Objective demonstration of eyelid spasm relief with smartphone and custom software in hemifacial spasm patients.

PURPOSE: To objectively demonstrate eyelid spasms relief in hemifacial spasm (HFS) patients using a smartphone and a custom-made software. METHODS: Nineteen patients with HFS had standardized videos recorded with a smartphone (iPhone 6S, Apple) camera before and 15 days after receiving onabotulinumtoxinA injections. Nineteen age-matched control subjects were also assessed. The Eye Aspect Ratio (EAR) is an algorithm previously described to determine whether the eye is opened or closed. When the eye is closed, EAR tends to be closer to zero. Analogously, if the eye is wide open, values are greater. A custom-made software using the EAR concept was developed and pre- and post-treatment EARs were analyzed to assess HFS patients. RESULTS: Botulinum toxin (BoNT) injections led to a significant increase in the average EAR of the affected side: + 10.4% (p = 0.0175) of HFS patients, compared to baseline. Mean EAR before BoNT applications were significantly lower (16.2%) on the affected side (0.25 ± 0.05) of HFS patients when compared to controls (0.30 ± 0.05, p = 0.004). After BoNT injections, no statistically significant difference was observed for the average EAR between the affected side of HFS patients (0.27 ± 0.04) and controls (p = 0.20). CONCLUSIONS: Use of a smartphone and custom-made software objectively demonstrated eyelid spasm relief in patients with HFS. Additional refinement of this system could permit more accurate assessments of treatment response rates for each patient, making it possible to be used in clinical practice.

Profile of patients with essential blepharospasm and hemifacial spasm in the two largest ophthalmology reference centers in Brazil / Perfil dos pacientes com blefaroespasmo essencial e espasmo hemifacial nos dois maiores centros de referência em oftalmologia no Brasil

ABSTRACT Purpose: Information is scarce regarding the comprehensive profile of patients with essential blepharospasm and hemifacial spasm in Brazil. The present study aimed to assess the clinical features of patients with these conditions, followed up in two reference centers in Brazil. Methods: The study included patients with essential blepharospasm and hemifacial spasm, followed up at the Departments of Ophthalmology at Universidade Federal de São Paulo and Universidade de São Paulo. Apart from demographic and clinical features, past stressful events related to the first symptoms (triggering event), aggravating factors, sensory tricks, and other ameliorating factors for the eyelid spasms were assessed. Results: A total of 102 patients were included in this study. Most patients were female (67.7%). Essential blepharospasm was the most frequent movement disorder [51/102 patients (50%)], followed by hemifacial spasm (45%) and Meige's syndrome (5%). In 63.5% of the patients, the onset of the disorder was associated with a past stressful event. Ameliorating factors were reported by 76.5% of patients; 47% of patients reported sensory tricks. In addition, 87% of the patients reported the presence of an aggravating factor for the spasms; stress (51%) was the most frequent. Conclusion: Our study provides information regarding the clinical features of patients treated in the two largest ophthalmology reference centers in Brazil.

RESUMO Objetivo: Há poucos dados sobre o perfil de pacientes com blefaroespasmo essencial e espasmo hemifacial no Brasil. O objetivo deste estudo é avaliar de forma mais abrangente as características clínicas dos pacientes portadores dessas doenças acompanhados em dois centros de referência em oftalmologia no Brasil. Métodos: Pacientes com blefaroespasmo essencial e espasmo hemifacial, acompanhados nos Departamentos de Oftalmologia da Universidade Federal de São Paulo e da Universidade de São Paulo foram incluídos neste estudo. Além dos dados clínicos e demográficos, foram avaliados também a presença de eventos estressantes relacionados ao início dos sintomas (evento desencadeante), fatores agravantes, truques sensoriais, e outros fatores de melhora. Resultados: Cento e dois pacientes foram incluídos no estudo. A maior parte dos pacientes era do sexo feminino (67,7%). Blefaroespasmo essencial foi a condição mais frequente, observada em 51 (50%) dos pacientes. Espasmo hemifacial correspondia a 45% dos casos, enquanto 5% dos pacientes apresentavam a Síndrome de Meige. 63,5% dos pacientes associaram o início dos sintomas com um evento estressante prévio. 76,5% dos pacientes relataram fatores de melhora para os espasmos; 47% relataram truques sensoriais. Além disso, 87% dos pacientes relataram fatores de piora; estresse (51%) foi o mais frequente. Conclusão: Este estudo fornece informações a respeito das características clínicas dos pacientes com blefaroespasmo essencial e espasmo hemifacial acompanhados nos dois maiores centros de referência em oftalmologia do Brasil.

Profile of patients with essential blepharospasm and hemifacial spasm in the two largest ophthalmology reference centers in Brazil.

PURPOSE: Information is scarce regarding the comprehensive profile of patients with essential blepharospasm and hemifacial spasm in Brazil. The present study aimed to assess the clinical features of patients with these conditions, followed up in two reference centers in Brazil. METHODS: The study included patients with essential blepharospasm and hemifacial spasm, followed up at the Departments of Ophthalmology at Universidade Federal de São Paulo and Universidade de São Paulo. Apart from demographic and clinical features, past stressful events related to the first symptoms (triggering event), aggravating factors, sensory tricks, and other ameliorating factors for the eyelid spasms were assessed. RESULTS: A total of 102 patients were included in this study. Most patients were female (67.7%). Essential blepharospasm was the most frequent movement disorder [51/102 patients (50%)], followed by hemifacial spasm (45%) and Meige's syndrome (5%). In 63.5% of the patients, the onset of the disorder was associated with a past stressful event. Ameliorating factors were reported by 76.5% of patients; 47% of patients reported sensory tricks. In addition, 87% of the patients reported the presence of an aggravating factor for the spasms; stress (51%) was the most frequent. CONCLUSION: Our study provides information regarding the clinical features of patients treated in the two largest ophthalmology reference centers in Brazil.

Blinking Parameters Do Not Normalize After Botulinum Toxin Therapy in Blepharospasm and Hemifacial Spasm Patients.

BACKGROUND: Little is known regarding changes induced by botulinum toxin injections on blinking parameters in blepharospasm (BSP) and hemifacial spasm (HFS) patients. The purpose of this study was to investigate objective changes induced by botulinum toxin (BoNT) injections on blinking parameters in BSP and HFS patients. METHODS: Thirty-seven patients with BSP and HFS were evaluated before and 30 days after receiving onabotulinumtoxinA injections. Twelve age-matched control subjects were also assessed. Pretreatment and post-treatment parameters were assessed and compared with normal controls. A high-speed camera and microlight-emitting diodes were used to register the blinking in patients and control groups. Outcomes were blinking frequency, amplitude, and maximum velocity of eyelid closure. RESULTS: BoNT injections led to a significant reduction in all parameters, compared with baseline, in BSP and on the affected side in HFS, respectively: 22% ( P < 0.001) and 20% ( P = 0.015) in amplitude; 21% ( P = 0.04) and 39% in frequency ( P = 0.002); and 41% ( P < 0.001) and 26% ( P = 0.005) in maximum closing velocity. Blinking amplitude ( P = 0.017 and P = 0.019) and velocity ( P < 0.001 for both groups) were significantly lower at 30 days on BSP and on the affected HFS side, when compared with controls. BSP and HFS patients presented a significantly lower velocity of eyelid closure, even before BoNT, compared with controls ( P = 0.004. and P < 0.001, respectively). CONCLUSIONS: Although blinking frequency became close to normal, amplitude and velocity after BoNT applications were significantly lower in BSP and on the affected side of HFS patients when compared with age-matched normal controls, demonstrating that blinking parameters do not normalize after treatment. The velocity of eyelid closure was shown to be significantly lower, even before BoNT treatment, when compared with control subjects.

Ocular Surface Metrics in Blepharospasm Patients After Treatment With Botulinum Toxin Injections.

PURPOSE: The purpose of this study was to assess blepharospasm patients regarding the effect of botulinum toxin in ocular surface parameters. METHODS: A prospective study was performed in blepharospasm patients treated with onabotulinumtoxinA. A smartphone (iPhone 6S, Apple) and custom-made software were used to record the eyelid movements for 3 minutes in a standardized manner. Optical coherence tomography of the tear meniscus was used to assess the tear meniscus area. Tear break-up time and the Ocular Surface Disease Index questionnaire were also evaluated. Patients were assessed before and 15 days after botulinum toxin injections. RESULTS: Forty eyes of 20 patients were evaluated. The frequency of the spontaneous eyelid movements was significantly reduced after treatment (23.18 ± 12.85 movements/min vs. 9.29 ± 6.87 movements/min; p < 0.0001). Significant increases in the tear meniscus area (0.020 ± 0.015 mm 2 vs. 0.057 ± 0.104 mm 2 ; p = 0.01) and in break-up time (4.2 ± 1.2 seconds vs. 5.1 ± 1.3 seconds; p = 0.03) were observed 15 days after treatment. A significant reduction in the Ocular Surface Disease Index (59.05 ± 19.04 vs. 21.2 ± 19.5; p < 0.0001) was also observed. CONCLUSION: Significant changes in the tear meniscus area, break-up time, and Ocular Surface Disease Index after treatment reflect the effect of botulinum toxin on the lacrimal pump and in the improvement of dry eye symptoms. Reduction of eyelid spasms after treatment in blepharospasm patients was demonstrated using a smartphone and custom-made software. Thus, beyond relieving eyelid spasms, botulinum toxin injections were associated with subjective and objective improvement of dry eye parameters in patients with blepharospasm.

Orbicularis Oculi Muscle Immunohistochemical, Metabolic, and Morphometric Differences in Affected and Nonaffected Sides in Hemifacial Spasm vs Healthy Subjects.

BACKGROUND: Subtle morphological alterations have been reported even in the nonaffected side of the orbicularis oculi muscle in patients with hemifacial spasm. However, no previous study assessed immunohistochemical, metabolic, and morphometric alterations in orbicularis oculi muscle fibers in affected and nonaffected sides in patients with this condition, compared with samples obtained from healthy subjects. The purpose of this study is to objectively assess and compare orbicularis oculi muscle (OOM) samples of hemifacial spasm affected and nonaffected sides and healthy subjects. METHODS: Orbicularis oculi samples from 8 patients with hemifacial spasm who had not been previously treated and 6 healthy subjects were prepared using hematoxylin and eosin, nicotinamide adenine dinucleotide tetrazolium reductase, cytochrome oxidase, succinate dehydrogenase, Gomori staining, and monoclonal antibodies against myosin slow and myosin fast. A digital image analysis software was used for objective analysis. RESULTS: OOM fiber area was significantly greater in both affected ( P = 0.0379) and nonaffected sides ( P = 0.0012) of HFS samples when compared with control subjects' fibers. A significantly greater number of oxidative fibers were observed in both affected and nonaffected sides of patients with HFS when compared with control subjects ( P < 0.001 for both). A significantly greater percentage of slow fibers was observed in the affected side of HFS patients ( P = 0.0012) compared with control subjects. CONCLUSIONS: This study's findings suggest that repeated contractions might lead to OOM fiber hypertrophy, increased mitochondrial metabolism, and possible conversion of fast-twitch orbicularis oculi muscle fibers into slow-twitch fibers in patients with HFS. Alterations were observed in affected and nonaffected sides, confirming initial findings that the nonaffected side is not normal in this unique condition.

Smartphone and custom-made software to assess the effect of botulinum toxin in essential blepharospasm: Initial results.

BACKGROUND AND PURPOSE: It is challenging to assess essential blepharospasm (EB) patients objectively because they exhibit chaotic patterns of abnormal eyelid movements. Previously employed objective approaches used systems with low levels of accuracy systems or were too complex to be applied in routine clinical practice. We aimed to develop a practical tool using a smartphone camera and custom-made software to objectively assess the therapeutic effects of botulinum toxin in blepharospasm patients. METHODS: Thirty-four patients with EB were evaluated before and 15 days after receiving onabotulinumtoxinA injections. The control group was composed of 19 age-matched healthy individuals. A smartphone (iPhone 6 S; Apple) was used to record spontaneous eyelid movements for 3 min, after which eyelid movement frequency was analysed using custom-made software. RESULTS: Before treatment, eyelid movement frequency was significantly higher in the EB group (21.55 ± 13.30 movements/min) compared to the control group (8.26 ± 8.89 eyelid movements/min; p < 0.001). The frequency of spontaneous eyelid movements was significantly reduced after treatment in the EB patients (8.46 ± 6.32 eyelid movements/min; p < 0.001). After treatment, no statistically significant difference in eyelid movement rate was observed between the EB patients and the control group (p = 0.32). CONCLUSIONS: Assessment of the spontaneous eyelid movements obtained with the smartphone camera and analysed with the custom-made software enabled us to objectively measure the therapeutic effects of botulinum toxin in patients with blepharospasm. Further refinement of this system could enable customized and fine adjustments to botulinum toxin doses based on each patient's needs.

A comparative study of conventional intermarginal split lamella with labial mucous membrane graft versus sutureless procedure using fibrin sealant to manage major trichiasis.

OBJECTIVE: In the intermarginal split lamella with labial mucous membrane graft procedure to manage major trichiasis, the graft is usually sutured in the receptor bed using 6-0 polyglactin sutures. We aimed to compare the use of fibrin sealant to seal the graft to the receptor bed versus the conventional technique using sutures. METHODS: This is a retrospective comparative study of patients who underwent conventional intermarginal split lamella with labial mucous membrane graft or sutureless procedure using fibrin sealant (Tisseel, Baxter Healthcare Corp) between 2016 and 2021. Etiology of the trichiasis, procedure duration, postoperative discomfort and edema, complications, and follow-up period were extracted from these patients' charts. RESULTS: Twenty-seven eyelids from 19 patients underwent the procedure: twelve patients underwent the sutureless procedure, while seven underwent the conventional procedure. Mean follow-up was 8.4 ± 2.9 months and 13.7 ± 6.5 months for the sutureless and conventional groups, respectively. Patients who underwent the sutureless procedure reported no postoperative foreign body sensation, while 71.4% of patients who underwent the conventional procedure reported some degree of ocular discomfort. In the sutureless group, operating time and postoperative edema were significantly reduced. Labial mucous membrane graft dehiscence was observed in one eyelid (8.3%) on the first postoperative day in the sutureless group. No dehiscence was observed in the conventional technique group. CONCLUSION: The use of fibrin sealant showed to be a good alternative to conventional absorbable sutures. Advantages include expedited operating time, decreased postoperative discomfort, and expedite postoperative recovery.

Management of eyelid retraction related to thyroid eye disease.

Eyelid retraction related to thyroid eye disease (TED) is a challenging condition. It is one of the main clinical signs and a major diagnostic criterion in TED. This condition may threaten vision due to exposure keratopathy, in addition to its esthetic alterations, which may lead to psychosocial implications and affect the patient's quality of life. Although it is more commonly observed in the upper eyelid, it may be present on both the upper and lower lids. Numerous surgical and nonsurgical treatment modalities have been described and will be reviewed in this article. Management should be based on an individual patient assessment, taking into consideration the disease stage, severity, and clinician experience.

Eyelid malignancies in young individuals: clinical peculiarities.

OBJECTIVE: The incidence of malignant eyelid tumors is considerably increasing, even in young patients. The purpose of this study was to identify particularities in individuals under 40 years of age affected by eyelid malignancies. METHODS: Clinical charts of patients under 40 years of age who underwent eyelid tumor excision from 2014 to 2020 in two reference centers, one in Brazil and one in the USA, were reviewed. Demographic and outcome measures included: age, gender, skin phototype, comorbidities, diagnosis, time until diagnosis, lesion location, recurrence and metastasis. In addition, associated characteristics, including chronic sun exposure, intentional tanning (outdoor or artificial), history of smoking, use of sunscreen, family history of skin cancer and exposure to pesticides or herbicides, were reviewed. RESULTS: A total of 24 malignant eyelid tumors from 17 patients were identified. Twelve (70.6%) patients were female, and the most prevalent tumor was basal cell carcinoma (62.5%). Three (17.6%) patients had xeroderma pigmentosum and presented with multiple lesions. Family history of skin cancer was reported by 47% of patients. Prolonged sun exposure was reported by 41.2%; history of smoking and intentional tanning were reported by 23.5 and 17.6%, respectively, and might have played a role in carcinogenesis. CONCLUSIONS: Although uncommon in young subjects, eyelid malignancies present some peculiarities in individuals under 40 years of age. Our results suggest that women with family history of skin cancer and history of chronic exposure to ultraviolet radiation are at risk. Association with genetic syndromes is also relevant among younger age groups.

Multiple Faces of Eyelid Involvement in Sarcoidosis.

PURPOSE: To report three cases of eyelid involvement by sarcoidosis. In one of them, it mimicked a malignant lesion. METHODS: Retrospective case reports. RESULTS: A 73-year-old man presented with destruction of the left lower eyelid for 2 years. He had granulomatous uveitis in the left eye. Chest CT scan showed parenchymal abnormalities that could correspond to sarcoidosis. Skin biopsy revealed noncaseating granuloma. Oral and topical corticosteroids resulted in improvement of the condition. A 72-year-old female patient presented with cutaneous infiltration of the left upper eyelid for 1 month. Biopsy was consistent with sarcoidosis. Endobronchial biopsies showed interstitial fibrosis. Oral prednisone improved the condition. A 65-year-old female patient presented with edema of the right upper eyelid for 2 months. Full-thickness biopsy showed granuloma without necrosis. There was an improvement with oral steroid. CONCLUSION: Although eyelid involvement in sarcoidosis is uncommon, different forms of presentation, including destructive lesions, can be observed.

Epidemiological Profile and Clinical Stage at Presentation of Eyelid Malignancies in a Multi-Ethnic Country.

ABSTRACT: Eyelid malignancies are frequently seen in clinical practice. There is a lack of studies that have assessed the features of these lesions in mixed population countries. The epidemiologic profile, clinical stage at presentation, management, and outcomes of patients with eyelid malignancies were assessed, in order to better understand the features of these lesions in a multi-ethnic country. The medical records of patients who underwent eyelid tumor excision in a tertiary service in Brazil, from 2014 to 2019 were retrospectively reviewed. It was recorded for each patient: age, gender, time of onset, location, diagnosis, management, and follow-up. The medical records of 298 patients who presented with eyelid tumors were evaluated and 67 (22.4%) were malignant. The mean age of patients with malignancies was 52.93 years and 50% were male. Basal cell carcinoma was the most prevalent (61.2%), followed by squamous cell carcinoma (SCC) (29.9%) and sebaceous gland carcinoma (3%). The average time it took from appearance to surgical treatment was 3 years; the lower eyelid was the most affected for both basal cell carcinoma and SCC; 70% of SCCs were locally invasive at presentation and metastasis occurred in 15%. Basal cell carcinoma was the most common eyelid malignancy observed, however, its frequency was lower when compared to other western countries. The advanced stage at presentation may reflect the lack of education of the population to seek early care, and the lack of specialized tertiary centers in remote areas, resulting in delayed diagnosis.

Possible Influence of Upper Blepharoplasty on Intraocular Pressure.

PURPOSE: There is anecdotal evidence that upper blepharoplasty might lead to raised intraocular pressure (IOP). If this association is confirmed, then patients with glaucoma and glaucoma suspects could be at risk if they underwent this procedure with no appropriate follow up. Here, the authors aimed to determine whether there are significant changes in IOP after upper blepharoplasty. METHODS: This prospective study evaluated the IOP at baseline and 1, 2, and 6 weeks after an upper blepharoplasty in individuals with mild to moderate dermatochalasis. Upper blepharoplasty might change the pressure exerted by the upper eyelid into the cornea, and this could affect the corneal surface and the IOP; thus, the corneal topography was also recorded before and at 6 weeks. RESULTS: The IOP of 40 eyes was evaluated. The mean (±SD) preoperative IOP was 14.19 ± 2.12 mm Hg. A statistically significant increase in IOP was observed at 1 (15.15 ± 2.27 mm Hg, p = 0.009), 2 (15.57 ± 2.29 mm Hg, p < 0.0001), and 6 weeks (15.21 ± 2.60 mm Hg, p = 0.001) postoperatively. A statistically significant increase in steep K (preoperative: 44.66 ± 2.06, 6 weeks: 44.78 ± 2.28, p = 0.007) and corneal astigmatism was also observed (preoperative: 0.78 ± 0.43, 6 weeks: 0.89 ± 0.45, p = 0.006) at 6 weeks. CONCLUSIONS: Upper blepharoplasty resulted in a mild and statistically significant increase in intraocular pressure postoperatively. The authors' results suggest that upper blepharoplasty should be carefully evaluated in glaucoma and glaucoma suspect patients.

Evaluation of botulinum toxin effects in hemifacial spasm patients: correlation between clinical rating scales and high-speed video system measurements.

The purpose of this study was to compare the scores of two clinical rating scales and high-speed video system measurements obtained during spontaneous eyelid movements in hemifacial spasm (HFS) patients before and after treatment. Patients were evaluated before and 30 days after receiving treatment with onabotulinumtoxinA injections. Using a high-speed video system, the eyelid movements were recorded bilaterally for 3 min and the energy power generated by the upper eyelid during spontaneous eyelid movements was assessed before and after treatment. The scores of the Jankovic rating scale (JRS) and Hemifacial Spasm Grading System (HSGS) were also assessed before and after treatment. The authors studied 22 patients. Significant reduction in JRS and HSGS scores and in the energy generated by the upper eyelid was observed after treatment. A power spectrum of less than 23,000 was associated with JRS and HSGS scores less than 4 and 6.25, respectively and a power spectrum greater than or equal to 23,000 was associated with JRS and HSGS scores greater than or equal to 4 and 6.25, respectively (p < 0.0001 and p = 0.0025). Rating systems are easy to use, but they may exhibit limitations in sensitivity to assess differences between distinct disease patterns and between subtle differences in treatment responses. The high-speed video system permits a greater degree of accuracy, which allows for the assessment of differences in eyelid movement patterns and would permit better tailoring of treatment to patients. However, simpler devices employing this system would need to be developed, so that it could be used in clinical practice.

Orbicularis Oculi Morphological Alterations in Affected and Nonaffected Sides in Hemifacial Spasm.

BACKGROUND: Although the nonaffected side appears to be clinically normal in hemifacial spasm (HFS), it is not known whether this side can be considered normal regarding histopathological findings. The purpose of this study was to objectively evaluate and compare orbicularis oculi samples of patients with HFS (not previously treated with botulinum toxin) and control patients undergoing cosmetic upper eyelid blepharoplasty. METHODS: Orbicularis oculi samples from 22 eyelids were evaluated. There were 7 samples from the affected and 7 samples from the nonaffected sides of patients with HFS who had not been previously treated with botulinum toxin, and 8 samples from normal control patients. Muscle samples were prepared using hematoxylin and eosin staining, and a digital image analysis software was used for objective analyses. RESULTS: When compared with normal controls, endomysial and perimysial connective tissue areas were significantly increased (P = 0.015) on the affected side in HFS, suggesting that this disorder is associated with chronic alterations that lead to muscle degeneration. Cell density was significantly reduced on the affected (P = 0.028) and also on the nonaffected sides in HFS (P = 0.003) compared with normal controls. This was observed, although, clinically, there were no signs or symptoms of increased muscular contraction on the nonaffected sides in any of the patients with HFS studied. CONCLUSIONS: Significant morphological differences in the orbicularis oculi muscle in patients with HFS were observed on both the affected and nonaffected sides. Our findings suggest a potential role for muscle homeostasis disturbances on both sides for patients with HFS. Affected sides in patients with HFS did, however, demonstrate muscle degeneration that was not present on the nonaffected sides.

Analysis of blink activity and anomalous eyelid movements in patients with hemifacial spasm.

To assess spontaneous blinking and anomalous eyelid movements in patients with hemifacial spasm with an emphasis on interocular differences. Spontaneous eyelid movements were registered bilaterally for 3 min using a high-speed video camera in 28 patients with hemifacial spasm (HFS) who had not been treated with botulinum toxin injections for at least 5 months. The degree of blink conjugacy, maximum velocity, and amplitude of the closing phase of the blinks were determined for the affected and non-affected sides. Out of the 28 subjects, 23 (82%) presented with abnormal nonconjugate spasms that were similar to blinks, and in 17 (61%), high-frequency eyelid twitches were detected between blinks on the affected eye. The rate of nonconjugate blink-like spasms ranged from 0.3 to 24.7 movements/min. With regard for conjugate blinks, there was no significant interocular difference in amplitudes or eyelid closure velocities. The amplitude and velocity were significantly lower for nonconjugate movements than for spontaneous blinks. HFS is a unique condition in which complex patterns of eyelid movements, including both conjugate and nonconjugate movements, are present. Conjugate movements correspond to spontaneous blinking, and the same metrics were observed in affected and non-affected eyes. Nonconjugate movements correspond to anomalous nonconjugate blink-like spasms and high-frequency eyelid twitches in the affected eye, both of which were characterized by lower amplitudes and velocities than were observed in conjugate movements.