Strabismus: A Neurodevelopmental Approach

This year marks the 25th anniversary of one of the best-kept secrets in ophthalmologic literature.  The slim volume I’m referring to reads more like a bound Ph.D. thesis than a book, and I recall skimming it 25 years ago in the SUNY library when it was published thinking: “Hmm … this is interesting”, but left it at that.  Apparently so did the rest of the field, because I don’t recall having come across it in the ensuing years.  So I treated myself to a copy through  a bookseller’s marketplace, and was delighted to rediscover it.

John T. Flynn is a pediatric ophthalmologist known primarily for his work in ROP, but wrote this book as a vision quest of sorts.  Convinced that strabismus is principally a design flaw in the development of the central nervous system rather than a localized problem originating in the eye muscles, Dr. Flynn’s book contains a number of passages that should resonate with you beginning with the first page:

“My topic, strabismus, has fascinated and perplexed me (among many others) for over a quarter of a century.  Often in despair of ever understanding anything about the topic, I have put aside inquiry into the many questions patients present when I examine them and have resorted to a mechanical way of thinking about the condition that persists in its worst form as sterile dogmatism – ‘if the eyes are in turn them out, and if they are out turn them in’.  But my demon will not go away.  And so it is that I have come to write this book.”

Toward the end of his introduction, Dr. Flynn continues:

“By now, I hope the reader has noted that I refer to strabismus as a visuomotor anomaly and I will continue to do so throughout this text.  The reason is to keep ever in mind the dual nature of strabismus.  We would not experience the phenomenon of vision as we humans do unless both parts of the system functioned as one.  This whole approach was aptly expressed for me in another context by von Monakow: ‘we see with our whole brains’.”

In deriving a generic model of strabismus, Dr. Flynn comments:

“Strabismus occurs, then, during the last stages of development of the visuomotor system. It is unaccompanied by other major neurological disorders, so  exclude here as well from consideration the strabismus that accompanies cerebral palsy states and other major neurological disorders of the neonatal and infant period.  That does not mean that strabismus in unaccompanied by other central nervous system developmental problems: rather, these other problems are more subtle and must be looked for in a different context than we are used to.”

What I interpret Dr. Flynn to mean is that exceptional forms of strabismus stem from diffuse motor control issues, as evidenced by the high percentage of children with CP how have misaligned eyes.  But the majority of patients seen in clinical vision/eyecare practice present with CNS developmental problems that are more subtle.  This is borne out as he elaborates his neurodevelopmental theory (p. 46):

“Strabismus is a specific response to an insult/injury of the central nervous system that, most importantly, occurred in a specific period (time) of development of the visual system and that may have both genetic and epigenetic components … The reason for the delay in appearance s not apparent but may involve the maturation of components of the visual nervous system coupled with environmental factors that as as triggers to elicit the clinical symptomology …”

Bear in mind that Flynn’s attribution of the importance of environmental influences on the expression of strabismus was written 25 years ago, long before the role of epigenetics was appreciated and we daresay is still under-appreciated in the eyecare profession.  Flynn should also be acknowledged for pondering the potential influences of therapy deeply:

“First, the observed behaviors or characteristics of strabismus are the external manifestations of the dysmorphology of the central nervous system which is the results of developmental injury.  Second, careful study of the strabismic patient’s behavior, both sensory and motor, yields important insights into the nature and extent of the injury that produced the strabismus … Third, because of the very global nature of central nervous system development, careful study of the strabismic patient will yield evidence, though probably subtle, of defects in development of other systems, for example, auditory, somasthetic, motor, and early developmental learning, which, although mild, nevertheless accompany the developmental defect we recognize as strabismus.”

Flynn insightfully views the preponderance of strabismus in infancy being in the esotropic direction as a timeline during which the developmental process went awry earlier, as opposed to a primary muscular imbalance in the lateral recti.  Similarly he views the ocular motor abnormalities that accompany infantile esotropia as signposts of the failure of primitive neural circuitry to be pruned back after synaptogenesis to a more efficient, flexible, and adapted normal circuitry.  Think about that for a moment:  abnormal OKN, VOR, and DVD as persistence of primitive reflexes in the CNS manifest in the ocular motor pathway at the level of the eyeballs.  Flynn then proposes an intriguing basis for looking anew at strabismus (p. 64), and one that we might dub quantum strabismus:

“We begin, for didactic reasons only, by separating sensory and motor, not because there is any real separation between them – we see with our shoe visuomotor brain.  Rather, the duality of the system is enforced by our primitive conceptions of how the system works.  It is much like the wave-particle duality of the photon of light or the electron; both viewpoints must be kept in consciousness to fully understand the behavior of the entity, though one aspect of its behavior may best be explained by employed one or the other frame of reference.  So it is with strabismic dysmorphology: Its behavior is best accounted for clinically by examining it from the universal viewpoint of excess or surplus of connections that we postulate are excitatory and reciprocal in nature, which means that a type of instant reversibility exists between the disconnected areas.”

This naturally leads Flynn to accept that their can be co-variation in correspondence regarding spatial localization, and readily resolve apparent paradoxes in clinical response to normal vs. anomalous correspondence based on testing conditions.  This prompts him to call the question that should be on the mind of his fellow surgeons (p.78):

“Second, we need to know what manipulations of motor behavior, other than surgery, will  change correspondence.  Will manipulation of the accommodative, convergence, optokinetic, and/or vestibular systems change localization behavior?  What is the relationship between induced errors of localization (by surgery), so-called paradoxical diplopia, and the postoperative behavior of eye movements?  How do these two variables change with respect to each other over time?”