aetiology of concomitant strabismus

Question 1

define concomitant strabismus

Answer 1

Remains the same
All directions
Whichever eye is fixing I.E Deviation measures the same fixing e.e
It is associated with full or nearly full ocular motility
Is primarily horizontal in nature
Most concomitant squints are either congenital or arise in early childhood.

Question 2

what is found in a normal deviation prior to binocular vision

Answer 2

Transient deviations common: 1-4/12, reducing by 2/12, gone by 4/12
Duration: momentary - 60 mins
Unilateral / bilateral
Eso > exo
Large angle - >30PD
No specific stimulus
Later - on near fixation

Convergence to mothers face
43% age 1/52
98% age 4/12
NM before conv
Increased freq NM = earlier conv

nm= neo misalignement

hyperopes showd first convergence latest

Question 3

in normal deviations when do normal infants grow out of their deviations

Answer 3

Most normal infants
‘growing out of NM’ by 2/12, stopped by 4/12
Normal ocular alignment, BSV & emmetropia

Referral if:
NM worsening after 2/12
Intermittent deviation after 4/12
Excessive amount NM
Associated with higher incidence of refractive error (+) or strabismus later in childhood

Question 4

what is the cause of neomisalignment

Answer 4

defective vergence

unknown cause

going on to influence refractive error and strabismus

genetic predisposition

Question 5

what are act defects caused by

Answer 5

accomodarono convergence defects

caused by abnormalities of ac synkeneisis (relationship)

high Academic ratio and convergence XS et

query caused by inability to correctly adjust level of tonic vergence

tonic accommodation

values of cross links between a and c

Question 6

what is hypoaccomodation

Answer 6

rare disorder - accommodation defect

et

difficulty/ under accommodation for nr

to see nr target clearly

excess accommodation

induces over convergence and esotropia at near

Question 7

what are reasons for a abnormal esotropia

Answer 7

Anaesthesia evidence
Normally Diverge while anaesthesia
Under Anaesthesia controls and XT – no EMG Signal
In ET both MR firing
This suggests in ET MR may receive:
Abnormal innervation
Abnormal feedback signals

Question 8

how does active divergence contribute to the development of exotropia

Answer 8

Hypothesis for Exotropia development
Divergence is an active mechanism proposed by Duane’s theory
Not a relaxation of convergence
Little Evidence

Question 9

what innervation abnormalities are known to cause strabismus that have been found in animals

Answer 9

Increase in severity of signs with increased duration of disrupted BSV
Vergence & gaze deficits
Reduced anatomic connections for binocularity
if surgically aligned soon after onset can regain fusion and stereopsis
No evidence of primary abnormalities in EOM, Motor Neurone or Brainstem Abnormality

Natural default
Immature, unstable vergence & nasally biased gaze system
Interference with normal maturation from intrinsic / extrinsic factors which occurs during the 1st weeks and months of life

Question 10

what factors cause emmetropisaition

Answer 10

refractive error and emmetropisation

Question 11

how are refractive error and emmetropisation linked

Answer 11

Longitudinal study – followed a cohort of patients for a period of time
Recruited patients with FH strabismus
17.6% developed strabismus
All 17.6% = hypermetropic
Only those who failed to emmetropise developed ET

Patient with a FH of strabismus were compared to a control group
FH only not as important as FH & hypermetropia
FH only 10% risk developing strabismus
FH & hypermetropia (>3DS) nearly 50% risk

Systematic review & meta-analysis (7 studies)Risk of concomitant strabismus due to refractive errors
Myopia associated with exotropia
5 times increased risk
Hypermetropia strongly associated with esotropia
dose-related effect
above +2DS

Study looking at the factors associated with strabismus
Multi-ethnic cohort (Bradford), age 4-5 years (screening)
Ethnicity
White British x2 odds of having ET (compared to Pakistani children)
Hypermetropia
Odds of having ET highest in all children with hypermetropia
Interaction between ethnicity and hypermetropia (in ET)
Exotropia
Not associated with refractive error, ethnicity or other early life factors

Question 12

how are inheritance and concomitant strabismus related

Answer 12

inheritance

Twin studies
Monozygous (identical twins) and Dizygous (Non-identical twins)
Detect the genetic against environmental influence on a condition developing using concordance rates
Family studies
Detect prevalence in families
Mode of inheritance
Genetic studies
locate genes, or potential loci where mutations may cause the development of a condition

Manifest strabismus
Genetic factors necessary to cause strabismus
Significantly higher concordance in monozygotic twins
? Environmental risk factors interact with pre-existing genetic liability
e.g. Low birth weight / prematurity / maternal smoking / paternal lead exposure / abnormalities in pregnancy or delivery

Only Eso deviation had a hereditary component
Refractive error also had a hereditary component that was independent of eso inheritance

Question 12

how are inheritance and concomitant strabismus related

Answer 12

inheritance

Twin studies
Monozygous (identical twins) and Dizygous (Non-identical twins)
Detect the genetic against environmental influence on a condition developing using concordance rates
Family studies
Detect prevalence in families
Mode of inheritance
Genetic studies
locate genes, or potential loci where mutations may cause the development of a condition

Manifest strabismus
Genetic factors necessary to cause strabismus
Significantly higher concordance in monozygotic twins
? Environmental risk factors interact with pre-existing genetic liability
e.g. Low birth weight / prematurity / maternal smoking / paternal lead exposure / abnormalities in pregnancy or delivery

Only Eso deviation had a hereditary component
Refractive error also had a hereditary component that was independent of eso inheritance

Question 13

does fh of concomitant strabismus predispose someone to the development of it

Answer 13

One study looking at family history in strabismus:
345 1st degree relatives with strabismus
51% developed strabismus same age
96.5% had strabismus same type

All family studies report conflicting inheritance patterns and propose a polygenic inheritance pattern

Question 14

how are genetics involved ion the devlopement of concomitant strabismus

Answer 14

Multiple susceptible loci found
Different studies disagree / find different results
Chromosomes 4, 6, 7, 8, 12, 16, 18, 19
Parent of Origin – Paternal Inheritance - Non-Accommodative esotropia
7p22.1 – STBMS1
Potential genes WRB and TSPAN10 (consistently found in large cohort studies)
Rare copy number variants founds more frequently in esotropia than controls.

Question 15

how are neurological disorders related to the development of concomitant strabismus

Answer 15

Higher incidence of strabismus in:
Neurological conditions
Cerebral palsy
ET 3x more common than XT
Schizophrenia and XT
Other genetic disorders and higher risk of Strabismus i.e. downs syndrome

Question 16

what environmental factors are involved in the development of concomitant strabismus

Answer 16

Prematurity
Particularly to Esotropia and between 33 and 36 weeks (OR 1:39)(Torp-Pedersen et al, 2010)
Low birth weight (Huang et al, 2022)
ROP severity and Cicatricial ROP (scarring)
Refractive errors more common 29.6%
incidence of myopia and other refractive errors is high in preterm infants when retested at 10 years of age

Question 17

what pregnancy related environmental factors are related in the development of concomitant strabismus

Answer 17

Smoking during pregnancy
>10 cigarettes (OR 1.83/2.0) (Chew et al, 1994; Pathai et al, 2010; Torp-Pedersen, 2010)
Throughout pregnancy
Maternal Factors
Age: 30-34yrs compared to 20-24yr (OR 1.43)(Chew et al, 1994)
Maternal History of Hypertension (XT only – Lingham et al, 2019)
Excessive drug and alcohol exposure ie Fetal Alcohol syndrome
Tsang et al (2022)
Paternal Age, Sickness throughout Pregnancy, Social status (conflicting)

Question 18

what are the causes of secondary strabismus

Answer 18

Unilateral loss of vision
ET / XT ~ unknown

Theories – review notes from year 1
Age of onset of visual loss
XT drift into divergent position of rest
Tonic divergence when no fusion possible
Pre existing heterophoria
Other factors
mechanical / innervational / accommodative

Question 19

what anatomical / mechanical effects may cause strabismus

Answer 19

Properties of extrabulbar tissues
Shape orbits
Axis of orbits
IPD
Size of globe

? combination mechanical / innervational factors
(von Noorden, 1996).

Question 20

what have functional mris revealed about the developement of strabismus

Answer 20

Concomitant ET
MR larger (39%)
Increased contractility of MR (60%)
LR larger

? Abnormal central vergence system – interact with other factors to cause concomitant strabismus
? Muscle changes later
? Muscle changes develop at same time as abnormal innervational commands

More recent advances in technology have enable detailed studies of the extra ocular muscles, the surrounding tissues and the muscle pulley system. Using functional MRI, Schoeff et al (2013) have shown in concomitant esotropia the medial rectus muscle is larger than in orthotropic controls. The lateral rectus was also larger, but not significantly so. Medial rectus cross sections were up to 39% larger and the contractility of the medial rectus was increased by up to 60% compared to controls. It is suggested that an abnormality of the central vergence system may interact with optical or environmental factors to cause concomitant strabismus. The functional anatomical changes in the horizontal rectus muscles demonstrated in concomitant esotropia may then be the consequence of abnormal innervational patterns. Also it is acknowledged that changes in the extra ocular muscles may even develop together with abnormal innervational commands, making the aetiology of concomitant strabismus even more complex

Question 21

how is the oculomotor system involved in the development of strabismus

Answer 21

Schiavi (2016) in a review article looking at the evidence of EOM tension, tonus and proprioception in infantile strabismus concluded that the EOM’s in patients with strabismus are essentially ‘normal’, but the EOM proprioceptors are an area for further study. Some ultrastructural changes have been identified in the EOM proprioceptors of children with infantile strabismus, but not in those with adult onset strabismus. EOM force and tension is again considered to be normal in concomitant strabismus, but there are some cases where imbalance has been identified between the MR & LR muscles. It is however, suggested these are secondary EOM changes in the presence of a longstanding strabismus, rather than the primary cause of the strabismus.

Question 22

what is febrile illness

Answer 22

Measles
Can cause encephalomyelitis
Damage cells within brain
Damage CNS
Cause / precipitating factor
Viral illness - 6th N palsy

Careful differential diagnosis

Question 23

what is acute onset et

Answer 23

A concomitant esotropia can present with a history of acute or sudden onset; careful examination is required to exclude 6th nerve palsy in such cases. Concomitant esotropia can occur following occlusion or visual loss, due to a decompensation of an esophoria or microtropia, for an unknown reason, or due to myopia (Burian & Miller, 1958; Hoyt & Good, 1995). Acute acquired concomitant esotropia is not a common strabismus, it is reported to account for <1% of strabismus which requires surgical treatment & it is often associated with low hypermetropia. In a retrospective study, 48 cases were reported that presented over 13 years (Buch and Vinding, 2015). It usually presents during infancy or early childhood (Lyons et al, 1999; Sturm et al, 2011), however when it presents in adulthood it is more commonly associated with myopia & may be due to a different mechanism (Spierer, 2003

Question 24

what is the aetiology of acute onset et

Answer 24

excessive close work
Increased prevalence with more hours of close work particularly without the use of glasses
Increased time on screens and smartphones
Evidence of increased prevalence post-pandemic in children

Zhang et al (2022); Sefi-Yurdaku (2022); Mohan et al (2021);

space occupying lesions

Neuro disease / hydrocephalus / SOL
Incomitant deviations
Concomitant ET
Neurological signs / symptoms
Nystagmus / diplopia / pupil / VF
Atypical features
No potential BSV
No hypermetropia

Question 25

how is acute onset et and chair malformation related to the aetiology of acute onset et

Answer 25

Cessation heroin use (n=3) (Firth, 2001)
Prospective study, detox (heroin/methadone)
Eso tendency (Dist>Nr)
No 6th N palsy / divergence paralysis found
(Firth et al, 2004)

Rare in Chiari I malformation
May resolve following neuroSx
Treatment with:
Prisms
BT

(Firth & Burke, 2006)

Question 26

what is the treatment for acute onset et

Answer 26

Sx
Prisms
BT

aiming to restore bsv

Sturm et al, 2011
Retrospective review (n=25)
84% stereo post-op
Mean 18/12 (range 2-58/12) to achieve stereo

Question 27

what are the main ateiolgies for concomitant strabismus

Answer 27

Multifactorial & complex
Genetic
Refractive error & emmetropisation
Neonatal misalignments – vergence system
Infantile ET – interruption of maturation of visual system
Acute onset ET
At risk groups
Innervation
Loss of vision
Others