1. Infantile nystagmus syndrome

Infantile nystagmus syndrome (INS) is a permanent, non-progressive condition causing involuntary oscillations of the eyes. It first appears within the first six months of life and is often associated with a congenital pathology of the visual system. In many cases however, no defect of the visual system can be found, in which case it is classified as 'idiopathic' INS. The oscillations in INS are usually conjugate (the same in both eyes) and horizontal in all directions of gaze. There is usually a particular direction of gaze in which the oscillations are at a minimum; this angle of gaze is known as the null zone. Over time, an abnormal head position may develop in order to use the better vision offered by this position.

Other factors are also known to affect the INS oscillations: relaxation, convergence and closing the eyes all tend to reduce the nystagmus intensity. Conversely, stress and tiredness will usually result in an increase in intensity. The inheritance of INS is governed by the type of inheritance shown by the sensory defect that has caused the nystagmus. In the case of idiopathic INS, inheritance can be autosomal dominant, but other forms of inheritance are  known to occur.

Diagnosis

INS is usually diagnosed within the first six months of life. INS rarely presents at birth. The average age of onset is estimated to be 1.9 months (Gottlob 1997). However, in cases of very low amplitude nystagmus, the condition may go unnoticed for many years.

Since INS often presents in conjunction with a pathology of the visual pathway, a full ophthalmological workup is required in any child presenting with nystagmoid eye movements for the first time. If no comorbid ocular pathology can be found, the INS is described as ‘idiopathic’.

The exact type of INS can be diagnosed through the use of eye tracking equipment. Such technology is rarely found in hospitals.

Prognosis / impact

INS is a permanent condition, which at present has no known cure. Unlike acquired nystagmus, INS does not usually cause oscillopsia (the illusory perception that the world is moving). The condition is also non-progressive; i.e. vision does not worsen, and the eye movements rarely increase, unless exacerbated by extraneous factors such as stress or ill health. A recent study identified the main aspects of daily life affected by nystagmus (McLean, Windridge and Gottlob 2012). The study identified issues including restricted mobility, difficulties forming relationships, and not wishing to stand out as being different.

Incidence

Based on a large scale study of the population of Leicestershire, the incidence of INS is believed to be 14 in 10,000 (Sarvananthan et al. 2009).

Sensory defect infantile nystagmus syndrome

Around 70% of cases of INS are associated with some sort of ocular defect. There are a large range of seemingly unrelated conditions that are associated with INS. In all cases however, the ocular defect in some way impairs vision, usually bilaterally.

The most commonly associated conditions are albinism, cataract, aniridia, coloboma, cone dysfunction, achromatopsia and congenital stationary night-blindness.

The link between visual impairment at birth and the development of INS has led to the theory that nystagmus develops as a response to poor image quality (Harris and Berry 2006).

Idiopathic infantile nystagmus syndrome

When non-acquired nystagmus presents in the first six months of life with no other detectable abnormality of the eyes, it is referred to as ‘idiopathic infantile nystagmus syndrome’ (IINS). Idiopathic literally means ‘of unknown cause’, and at present it is not known in these cases whether nystagmus is the primary defect, or if an undetectable visual system abnormality exists. In some cases, there is a genetic link between individuals with IINS. Several mutations have been found in the ‘FERM domain containing 7’ (FRMD7) gene in X-linked IINS (Tarpey et al. 2006; Self and Lotery 2007; Xiao et al. 2011; Li et al. 2012; Radhakrishna et al. 2012).

Null zone and abnormal head positions

The intensity of nystagmus movement varies with direction of gaze. The position(s) of gaze in which nystagmus intensity is at a minimum is known as the ‘null zone’.

In a study of 224 people with INS, 73% were found to have a null zone within 10° of the primary position. Around 44% of nystagmats also exhibit a dampening of eye movements with convergence; therefore near vision may be better than distance in some situations (Abadi and Bjerre 2002).

Since the null zone position of gaze affords the individual better vision, often an abnormal head position (AHP) develops to put the eyes in the optimum position whilst looking straight ahead. In Abadi and Bjerre’s 2002 study, 69% of subjects with an eccentric null zone exhibited an AHP. When the null zone was ≥20° from the primary position, all nystagmats exhibited an AHP.

AHPs are one of the reasons that some individuals feel their nystagmus makes them stand out as being different (McLean, Windridge and Gottlob 2012). Often, the individual will have to choose between using a socially ‘normal’ head position, and adopting their AHP to maximise their ability to interpret social cues.

Effects on visual capability

Nystagmus can have many adverse effects on visual capability. The exact nature and extent of these effects is determined by the nature of the nystagmus, its waveform, intensity, fixation effort, viewing distance, stress and, if an eccentric null zone is present, head posture.

The presence of oscillating eye movements results in the motion of the visual image across the retina. Contrast sensitivity of the visual system is highly sensitive to even small image movements of a few degrees per second, especially at high spatial frequencies (fine detail). The oscillations in the slow-phase of nystagmus oscillations can reach speeds of 100 degrees per second which will obviously cause a large reduction in contrast sensitivity. Contrast sensitivity is what determines our ability to discriminate objects of different brightnesses apart and in the majority of situations contrast between objects is low. A reduced contrast sensitivity can therefore have a large impact on an individual's ability to navigate their way around their surroundings. Contrast sensitivity in nystagmus is determined by the speed of the slow-phases which are known as 'foveation periods'; the longer these foveation periods are, the better the vision will be. The reduction in sensitivity also causes nystagmats to be highly sensitive to visual 'crowding'. This causes increased difficulty in discriminating two objects that are close together.

Another factor which relates to the level of visual capability in nystagmus is the ability to align the fovea with the object of fixation during the foveation periods. This alignment of the fovea with the target is generally more accurate in adults with nystagmus than children, possibly due to adaptation of the visual system.

Nystagmats have a high incidence of with-the-rule astigmatism in which the eye has a higher power in the vertical meridian than the horizontal meridian. This may be due to a mechanical deformation of the eye or a response by the visual system to the blur caused by the oscillations. This will cause the eye to develop a higher power in one direction than the other in an effort to clarify the vision. Meridional amblyopia is also present, caused by the oscillations which occur along the meridian at 90 degrees to the direction of the oscillations which deprive the visual system of stimuli along that meridian.

Rarely, individuals with INS suffer from oscillopsia (the illusion that the world is moving), although this is much more common in acquired nystagmus.

Therapies

No ‘cure’ for INS has yet been discovered; however there are a large number of interventions that have been shown to be effective in reducing the eye movements, moving the null zone, and/or improving visual function.

Contact lenses

Contact lenses provide superior refractive correction over conventional spectacle lenses for nystagmats due to the reduction in aberrations, and induced prismatic effect experienced as the eye moves away from the primary position. Allen and Davies (1983) found an increase in visual acuity of at least one Snellen line in seven out of eight nystagmats using contact lenses compared to when wearing spectacles. This was confirmed by Biousse et al. (2004). Contact lenses also appear to dampen nystagmus eye movements in INS, but this effect is not present when the eye is anaesthetised (Dell’Osso et al. 1988). This finding suggests that the presence of the lens touching the eye – rather than the optical effects of the lens – serve to reduce the movement, which implies that nystagmus intensity is partially governed by signals from nerves in this region. Dell’Osso, Leigh and Daroff (1991) went on to show that cutaneous stimulation of the ophthalmic division of the trigeminal nerve can cause a reduction of nystagmus intensity, using gentle touches, vibrations, pressing and rubbing of the forehead and upper eyelids.

Prism correction

The fact that many nystagmats have a convergent null zone led to the suggestion that prescribing base out prism (to drive convergence) could improve visual function. A study by Dickinson (1986) found no improvement in the contrast sensitivity function with this method; nystagmus intensity was, however, reduced. Rarely, the null zone is in the divergent position, in which case base in prism has been shown to be useful. A study by Dell’Osso (2002) found an improvement in visual acuity of two Snellen lines when prisms were used both to drive convergence and to place the eyes into a null zone of gaze. As ever when prescribing prism, care must be taken to balance the refractive and prismatic prescriptions with respect to the accommodative convergence : accommodation ratio (Dell’Osso 2002).

Surgery

Several surgical procedures have been advocated for INS. These include:

Anderson-Kestenbaum surgery

In 1953, Kestenbaum devised a surgery intended to move the null zone towards the primary position, thus reducing any AHP present. This procedure involves a recession of the rectus muscles with action in the direction of the face turn, and resection of the antagonists. A form of this procedure is still used today and is effective in reducing AHPs (Lee 2002).

Artificial divergence

Using a similar principle to base out prisms, performing resections in both lateral recti induces a latent exophoria which is overcome by employing fusional convergence (in patients with sufficient fusional reserves). This serves to reduce the intensity of nystagmus. In a surgical study by Zubcov et al. (1993), three out of six patients undergoing artificial divergence surgery experienced a measurable improvement in visual acuity. Five patients underwent combined Anderson-Kestenbaum and artificial divergence surgery, four of whom gained two or more lines of Snellen acuity.

Horizontal rectus recession

The recession of all four horizontal recti has been shown to increase visual acuity whilst reducing nystagmus intensity. It has been suggested as an easier-to-perform alternative to Anderson-Kestenbaum surgery. In a study on ten subjects with INS undergoing this procedure, eight exhibited a reduction in the amplitude of their nystagmus with a concordant average improvement in visual acuity of one line.

Tenotomy

The ‘anterior tenotomy’ procedure was pioneered in 1999 (Dell’Osso et al.) on an achiasmatic mutant Belgian sheepdog with INS. The procedure was later performed on ten human subjects with no adverse events, leading to improved clinical visual acuity in five subjects, improved subjective visual function in nine subjects, and increased foveation periods in these same nine subjects. The procedure, which involves severing the horizontal recti, followed by reattachment at the original site, was first proposed in 1998 (Dell’Osso).

Combination surgery

Given the number of surgical approaches available, surgeons have recently been implementing combinations and modifications of the above procedures, with generally positive outcomes in both the nystagmus intensity, and clinical visual acuity (Bishop 2011; Kumar et al. 2011).

Pharmacological

Many medicines are known to reduce the intensity of nystagmus. In 2002, a list of fourteen treatments reported to improve the condition was published (Stahl, Plant, and Leigh). Of these, four have been shown to effectively dampen nystagmus intensity in INS (memantine, gabapentin, baclofen and cannabis). Memantine (20-24mg) and gabapentin (up to 2400mg) both reduce nystagmus intensity and improve visual acuity in INS, and have been validated in a controlled, double-masked randomised trial (Sarvananthan et al. 2006; Shery et al. 2006; McLean et al. 2007). One case report of a subject with IINS showed that smoking cannabis can cause a reduction in nystagmus intensity and an improvement in clinical visual acuity (Pradeep et al. 2008). Baclofen is often used in patients with periodic alternating nystagmus, as it is known to reduce nystagmus amplitude, improve visual acuity and alleviate AHP (Solomon et al. 2002; Comer et al. 2006).

Dexedrine, a stimulant used to treat attention deficit hyperactivity disorder, has been shown to increase foveation duration, improve stereopsis, reduce an exotropic deviation and improve visual acuity in a patient with INS associated with rod-cone dystrophy (Hertle et al. 2001).

A recent study demonstrated that brinzolamide, applied topically, can cause an improvement in NAFX in a patient with INS, providing hope for non-systemic approaches to nystagmus pharmaceuticals (Dell’Osso et al. 2011).

The mechanisms of the above medications are currently unknown, although their mode of action is suspected to be through sedation rather than specifically reducing the eye movements (Abel 2006). For a detailed account of the pharmacological treatments available for INS, the reader is directed to McLean and Gottlob (2009) and Strupp et al. (2011).

Other

Biofeedback: Auditory biofeedback, derived from live eye movement recordings, provide nystagmats with direct feedback from their nystagmus, and with practice, patients are able to reduce the intensity of their nystagmus (Mezawa et al. 1990). This suggests that with practice, nystagmats can learn to consciously control their eye movements. After six half-hour sessions of auditory biofeedback, a study by Sharma et al. (2000) found nystagmus amplitude to be reduced by 51% and intensity reduced by 60%, with a subjective improvement in quality of vision. Abadi, Carden and Simpson (1980) found an objective improvement in visual acuity between 0.13 and 0.32 (logMAR). However, these improvements are generally not sustained following discontinuation of the therapy (Sharma et al. 2000), but in a study by Ciuffreda, Goldrich and Neary (1982), one subject was able to reduce their nystagmus eye movements to 50% of the pre-training level on demand, without biofeedback.

Acupuncture: In 1987 (Ishikawa, Ozawa, and Fujiyama), acupuncture was shown to reduce nystagmus intensity in nine out of 16 subjects tested. Blekher et al. (1998) showed that insertion of two acupuncture needles in the sternocleidomastoid muscles of the neck caused a significant increase in foveation durations in four out of six patients, which was observed five minutes following the end of treatment. In this experiment, one subject who was particularly responsive to the treatment later had a sham treatment administered, which caused exacerbation of his nystagmus. In this instance, foveation periods reduced at the times when the needle guide tubes were tapped, in contrast to an observed increase in foveation time during genuine acupuncture treatment.

2. Fusion maldevelopment nystagmus syndrome

Formerly known as ‘latent nystagmus’, fusion maldevelopment nystagmus syndrome (FMNS), is perhaps the most commonly seen form of pathological nystagmus, due to the fact that its onset often follows an infantile strabismus (squint). FMNS oscillations are conjugate (the same in both eyes) and display a jerk waveform with decelerating slow phases. The oscillations beat towards the fixing eye (more accurately, the eye that the subject believes they are fixing with). The oscillation intensity increases with abduction of the fixing eye (looking outwards) and decreases with adduction of the fixing eye (looking inwards). A head turn may be adopted in the direction of the fixing eye as the reduced nystagmus intensity in this position allows better vision. FMNS can be manifest or latent (See classification).

3. Spasmus nutans syndrome

Spasmus nutans syndrome is a rare disorder, which causes (in combination): a high frequency, low amplitude nystagmus of a disconjugate nature, irregular head nodding and an AHP. Its onset is usually within the first year of life and the condition ceases spontaneously, usually within two years of onset, although it has been known to persist for over eight years. A low-amplitude nystagmus (not detectable clinically) may persist until at least five to twelve years of age (Gottlob et al. 1995). The pathogenesis of spasmus nutans syndrome is unknown (Leigh and Zee 2006).