Botulinum toxin A for the treatment of strabismus in children with neurological impairment / Toxına botulínica tipo A para o tratamento de estrabısmo em crianças neurologicamente comprometidas

ABSTRACT Purposes: To assess the efficacy of botulinum toxin A injection in the treatment of strabismus in patients with neurological impairment and evaluate the factors associated with treatment success. Methods: The study included 50 patients with strabismus and neurological impairment. In all children, botulinum toxin injection was performed into the appropriate extraocular muscle. The relationship between demographic features, clinical characteristics, and treatment success were analyzed. Results: In the study group, 34 patients had esotropia, and 16 patients had exotropia. As neurological problems, 36 patients had cerebral palsy, and 14 had hydrocephalus. The average follow-up period was 15.3 ± 7.3 months. The mean number of injections was 1.4 ± 0.6. The mean angle of deviation was 42.5 ± 13.2 PD before the treatment, which decreased to 12.8 ± 11.9 PD after the treatment. Successful motor alignment (orthotropia within 10 PD) was achieved in 60% of the patients. Binary logistic regression analysis revealed that esotropic misalignment and shorter duration of strabismus was significantly associated with treatment success in the study group. Patients with esotropia and lower angles of misalignment were more likely to be treated with a single injection. Conclusion: The use of botulinum toxin A for the treatment of strabismus in children with neurological impairment is a good alternative to conventional surgical therapy with a lower risk of overcorrection. The treatment outcome is better in esodeviations and shorter duration of strabismus, implying an advantage of early treatment.

RESUMO Objetivos: Avaliar a eficácia do uso de toxina bo-tulínica tipo A no tratamento do estrabismo em pacientes com comprometimento neurológico e avaliar os fatores associados ao sucesso do tratamento. Métodos: Cinquenta pacientes com estrabismo e comprometimento neurológico foram incluídos no estudo. Em todas as crianças, a toxina botulínica tipo A foi injetada no músculo extraocular apropriado. A relação entre características demográficas, características clínicas e o sucesso do tratamento foram analisadas. Resultados: No grupo de estudo, 34 pacientes tiveram esotropia e 16 pacientes tiveram exotropia, sendo trinta e seis pacientes com paralisia cerebral e 14 pacientes com hidrocefalia. O tempo médio de acompanhamento foi de 15,3 ± 7,3 meses. O número médio de aplicações foi de 1,4 ± 0,6. O ângulo de desvio médio foi de 42,5 ± 13,2 DP antes do tratamento e diminuiu para 12,8 ± 11,9 DP após o tratamento. Alinhamento motor bem sucedido (ortotropia dentro de 10 DP) foi alcançado em 60% dos pacientes. A análise de regressão logística binária revelou que o desalinhamento esotrópico e uma menor duração do estrabismo foram significativamente associados ao sucesso do tratamento no grupo de estudo. Pacientes esotrópicos com ângulos de desalinhamento menores são mais propensos a serem tratados com uma única aplicação. Conclusão: O uso da toxina botulínica tipo A para o tratamento de estrabismo em crianças com comprometimento neurológico é uma boa alternativa para a terapia cirúrgica convencional com menor risco de hipercorreção. O resultado do tratamento é melhor em exodesvios e em pacientes com estrabismo de menor duração, implicando em vantagem para o tratamento precoce.

Golden Indications and an Overview on the Use of Botulinum Toxin in Strabismus.

Botulinum toxin A (BTXA) is considered a pharmacological agent that may provide an alternative treatment to surgery in strabismus. It can be used as both a diagnostic and therapeutic agent in various concomitant, paralytic, and restrictive disorders. The major advantage of BTXA treatment is that it is non-invasive and does not impact the patient's chance for future surgery in case of an unfavorable response. In some selected disorders, BTXA has become the primary choice of treatment, whereas surgery is found to be more effective in others. Accumulated knowledge and experience have demonstrated that BTXA is more than merely an alternative treatment and has additional specific indications such as in unstable deviations and as an adjunct to surgery. Patients with recurrent deviations despite multiple surgeries are also good candidates for BTXA treatment. Although the major expectation is to obtain a permanent result, BTXA can also be used as a maintenance treatment. This paper mainly focuses on the current indications for the use of BTXA in strabismology, with special emphasis on ideal first-choice applications referred to as "golden indications," within the scope of the author's own experience with the use of BTXA over 30 years.

Botulinum toxin A for the treatment of strabismus in children with neurological impairment.

PURPOSES: To assess the efficacy of botulinum toxin A injection in the treatment of strabismus in patients with neurological impairment and evaluate the factors associated with treatment success. METHODS: The study included 50 patients with strabismus and neurological impairment. In all children, botulinum toxin injection was performed into the appropriate extraocular muscle. The relationship between demographic features, clinical characteristics, and treatment success were analyzed. RESULTS: In the study group, 34 patients had esotropia, and 16 patients had exotropia. As neurological problems, 36 patients had cerebral palsy, and 14 had hydrocephalus. The average follow-up period was 15.3 ± 7.3 months. The mean number of injections was 1.4 ± 0.6. The mean angle of deviation was 42.5 ± 13.2 PD before the treatment, which decreased to 12.8 ± 11.9 PD after the treatment. Successful motor alignment (orthotropia within 10 PD) was achieved in 60% of the patients. Binary logistic regression analysis revealed that esotropic misalignment and shorter duration of strabismus was significantly associated with treatment success in the study group. Patients with esotropia and lower angles of misalignment were more likely to be treated with a single injection. CONCLUSION: The use of botulinum toxin A for the treatment of strabismus in children with neurological impairment is a good alternative to conventional surgical therapy with a lower risk of overcorrection. The treatment outcome is better in esodeviations and shorter duration of strabismus, implying an advantage of early treatment.

A comparative multicentric long-term study of un-augmented modified Nishida procedure vs augmentation in unilateral sixth nerve palsy.

PURPOSE: To compare the effectiveness of three procedures: modified Nishida procedure alone vs modified Nishida procedure combined with medial rectus recession (MRc) vs modified Nishida procedure combined with MRc and botulinum toxin (BT) for severe unilateral sixth nerve palsy. DESIGN: Consecutive, interventional case series. METHODS: The medical records of a consecutive series of patients with severe unilateral sixth nerve palsy who underwent modified Nishida procedure in multiple centres were reviewed. Surgical technique was decided preoperatively at the surgeon's discretion. The preoperative and postoperative findings were compared. RESULTS: Of the 43 patients with abducens palsy that received the procedure, 32 were included (mean age 38.6 ± 19.8 years). Mean preoperative deviation was 63.0 ± 27.3 prism dioptres (PD) and mean limitation of abduction -4.5 ± 1.2. Five patients underwent a modified Nishida procedure alone, 24 patients had an additional MRc and 3 patients were also injected with BT. Overall, the average correction of modified Nishida technique by itself was 29.4 ± 6.6 PD (range 20-36) and adding a MRc corrected 62.6 ± 23.8 PD (range 24-120). Modified Nishida procedure, MRc and BT altogether corrected 95.0 ± 18.0 PD (range 75-110). No postoperative complications were observed in any of the patients. CONCLUSIONS: Excellent outcomes with fewer complications are obtained with modified Nishida procedure alone. The need for additional procedures such as MRc and BT which increase the effect in primary position can be determined depending on passive duction and preoperative horizontal deviation.

The role of hepatic and renal functions in the development of retinopathy of prematurity: Is proteinuria a new risk factor?

PURPOSE: To investigate the association of hepatic and renal parameters with the development of retinopathy of prematurity (ROP) in premature infants with a gestational age ≤ 32 weeks. METHODS: Medical records of 240 preterm infants were reviewed retrospectively, 85 of them were grouped as type 1, type 2 ROP, and control group. The 4th week hepatic and renal function test results of the groups, on the day of their first ROP examinations, were compared for the risk of development of ROP and the development of type 1 ROP. RESULTS: In this study, 12, 35, and 38 infants were enrolled in the type 1, type 2 ROP, and control group, respectively. The average gestational age and birth weight were higher; however, the duration of oxygen treatment was lower in the control group (p < 0.001). The blood glucose level was significantly higher in the type 1 ROP group than in the other groups (p = 0.023). The mean of total serum bilirubin of the type 1 ROP group was significantly lower than those of the type 2 ROP and control group (p = 0.032). Proteinuria was present in 85.7% of preterms with treatment-requiring ROP and proteinuria increased the risk of ROP by 3.9 times (OR with 95% CI 3.9 (1.19-12.75), p = 0.042). CONCLUSION: We found significantly higher blood glucose and lower total bilirubin level in the type 1 ROP group. Moreover, our findings suggest that proteinuria may not be only a comorbidity factor but also related to a higher frequency of ROP and type 1 ROP in preterm infants.

Role of Botulinum Toxin Type A in Cyclic Esotropia: A Long-Term Follow-up.

PURPOSE: To describe two patients with childhood cyclic esotropia 8 and 9 years after they underwent botulinum toxin type A treatment to report its long-term outcome. METHODS: Two patients with sudden onset cyclic esotropia aged 2 and 4 years were included. Botulinum toxin type A injections were performed on the appropriate muscles. RESULTS: The first patient was a 2-year-old boy with left dominant alternating esotropia on a cyclic basis. His strabismus ranged from 25 to 45 prism diopters (PD) at near and distance. A botulinum toxin type A injection into the left medial rectus muscle revealed orthotropia at near and distance with a stereopsis of 60 seconds of arc (arcsec). During the 9 years of follow-up, he remained stable. The second patient was a 4-year-old girl who complained of double vision and strabismus. Her deviation was 40 PD at near and 35 PD at distance on a cyclic pattern. She became orthotropic with glasses after a bimedial botulinum toxin A injection. During the 8 years of follow-up, she remained stable with a stereo-acuity of 120 arcsec. CONCLUSIONS: Considering the consecutive and recurrent deviations with surgical treatment in previous reports, botulinum toxin type A is an appropriate first-line option for the treatment of cyclic deviations, despite its limitations. The results suggest that botulinum toxin type A is an effective method to break the cycle in cyclic esotropia permanently. [J Pediatr Ophthalmol Strabismus. 2019;56(6):360-364.].

Innovative techniques for the treatment of adult strabismus.

Adult strabismus is often characterized by surgical complexity. In recent years, several innovative techniques for the management of complex strabismus have been developed. Strabismus surgeons should understand the indications for various strabismus surgical techniques in the management of these difficult cases. This workshop describes several new surgical techniques to manage complex strabismus, including small-angle incomitant and very large-angle strabismus, torsional diplopia, and restrictive, paralytic, and secondary strabismus. Because strabismus surgery is an ever-evolving field, it is important to continue to refine our surgical armamentarium. Strabismus surgeons may wish to add these techniques to their surgical repertoire for select cases.

The efficacy of superior rectus recession with simultaneous inferior oblique disinsertion on superior oblique palsy with superior rectus contracture.

PURPOSE: The information about superior rectus (SR) recession in cases with SR contracture coexisting with superior oblique palsy (SOP) is very limited in previous literature. The aim of this study is to evaluate the effect of SR recession, as a combined procedure with inferior oblique (IO) disinsertion, in long-standing SOP with secondary SR contracture. METHODS: The medical records of the 145 patients operated for SOP were retrospectively reviewed and 15 patients who underwent SR recession met the inclusion criteria. The mean follow-up was 50.4 months. RESULTS: The preoperative angle of deviation was within the range of 16-35 prism dioptres (PD) with a mean of 23.0 ± 5.03 PD. In all of the cases, SR recession was performed in combination with IO disinsertion. Adult patients (12) underwent adjustable SR recession. Postoperative overcorrection developed in 3 cases (20%), and in 12 patients, the postoperative vertical deviation was within the range of 0-5 PD with a mean of 1.41 ± 1.88 PD. The overcorrected three patients underwent botulinum toxin A (BTXA) injection into the ipsilateral inferior rectus muscle. The deviation is well controlled by BTXA injection in two patients, whereas the other one was considered as masked bilateral SOP and underwent IO disinsertion in the other eye. CONCLUSION: Our results suggested that SR recession in combination with IO disinsertion is an effective procedure to control large vertical deviations in SOP with SR contracture in the majority of cases. However, the risk of overcorrection should be considered despite adjustable SR weakening and BTXA injection seems efficient to rescue overcorrections in long term.

Pearls and pitfalls in the management of Duane syndrome.

Duane syndrome (DS) is a common form of congenital cranial dysinnervation disorders. The ocular motility pattern lies in a wide clinical spectrum, and the choice of treatment must be individualized depending on the severity of the clinical findings. There is no perfect method of treatment and no real "cure" in DS. In this paper, the aim is to give some guidelines to the reader for selection of the most appropriate treatment method for the patient.

Role of botulinum toxin A in treatment of intractable diplopia.

PURPOSE: To evaluate the effect of botulinum toxin A (BTXA) in patients with intractable diplopia related to intracranial problems or long-term interruption of fusion due to cataract or uncorrected aphakia and to identify the group of resistant cases who have no potential to fuse the two images. METHODS: The medical records of patients seen by the senior author (SBÖ) over a period of 20 years were reviewed retrospectively to identify those who underwent BTXA treatment for intractable diplopia. All cases had horizontal and/or vertical deviations. The diagnostic criterion was persistence of diplopia in free space despite neutralization of the deviation by prisms or synoptophore. BTXA was injected into the appropriate extraocular muscle to control the deviation in the identified patients. RESULTS: A total of 22 patients were identified: 13 developed intractable diplopia following head trauma, intracranial surgery, or stroke; 9 had a history of binocular sensory deprivation due to traumatic cataract or uncorrected aphakia. The duration of sensory deprivation ranged from 2 to 41 years. BTXA was injected into the appropriate extraocular muscle(s). Diplopia resolved completely in 14 patients, resolved incompletely with short-term single vision in 3 cases, and persisted in 5 patients despite correction of the deviation by BTXA. CONCLUSIONS: Our results suggest that BTXA offers the advantage of a temporary decrease of the deviation without altering image quality that allows the visual system to recover fusion under real-life conditions. Permanent treatment with surgical correction of the deviation should be reserved for those who achieve fusion during the orthotropic period provided by BTXA.

Restrictive problems related to strabismus surgery.

Strabismus surgery may be responsible for some restrictions in ocular motility that may cause new problems after surgery. Most of the time these restrictions present as a complex motility problem after surgery that requires further treatment. There may be various reasons that cause motility restriction following strabismus surgery. Those are excessive shortening or inadvertent capture of extraocular muscles, transposition procedures and, the most challenging problem, postoperative scar tissue-adhesion formation. In this review the potential reasons for postoperative restrictive problems, preventive measures and finally the treatment options for such problems are overviewed.

Hypoplastic inferior rectus muscle in association with accessory extraocular muscle and globe retraction.

Ocular motility problems related to congenital abnormalities of extraocular muscles are rare conditions. Such congenital abnormalities may present in a spectrum from accessory additional rectus muscles to absence of extraocular muscles. Absence of one or more extraocular muscles is a rare condition usually seen in association with craniofacial syndromes and only rarely in isolation. None of the cases with the absence of an extraocular muscle were reported to be in association with an accessory extraocular muscle or paradoxical contraction of an extraocular muscle. We present a case with bilateral hypoplasia of the inferior rectus muscle with an accessory extraocular muscle in association with globe retraction and lambda-pattern exodeviation.

Fibrotic superior oblique and superior rectus muscles with an accessory tissue band.

Congenital fibrosis of extraocular muscles may rarely present by involvement of isolated extraocular muscles. We report a case with an unusual form of congenitally fibrotic superior oblique and superior rectus muscles with an accessory tissue band passing toward the limbus. Magnetic resonance imaging (MRI) findings as well as histopathological and surgical results were evaluated. To the best of our knowledge, there is only one partially similar case in the literature with coexistence of congenitally fibrotic superior rectus and superior oblique muscles, and the features of that case differ from those of our case.

The effect of strabismus surgery on retrobulbar hemodynamics.

PURPOSE: To investigate the potential alterations of ocular hemodynamics after strabismus surgery using color Doppler ultrasonography. MATERIALS AND METHODS: Twenty eyes of 18 patients and the left eyes of 20 healthy age- and sex-matched volunteers were evaluated. Patients were divided into two groups according to the number of operated muscles. Group 1 included seven patients with surgery on one rectus muscle; group 2 included 13 patients with surgery on two rectus muscles. Nine patients underwent adjustable suture eye muscle surgery. The ophthalmic artery, central retinal artery, short posterior ciliary artery, long posterior ciliary artery, and central retinal veins of both groups were examined. With spectral analysis, peak systolic velocity, end-diastolic velocity, resistivity, and pulsatility indices were calculated. RESULTS: There was no difference in the Doppler ultrasonography parameters between the group with surgery on one-horizontal rectus muscle and the group with surgery on two-horizontal rectus muscles. The adjustable suture procedure did not affect retrobulbar hemodynamics. There was no difference between the preoperative and postoperative Doppler examinations. CONCLUSIONS: In contrast with some recent studies, our results suggest that the strabismus surgery involving one- or two-horizontal rectus muscles does not have a measurable effect on retrobulbar blood flow.

The role of botulinum toxin A in augmentation of the effect of recession and/or resection surgery.

PURPOSE: The aim of this study is to assess the effectiveness of intraoperative botulinum toxin A (BTA) injection as an adjunct to the surgical treatment of large-angle esotropia or exotropia. METHODS: Ten patients were included in the study. Mean age of the patients was 27+/-20 years. Of these 10 patients, 7 were esotropic and 3 exotropic. The average preoperative esodeviation was 73.6+/-16.5 prism diopters and exodeviation was 76.7+/-5.8 PD. Five units of BTA were injected intraoperatively into one of the recessed horizontal rectus muscles in all of the patients. RESULTS: The average follow-up was 14+/-10 months (range, 8 to 40 months). The average final deviation in the esotropia group was 13+/-9.6 PD of esotropia. The average final deviation in the exotropia group was 4.7+/-5 PD of exotropia. The final deviation of the 70% patients was within 10 PD of esotropia or exotropia. CONCLUSION: The results of this study suggest that the combination of BTA injection with recession may increase the expected correction of a conventional horizontal rectus muscle surgery.

Medical control of intraocular pressure after phacoemulsification.

PURPOSE: To compare the effectiveness of oral acetazolamide, topical brinzolamide 1%, and no ocular hypotensive medication after phacoemulsification. SETTING: Adnan Menderes University Department of Ophthalmology, Aydin, Turkey. METHODS: This prospective randomized double-blind study comprised 60 eyes of 52 patients having phacoemulsification under topical anesthesia. There were no intraoperative complications. Eyes were randomized to receive oral acetazolamide 500 mg 1 hour preoperatively followed by 250 mg acetazolamide every 6 hours, 1 drop of brinzolamide 1% every 12 hours starting immediately after speculum removal, or no ocular hypotensive medication. Intraocular pressure (IOP) was measured using a Perkins tonometer preoperatively and 4 to 6 hours and 18 to 24 hours postoperatively. RESULTS: The preoperative IOP was not significantly different between the 3 groups. Four to 6 hours postoperatively, the acetazolamide group (P=.002) and brinzolamide group (P=.001) had significantly lower IOP than the control group. The same trend was observed at 18 to 24 hours in the brinzolamide group (P=.001) but not the acetazolamide group (P=.018). The IOP levels were not significantly different between the acetazolamide group and brinzolamide group at any postoperative time point. No eye receiving medication and 2 eyes (10%) in the control group had an IOP of 30 mm Hg or higher 4 to 6 hours postoperatively. Compared with preoperatively, an IOP increase of more than 5 mm Hg was seen at 4 to 6 hours in 3 eyes (15%), 2 eyes (10%), and 14 eyes (70%) in the acetazolamide, brinzolamide, and control group, respectively. CONCLUSION: Brinzolamide was as effective as acetazolamide in preventing IOP elevation 4 to 6 hours after phacoemulsification and more effective than acetazolamide at 18 to 24 hours.

Effect of single-dose fentanyl on the cardiorespiratory system in elderly patients undergoing cataract surgery.

STUDY OBJECTIVES: To evaluate the effects of fentanyl on the cardiorespiratory system in elderly patients undergoing cataract surgery with phacoemulsification method. DESIGN: Randomized, prospective, double-blind study. SETTING: University hospital. PATIENTS: 70 ASA physical status I, II, and III patients (>60 years) who underwent cataract surgery with topical anesthesia. INTERVENTIONS: Patients were randomly divided into two groups. The fentanyl group (35 patients) received fentanyl in 0.7 microg/kg bolus doses in a 2-mL balanced salt solution prior to surgery. The control group (35 patients) received a 2-mL balanced salt solution without any analgesic drug. MEASUREMENTS AND MAIN RESULTS: Systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), heart rate (HR), peripheral oxygen saturation (SpO(2)), respiratory rate (RR), end-tidal carbon dioxide (ETCO(2)), inspired CO(2) concentration, and sedation scores were measured preoperatively and at 5, 10, 15, 20, and 30 minutes intraoperatively. Postoperatively, patients were questioned about the presence of intraoperative pain. In the fentanyl group, no significant differences were observed in SPB, DBP, MAP, RR, or peripheral SpO(2). In the control group, RR was higher than baseline values at 10, 15, and 20 minutes. Diastolic blood pressure was higher than baseline values at 20 minutes. End-tidal CO(2) and inspired CO(2) levels were higher than baseline levels in both groups at all measurement times. Intraoperative ETCO(2) levels were higher in the fentanyl group than the control group (p < 0.01). Finally, no hypoxemia was observed in either group. CONCLUSION: Fentanyl can be used safely in 0.7-microg/kg dosages in elderly patients to improve patient comfort without any cardiorespiratory side effects, when undergoing cataract surgery with topical anesthesia.

The effect of Seprafilm on adhesions in strabismus surgery-an experimental study.

PURPOSE: Seprafilm (Genzyme, Cambridge, MA) is a bioabsorbable membrane composed of sodium hyaluronate and carboxymethylcellulose. Adhesions occurring after strabismus surgery may affect surgical outcome. The purpose of our study was to histopathologically evaluate the influence of Seprafilm on postoperative adhesions. METHODS: Seven adult male New Zealand albino rabbits were used. The superior rectus muscle was resected 3 mm, and a fornix-based limbal conjunctival dissection was made inferonasally in both eyes. In one eye of each rabbit, Seprafilm was inserted between the conjunctiva and superior rectus and under the dissected inferonasal conjunctiva. The fellow eye of each rabbit, having undergone superior rectus resection and inferonasal conjunctival dissection without Seprafilm, served as the control group. The rabbits were killed and the eyes were enucleated at 6 weeks after surgery. Histopathological sections were analyzed for inflammation and fibrosis by staining them with hematoxylin-eosin and Masson trichrome, respectively. Inflammation and fibrosis were graded on a scale of 0 to 4. RESULTS: Compared with the control eyes, there was no significant difference with regard to inflammation either at the area of superior rectus resection or the area of conjunctival dissection (P.655 and P.157, respectively). Significantly less fibrosis occurred in the surgical areas where Seprafilm was used compared with the control group (P.046 and P.015, respectively) both at the area of superior rectus resection and the area of conjunctival dissection. CONCLUSION: This study shows that Seprafilm significantly decreases postoperative adhesions between the conjunctiva, muscle, and sclera. Application of Seprafilm may prove useful in strabismus surgery especially where adhesion formation may influence the outcome and in cases where recurrent conjunctival dissection may be needed.