[Ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus].

Objective: To explore the ultrastructural alteration of extraocular muscle proprioceptor in congenital idiopathic nystagmus (CIN). Methods: Case-control study. Ten extraocular muscle samples were collected from five CIN children who underwent nystagmus surgeries in Beijing Children's Hospital from March 2015 to March 2016. Another ten extraocular muscle specimens were collected from five strabismus children in surgery at the same period as normal contrast. There were 3 male patients and 2 female patients of CIN with age of 61-147 months (median age: 91 months). The ultrastructure of extraocular muscle proprioceptors was compared between these two groups by transmission electron microscope. Results: Twenty-three proprioceptors were found in extraocular muscle specimens of CIN children, whereas thirty-three proprioceptors were detected in strabismus children. The ultrastructure of extraocular muscle proprioceptor of CIN altered greatly comparing with that of the control. Fourteen extraocular muscle proprioceptors of CIN were discovered much smaller and vacuolated not only at inner capsules but also at the space between inner and outer capsules with lipofuscins and myeloid bodies in the intrafusal muscle fibers. Sensory nerve fibers degenerated greatly with a lot of lipofuscins and myeloid bodies in these sensory nerve fibers. Demyelination also appeared in some severe cases. Nine extraocular muscle proprioceptors of CIN showed significant dissolving degeneration of myofibrils and proliferation of collagen fibrils. The normal structures could not be distinguished in these proprioceptors. And these structural disorders also appeared in extrafusal muscle fibers and nerve endings. Conclusion: The ultrastructure of extraocular muscle proprioceptor in CIN turned much smaller and had significantly structural disorder.(Chin J Ophthalmol, 2017, 53: 136-139).

[Clinical characteristics and surgical treatment of idiopathic congenital nystagmus in 224 patients].

OBJECTIVE: To study clinical characteristics and surgical treatment of idiopathic congenital nystagmus (ICN). METHODS: A retrospective study was conducted in 224 patients with ICN in Tianjin eye hospital from July 2007 to February 2013. RESULTS: There were 224 patients, 158 (70.54%) males and 66 (29.5%) females, mean age was (11.6±8.4) years and (11.4±6.4) years separately. Horizontal nystgamus happened in 215 cases, 3 cases were vertical type and 6 cases were mixed. 214 cases were with no history of operation and 10 patients had ever underwent surgeries before. Furthermore, 151 patients combined with strabismus and refractive error, anterior segment or retinal disorders, which accounting for 67.4% of all the patients. 48 patients were associated myopia, 30 patients with hyperopia, 43 patients with strabismus. Among them, 153 cases of compensatory head position direction were horizontal with face turn, 43 cases (43/153, 28.1%) showed face turning to the left, 110 cases (110/153, 71.9%) showed face turning to the right. Surgeries were designed according to the compensatory head position and head retroversion angle. For 15 patients with double intermediate zones, the position which was often used with good visual function was chosen for operation design. As for the patients with nystagmus and strabismus, the transfer null zone to primary position for the dominant eye and strabismus surgery for the other eye was chosen. And for complicated patients with compensative head position, the dominant head posture were designed for surgery. CONCLUSIONS: ICN is dominated by male with variable clinical manifestations. Surgical choice for ICN depends on the direction of head position and if there is strabismus accompanying it.The aim of ocular muscle surgery is to transfer null zone to primary position. (Chin J Ophthalmol, 2016, 52: 574-578).

[Efficacy of surgery on congenital nystagmus with convergence damping].

OBJECTIVE: To evaluate the efficacy of surgery in the treatment of congenital nystagmus with convergence damping. METHODS: Retrospective and comparative case series. Eight patients diagnosed as congenital nystagmus with convergence damping at Beijing Children's Hospital between September 2010 and September 2012 were enrolled in this study. The ages were 9.5 (12, 6) years old, and follow-up was 9 (24, 6) months. All patients received prism induced convergence and the same surgery of bimedial rectus recession and bilateral rectus tenotomy. The best corrected visual acuity, the range of fusion and the nystagmus waveforms were analyzed before and after surgery. RESULTS: The range of fusion was -3.75±1.83° to +19.38±3.16° before surgery and -3.88±1.55° to +19.00±3.02° after surgery; there was no significant difference (t=0.24, P=0.82). The binocular visual acuity increased from 0.21±0.15 without convergence to 0.28±0.18 using convergence; there was significant difference (t=-4.43, P=0.00). The visual acuity was 0.32±0.20 after surgery, significantly different from that before surgery without convergence (t=-5.29, P=0.00), but not significantly different from that before surgery using convergence (t=-2.12, P=0.07). Patients had significant improvements in the frequency (t=3.28, 3.02, P<0.05) and intensity of the nystagmus waveforms when using convergence and postoperatively (t=3.27, 3.48; P<0.05), but there was no significant improvement in the amplitude of the waveforms (t=1.31, 1.57, 0.31, P>0.05). CONCLUSIONS: Surgery for congenital nystagmus with convergence damping can provide expectations for ocular motor and visual results. The range of fusion should be wide enough, and the effect of convergence on the frequency is greater than that on the amplitude.

[Quantitative assess the efficacy of congenital idiopathic nystagmus surgery by digital eye tracker].

OBJECTIVE: To evaluate the feasibility of independently developed digital eye tracker in determining the efficacy of congenital idiopathic nystagmus (CIN) surgery. METHODS: Aprospective selfpairing study. The surgical efficacy was evaluated by independently developed eye tracker in 16 CIN patients. The null zone and the frequency, amplitude, intensity of nystagmus in various gazing position were recorded with eye tracker pre and post operatively. The consistency of null zone determined by digital eye tracker and clinical investigation were evaluated. The preoperative and postoperative rectification of horizontal and vertical nystagmus in the horizontal direction of individual patient were compared by paired samples t-test. The improvement or aggravation quantity were recorded by comparing preoperative and postoperative intensity of nystagmus every 5° within 25°. RESULT: The null zone got from digital eye tracker and clinical investigation were highly consistent (r = 0.952, P < 0.01). The horizontal and vertical intensity improved in 9 patients (t = 2.335-6.609, P < 0.05) and 5 patients (t = 2.176-5.471, P < 0.05) respectively after surgery. There were 67.63% (117/173) horizontal intensity and 69.94% (121/173) vertical intensity improvement. CONCLUSION: The independently developed digital eye tracker can quantitatively evaluate the pre and post-operative nystagmus and analyze the surgical efficacy for CIN patients.

What we know about the generation of nystagmus and other ocular oscillations: are we closer to identifying therapeutic targets?

Mechanisms underlying acquired nystagmus are better understood than those leading to infantile nystagmus. Accordingly, further progress has been made in the development of effective therapies for acquired nystagmus, mainly through pharmacological interventions. Some of these therapies have been developed under the guidance of findings from experimental animal models. Although mechanisms behind infantile nystagmus are less understood, progress has been made in determining the genetic basis of nystagmus and characterizing associated sensory deficits. Pharmacological, surgical, and other treatments options for infantile nystagmus are now emerging. Further investigations are required for all forms of nystagmus to produce high-quality evidence, such as randomized controlled trials, upon which clinicians can make appropriate treatment decisions.

Surgery for the treatment of vertical head posturing associated with infantile nystagmus syndrome: results in 24 patients.

BACKGROUND: The study of the clinical and electrophysiological effects of eye muscle surgery on patients with infantile nystagmus has broadened our knowledge of the disease and its interventions. DESIGN: Prospective, comparative, interventional case series. PARTICIPANTS: Twenty-four patients with a vertical head posture because of electrophysiologically diagnosed infantile nystagmus syndrome. The ages ranged from 2.5 to 38 years and follow up averaged 14.0 months. METHODS: Thirteen patients with a chin-down posture had a bilateral superior rectus recession, inferior oblique myectomy and a horizontal rectus recession or tenotomy. Those 11 with a chin-up posture had a bilateral superior oblique tenectomy, inferior rectus recession and a horizontal rectus recession or tenotomy. MAIN OUTCOME MEASURES: Outcome measures included: demography, eye/systemic conditions and preoperative and postoperative; binocular, best optically corrected, null zone acuity, head posture, null zone foveation time and nystagmus waveform changes. RESULTS: Associated conditions were strabismus in 66%, ametropia in 96%, amblyopia in 46% and optic nerve, foveal dysplasia or albinism in 54%. Null zone acuity increased at least 0.1 logMAR in 20 patients (P < 0.05 group mean change). Patients had significant (P < 0.05) improvements in degrees of head posture, average foveation time in milliseconds and infantile nystagmus syndrome waveform improvements. CONCLUSIONS: This study illustrates a successful surgical approach to treatment and provides expectations of ocular motor and visual results after vertical head posture surgery because of an eccentric gaze null in patients with infantile nystagmus syndrome.

A systematic approach to eye muscle surgery for infantile nystagmus syndrome: results in 100 patients.

PURPOSE: To report a systematic approach to, and the visual and electrophysiological effect of, eye muscle surgery in 100 patients with infantile nyustagmus syndrome (INS). METHODS: Prospective, interventional case cohort analysis of clinical and eye movement data in 100 patients with INS who had virgin extraocular eye muscles operated on for nystagmus with or without combinations of strabismus and an anomalous head posture. All patients were followed at least 9 months after surgery. Outcome measures, part of an IRB approved study, included binocular visual acuity, head position, strabismic deviation, and eye movement recordings, from which waveform types and an Automated Nystagmus Acuityn Function (ANAF) was calculated. Computerized parametric and non-parametric statistical analysis of data were performed using standard software on both individual and group data. RESULTS: There were 9 consistent surgical procedures used with the most common being that for a horizontal head posture alone (22%). Age at surgery averaged 14 years with 11 months followup. Sixty-eight percent had associated eye disease (optic nerve, retinal, amblyopia, cataracts). Group means in binocular acuity, strabismic deviation, head posture, abd ANAF measures from eye improved for all procedures. There were 12 (12%) reoperations without any serious surgical complications. Individual analysis revealed only age and head posture differences in outcome measures between the 9 procedures. CONCLUSIONS: Using this approach, surgery on the extraocular muscles in patients with INS results in improvements in multiple aspects of ocular motor and visual function.

Comparison of Techniques for Correction of Chin-down Vertical Abnormal Head Position Associated with Infantile Nystagmus Syndrome.

PURPOSE: We evaluated the relative effectiveness of combined recession-resection of vertical rectus muscles versus superior rectus recession with inferior oblique weakening for patients who underwent surgical correction of chin-down abnormal head position (AHP) associated with infantile nystagmus syndrome (INS). DESIGN: Retrospective interventional case series. METHODS: This is a review of 22 patients who underwent surgical correction of chin-down vertical AHP associated with INS at an academic institution. The primary outcome was collapse of AHP. Unfavorable outcomes included repeat surgery and induced strabismus, in addition to failure of collapse of AHP. RESULTS: Twenty-two patients had chin-down AHP. Recession-resection (bilateral superior rectus recession 6-9 mm; bilateral inferior rectus resection 5-9 mm) was performed in 11 cases; weakening of both elevators (bilateral superior rectus recession 5-8 mm, bilateral inferior oblique recession or myectomy) occurred in 11 cases. Unfavorable outcome rates were 64% (7/11) compared with 18% (2/11), respectively (P = .03). Reoperation was performed for 6 of 22 patients. Five patients were from the recession-resection group, namely 3 for induced V-pattern esotropia, 1 for alternating esotropia, and 1 to correct recurrent AHP. The last of the 6 who required reoperation was in the elevator weakening group, and required correction of a recurrent AHP (P = .06). CONCLUSIONS: While recession-resection of the vertical recti and weakening of both elevators each produce acceptable collapse of chin-down AHP, the former frequently induces a V-pattern esotropia requiring reoperation.

Clinical evaluation of graded Anderson's procedure in idiopathic infantile nystagmus.

Aim: To study the efficacy of graded, bilateral, single, horizontal yoked rectus muscle recession for correction of anomalous head posture (AHP) in idiopathic infantile nystagmus (IIN). We hypothesize that the above procedure would sufficiently correct AHP in IIN. Methods: Case records of patients who presented with IIN and AHP due to eccentric null position were included in a retrospective study following IRB approval. Best-corrected visual acuity (binocular Snellen's acuity for distance, in both null position and primary position), anterior segment evaluation using slit lamp biomicroscopy, fundus examination, ocular motility examination and stereopsis (using TNO for adults and older children, Titmus fly test for younger children) were recorded. In all cases recession of the yoke muscles was performed with a gradation of recession, depending on the initial head turn as elaborated in Table 1. AHP was recorded before surgery and 1 and 3 months after surgery. Visual acuity and stereopsis before and after surgery were recorded. Results: Mean AHP improved from 22.5 ± 6.12 degrees of head turn preoperatively to 7.58 ± 3.62 degrees at 1-month postoperative visit (p < .001). The mean binocular visual acuity improved from 0.47 ± 0.15 preoperatively to 0.25 ± 0.17 after surgery (p < .001). Conclusion: Graded yoke muscle recession based on the initial head turn was found to be successful in correcting moderate AHP in patients with IIN. This procedure leaves behind two recti muscles for further surgical intervention in cases with residual AHP.

Management of Strabismus Associated With Infantile Nystagmus Syndrome: A Novel Classification to Assist in Surgical Planning.

PURPOSE: There is no consensus on the surgical management of head position associated with infantile nystagmus syndrome (INS) when strabismus coexists, and few outcome data have been published. We propose classifying strabismus into concordant or discordant based on the relationship between head positioning and strabismus and then modifying surgery accordingly. Our objective is to describe this system and to review surgical outcomes. DESIGN: Retrospective observational case series. METHODS: Twenty-eight patients with INS and coexisting horizontal strabismus underwent surgery for horizontal head positioning and had ≥2 months of follow-up from 1995-2018 at the Vanderbilt Eye Institute. Outcome variables included head positioning (minimal, ≤10°; mild, 11-30°; moderate 31-44°; and severe ≥45°), strabismus (range 0-70 prism diopters [PDs]; minimal ≤10 PD), and reoperation rates. Nonparametric Wilcoxon signed rank, Fisher exact, and Mann-Whitney U tests were used for statistical analysis. RESULTS: Twenty-one cases were concordant and 7 were discordant; the mean follow-up was 4.1 years. Ninety-six percent of patients had moderate to severe head positioning at baseline. Correction rates (to minimal) were 100% at 2-5 months postoperatively and 86% at last follow-up (P < .0001 at both time points compared with preoperatively). The magnitude of strabismus decreased compared with preoperative strabismus (30.8 ± 10.8 PDs; n = 28), strabismus at 2-5 months (9.1 ± 11.9 PDs; P = .0001; n = 26), and last follow-up (12.0 ± 14.1 PDs; P = .0003; n = 28). The overall reoperation rate was 32%. CONCLUSIONS: Our classification system in patients with INS allows a systematic way to surgically improve head positioning and strabismus in cases of moderate to severe baseline head positioning.

Tenotomy procedure alleviates the "slow to see" phenomenon in infantile nystagmus syndrome: model prediction and patient data.

Our purpose was to perform a systematic study of the post-four-muscle-tenotomy procedure changes in target acquisition time by comparing predictions from the behavioral ocular motor system (OMS) model and data from infantile nystagmus syndrome (INS) patients. We studied five INS patients who underwent only tenotomy at the enthesis and reattachment at the original insertion of each (previously unoperated) horizontal rectus muscle for their INS treatment. We measured their pre- and post-tenotomy target acquisition changes using data from infrared reflection and high-speed digital video. Three key aspects were calculated and analyzed: the saccadic latency (Ls), the time to target acquisition after the target jump (Lt) and the normalized stimulus time within the cycle. Analyses were performed in MATLAB environment (The MathWorks, Natick, MA) using OMLAB software (OMtools, available from http://www.omlab.org). Model simulations were performed in MATLAB Simulink environment. The model simulation suggested an Lt reduction due to an overall foveation-quality improvement. Consistent with that prediction, improvement in Lt, ranging from approximately 200 ms to approximately 500 ms (average approximately 280 ms), was documented in all five patients post-tenotomy. The Lt improvement was not a result of a reduced Ls. INS patients acquired step-target stimuli faster post-tenotomy. This target acquisition improvement may be due to the elevated foveation quality resulting in less inherent variation in the input to the OMS. A refined behavioral OMS model, with "fast" and "slow" motor neuron pathways and a more physiological plant, successfully predicted this improved visual behavior and again demonstrated its utility in guiding ocular motor research.

Clinical and ocular motor complications of extraocular muscle extirpation for infantile nystagmus syndrome.

PURPOSE: To describe the effects of extraocular muscle extirpation performed after previous eye muscle surgery in a 20-year-old woman with infantile nystagmus syndrome (INS) for whom we have 19 years of follow-up data. METHODS: Clinical examinations were performed. Eye movement data analysis was carried out using the eXpanded Nystagmus Acuity Function (NAFX) and longest foveation domain (LFD). RESULTS: The patient re-presented to the authors at age 20, 2 years after bilateral anterior myectomy of the horizontal rectus muscles, bilateral anterior nasal transposition of the inferior oblique muscle, and bilateral superior oblique recessions. Evaluation revealed deterioration in nystagmus at lateral gaze angles, new incomitant strabismus with severe loss of convergence, limited ductions, saccadic hypometria, slow saccades, and hypo-accommodation. Also, there was a pre- to post-extirpation minimal change of 21% in her peak NAFX, a 50% decrease in LFD, plus a predominant, asymmetric, multiplanar oscillation. CONCLUSIONS: It appears that in this patient, horizontal extirpation failed to abolish the nystagmus and caused significant, new, symptomatic deficits interfering with many of the patient's visual functions.

Longitudinal Studies and Eye-Movement-Based Treatments of Infantile Nystagmus Syndrome: Estimated and Measured Therapeutic Improvements in Three Complex Cases.

INTRODUCTION AND PURPOSE: To demonstrate the utility of using eye-movement data to reveal the diagnostic characteristics of infantile nystagmus syndrome (INS), determine treatment, and both estimate and document therapeutic improvements in three patients with well-developed foveation periods, fairly broad, lateral gaze "nulls," head turns, strabismus, and complex, multiplanar nystagmus. PATIENTS AND METHODS: Infrared reflection, magnetic search coil, and high-speed digital video systems were used to record the eye movements of INS patients, pre- and post-Kestenbaum null-point correction surgery (horizontal or vertical). Data were analyzed and estimations made, using the eXpanded Nystagmus Acuity Function (NAFX) that is part of the OMtools toolbox for MATLAB. RESULTS: In all three subjects (S1-S3), both peak NAFX and longest foveation domain (LFD) improved from their pre-Kestenbaum values. S1: 0.700-0.745 (6.4%) and 25-34° (36%), respectively. S2: 0.445-0.633 (42.4%) and >40° to >50° (10%), respectively. S3: 0.250-0.300 (20%) and 13° to ≫18° (see text), respectively. CONCLUSIONS: S1: Even at the high ends of the pre-therapy NAFX and LFD spectra, INS foveation (and therefore, visual-function) improvements may be adequate to justify nystagmus surgery and provide clinical improvements beneficial to the patient. S2: INS foveation improvements in the vertical plane are equal to those originally estimated using the horizontal data in prior patients. S3: Two apparent NAFX peaks can be converted into a very broad peak by surgery based on the preferred lower peak.

Infantile esotropia with nystagmus: a treatable cause of oscillatory head movements in children.

OBJECTIVE: To document the resolution of oscillatory head movements following surgical realignment of the eyes in children with infantile esotropia and nystagmus. METHOD: Retrospective review of 3 children who had infantile esotropia, nystagmus, and unexplained head shaking or head nodding. RESULTS: Strabismus surgery restored ocular alignment and produced resolution of the head shaking in all patients. In 1 patient, head shaking accompanied recurrence of the esotropia and again resolved following surgical realignment of the eyes. CONCLUSIONS: Head shaking or head nodding can rarely be associated with infantile esotropia and nystagmus. In this syndrome, surgical realignment of the eyes may produce simultaneous resolution of the head oscillations.

Superior oblique tendon expanders with inferior rectus recessions for chin-up null point nystagmus.

Three patients with chin-up head postures caused by a nystagmus null point in downgaze were treated using bilateral superior oblique tendon expanders and inferior rectus muscle recessions. Preoperative chin-up head postures measured from 25 to 45 degrees. Postoperatively, 2 patients had complete resolution of their abnormal vertical head postures, and the third showed improvement.

Outcome study of two standard and graduated augmented modified Kestenbaum surgery protocols for abnormal head postures in infantile nystagmus.

BACKGROUND AND PURPOSE: Since Kestenbaum and Anderson, several ophthalmologists have reported the results of different surgical procedures, for abnormal head posture in infantile nystagmus. In this study, we tried to evaluate the surgical results of Parks' original 5-6-7-8 mm modified Kestenbaum procedure and our own 6-7-6-7 mm modified Kestenbaum procedure, designed to reduce some of the problems encountered with other variations of these techniques. METHODS: Medical records of 92 patients, who had modified Kestenbaum surgery (5-6-7-8 mm or 6-7-6-7 mm) at The Yonsei Medical Center, from March 1991 to September 2001 with a follow-up period of more than 6 months, were reviewed retrospectively. We compared Parks' modified Kestenbaum surgery (5- 6-7-8 mm) performed on 51 patients with our own modified Kestenbaum surgery (6-7-6-7 mm) on 41 patients. Each procedure was done with graded augmentation according to the amount of the face turn and the null point in electro-oculography. RESULTS: In the follow-up of an average 33 months, 45 out of 51 patients (88.2%) who underwent Parks' modified procedures showed face turn less than 10 degrees. In the follow-up of an average 29 months, 36 out of 41 patients (87.8%) with 6-7-6-7 mm procedure had face turn less than 10 degrees. CONCLUSIONS: We suggest that 6-7-6-7 mm modified Kestenbaum procedures with a graded augmentation may be a safe and efficient procedure to correct abnormal head posture in infantile nystagmus with a minimum decrease in ocular motility.

Small-incision lenticule extraction in a patient with congenital nystagmus.

We report a case of a 23-year-old woman with congenital nystagmus who had small-incision lenticule extraction (SMILE) procedure to correct refractive errors. The manifest refraction was -5.50 -1.75 × 180 in the right eye, -5.0 -2.50 × 180 in the left eye, and the patient presented with horizontal pendular nystagmus with an amplitude range of 5 to 10 degrees. Uneventful simultaneous bilateral small-incision lenticule extraction was performed. Six months postoperatively, the uncorrected distance visual acuity was 20/18 with -0.25, -0.25 × 80 in the right eye, and 20/20 with +0.25 -0.5 × 50 in the left eye. The case suggests that small-incision lenticule extraction can be an effective alternative for correcting myopic astigmatism in patients with nystagmus.

Tenotomy does not affect saccadic velocities: support for the "small-signal" gain hypothesis.

We investigated the effects of four-muscle tenotomy on saccadic characteristics in infantile nystagmus syndrome (INS) and acquired pendular nystagmus (APN). Eye movements of 10 subjects with INS and one with APN were recorded using infrared reflection, magnetic search coil, or high-speed digital video. The expanded nystagmus acuity function (NAFX) quantified tenotomy-induced foveation changes in the INS. Saccadic characteristics and peak-to-peak nystagmus amplitudes were measured. Novel statistical tests were performed on the saccadic data. Six out of the 10 INS subjects showed no changes in saccadic duration, peak velocity, acceleration, or trajectory. In the other four, the differences were less than in peak-to-peak amplitudes (from 14.6% to 39.5%) and NAFX (from 22.2% to 162.4%). The APN subject also showed no changes despite a 50% decrease in peak-to-peak amplitude and a 34% increase in NAFX. The "small-signal" changes (peak-to-peak nystagmus amplitude and NAFX) were found to far exceed any "large-signal" changes (saccadic). Tenotomy successfully reduced INS and APN, enabling higher visual acuity without adversely affecting saccadic characteristics. These findings support the peripheral, small-signal gain reduction (via proprioceptive tension control) hypothesis. Current linear plant models, limited to normal steady-state muscle tension levels, cannot explain the effects of the tenotomy.