A Story of Discovery and Change: What We Learned from Studying Nystagmus in Infancy and Childhood.

The last 40 years of clinical experience and investigation of nystagmus in infancy and childhood have resulted in a clearer understanding and characterization of the disorder and provided guidelines for the beneficial effects of increased medical, optical, and surgical treatments. Our modern understanding is due to the results of contribution by scientists and clinicians representing vision, neurology, bioengineering, genetics, and pediatrics. From this group, a new classification system was developed. The routine use of eye-movement recordings (EMR) and its characteristics have made the largest contribution to this increased knowledge. The value of EMR is due to the observation of specific waveforms, which are the basis for classification, neuro-pathophysiology, effect on vision, and a measure of nystagmus response to treatment. Successful treatment of the visual system is now directed toward associated afferent system abnormalities (decreased acuity, amblyopia, ametropia, retinal and optic pathway disease, and photophobia), centrally at the neuronal level responsible for the oscillations (oral and topical medications) and peripherally to reduce the underlying oscillation (eye-muscle surgery and botulinum toxin). Evidence over the last 40 years has shown that these treatments result in increased spatial acuity, contrast sensitivity, visual recognition time, motion processing, gaze-dependent visual acuity, and anomalous head posturing. The hope of this review is that clinicians now provide hope for these patients and families and can be counseled that nystagmus treatment is available.

Clinical and Electrophysiological Outcomes After Eye Muscle Surgery in 81 Adults With Infantile Nystagmus Syndrome.

PURPOSE: To characterize the effects of eye muscle surgery on patients older than 18 years with infantile nystagmus syndrome (INS) who have had only optical treatment. METHODS: This was a prospective, single-center, interventional case series analysis of clinical and electro-phyisological data before and after surgery. Outcome measures included: clinical characteristics, surgical procedure, and preoperative and postoperative binocular best corrected visual acuity (BCVA) in the null position, anomalous head posture (AHP), contrast sensitivity, strabismic deviation, and nystagmus acuity function (NAFX). Postoperative data used were collected for a minimum of 12 months after surgery. Parametric and non-parametric statistical analysis of the outcome measures was performed. RESULTS: Ages ranged from 18 to 72 years (average: 36 years) and follow-up from 12 to 74 months (average: 26 months). A surgical algorithm of nine separate procedures involving at least two recti muscles on each eye was used for each patient. Most patients had associated systemic and/or ocular diagnoses, including albinism (35%), amblyopia (23%), optic nerve or retinal disorders (48%), refractive error (80%), AHP (44%), aperiodicity (27%), and strabismus (69%). There were no serious surgical complications, with a reoperation rate of 12%. There were significant group mean increases in BVCA, AHP, contrast sensitivity, strabismic deviation, and NAFX after surgery. Sixty percent of patients who were legally ineligible for driving prior to surgery became eligible after eye muscle surgery. CONCLUSIONS: Adult patients with INS showed sustained improvement in many afferent and efferent measures of visual function after eye muscle surgery. [J Pediatr Ophthalmol Strabismus. 2021;58(2):93-104.].

Treatment of Ocular Neuralgia After Refractive Surgery With Bilateral Orbital Steroid and Anesthetic Injections.

PURPOSE: To describe a patient with chronic periocular pain after bilateral photorefractive keratectomy (PRK) and ocular neuralgia that was controlled with regular orbital steroid and anesthetic injections. METHODS: Case report. RESULTS: A 21-year-old man presented 3 months following bilateral PRK surgery in severe bilateral orbital pain. Previous treatments included topical (artificial tears, corticosteroids, and nonsteroidal anti-inflammatory drugs [NSAIDs) and oral (NSAIDs, opioids, and pregabalin) therapies with minimal pain relief. A bilateral orbital triamcinolone acetonide 40 mg/cc and 0.25% bupivacaine injection was done after a successful, diagnostic unilateral 0.25% bupivacaine injection. Following bilateral bupivacaine and triamcinolone acetonide injections, pain intensity improved from 7 of 9 to 1 of 3 out of 10. Repeat injections have been regularly performed over the past 3 years, allowing the patient to experience improved symptoms lasting from 4 to 9 months. CONCLUSIONS: In this case, orbital nerve blocks provided relief and may be considered as a potential treatment for orbital neuralgia after refractive surgery. [J Refract Surg. 2019;35(8):534-537.].

Visual electrodiagnostics and eye movement recording - World Society of Pediatric Ophthalmology and Strabismus (WSPOS) consensus statement.

Visual electrodiagnostics and eye movement recording are important additional clinical tools in evaluation, diagnosing and management of ophthalmic and neurological disorders. Due to their objectiveness and non-invasiveness they can play an important role in pediatric ophthalmology. The WSPOS (World Society of Pediatric Ophthalmology and Strabismus) consensus statement gives insight into basic principles and highlights the clinical application of both visual electrodiagnostic tests and eye movement recording.

Clinical and electrophysiological results of eye muscle surgery in 17 patients with downbeat nystagmus.

PURPOSE: To test the hypothesis that eye muscle surgery in treatment of patients with acquired downbeat nystagmus results in improvement measures of visual and ocular motor function. METHODS: This is a prospective, interventional case series analysis of clinical and electrophyisological data before and after eye muscle surgery in 17 patients with acquired downbeat nystagmus who did not respond to medical treatments. Outcome measures included: 1) routine demography and clinical characteristics, 2) subjective oscillopsia (SO), 3) binocular best-corrected visual acuity in the null position (BVA), 3) primary position strabismic deviation (SD), 5) anomalous head posture (AHP), 6) contrast sensitivity function (CS), and 7) nystagmus slow phase velocity (SPV). All patients were followed at least 12 months. Parametric and non-parametric statistical analysis of outcome measure data above pre- and post-treatment were perfomed using standard software on grouped data using computerized software. RESULTS: Patients' age ranged from 5 to 85 years (average 27 years). About 59% were male. Follow up ranged from 1-10 years (average 2.0 years). Around 70% had an associated central nervous systemic diagnosis, 100% had an AHP, oscillopsia and decreased CS, 53% had other eye disease, and 59% had strabismus. There were no complications from surgery. There were signficant post-treatment improvements in mean/median group BVA, SO, SD, AHP, CS, and SPV. CONCLUSION: This study supports the hypothesis that eye muscle surgery as treatments for patients with acquired downbeat nystagmus can result in improvements in multiple aspects of ocular motor and visual functions.

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.

Postmortem vitreous bevacizumab levels of an infant treated for retinopathy of prematurity.

We report the vitreous concentration of bevacizumab after injection for the treatment of retinopathy of prematurity (ROP). A premature neonate diagnosed with type 1 ROP was treated in both eyes with 0.625 mg intravitreal bevacizumab injection at 32 weeks' postconceptual age. Eleven weeks later there was complete regression clinically, but the patient died. Vitreous samples taken at autopsy revealed a bevacizumab vitreous concentration of 41.57 ng/ml. Histopathology of the retina showed residual preretinal neovascularization. Bevacizumab elimination from the infant vitreous is similar to that of adults, and, although complete regression was clinically apparent, it was not confirmed histopathologically.

Plication augmentation of the modified Hummelsheim procedure for treatment of large-angle esotropia due to abducens nerve palsy and type 1 Duane syndrome.

BACKGROUND: Multiple procedures have been described to treat a large-angle esodeviation with an associated abduction deficit. We report a plication augmentation of the Hummelsheim procedure for the management of esotropia and severe abduction deficit due to abducens nerve palsy or type 1 Duane syndrome. METHODS: The medical records of patients operated on using the plication augmentation Hummelsheim procedure at two tertiary centers were retrospectively reviewed. The surgery involved ipsilateral lateral rectus plication, half muscle transposition of the vertical rectus muscles to the paralytic plicated lateral rectus, Foster augmentation sutures, and ipsilateral medial rectus recession or botulinum toxin injection if it was found to be tight on intraoperative forced duction testing. Pre- and postoperative deviations, ocular motility findings, and complications were noted. RESULTS: A total of 13 patients were included, all of whom had an esotropia with profound abduction deficit (-4 or more). Postoperative deviations ranged from 14(Δ) of esotropia to 14(Δ) of exotropia, with significant improvement of the abductive motion. No patient developed anterior segment ischemia. CONCLUSIONS: The plication augmentation Hummelsheim procedure resulted in correction of even very large esodeviations and improvement of the abduction force. This procedure may also better preserve the blood supply to the anterior segment compared to other surgical approaches.

Oculocutaneous albinism in sub-Saharan Africa: adverse sun-associated health effects and photoprotection.

Oculocutaneous albinism (OCA) is a genetically inherited autosomal recessive condition. Individuals with OCA lack melanin and therefore are susceptible to the harmful effects of solar ultraviolet radiation, including extreme sun sensitivity, photophobia and skin cancer. OCA is a grave public health issue in sub-Saharan Africa with a prevalence as high as 1 in 1000 in some tribes. This article considers the characteristics and prevalence of OCA in sub-Saharan African countries. Sun-induced adverse health effects in the skin and eyes of OCA individuals are reviewed. Sun exposure behavior and the use of photoprotection for the skin and eyes are discussed to highlight the major challenges experienced by these at-risk individuals and how these might be best resolved.

An interesting case of bilateral bifid insertion of superior rectus muscle as an intra-operative finding in a patient with oculocutaneous albinism.

We report a case of bilateral bifid insertion of superior rectus muscles, in a patient with oculocutaneous albinism as an incidental intraoperative finding during eye muscle surgery. The muscle was successfully operated on and the patient did well postoperatively. To our knowledge, this is the first report of this anomaly.

Binocular ocular motility: breaking with the past: how understanding dynamic ocular motor control and central nervous system plasticity promote novel discovery and therapy of nystagmus.

INTRODUCTION: The lure of studying the ocular motor system stems from its anatomic and physiological accessibility, ease of measurement and analysis of function, as well as the promise of providing a direct window into the brain. There is an increasing body of knowledge on how the brain responds to peripheral eye muscle manipulation (surgery, medications, denervation, genetic therapy). Investigations in both animals and humans have established that plasticity within the brain occurs after peripheral neuromuscular (medical or surgical) disruption and repair. PURPOSE: This paper will review and summarize neurophysiological concepts resulting from recent investigations of the ocular motor system and treatment of involuntary oscillations such as nystagmus. METHODS: Review of both a multidisciplinary literature and the authors 25 years experience evaluating, treating and investigating the ocular motor system. CONCLUSIONS: The ocular motor system in man is a continuously controlled, malleable brain-eye system, which is genetically programmed, environmentally modified and contains powerful reparative processes. It begins during development, extends throughout life and is subject to external manipulation in both health and disease. These ideas challenge the historically significant axiom, i.e., that there is eventual (and a final maturing to an end state) "hard-wiring" of much of both the ocular motor and afferent visual systems. Rather, they now are shown to maintain some degree of plasticity throughout life.

Effects of topical brinzolamide on infantile nystagmus syndrome waveforms: eyedrops for nystagmus.

BACKGROUND: Recent advances in infantile nystagmus syndrome (INS) surgery have uncovered the therapeutic importance of proprioception. In this report, we test the hypothesis that the topical carbonic anhydrase inhibitor (CAI) brinzolamide (Azopt) has beneficial effects on measures of nystagmus foveation quality in a subject with INS. METHODS: Eye movement data were taken, using a high-speed digital video recording system, before and after 3 days of the application of topical brinzolamide 3 times daily in each eye. Nystagmus waveforms were analyzed by applying the eXpanded Nystagmus Acuity Function (NAFX) at different gaze angles and determining the longest foveation domain (LFD) and compared to previously published data from the same subject after the use of a systemic CAI, contact lenses, and convergence and to other subjects before and after eye muscle surgery for INS. RESULTS: Topical brinzolamide improved foveation by both a 51.9% increase in the peak value of the NAFX function (from 0.395 to 0.600) and a 50% broadening of the NAFX vs Gaze Angle curve (the LFD increased from 20° to 30°). The improvements in NAFX after topical brinzolamide were equivalent to systemic acetazolamide or eye muscle surgery and were intermediate between those of soft contact lenses or convergence. Topical brinzolamide and contact lenses had equivalent LFD improvements and were less effective than convergence. CONCLUSIONS: In this subject with INS, topical brinzolamide resulted in improved-foveation INS waveforms over a broadened range of gaze angles. Its therapeutic effects were equivalent to systemic CAI. Although a prospective clinical trial is needed to prove efficacy or effectiveness in other subjects, an eyedrops-based therapy for INS may emerge as a viable addition to optical, surgical, behavioral, and systemic drug therapies.

Improvement in visual acuity following surgery for correction of head posture in infantile nystagmus syndrome.

PURPOSE: To report the effect of the abnormal head posture (AHP) correcting procedures on the visual acuity improvement in patients with infantile nystagmus syndrome (INS) and the visual acuity improvement outcomes in different AHP correcting surgeries in INS. METHODS: This was a prospective, non-randomized, interventional study. Twenty-eight patients underwent the Anderson-Kestenbaum procedure or the modified Anderson procedure with or without tenotomy of at least one horizontal recti for correction of AHP. Best-corrected binocular null zone acuity and degree of AHP was recorded preoperatively and compared with those done 1 month postoperatively. RESULTS: The average null zone logarithm of the minimum angle of resolution acuity was 0.42 preoperatively, which improved significantly to 0.33 postoperatively (P = .002). The AHP ranged from 10° to 40° (mean: 20.89°), which improved significantly to a mean of 3.21° (P = .000). No significant difference (P = .65) was found in the visual acuity improvement among patients who underwent the Anderson-Kestenbaum procedure or the modified Anderson procedure with or without tenotomy. No significant difference in the visual acuity improvement was seen in patients who underwent tenotomy of at least one horizontal rectus muscle along with the modified Anderson procedure compared to those who underwent the modified Anderson procedure alone (P = .28). CONCLUSION: The procedures used mainly for correction of AHP in INS do yield significant improvement in the visual acuity. This improvement is seen in patients undergoing surgery for both horizontal and vertical AHP.

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.

Eye muscle surgery for infantile nystagmus syndrome in the first two years of life.

PURPOSE: To report visual and elctrophysioloigcal effects of eye muscle surgery in young patients with infantile nystagmus syndrome (INS). METHODS: Prospective, interventional case cohort of 19 patients aged under 24 months who were operated on for combinations of strabismus, an anomalous head posture, and nystagmus. All patients were followed at least nine months. Outcome measures, part of an institutionally approved study, included Teller acuity, head position, strabismic deviation, and eye movement recordings, from which waveform types and a nystagmus optimal foveation fraction (NOFF). Computerized parametric and nonparametric statistical analysis of data were perfomed using standard software on both individual and group data. RESULTS: Age averaged 17.7 months (13.1-month follow-up). Thirteen (68%) patients had associated optic nerve or retinal disease. 42% had amblyopia, 68% had refractive errors. Group means in binocular Teller acuity (P < 0.05), strabismic deviation (P < 0.05), head posture (P < 0.001), and the NOFF measures (P < 0.01) from eye movement recordings improved in all patients. There was a change in null zone waveforms to more favorable jerk types. There were no reoperations or surgical complications. CONCLUSIONS: Surgery on the extraocular muscles in patients aged less than two years with INS results in improvements in multiple aspects of ocular motor and visual function.

Pediatric orbital fractures: classification, management, and early follow-up.

BACKGROUND: Scarce literature exists addressing the presentation, classification, and management of pediatric orbital fractures. The aim of this study is to review the authors' experience with the presentation, management, and early follow-up of pediatric orbital fractures. METHODS: A retrospective review of pediatric orbital fractures presenting to the Children's Hospital of Pittsburgh between 2003 and 2007 was performed. Demographics, associated injuries, computed tomographic scan findings, management, and follow-up were collected. From these data, a pediatric orbital fracture classification system was devised. RESULTS: Seventy-four patients (81 orbits) were reviewed. Average age at presentation was 8.6 years. Fractures were distributed as follows: type 1, 40.7 percent; type 2, 33 percent; and type 3, 25.9 percent. Twenty-three orbits were treated surgically and 58 were treated nonoperatively. The operative rates were as follows: type 1, 9.1 percent; type 2, 14.8 percent; and type 3, 76.2 percent. Complications included minor enophthalmos in seven patients, and persistent cerebrospinal fluid leak in two growing skull fractures. For type 1 (pure orbital) fractures, three (12 percent) underwent surgical treatment for acute enophthalmos, vertical orbital dystopia, or muscle entrapment. Twenty-two orbits (88 percent) were managed nonoperatively. At an average follow-up of 13 months, minimal enophthalmos (1 to 2 mm) was found in one of the surgically treated fractures (33 percent) and in three of the conservatively managed fractures (13.6 percent). CONCLUSIONS: For type 1 (pure orbital) fractures, unless there is evidence of acute enophthalmos, vertical orbital dystopia, or muscle entrapment, a nonoperative approach is advocated. Type 2 (craniofacial) fractures should be followed with serial computed tomographic scans; and type 3 (common fracture patterns) fractures have a greater chance of requiring surgery.

Safety and efficacy of gene transfer for Leber's congenital amaurosis.

Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.