Where BioEye could help improve health outcomes

Concussion

Drug and alcohol impairment

Cognitive Decline

Why the Eye?

The problem

  • Neurological examination is rudimentary and subjective ~10% of brain
  • Neuropsychological examination is costly/inaccessible

The solution

  • Assessment of the visual-ocular motor system
  • >50% of the brain (direct connections)
  • Affordable, accessible
  • Damage at any point = measurable abnormalities in eye movement
  • Can show impairment in both higher and lower-order brain functions
  • Current in-app tests are Smooth Pursuit (SMP) and Pupillary Light Reflex (PLR), with Near Point Convergence (NPC) coming soon.

Why the Eye?

The problem

  • Neurological examination is rudimentary and subjective ~10% of brain
  • Neuropsychological examination is costly/inaccessible

The solution

  • Assessment of the visual-ocular motor system
  • >50% of the brain (direct connections)
  • Affordable, accessible
  • Damage at any point = measurable abnormalities in eye movement
  • Can show impairment in both higher and lower-order brain functions

Current in-app tests: Smooth Pursuit (SMP) & Pupillary Light Reflex (PLR)

In app tests
In app test content
In app test content

In-app tests: Pupillary Light Reflex (PLR)

The BioEye appThe PLR is largely used to assess brain stem function. A slowed or even absent PLR may be found in the context of:

  • Optic nerve injury.
  • Oculomotor nerve damage.
  • Brain stem lesions, such as tumours.
  • Concussion.
  • Medications, such as barbiturates.

Dysfunctional PLR results may be a function of:

  • Dysfunctional PLR results may be a function of:
  • Head or eye injuries, stroke or tumour may cause static changes to pupil size.
  • Medications that dilate the pupil (mydriasis) include sympathomimetics (e.g. phenylephrine, adrenaline) and antimuscarinics (e.g. cyclopentolate, tropiocamide, atropine), tricyclic antidepressants, amphetamines and ecstasy.
  • Medications that constrict the pupil (miosis) include muscarinic agonists (e.g. pilocarpine) and opiates (e.g. morphine).
  • PLR changes have also been recently taken into consideration as potential markers of Alzheimer’s disease, in particular, decreased maximum velocity of constriction maximum constriction acceleration.


Application within a broader brain health context

Given the breadth of the circuitry involved in the control of vision and eye movements it is perhaps not surprising that SMP, PLR and NPC changes are seen in many other neurological conditions.

Smooth Pursuit (SMP)

Although non-specific, SMP eye movement abnormalities are evident in a large number of patient populations/neuropathologies consistent with the extent of the system supporting their integrity. Using different types of stimuli (circular horizontal, vertical, sinusoidal, step ramp), velocities and stimuli sizes/shapes, SMP changes include:

  • Multiple sclerosis – reduced gain, increased latencies, high amplitude saccades [21]
  • Parkinson’s disease – reduced gain, inadequate catch up saccades [22]
  • Multiple System Atrophy – reduced gain, catch up and/or anticipatory saccades [23]
  • Progressive Supranuclear Palsy – reduced range vertically, many catch up saccades vertically [23]
  • Alzheimer’s disease – reduced peak velocities, increased number and amplitude of anticipatory saccades [24]
  • Cerebellar ataxias (not SCA7 or 2) – saccadic pursuit [25]
  • Amyotrophic Lateral Sclerosis – square wave jerk, saccadic pursuit [26]
Smooth Pursuit (SMP)
Pupillary Light Reflex (PLR)

Pupillary Light Reflex (PLR) and other pupil changes

The PLR is largely used to assess brain stem function, although a slowed or even absent PLR may be found in the context of:

  • optic nerve injury
  • oculomotor nerve damage
  • brain stem lesions, such as tumours
  • medications, such as barbiturates [27].

Head or eye injuries, stroke or tumour may cause static changes to pupil size. However, medications that dilate the pupil (mydriasis) include sympathomimetics (e.g. phenylephrine, adrenaline) and antimuscarinics (e.g. cyclopentolate, tropicamide, atropine), tricyclic antidepressants, amphetamines and ecstasy. Medications that constrict the pupil (miosis) include muscarinic agonists (e.g. pilocarpine) and opiates (e.g. morphine).

PLR changes have also been recently taken into consideration as potential markers of Alzheimer’s disease, in particular, decreased maximum velocity of constriction and maximum constriction acceleration [28].

Pupillary Light Reflex (PLR) and other pupil changes

The PLR is largely used to assess brain stem function, although a slowed or even absent PLR may be found in the context of:

  • optic nerve injury
  • oculomotor nerve damage
  • brain stem lesions, such as tumours
  • medications, such as barbiturates [27].

Head or eye injuries, stroke or tumour may cause static changes to pupil size. However, medications that dilate the pupil (mydriasis) include sympathomimetics (e.g. phenylephrine, adrenaline) and antimuscarinics (e.g. cyclopentolate, tropicamide, atropine), tricyclic antidepressants, amphetamines and ecstasy. Medications that constrict the pupil (miosis) include muscarinic agonists (e.g. pilocarpine) and opiates (e.g. morphine).

PLR changes have also been recently taken into consideration as potential markers of Alzheimer’s disease, in particular, decreased maximum velocity of constriction and maximum constriction acceleration [28].

Pupillary Light Reflex (PLR)

Near Point Convergence (NPC)

Finally, convergence disorders have been reported in individuals with Parkinson’s disease [29], dorsal midbrain syndrome [30], Alzheimer’s disease [31], and medial rectus weakness from conditions like multiple sclerosis [32].

Published evidence

Published Evidence table
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Sports industry spotlight

Why better concussion diagnosis and management is critical?

1

1/3 of athletes have a sustained blow

The Prevalence of Undiagnosed Concussion in Athletes (2013)

2

Around 50% of concussions go unreported or undiagnosed.

Sports Medicine

3

Concussions can lead to acute brain swelling with mortality rate close to 50% and morbidity rate almost 100%.

Sports Guidelines for treatment of sport related concussions, Academy of Physicians (2007)

The utility of eye movements in measuring neurological function

The brain circuits involved in the processing of vision and the control of eye movement are highly distributed, extending to include a large proportion of the cerebral cortex and subcortex. Indeed, they comprise over 50% of all neurons entering and leaving the central nervous system. Any change in brain function therefore manifests in a measurable change in the generation of eye movement.

Concussions

Concussion

Many of these brain circuits are in regions especially vulnerable to concussion, including the frontal lobes, responsible for volitional aspects of movement, and the brainstem, responsible for the final programming of movement [1]. Concussion invariably manifests in a reduction in our capacity to generate and execute appropriate eye movements, and a subset of well-recognized concussive symptoms reflect this including dizziness, blurred vision, and trouble focusing. Of the myriad of eye movement changes that might signal a concussion, among the most salient are those that impact the integrity of versional eye movements (including smooth pursuit eye movements), near point convergence and pupil function. Impaired generation of each of these movement types has been reported in up to 69% of athletes following concussion [2]. A growing body of research supports the conclusion that eye movements are a relevant and useful tool to detect and help diagnose concussion.

Smooth Pursuit Eye movements (SMP)

SMP eye movements implicate a complex neural system with long ranging brain connections spanning the visual pathways from retina to cortex, brainstem, cerebellum, basal ganglia and multiple visual, temporal, parietal and frontal cortical regions. Given the complexity of the system, it is perhaps unsurprising that a range of SMP metrics distinguish concussed from non-concussed individuals. Although studies have used several types of stimuli (circular horizontal, vertical, sinusoidal, step ramp), many different velocities and stimuli sizes/shapes, results variously demonstrate that following a concussion, SMP eye movements may:

  • be inaccurate (e.g. lag behind a moving target with reduced velocity) [3-9]
  • be dysconjugate (eyes movements are asymmetrical) [5, 10, 11]
  • have increased initiation latencies [6]
  • be interrupted by saccades (or feature many catch up saccades) [7, 8]
  • show greater intra-individual variability in accuracy [9]
Smooth Pursuit Eye movements (SMP)
Smooth Pursuit Eye movements (SMP)

Smooth Pursuit Eye movements (SMP)

SMP eye movements implicate a complex neural system with long ranging brain connections spanning the visual pathways from retina to cortex, brainstem, cerebellum, basal ganglia and multiple visual, temporal, parietal and frontal cortical regions. Given the complexity of the system, it is perhaps unsurprising that a range of SMP metrics distinguish concussed from non-concussed individuals. Although studies have used several types of stimuli (circular horizontal, vertical, sinusoidal, step ramp), many different velocities and stimuli sizes/shapes, results variously demonstrate that following a concussion, SMP eye movements may:

  • be inaccurate (e.g. lag behind a moving target with reduced velocity) [3-9]
  • be dysconjugate (eyes movements are asymmetrical) [5, 10, 11]
  • have increased initiation latencies [6]
  • be interrupted by saccades (or feature many catch up saccades) [7, 8]
  • show greater intra-individual variability in accuracy [9]
Pupillary Light Reflex (PLR)

Pupillary Light Reflex (PLR)

Pupil abnormalities are common immediately following a concussion and while they often resolve over a short period of time, can persist indefinitely. Notably, pupillary size, shape, and reactivity to light are regulated by the autonomic nervous system – central autonomic control nuclei and pathways are mainly integrated within the brainstem, shown in histopathological studies to be an important site of axonal injury following concussion. Although studies have tested subjects with different stimulus conditions, at various ages, at various time points following concussion, results variously demonstrate that following a concussion, pupillary changes to:

  • steady-state pupil size [12-14]
  • pupil size following constriction in response to a light stimulus [12-14]
  • latencies (time to maximum constriction in response to a light stimulus) [14]
  • peak and average constriction velocities [12-15]
  • peak and average dilation velocities [12, 14, 15]
  • T75 (time to 75% pupillary redilation) [15]
  • constriction amplitudes [12]

Near Point Convergence (NPC)

The structures and pathways responsible for mediating vergence eye movements are not well understood but are thought to extend from extrastriate areas in the occipital lobe to vergence centres in the brainstem via the basal ganglia and thalamus. NPC abnormalities have been reported in up to 45% of concussed individuals acutely and 89% chronically [16-20], specifically resulting in difficulty converging the eyes smoothly as an object of regard moves from distance to near, and:
a receded NPC distance (point at which double vision resolves).

Convergence insufficiency is also common, described as a receded NPC in combination with:

  • an exophoria (a tendency for the eyes to drift apart) of larger magnitude at near-viewing distances than at far-viewing distances

In a recent study, 89% of symptomatic post-concussion patients had receded NPC, only 36% met the criteria for convergence insufficiency [20].

New Point Convergence (NPC)
New Point Convergence (NPC)

Near Point Convergence (NPC)

The structures and pathways responsible for mediating vergence eye movements are not well understood but are thought to extend from extrastriate areas in the occipital lobe to vergence centres in the brainstem via the basal ganglia and thalamus. NPC abnormalities have been reported in up to 45% of concussed individuals acutely and 89% chronically [16-20], specifically resulting in difficulty converging the eyes smoothly as an object of regard moves from distance to near, and:
a receded NPC distance (point at which double vision resolves).

Convergence insufficiency is also common, described as a receded NPC in combination with:

  • an exophoria (a tendency for the eyes to drift apart) of larger magnitude at near-viewing distances than at far-viewing distances

In a recent study, 89% of symptomatic post-concussion patients had receded NPC, only 36% met the criteria for convergence insufficiency [20].

References

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