a feedback loop comparing its output to desired eye position; it can therefore ignore pulse-generator pulses that would increase its output beyond its desired value.
(Abel, L. A., Dell'Osso, L. F., & Daroff, R. B. (1978). Analog model for gaze-evoked nystagmus. IEEE Trans Biomed Engng, BME(25), 71-75.)
The Anderson-Kestenbaum surgery has secondary effects: null broadening, off-null damping, and damping at the null.
(Dell'Osso, L. F., & Flynn, J. T. (1979). Congenital nystagmus surgery: a quantitative evaluation of the effects. Arch Ophthalmol, 97, 462-469.)
LMLN slow phases are linear or decelerating.
(Dell'Osso, L. F., Schmidt, D., & Daroff, R. B. (1979). Latent, manifest latent and congenital nystagmus. Arch Ophthalmol, 97, 1877-1885.)
LMLN is caused by egocentric confusion.
(Dell'Osso, L. F., Schmidt, D., & Daroff, R. B. (1979). Latent, manifest latent and congenital nystagmus. Arch Ophthalmol, 97, 1877-1885.
Dell'Osso, L. F., & Daroff, R. B. (1981). Clinical disorders of ocular movement. In B. L. Zuber (Ed.), Models of Oculomotor Behavior and Control (pp. 233-256). West Palm Beach: CRC Press Inc.)
Strabismus is a necessary condition for LMLN.
(Dell'Osso, L. F., Schmidt, D., & Daroff, R. B. (1979). Latent, manifest latent and congenital nystagmus. Arch Ophthalmol, 97, 1877-1885.
Dell'Osso, L. F., Traccis, S., & Abel, L. A. (1983). Strabismus - A necessary condition for latent and manifest latent nystagmus. Neuro-ophthalmol, 3, 247-257.)
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1980-1989
Excess positive feedback in the neural integrator may cause the accelerating slow phases of jerk waveforms in CN.*
(Dell'Osso, L. F., & Daroff, R. B. (1981). Clinical disorders of ocular movement. In B. L. Zuber (Ed.), Models of Oculomotor Behavior and Control (pp. 233-256). West Palm Beach: CRC Press Inc.)
Early strabismus surgery may convert MLN to LN.
(Dell'Osso, L. F., Traccis, S., & Abel, L. A. (1983). Strabismus - A necessary condition for latent and manifest latent nystagmus. Neuro-ophthalmol, 3, 247-257.)
Smoth pursuit is normal in CN.
During pursuit, the CN neutral zone shifts in a direction opposite to the pursuit.
(Dell'Osso, L. F. (1986). Evaluation of smooth pursuit in the presence of congenital nystagmus. Neuro-ophthalmol, 6, 383-406.)
Ocular dominance is genetically predetermined and independent of early visual experience.
(Dell'Osso, L. F., Abel, L. A., & Daroff, R. B. (1987). Latent/manifest latent nystagmus reversal using an ocular prosthesis. Implications for vision and ocular dominance. Invest Ophthalmol Vis Sci, 28, 1873-1876.)
Sensory feedback of eye motion can be used to damp CN.
(Dell'Osso, L. F., Traccis, S., Abel, L. A., & Erzurum, S. I. (1988). Contact lenses and congenital nystagmus. Clin Vision Sci, 3, 229-232.)
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1990-1999
OSOP is suppressed in CN by foveation periods within a foveation window.*
(Dell'Osso, L. F., & Leigh, R. J. (1990). Foveation periods and oscillopsia in congenital nystagmus. Invest Ophthalmol Vis Sci, 31, 122.
Dell'Osso, L. F., & Leigh, R. J. (1992). Foveation period stability and oscillopsia suppression in congenital nystagmus. An hypothesis. Neuro-ophthalmol, 12, 169-183.)
OSOP in each plane is suppressed in CN by foveation periods within a foveation window in that plane.*
The plane of OSOP in CN is determined by the plane of position or velocity scatter of the foveation periods and not the plane of the CN waveform unless the foveation periods in neither plane are well developed.*
(Dell'Osso, L. F. (1991). Eye movements, visual acuity and spatial constancy. Neuro-ophthalmol, 11, 151-156.
Dell'Osso, L. F., & Leigh, R. J. (1992). Ocular motor stability of foveation periods. Required conditions for suppression of oscillopsia. Neuro-ophthalmol, 12, 303-326.)
CN is not caused by a primary fixation deficit.
(Dell'Osso, L. F., Van der Steen, J., Steinman, R. M., & Collewijn, H. (1992). Foveation dynamics in congenital nystagmus I: Fixation. Doc Ophthalmol, 79, 1-23.)
The CN neutral-zone shift during pursuit is an asymmetric function of eye velocity.
(Dell'Osso, L. F., Van der Steen, J., Steinman, R. M., & Collewijn, H. (1992). Foveation dynamics in congenital nystagmus II: Smooth pursuit. Doc Ophthalmol, 79, 25-49.)
The CN neutral-zone shift during VOR is similar to that during pursuit.
(Dell'Osso, L. F., Van der Steen, J., Steinman, R. M., & Collewijn, H. (1992). Foveation dynamics in congenital nystagmus III: Vestibulo-ocular reflex. Doc Ophthalmol, 79, 51-70.)
Excess positive feedback in the neural integrator does not cause the accelerating slow phases of jerk waveforms in CN.
(Dell'Osso, L. F., Weissman, B. M., Leigh, R. J., Abel, L. A., & Sheth, N. V. (1993). Hereditary congenital nystagmus and gaze-holding failure: The role of the neural integrator. Neurology, 43, 1741-1749.)
The ocular motor system is organized on an individual eye (muscle) basis.
(Dell'Osso, L. F. (1994). Evidence suggesting individual ocular motor control of each eye (muscle). J Vestib Res, 4, 335-345.)
CN can be damped by use of afferent (electrical or mechanical) stimulation of the forehead or neck.
The best-corrected visual acuity in CN (LN etc.) can be determined by use of waveform characteristics in the NAF.
(Sheth, N. V., Dell'Osso, L. F., Leigh, R. J., Van Doren, C. L., & Peckham, H. P. (1995). The effects of afferent stimulation on congenital nystagmus foveation periods. Vision Res, 35, 2371-2382.)
The fast phases of LMLN may be either foveating or defoveating.
The same criteria for high visual acuity apply to LMLN as to CN.
(Dell'Osso, L. F., Leigh, R. J., Sheth, N. V., & Daroff, R. B. (1995). Two types of foveation strategy in 'latent' nystagmus. Fixation, visual acuity and stability. Neuro Ophthalmol, 15, 167-186.)
OSOP is determined by ECPY and not by foveation periods.
(Dell'Osso, L. F., Averbuch-Heller, L., & Leigh, R. J. (1997). Oscillopsia suppression and foveation-period variation in congenital, latent, and acquired nystagmus. Neuro Ophthalmol, 18, 163-183.)
Achiasma alone may cause see-saw nystagmus.
(Dell'Osso, L. F., & Williams, R. W. (1995). Ocular motor abnormalities in achiasmatic mutant Belgian sheepdogs: Unyoked eye movements in a mammal. Vision Res, 35, 109-116.
Dell'Osso, L. F. (1996). See-saw nystagmus in dogs and humans: An international, across-discipline, serendipitous collaboration. Neurology, 47, 1372-1374.
Dell'Osso, L. F., Williams, R. W., Jacobs, J. B., & Erchul, D. M. (1998). The congenital and see-saw nystagmus in the prototypical achiasma of canines: comparison to the human achiasmatic prototype. Vision Res, 38, 1629-1641.
Dell'Osso, L. F. (2006). Original Ocular Motor Analysis of the First Human with Achiasma: Documentation of Work Done in 1994. OMLAB Report #090506, 1-21. http://www.omlab.org//Teaching/teaching.html)
CN is an instability waiting to happen since it is an exacerbation of the normal ocsillatory behavior of the horizontal (more than the vertical) smooth pursuit system.
(Dell'Osso, L. F., & Jacobs, J. B. (1998). A Preliminary Model of Congenital Nystagmus (CN) Incorporating Braking Saccades. Invest Ophthalmol Vis Sci 39:S149.)
Hemichiasma may also cause see-saw nystagmus.
(Dell'Osso, L. F., & Daroff, R. B. (1998). Two additional scenarios for see-saw nystagmus: Achiasma and hemichiasma. J Neuro-ophthalmol, 18, 112-113.
Dell'Osso, L. F., Hogan, D., Jacobs, J. B., & Williams, R. W. (1999). Eye movements in canine hemichiasma: does human hemichiasma exist? Neuro-ophthalmol, 22, 47-58.)
Simple dissection and suture (four-muscle tenotomy) can damp CN.
Tenotomy effectively reduces the small-signal gain of the ocular motor plant.
The extraocular motor tendons contain the neural substrate for a tension-control feedback loop.
(Dell'Osso, L. F., Hertle, R. W., Williams, R. W., & Jacobs, J. B. (1999). A new surgery for congenital nystagmus: effects of tenotomy on an achiasmatic canine and the role of extraocular proprioception. J AAPOS, 3, 166-182.
Dell'Osso, L. F. (2002). Development of new treatments for congenital nystagmus. In H. J. Kaminski & R. J. Leigh (Eds.), Neurobiology of Eye Movements. From Molecules to Behavior - Ann NY Acad Sci 956 (Vol. Ann NY Acad Sci 956, pp. 361-379). New York: NYAS.
Hertle, R. W., Dell'Osso, L. F., FitzGibbon, E. J., Thompson, D., Yang, D., & Mellow, S. D. (2003). Horizontal rectus tenotomy in patients with congenital nystagmus. Results in 10 adults. Ophthalmology, 110, 2097-2105.
Hertle, R. W., Dell'Osso, L. F., FitzGibbon, E. J., Yang, D., & Mellow, S. D. (2004). Horizontal rectus muscle tenotomy in children with infantile nystagmus syndrome: A pilot study. JAAPOS. 8, 539-548.)
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2000-2009
An internal brain stem monitor (efference copy) is necessary for OM control in LMLN.
(Dell'Osso, L. F., & Jacobs, J. B. (2001). A normal ocular motor system model that simulates the dual-mode fast phases of latent/manifest latent nystagmus. Biological Cybernetics, 85, 459-471.)
An extended NAF (NAFX) can predict best corrected visual acuity across subjects.
(Dell'Osso, L. F., & Jacobs, J. B. (2002). An expanded nystagmus acuity function: intra- and intersubject prediction of best-corrected visual acuity. Doc Ophthalmol, 104, 249-276.)
Most CN has a torsional component reflecting an additional plane of instability.
(Averbuch-Heller, L., Dell'Osso, L. F., Leigh, R. J., Jacobs, J. B., & Stahl, J. S. (2002). The torsional component of 'horizontal' congenital nystagmus. J Neuro-ophthalmol, 22, 22-32.)
Four-muscle tenotomy damps CN and SSN and possibly some forms of AN.
(Hertle, R. W., Dell'Osso, L. F., FitzGibbon, E. J., Thompson, D., Yang, D., & Mellow, S. D. (2003). Horizontal rectus tenotomy in patients with congenital nystagmus. Results in 10 adults. Ophthalmology, 110, 2097-2105.
Hertle, R. W., Dell'Osso, L. F., FitzGibbon, E. J., Yang, D., & Mellow, S. D. (2004). Horizontal rectus tenotomy in children with infantile nystagmus syndrome. A pilot study. JAAPOS, 8, 539-548.)
An internal brain stem monitor (efference copy) is necessary for OM control in CN.
Many CN waveforms reflect the effects of normal saccadic and fixation subsystem attempts to overcome an underlying pursuit-system oscillation (i.e., pursuit-system nystagmus).
(Jacobs, J. B., & Dell'Osso, L. F. (2004). Congenital nystagmus: hypothesis for its genesis and complex waveforms within a behavioral ocular motor system model. JOV, 4(7), 604-625, http://journalofvision.org/4/7/7/.)
Four-muscle tenotomy also damps acquired nystagmus, improving visual acuity.
Corollary: Four-muscle tenotomy damps acquired pendular nystagmus, improving visual acuity.
(Tomsak, R. L., Dell'Osso, L. F., Rucker, J. C., Leigh, R. J., Bienfang, D. C., & Jacobs, J. B. (2005). Treatment of Acquired Pendular Nystamgus from Multiple Sclerosis with Eye Muscle Surgery Followed by Oral Memantine. DJO 11: 4, 1-11. http://www.djo.harvard.edu/site.php?url=/physicians/oa/845)
Corollary: Four-muscle tenotomy damps acquired jerk nystagmus, improving visual acuity.
(Wang, Z. I. & Dell'Osso, L. F. (2007). Combining Recessions (Nystagmus and Strabismus) with Tenotomy Improved Visual Function and Decreased Oscillopsia and Diplopia in Acquired Downbeat Nystagmus and in Horizontal Infantile Nystagmus Syndrome. JAAPOS 11:135-141.)
The beneficial proprioceptive effects of tenotomy result from changes in the small-signal gain of the ocular motor plant; saccades are not affected.
(Wang, Z., Dell'Osso, L. F., Zhang, Z., Leigh, R. J., & Jacobs, J. B. (2006). Tenotomy Does Not Affect Saccadic Velocities: Support for the "Small-Signal" Gain Hypothesis. Vision Res. 46:2259-2267.)
Four-muscle tenotomy broadens the high-foveation-duration range of gaze angles.
(Serra, A., Dell'Osso, L. F., Jacobs, J. B., & Burnstine, R. A. (2006). Combined Gaze-Angle and Vergence Variation in Infantile Nystagmus: Two Therapies that Improve the High-Visual Acuity Field and Methods to Measure It. Invest. Ophthalmol. Vis. Sci. 47:2451-2460.
Wang, Z., Dell'Osso, L. F., Jacobs, J. B., Burnstine, R. A., & Tomsak, R. L. (2006). Effects of Tenotomy on Patients with Infantile Nystagmus Syndrome: Foveation Improvement Over a Broadened Visual Field. JAAPOS 10:552-560.)
Individuals with INS are "slow to see," further reducing their visual function.
(Wang, Z. I. & Dell'Osso, L. F. (2007). Being "Slow to See" is a Dynamic Visual Function Consequence of Infantile Nystagmus Syndrome: Model Predictions and Patient Data Identify Stimulus Timing as its Cause. Vision Res. 47:1550-1560.)
Proprioception is responsible for the beneficial effects on INS of contact lenses, convergence, and tenotomy.
(Taibbi, G., Wang, Z. I., & Dell'Osso, L. F. (2008). Infantile Nystagmus Syndrome:
Broadening the High-Foveation-Quality Field with Contact Lenses. Clin. Ophthalmol. 2:1-5.
Dell'Osso, L. F. & Wang, Z. I. (2008). Extraocular Proprioception and New Treatments for Infantile Nystagmus Syndrome. In "Using Eye Movements as an Experimental Probe of Brain Function. A Symposium in Honour of Jean Buettner-Ennever," edited by C. Kennard and R.J. Leigh, Publisher, City, pp. 67-75.)
Four-muscle tenotomy alleviates the "slow to see" problem in INS patients, further improving their visual function.
(Wang, Z. I. & Dell'Osso, L. F. (2008). Tenotomy Procedure Alleviates the "Slow to See" Phenomenon in Infantile Nystagmus Syndrome: Model Prediction and Patient Data. Vision Res. 48:1409-1419.)
Wavelet analysis is too insensitive to detect foveation improvements produced by INS therapy such as, the tenotomy and reattachment procedure.
(Abel, L. A., Wang, Z. I., & Dell'Osso, L. F. (2008). Wavelet Analysis in Infantile Nystagmus Syndrome: Limitations and Abilities. Invest. Ophthalmol. Vis. Sci. 49:3413-3423.)
Smooth Pursuit accuracy and timing in INS are a function of target timing and foveation capability.
(Wang, Z. I. & Dell'Osso, L. F. (2009). Factors Iinfluencing Pursuit Ability in Infantile Nystagmus Syndrome: Target Timing and Foveation Capability. Vision Res. 49:182-189.)
Additional tendon sutures in the tenotomy and reattachment procedure for INS may improve its therapeutic effects.*
Corollary: Multiple tendon sutures alone may preclude the need for the four-muscle tenotomy.*
(Dell'Osso, L. F., Tomsak, R. L., and Thurtell, M. J. (2009). Two Hypothetical Nystagmus Procedures: Augmented Tenotomy and Reattachment and Augmented Tendon Suture. (Sans Tenotomy). J. Pediatr. Ophthalmol. Strab. 46:337-344.)
The ocular motor system may not have a sensitive period beyond which recalibration cannot be made.
(Jacobs, J. B., Dell'Osso, L. F., Wang, Z. I., Acland, G. M., and Bennett, J. (2009). Using the NAFX to Measure the Effectiveness over Time of Gene Therapy in Canine LCA. Invest. Ophthalmol. Vis. Sci. 50:4685-4692.)
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2010-Present
The NAFX may be extended to assess foveation capability in vertical and multiplanar nystagmus.
(Jacobs, J. B., and Dell'Osso, L. F. (2010). Ectending the eXpanded Nystagmus Acuity Function for Vertical and Multiplanar Data. Vision Res. 50:271-278.)
The therapeutic effects of systemic acetazolamide on INS suggest action at peripheral as well as central sites.
(Thurtell, M. J., Dell'Osso, L. F., Leigh, R. J., Matta, M., Jacobs, J. B., and Tomsak, R. L. (2010). Effects of Acetazolamide on Infantile Nystagmus Syndrome Waveforms: Comparisons to Contact Lenses and Convergence in a Well-Studied Subject. Open Ophthalmol. J. 4:42-51.)
Loss of pursuit-system damping is responsible for both the pendular and jerk INS waveforms.
(Wang, Z. I., and Dell'Osso, L. F. (2011). A Unifying Model-Based Hypothesis for the Diverse Waveforms of Infantile Nystagmus Syndrome. J. Eye Movement Res. 4:11-18.)
A topical drug (brinzolamide) in the form of eye drops, can provide the therapeutic effects of tenotomy and reattachment on INS.
(Dell'Osso, L. F., Hertle, R. W., Leigh, R. J., Jacobs, J. B., King, S., and Yaniglos, S. (2011). Effects of Topical Brinzolamide on Infantile Nystagmus Syndrome Waveforms: Eye Drops for Nystagmus. J. Neuro-Ophthalmol. 31:228-233.)
Normal smooth pursuit may be impaired by target-motion timing and prior saccades.
(Wang, Z. I., Dell'Osso, L. F., Prakash, S., and Chen, X. (2012). Smooth-Pursuit Changes after the Tenotomy and Reattachment Procedure for Infantile Nystagmus Syndrome: Model Predictions and Patient Data. Pediatr. Ophthalmol. Strab. 49:285-302.
Dell'Osso, L. F. and Jacobs, J. (2013). Normal Pursuit-System Limitations -- First Discovered in Infantile Nystagmus Syndrome. J Eye Movement Res. 6(1):2, 1-24.)
Additional tendon sutures in the tenotomy and reattachment procedure for INS do not improve its therapeutic effects.
Corollary: Single tendon sutures alone may preclude the need for the four-muscle tenotomy.
(Dell'Osso, L. F., Orge, F. H., and Jacobs, J. B. (2016). Effects of Augmented Tenotomy and Reattachment in the Infantile Nystagmus Syndrome. DJO 22:1-12.
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