Fusion Maldevelopment Nystagmus Syndrome Research Articles

A Case Study of Infantile Nystagmus Syndrome (Congenital)

Infantile nystagmus (IN), formerly known as congenital nystagmus, is an involuntary to-and-fro movement of the eyes that persists throughout life. IN is one of three types of early-onset nystagmus that first appear in infancy, alongside fusion maldevelopment nystagmus syndrome and spasmus nutans syndrome. Patients with acquired nystagmus may also be seen by optometrists. The features of IN overlap largely with those of fusion maldevelopment nystagmus syndrome, spasmus nutans syndrome, and acquired nystagmus, yet the management for each subtype is different. We report a case of bilateral congenital sensory nystagmus with bilateral megalocornea with left-sided relative afferent pupil defect with left eye global enlargement in ap axis with reduced caliber in left optic artery with pseudo polycorea with reduced visual acuity in the bilateral eye with buphthalmos with haab striae.

Demographic and Clinical Characteristics of 600 Children With Nystagmus.

To characterize a large, international cohort of children with nystagmus. Data were collected from a single-center, prospectively developed database on patients with nystagmus. Outcome variables for this study included: (1) demographic characteristics, (2) nystagmus type, (3) clinical characteristics, (4) associated ophthalmic conditions, (5) associated non-ophthalmic conditions, (6) special testing findings, and (7) treatments. Six hundred patients from 38 states and 30 countries were included. Age ranged from birth to younger than 18 years (mean: 15.2 years), 58% were female, 55% were race other than White, 75% had infantile nystagmus syndrome, 17% had neurologically significant nystagmus, 7% had fusion maldevelopment nystagmus syndrome, 64% had strabismus, 56% had an anomalous head posture, 94% had a significant refractive error, 64% had an associated ophthalmic abnormality (excluding ametropia), and 45% had an associated systemic condition. Special testing showed abnormalities in 67% and 95% had treatment directed at their nystagmus. The most common diagnosis in this cohort is neurologically non-significant infantile nystagmus syndrome. Eye movement recordings provide a path toward accurate diagnosis and classification. There was a high prevalence of underlying ocular and/or systemic conditions requiring ophthalmic special testing as part of a diagnostic routine. Clinical treatments are available to most patients. [J Pediatr Ophthalmol Strabismus. 2023;60(6):406-410.].

High-dose medialis recession in latent nystagmus

Large muscle recessions reduce anomalous head turn (AHT) in infantile nystagmus syndrome (INS). Their quantitative effect to reduce AHT in fusion maldevelopment nystagmus syndrome (FMNS) is unknown. To evaluate the reduction of AHT by large medial rectus muscle recession in patients with FMNS. We analyzed data of 12patients with pure FMNS who received large medial rectus muscle recessions on the sound eye or only eye between 2014 and 2019. Medians and ranges (min-max) were: age at surgery 14years (3-43 years); decimal BCVA sound eye/fellow eye 0.56 (0.4-1.0)/0.01 (0-0.4); AHT at 5 m/0.3 m fixation distance 35° (15-45°)/20° (0-45°); amount of recession 13 mm (11.5-15 mm); follow-up13 (4-39) months. At the final visit, AHT at 5 m/0.3 m was 10° (0-20°/0-15°). The individual reduction of AHT at 5 m amounted to 25° (8-35°) without any overcorrection. The available visual field of functionally monocular patients increased correspondingly. Slight overcorrection at 0.3 m occurred in 2cases. Adduction of the sound eye was limited to 25e-40°). BCVA and anomalous head posture in vertical and frontal planes did not improve. Large medial rectus muscle recession on the sound eye improves AHT in FMNS by asimilar amount compared to INS and the available visual field of functionally monocular patients.

The Developmental Eye Movement Test Does Not Detect Oculomotor Problems: Evidence from Children with Nystagmus.

SIGNIFICANCEThe Developmental Eye Movement (DEM) test, a test purported to assess oculomotor skills, does not detect eye movement disorder in nystagmus syndromes. The test should not be used for the clinical evaluation of oculomotor disorders.PURPOSEThe DEM test ratio compares a horizontal number naming subtest with a vertical one to identify oculomotor problems independent of a child's visual-verbal naming skills. Here, we tested the construct validity of this method by comparing scores of children with and without pathologic nystagmus. Such a nystagmus disturbs normal fixation and saccadic behavior because of the presence of involuntary rhythmic oscillations of the eyes. Therefore, if the ratio is indeed a comprehensive measure of oculomotor problems, children with nystagmus should show an increased ratio score.METHODSThe DEM test performances of normally sighted children (n = 94), children with ocular visual impairments (VIo; n = 33), and children with cerebral visual impairment (n = 30) were analyzed using linear regression. Part of the children with VIo and cerebral visual impairment had either fusion maldevelopment nystagmus syndrome (n = 8) or infantile nystagmus syndrome (n = 20), whereas the others showed no pathologic nystagmus.RESULTSThe times needed for the horizontal and vertical subtests were significantly different between children with normal vision, VIo, and cerebral visual impairment (P < .001). However, the presence of nystagmus did not add significantly to the horizontal and vertical times (P > .20), nor did it have an effect on the ratio (P > .10).CONCLUSIONSThe DEM test ratio is not sensitive to fixation and saccade abnormalities associated with nystagmus, indicating that it does not have general construct validity to detect true eye movement disorders. Although not suitable for the evaluation of oculomotor disorders, the subtests do have clinical relevance in the diagnosis of cerebral visual impairment.

Demographic and clinical characteristics of 600 children with nystagmus

To characterize a large, international cohort of children with nystagmus.Data were collected from a single-center, prospectively developed database on patients with nystagmus. Outcome variables for this study included: (1) demographic characteristics, (2) nystagmus type, (3) clinical characteristics, (4) associated ophthalmic conditions, (5) associated non-ophthalmic conditions, (6) special testing findings, and (7) treatments.Six hundred patients from 38 states and 30 countries were included. Age ranged from birth to younger than 18 years (mean: 15.2 years), 58% were female, 55% were race other than White, 75% had infantile nystagmus syndrome, 17% had neurologically significant nystagmus, 7% had fusion maldevelopment nystagmus syndrome, 64% had strabismus, 56% had an anomalous head posture, 94% had a significant refractive error, 64% had an associated ophthalmic abnormality (excluding ametropia), and 45% had an associated systemic condition. Special testing showed abnormalities in 67% and 95% had treatment directed at their nystagmus.The most common diagnosis in this cohort is neurologically non-significant infantile nystagmus syndrome. Eye movement recordings provide a path toward accurate diagnosis and classification. There was a high prevalence of underlying ocular and/or systemic conditions requiring ophthalmic special testing as part of a diagnostic routine. Clinical treatments are available to most patients. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Nystagmus in Down Syndrome - a Retrospective Notes Review.

Introduction:Nystagmus has been reported in up to 30% of people with Down Syndrome (DS), and yet is still not well understood. Our study aims to characterise the clinical features of patients with DS and nystagmus.Methods:A retrospective medical-records review was conducted of all patients with a diagnosis of DS and nystagmus seen at Moorfields Eye Hospital over a ten-year period.Results:Fifty-one subjects were identified, with complete data in 48. The mean age at presentation was 5.1 years (range 0–26 years). The mean binocular LogMAR visual acuity was 0.55(95%CI 0.53–0.57), mean refractive error was –1.8 Dioptre Sphere, DS (95% CI – 5.251.63) with –1.2 Dioptre Cylinder, DC (95% CI – 1.6–0.7). Ocular misalignment was found in 50% of patients. A diagnosis of Fusion Maldevelopment Nystagmus Syndrome (FMNS) was made in 6.3%, Infantile Nystagmus Syndrome (INS) in 8.4% and ABducting nystagmus/Inter-Nuclear Ophthalmoplegia (INO) in 2.1%. The descriptive term ‘Manifest Horizontal Nystagmus’(MNH) was used in the majority, highlighting the difficulties in clinically differentiating the subtypes of nystagmus in DS. Eleven patients had associated cataract. Additional diagnoses unrelated to DS were made in 10.4%.Conclusions:The most frequent type of nystagmus in our cohort was ‘presumed’ INS. This study highlights the importance of differentiating between FMNS and INS (with a latent component), so that further investigations can be performed as appropriate. Almost 25% had associated cataract, and a further 10% other diagnoses un-associated to DS. Despite INS being known to be associated with DS, further investigations may be required in a small subset with true INS after careful clinical assessment and use of eye movement recordings (where available).

Visual acuity and stereoacuity improvement in children with and without fusion maldevelopment nystagmus syndrome

To evaluate visual acuity and stereoacuity improvement in children with and without associated fusion maldevelopment nystagmus syndrome (FMNS) treated with part-time patching.

Monocular and Binocular Visual Function Deficits in Amblyopic Patients with and without Fusion Maldevelopment Nystagmus.

PurposeThe aim of the study is to examine the association between amblyopia type and the presence of nystagmus on binocular and monocular functions of the fellow (FE) and amblyopic eye (AE).MethodsWe recruited 19 controls and 44 amblyopes (anisometropes=13, strabismic=10, mixed=21). We measured visual, grating, and vernier acuities and high/low spatial frequency (SF) contrast sensitivities in each eye using a staircase method. Stereoacuity was measured with the Titmus fly test. We recorded fixation eye movements (FEM) using high-resolution video-oculography. Subjects were classified as having either no nystagmus (n=18), fusion maldevelopment nystagmus syndrome (FMNS) (n=12), or nystagmus without any structural anomalies that does not meet the criteria for FMNS or infantile nystagmus (n=14).ResultsAnalysis of visual function by clinical amblyopia type showed that patients with strabismus/mixed amblyopia (F (2,54)=9.5, p<0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit. The FE of patients with anisometropia had greater contrast sensitivity deficits at low (F (2,43)=4.4, p=0.018) and high SF (F (2,42)=10.1, p<0.001). Analysis of visual function by FEM characteristics (low SF: (F (3,43)=4.3, p=0.010) and high SF: (F (3,42)=7.1, p=0.001) showed that the FE of patients with FMNS had worse low and high SF contrast sensitivities, whereas those without FMNS had greater contrast sensitivity deficits only at high SF compared to controls. Patients with FMNS (F (3,54) = 12.9, p<0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit compared to patients without FMNS. All amblyopic patients had worse high SF contrast sensitivity of the AE irrespective of type or FEM characteristics (Type = F (2,43)=8.8, p=0.001; FEM characteristics= F (3,43)=5.1, p=0.004).ConclusionThe presence of FMNS in patients with strabismic/mixed amblyopia is associated with poor/absent stereopsis. FE deficits vary across amblyopia type. Like FEM abnormalities, visual function deficits are seen in the FE of patients with and without nystagmus.

Fixational eye movements abnormalities and rate of visual acuity and stereoacuity improvement with part time patching

Residual amblyopia is seen in 40% of amblyopic patients treated with part-time patching. Amblyopic patients with infantile onset strabismus or anisometropia can develop fusion maldevelopment nystagmus syndrome (FMNS). The purpose of this study was to understand the effects of presence of FMNS and clinical subtype of amblyopia on visual acuity and stereo-acuity improvement in children treated with part-time patching. Forty amblyopic children who had fixation eye movement recordings and at least 12 months of follow-up after initiating part-time patching were included. We classified amblyopic subjects per the fixational eye movements characteristics into those without any nystagmus, those with FMNS and patients with nystagmus without any structural anomalies that do not meet the criteria of FMNS or idiopathic infantile nystagmus. We also classified the patients per the clinical type of amblyopia. Patching was continued until amblyopia was resolved or no visual acuity improvement was noted at two consecutive visits. Children with anisometropic amblyopia and without FMNS have a faster improvement and plateaued sooner. Regression was only seen in patients with strabismic/mixed amblyopia particularly those with FMNS. Patients with FMNS had improvement in visual acuity but poor stereopsis with part-time patching and required longer duration of treatment.

Infantile nystagmus: an optometrist&amp;rsquo;s perspective

Infantile nystagmus (IN), previously known as congenital nystagmus, is an involuntary to-and-fro movement of the eyes that persists throughout life. IN is one of three types of early-onset nystagmus that begin in infancy, alongside fusion maldevelopment nystagmus syndrome and spasmus nutans syndrome. Optometrists may also encounter patients with acquired nystagmus. The features of IN overlap largely with those of fusion maldevelopment nystagmus syndrome, spasmus nutans syndrome, and acquired nystagmus, yet the management for each subtype is different. Therefore, the optometrist’s role is to accurately discern IN from other forms of nystagmus and to manage accordingly. As IN is a lifelong condition, its presence not only affects the visual function of the individual but also their quality of life, both socially and psychologically. In this report, we focus on the approaches that involve optometrists in the investigation and management of patients with IN. Management includes the prescription of optical treatments, low-vision rehabilitation, and other interventions such as encouraging the use of the null zone and referral to support groups. Other treatments available via ophthalmologists are also briefly discussed in the article.

Nystagmus in Infancy and Childhood: Clinical and Eye Movement Characteristics

ABSTRACTThe most common forms of nystagmus in infancy and childhood are Infantile Nystagmus Syndrome (INS), Fusion Maldevelopment Nystagmus Syndrome (FMNS), and Spasmus Nutans Syndrome (SNS). This review will sumamrize the clinical and eye movement recording characteristics of these disorders, thus reinforcing the importance of eye movement technology in both the discoveries underlying pathophysiology and the guidance of clinical interventions.

Quick phases of infantile nystagmus show the saccadic inhibition effect.

Infantile nystagmus (IN) is a pathological, involuntary oscillation of the eyes consisting of slow, drifting eye movements interspersed with rapid reorienting quick phases. The extent to which quick phases of IN are programmed similarly to saccadic eye movements remains unknown. We investigated whether IN quick phases exhibit 'saccadic inhibition,' a phenomenon typically related to normal targeting saccades, in which the initiation of the eye movement is systematically delayed by task-irrelevant visual distractors. We recorded eye position from 10 observers with early-onset idiopathic nystagmus while task-irrelevant distractor stimuli were flashed along the top and bottom of a large screen at ±10° eccentricity. The latency distributions of quick phases were measured with respect to these distractor flashes. Two additional participants, one with possible albinism and one with fusion maldevelopment nystagmus syndrome, were also tested. All observers showed that a distractor flash delayed the execution of quick phases that would otherwise have occurred approximately 100 ms later, exactly as in the standard saccadic inhibition effect. The delay did not appear to differ between the two main nystagmus types under investigation (idiopathic IN with unidirectional and bidirectional jerk). The presence of the saccadic inhibition effect in IN quick phases is consistent with the idea that quick phases and saccades share a common programming pathway. This could allow quick phases to take on flexible, goal-directed behavior, at odds with the view that IN quick phases are stereotyped, involuntary eye movements.

Fusion Maldevelopment (Latent/Manifest Latent) Nystagmus Syndrome: Effects of Four-Muscle Tenotomy and Reattachment

To examine the waveform and clinical effects of the four-muscle tenotomy and reattachment procedure in fusion maldevelopment nystagmus syndrome (FMNS) and to compare them to those documented in infantile nystagmus syndrome (INS) and acquired nystagmus. Both infrared reflection and high-speed digital video systems were used to record the eye movements in a patient with FMNS (before and after tenotomy and reattachment). Data were analyzed using the eXpanded Nystagmus Acuity Function (NAFX) that is part of the OMtools software. Model simulations and predictions were performed using the authors' behavioral ocular motor system model in MATLAB Simulink (The MathWorks, Inc., Natick, MA). The model predicted, and the patient's data confirmed, that the tenotomy and reattachment procedure produces improvements in FMN waveforms across a broader field of gaze and decreases the Alexander's law variation. The patient's tenotomy and reattachment plots of NAFX after surgery versus gaze angle were higher and had lower slope than before surgery. Clinically, despite moderate improvements in both peak measured acuity and stereoacuity, dramatic improvements in the patient's abilities and lifestyle resulted. The four-muscle tenotomy and reattachment nystagmus surgery produced beneficial therapeutic effects on FMN waveforms that are similar to those demonstrated in INS and acquired nystagmus. These results support the authors' prior recommendation that tenotomy and reattachment nystagmus should be added to required strabismus procedures in patients who also have FMNS (ie, perform tenotomy and reattachment on all unoperated muscles in the plane of the nystagmus). Furthermore, when strabismus surgery is not required, four-muscle tenotomy and reattachment may be used to improve FMN waveforms and visual function.

Oscillopsia and the Influence of Stress and Motivation in Fusion Maldevelopment Nystagmus Syndrome

We examined factors influencing perceptual stability in observers with fusion maldevelopment nystagmus syndrome (FMNS). In addition, we also investigated the effect of visual demand, task-related physiologic stress, and motivation on the nystagmus waveform. Perception of oscillopsia during daily activities was assessed via a questionnaire. Perception of oscillopsia in the laboratory was assessed using central and peripheral (10°) light emitting diodes (LEDs) in front of a background display of random, fixed-contrast shapes. Task-induced stress was achieved via a time restricted acuity task with or without concurrent mental arithmetic challenge, and motivation varied using a reward-penalty paradigm. The experiments have been previously described elsewhere. Six out of nine subjects reported experiencing oscillopsia in certain daily activities. in the laboratory, the percentages of trials with perceptions of motion of the led and background were as follows: neither, 60% to 70%; background only, 20% to 30%; both, 5% to 15%, and LED only, 5% to 15%. Over all trials, six of nine experienced oscillopsia for both the low- and high-contrast image respectively (i.e., three subjects never experienced oscillopsia). The background was frequently seen moving for both images regardless of contrast and/or condition. Trials with and without oscillopsia did not differ when comparing foveation. In the second experiment, task-related physiologic stress and motivation were reflected in an increase in heart rate; nystagmus waveform intensity increased and foveation decreased. The magnitude of changes in heart rate was uncorrelated with changes in waveform parameters for all experiments, however. Preliminary results suggest that the FMNS group does perceive spatially inhomogeneous oscillopsia, similar to infantile nystagmus syndrome (INS), in certain visual environments. In investigating the effect of stress and motivation on FMNS, a new, if tentative, finding suggests that task-induced stress and/or motivation may have a negative impact on the nystagmus. Taken together, our findings provide an insight into the particular environments and tasks that are likely to present particular challenges to persons with FMNS.

The mechanism of oscillopsia and its suppression

We studied the mechanisms of oscillopsia suppression in subjects with infantile nystagmus syndrome, fusion maldevelopment nystagmus syndrome, and acquired nystagmus (AN). Hypothetical possibilities for perceptual stability were the following: (1) epochs of clear and stable vision during foveation periods of nystagmus waveforms; (2) cancellation by efference copy of motor output; (3) a combination of the effects of both foveation-period stability and efference-copy cancellation; or (4) elevated motion-detection threshold and vision suppression. Observations, studies, and models of oscillopsia suppression allowed comparison of these possibilities. Data from individual subjects supported some of the putative hypotheses. However, only one hypothesis remained viable that could explain how all subjects maintained perceptual stability despite their different nystagmus types, waveforms, and variability. Robust suppression of oscillopsia was only possible using efference-copy feedback of the motor output containing these specific nystagmus signals to cancel that motion from the retinal error signals. In cases of AN, where oscillopsia could not be suppressed, the deficit was postulated to interfere with or lie outside of this efference-copy feedback loop.

“Sensory” and “Motor” Nystagmus

Most patients with infantile nystagmus syndrome (INS) 1 (formerly known as congenital nystagmus) exhibit nystagmus with several of the waveforms first identified in 1975. 2 The past 45 years of recording and analyzing nystagmus waveforms have repeatedly demonstrated that most INS waveforms result from the same deficit in one of the several ocular motor subsystems, specifically smooth pursuit. 3-6 This applies to all patients with INS whether they have associated visual sensory deficits, are familially predisposed to have INS (ie, there is a true genetic anomaly), or exhibit INS without an associated ocular or central nervous system deficit (so-called idiopathic). Despite this eye-movement data, textbooks in ophthalmology, neuro-ophthalmology, and neurology as well as current peer-reviewed literature continue to use the terms sensory and motor nystagmus to describe the ocular oscillations of INS. Those descriptions imply not only that there are at least 2 different types of nystagmus but also that they have independent pathophysiology caused by different primary developmental deficits; both implications are unsupported by decades of ocular motor electrophysiological data. The adoption of this terminology and its presumed ability to clinically differentiate pendular from jerk waveforms are responsible for the misdiagnosis of many cases of INS. Ocular motor recordings demonstrate that owing to the complexity of INS waveforms, clinical differentiation is impossible in many patients. These recordings also show that another type of nystagmus of infancy, fusion maldevelopment nystagmus syndrome (formerly known as latent/manifest latent nystagmus), cannot be differentiated from INS with a latent component; Alfred Kestenbaum, MD, first noted the existence of these 2 clinically similar types of nystagmus in his 1946 textbook and its expanded 1961 second edition.