Effect of topical brinzolamide on visual function and waveform in patients of infantile nystagmus syndrome: A randomized control trial.

PURPOSE: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). DESIGN: Prospective, placebo-controlled, double-blind, cross-over study. METHODS: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. RESULTS: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. CONCLUSIONS: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.

Topical lambda-cyhalothrin in reducing eye oscillations in a canine model of infantile nystagmus syndrome.

PURPOSE: To determine the ocular and systemic safety of using topical Lambda-Cyhalothrin (LCL) in a canine model of infantile nystagmus syndrome (INS). The rationale for this proposal is based on a case study of a patient whose INS improved after inadvertent ocular exposure to a pyrethroid pesticide containing LCL. METHODS: After in-vitro safety testing and IUCAC approval, we studied increasing concentrations of topical LCL drops (0.002% to 0.07%) in canines with a purposely bred defect in the RPE65 gene resulting in both retinal degeneration and INS. We collected data on ocular and systemic effects and performed eye-movement recordings (EMR). RESULTS: At the 0.07% concentration dose of LCL, there was minimal, reversible, conjunctival hyperemia. There was no other ocular or systemic toxicity. At the 0.06% dose, there was a visible decrease in the INS and EMR showed a 153%-240% increase in the nystagmus acuity function and a 30%-70% decrease in amplitude across gaze. There was also a 40%-60% decrease in intraocular pressure while on the drop in both eyes. CONCLUSION: This animal study suggests this new pharmacological agent has potential for topical treatment of both INS and diseases with raised intraocular pressure. Further, this new treatment approach confirms the importance of extraocular muscle proprioception in ocular motor diseases and their treatment.

Brinzolamida tópica en el nistagmo congénito: Estudio retrospectivo / Topical brinzolamide in congenital nystagmus: A retrospective study

Objetivo: Evaluar los efectos del tratamiento con brinzolamida tópica en la agudeza visual y en la intensidad del nistagmo en pacientes con nistagmo congénito. Material y métodos: Se diseñó un estudio retrospectivo en el que se revisaron las historias clínicas de 11 pacientes con nistagmo congénito. A todos los pacientes se les realizó una exploración oftalmológica completa y una videooculografía mediante VOG-Perea, antes y a los 3 días de iniciar el tratamiento con brinzolamida tópica (Azopt) cada 8horas. Cinco investigadores expertos evaluaron la intensidad del nistagmo de forma enmascarada mediante un vídeo antes y después del tratamiento. Por último, se registró la mejoría subjetiva de los pacientes. Resultados: Se encontraron diferencias estadísticamente significativas en la agudeza visual binocular de cerca previa y posterior al tratamiento. Se encontró un leve aumento de la frecuencia del nistagmo, que fue estadísticamente significativa en la mirada horizontal hacia la izquierda y con la mirada hacia abajo (p = 0,04, p = 0,03 significativo). El índice Kappa de concordancia entre los investigadores evaluando la intensidad del nistagmo fue de 0,014. Solo 2 de los pacientes notaron mejoría en la agudeza visual y un paciente notó mejoría en el aspecto estético. Conclusiones: A pesar de producirse una mejoría en el nistagmo, esta es leve, no apreciable cosméticamente por los pacientes en la mayoría de los casos, y no se relacionó con una mejoría significativa en la agudeza visual ni en la calidad de vida de los pacientes. Son necesarios nuevos estudios para evaluar los efectos de la brinzolamida tópica y establecer las posibles indicaciones terapéuticas en el nistagmo (AU)

Objective: To evaluate the effect of treatment with topical brinzolamide on visual acuity and nystagmus intensity in patients with congenital nystagmus. Material and methods: A retrospective study was designed in which the clinical records of 14 patients with congenital nystagmus were reviewed. All patients underwent a complete ophthalmological examination and a Perea video-oculography (VOG) before, and three days after, initiation of treatment with topical brinzolamide (Azopt). Five expert researchers evaluated the intensity of nystagmus by video before and after treatment. Finally, the subjective improvement of the patients was recorded. Results: Statistically significant differences were found in pre- and post-treatment binocular near visual acuity. A slight increase in the frequency of nystagmus was found, which was statistically significant with the horizontal gaze to the left and with the gaze downwards (P = .04, P = .03, respectively). The kappa index concordance between the researchers evaluating the intensity of nystagmus was 0.014. Only two of the patients noticed improvement in visual acuity, and one patient noticed improvement in the aesthetic aspect. Conclusions: In spite of an improvement in nystagmus, it was slight, not cosmetically appreciable by patients in most cases, and was not related to a significant improvement in visual acuity or in patient quality of life. Further studies are needed to evaluate the effects of topical brinzolamide, and to establish potential therapeutic indications in nystagmus (AU)

Topical brinzolamide in congenital nystagmus: A retrospective study. / Brinzolamida tópica en el nistagmo congénito: Estudio retrospectivo.

OBJECTIVE: To evaluate the effect of treatment with topical brinzolamide on visual acuity and nystagmus intensity in patients with congenital nystagmus. MATERIAL AND METHODS: A retrospective study was designed in which the clinical records of 14 patients with congenital nystagmus were reviewed. All patients underwent a complete ophthalmological examination and a Perea video-oculography (VOG) before, and three days after, initiation of treatment with topical brinzolamide (Azopt). Five expert researchers evaluated the intensity of nystagmus by video before and after treatment. Finally, the subjective improvement of the patients was recorded. RESULTS: Statistically significant differences were found in pre- and post-treatment binocular near visual acuity. A slight increase in the frequency of nystagmus was found, which was statistically significant with the horizontal gaze to the left and with the gaze downwards (P=.04, P=.03, respectively). The kappa index concordance between the researchers evaluating the intensity of nystagmus was 0.014. Only two of the patients noticed improvement in visual acuity, and one patient noticed improvement in the aesthetic aspect. CONCLUSIONS: In spite of an improvement in nystagmus, it was slight, not cosmetically appreciable by patients in most cases, and was not related to a significant improvement in visual acuity or in patient quality of life. Further studies are needed to evaluate the effects of topical brinzolamide, and to establish potential therapeutic indications in nystagmus.

Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases.

Purpose: Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects. Moreover, we described the influence of both medications on ocular motor functions in healthy zebrafish, evaluating possible iatrogenic effects. Methods: Ocular motor function and INS characteristics were assessed by eliciting optokinetic response, spontaneous nystagmus, and spontaneous saccades in light and in dark, in 5- to 6-day postfertilization bel larvae and heterozygous siblings. Single larvae were recorded before and after a 1-hour drug treatment (200 mM gabapentin/0.2 mM memantine). Results: Both interventions significantly reduced nystagmus intensity (gabapentin: 59.98%, memantine: 39.59%). However, while the application of gabapentin affected all tested ocular motor functions, memantine specifically reduced nystagmus amplitude and intensity, and thus left controls completely unaffected. Finally, both drug treatments resulted in specific changes in nystagmus waveform and velocity. Conclusions: Our study provides deeper insight into gabapentin and memantine treatment effect in the zebrafish INS model. Moreover, this study should establish zebrafish as a pharmacologic animal model for treating nystagmus and ocular motor disease, serving as a basis for future large-scale drug screenings.

[Use of botulinum toxin in a patient with pendular congenital nystagmus]. / Empleo de toxina botulínica en paciente con nistagmus congénito de tipo pendular.

CASE REPORT: We report the case of a 5 month-old male diagnosed with congenital nystagmus and oculocutaneous albinism. The initial examination showed pendular horizontal nystagmus with high amplitude and without blocking position or foveal fixation periods. A 2.5 IU injection of botulinum toxin was administered in the horizontal rectus muscles of both eyes in two sessions separated by 6 weeks. This led to a decrease in amplitude of nystagmus and early development of binocular visual acuity of 4.8cycles/cm. CONCLUSION: Faced with diagnosis of horizontal nystagmus in the early stages of development, and in order to avoid periods of foveal fixation, the use of botulinum toxin leads to a temporary reduction in its amplitude and an improvement in visual acuity with low complication rates. Given the possibility of spontaneous improvement described in these patients, studies are needed with longer follow-up to establish the advantage of long term treatment.

The pharmacological treatment of acquired nystagmus.

We review the latest literature on the neuropharmacological treatments for acquired nystagmus.Nystagmus may have a significant [corrected] impact on health, yet there is little scientific evidence on which to make firm recommendations for treatment. Acquired pendular nystagmus may respond to gabapentin or memantine; downbeat and upbeat nystagmus to aminopyridines; and periodic alternating nystagmus to baclofen. To improve treatment we need multi-centre, randomised controlled trials using standardised techniques in reporting objective outcomes, with good follow-up duration and careful reporting of side effects.

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.

The effect of 3,4-diaminopyridine on the patients with hereditary pure cerebellar ataxia.

BACKGROUND: Downbeat nystagmus (DBN) is often seen in patients with pure cerebellar type of spinocerebellar ataxia (SCA) like spinocerebellar ataxia type 6 (SCA6). DBN frequently presents with other cerebellar symptoms such as postural imbalance or ataxia. A potassium channel blocker 3,4-diaminopyridine (3,4-DAP) has been reported to reduce DBN by increasing the excitability of Purkinje cells. OBJECTIVE: The objective of this study is to determine whether 3,4-DAP has a beneficial effect on DBN along with postural imbalance and ataxic symptoms in 10 patients with SCA6 and five patients with chromosome 16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA). RESULTS: The patients took 20mg of 3,4-DAP twice a day for a week. DBN was observed in seven patients with SCA6 and two with 16q-ADCA. Although 3,4-DAP significantly reduced DBN (P<0.05), other ataxic symptoms did not improved. However, 3,4-DAP showed benefit in two patients with oscillopsia. CONCLUSION: 3,4-DAP may be effective on DBN and oscillopsia, although it was not proved to be effective on other symptoms of ataxia in SCA patients.

The pharmacological treatment of nystagmus: a review.

Nystagmus is an involuntary, to-and-fro movement of the eyes that can result in a reduction in visual acuity and oscillopsia. Mechanisms that cause nystagmus are better understood in some forms, such as acquired periodic alternating nystagmus, than in others, for example acquired pendular nystagmus, for which there is limited knowledge. Effective pharmacological treatment exists to reduce nystagmus, particularly in acquired nystagmus and, more recently, infantile nystagmus. However, as there are very few randomized controlled trials in the area, most pharmacological treatment options in nystagmus remain empirical.

Reduction of congenital nystagmus in a patient after smoking cannabis.

INTRODUCTION: Smoking cannabis has been described to reduce acquired pendular nystagmus in MS, but its effect on congenital nystagmus is not known. PURPOSE: To report the effect of smoking cannabis in a case of congenital nystagmus. METHODS: A 19-year-old male with congenital horizontal nystagmus presented to the clinic after smoking 10 mg of cannabis. He claimed that the main reason for smoking cannabis was to improve his vision. At the next clinic appointment, he had not smoked cannabis for 3weeks. Full ophthalmologic examination and eye movement recordings were performed at each visit. RESULTS: Visual acuity improved by 3 logMar lines in the left eye and by 2 logMar lines in the right eye after smoking cannabis. The nystagmus intensities were reduced by 30% in primary position and 44%, 11%, 10% and 40% at 20-degree eccentricity to the right, left, elevation and depression, respectively, after smoking cannabis. CONCLUSION: Cannabis may be beneficial in the treatment of congenital idiopathic nystagmus (CIN). Further research to clarify the safety and efficacy of cannabis in patients with CIN, administered for example by capsules or spray, would be important.

Congenital nystagmus: randomized, controlled, double-masked trial of memantine/gabapentin.

OBJECTIVE: Nystagmus consists of involuntary to and fro movements of the eyes. Although studies have shown that memantine and gabapentin can reduce acquired nystagmus, no drug treatment has been systematically investigated in congenital nystagmus. METHODS: We performed a randomized, double-masked, placebo-controlled study investigating the effects of memantine and gabapentin on congenital nystagmus over a period of 56 days. The primary outcome measure was logarithmic minimum angle of resolution (logMAR) visual acuity; the secondary outcome measures were nystagmus intensity and foveation, subjective questionnaires about visual function (VF-14) and social function. Analyses were by intention to treat. RESULTS: Forty-eight patients were included in the study. One patient in the placebo group dropped out. Patients were randomized into either a memantine group (n=16), gabapentin group (n=16), or placebo group (n=15). Mean visual acuity improvements showed a significant effect between treatment groups (F=6.2; p=0.004, analysis of variance) with improvement in both memantine and gabapentin groups. Participants with afferent visual defects showed poorer improvements in visual acuity to medication than those with apparently normal visual systems. However, eye movement recordings showed that both nystagmus forms improved in nystagmus intensity (F=7.7; p=0.001) and foveation (F=8.7; p=0.0007). Participants subjectively reported an improvement in vision after memantine and gabapentin treatment more often than in the placebo group (p=0.03). However, there were no significant differences between the treatment groups with visual function (VF-14) or social function questionnaires because all groups reported improvements. INTERPRETATION: Our findings show that pharmacological agents such as memantine and gabapentin can improve visual acuity, reduce nystagmus intensity, and improve foveation in congenital nystagmus.

Baclofen for patients with congenital periodic alternating nystagmus.

PURPOSE: To describe the clinical effect of baclofen on a group of patients with congenital periodic alternating nystagmus. METHODS: A retrospective review of case notes was carried out of all patients with congenital periodic alternating nystagmus (PAN) treated with baclofen between 1999 and 2004. Eight patients were identified, 6 males and 2 females with a mean age of 21 years (range 9 to 34 years). Clinical data were recorded for all patients pre- and post-treatment with the GABA agonist baclofen. Adverse effects of the treatment were recorded and a questionnaire was constructed to evaluate patient satisfaction with the treatment. RESULTS: All 8 patients had an abnormal head posture (AHP) before treatment which improved following treatment in 4 patients, one of whom had recurrence following treatment withdrawal. Binocular Snellen visual acuity (VA) improved by one line in 4 cases, while none of the other 4 patients suffered any loss of vision from the treatment. Three of the eight patients have continued on treatment long-term, in one case for 6 years. In the other five, treatment was withdrawn due to side effects in 4 cases, and in the fifth due to a lack of effect. The most commonly reported side effect was drowsiness, which occurred in 3 patients. Using a patient-centered survey, complete responses were obtained from 6 of the 8 patients treated. Five patients were either pleased or very pleased that they had tried the treatment. The reasons given were: improved vision or head posture, an appreciation of slowing of ocular movements, improved cosmesis and improved confidence. CONCLUSIONS: Baclofen may be effective in a select group of patients with congenital PAN and a trial of treatment may be worthwhile, prior to considering surgical intervention in this condition.

The effects of gabapentin and memantine in acquired and congenital nystagmus: a retrospective study.

BACKGROUND: Pharmacological treatment has been successful in some forms of acquired neurological nystagmus. However, drugs are not known to be effective in idiopathic infantile nystagmus or nystagmus associated with ocular diseases. METHODS: The authors retrospectively analysed Snellen visual acuity (VA), subjective visual function, and eye movement recordings of 23 patients with nystagmus (13 secondary to multiple sclerosis, three associated with other neurological diseases, two idiopathic infantile, and five with associated ocular diseases) treated with gabapentin or memantine. RESULTS: With gabapentin, 10 of 13 patients with nystagmus secondary to multiple sclerosis (MS) showed some improvement. Memantine improved the VA in all three patients with MS who did not improve on gabapentin. There was no change of nystagmus in other neurological disorders. Patients with congenital nystagmus showed reduction of nystagmus and their VA changes depended on the ocular pathology. CONCLUSION: Gabapentin and memantine may be effective in acquired nystagmus secondary to MS. To the authors' knowledge this is the first series of patients showing that gabapentin is effective in improving nystagmus in congenital nystagmus/nystagmus associated with ocular pathology. Memantine may be useful as an alternative drug in treating patients with nystagmus.

Eficacia de la toxina botulínica en el tratamiento del nistagmo congénito / Efficacy of botulinum toxin in the treatment of congenital nystagmus

En el presente trabajo investigamos la eficacia de la toxina botulínica y sus efectos adversos en el tratamiento del nistagmo congénito. Definimos eficacia como la mejoría de 3 o más de las siguientes variables: frecuencia y amplitud del nistagmo, agudeza visual real y subjetiva, posición compensadora de cabeza, teimpo de fijación y oscilopsia. Aplicamos toxina botulínica a 10 pacientes con nistagmo congénito. En 4 de ellos la inyección fue retroblbar y en 6 casos se aplicó en la vaina muscular de los rectos horizontales. La aplicación retrobulbar fue eficaz en todos los casos. La respuesta benéfica se hace evidente a partir de las 24 horas y se incrementa progresivamente hasta alcanzar su efecto máximo entre los 45 y 60 días para disminuir progesivamente, pero persistiendo aún a los 4 meses de la aplicación. Los efectos colaterales se presentaron a los 5 días post aplicación en 3 casos, resolviéndose antes de las cuatro semanas. La inyección de toxina en la vaina de los rectos horizontales fue eficaz en 5 de los 6 pacientes. También desde las 24 horas hay efectos benéficos que son máximos entre las 2 y las 8 semanas, para declinar progresivamente. Un paciente presentó ptosis y parálisis del músculo recto interno del mismo ojo y parálisis del recto superior en el otro ojo. Estas se resolvieron a las dos semanas. Dos casos presentaron hemorragia subconjuntival.

In the present study we investigated effectiveness of botulinum roxin in the treatment of congenital nystagmus, as well as its adverse effects. We defined effectiveness as the improvement of 3 or more of the following variables: frequency of nystagmus, real visual acuity, head posture, time of fixation, amplitude of nystagmus, oscillopsia, subjective visual acuity. We administered botullium toxin to 10 patients with congenital nistagmus who attended the Service of Strabismus of the Instituto Regional de Oftalmología. Botulinum toxin was injected directly into the sheath of the horizontal rectus muscles in six patients, and in four patients by retrobulbar injection. In the second group the effectiveness was 100 percent. The beneficial effects were evident as soon as 24 hours post application and they increased progressively until reaching its maximum effect between the 45 and 60 days. A progressive decrease was observed later but in all of them beneficial effects still persists after 4 months. 75 percent of patients development adverse effects like ptosis, paralysis of the external rectus muscle or the superior rectus muscle, appearing between 5 and 7 days post application and resolving before four weeks. In the first group, effectiveness was 83,3 percent, these beneficial effects appeared 24 hours post application and increased progressively until reaching its maximum effect between 2 and 8 weeks. A progressive diminution was observed later but in all of them benefits still persisted after 4 months. 16,6 percent of these patients developed ptosis and paralysis of the medial rectus muscle of the same eye and paralysis of the superior rectus in the other eye.

[Botulinum toxin A in the treatment of congenital nystagmus in children]. / Toksyna botulinowa A w leczeniu oczoplasu wrodzonego u dzieci.

PURPOSE: To evaluate the use of, botulinum toxin A in the treatment of congenital nystagmus in children. MATERIAL AND METHODS: 32 children with nystagmus and esotropia (group I), nystagmus and exotropia (group II) and horizontal and vertical nystagmus (group III). Intramuscular injections of botulinum toxin A was performed in all treated children. RESULTS: In group I the amplitude of nystagmus diminished of 50%, in group II of 42.9% and in group III of 28,6%. Near and distant visual acuity improved in all treated children. CONCLUSIONS: Treatment of congenital nystagmus with botulinum toxin A causes reduction of the amplitude of nystagmus, partial improvement of visual acuity and improvement of anomalous head posture.

Clinical and oculographic response to Tenuate Dospan (diethylpropionate) in a patient with congenital nystagmus.

PURPOSE: We report a female adult with congenital nystagmus who responded with improved visual function and oculographic parameters after taking the anorexic diet drug Tenuate Dospan (diethylproprionate; Watson Laboratories, Inc., Corona, California). METHODS: Observational case report. Clinical ophthalmic examination and ocular motility recordings were performed before and after administration of the drug Tenuate Dospan. RESULTS: The binocular visual acuity of the patient improved from 20/70 to 20/50, her exotropic deviation decreased from 12 to 4 prism diopters, her stereopsis increased from none to 200 seconds/arc, and her ocular motility recordings showed increased foveation periods and a broadened null zone. CONCLUSION: For unexplained reasons, the anorexic stimulant Tenuate Dospan "paradoxically" improved the nystagmus and binocular function in this patient with congenital nystagmus. This observation may be the basis for investigation of a new pharmacological treatment approach to patients with congenital nystagmus or strabismus.