Effect of hyperthyroidism on the orbicularis oculi muscle in rabbits

PURPOSE: To determine the effect of hyperthyroidism on both myofiber number and myosin heavy-chain isoform composition within the palpebral orbicularis oculi muscle in rabbits. METHODS: Four New Zealand White rabbits were made hyperthyroid by injection of 3,3,3'-triiodothyroinine intraperitoneally every other day for 1 month. Four rabbits were used as control animals. After 1 month the rabbits were euthanized, and the eyelids were excised and sectioned in a cryostat. The sections were immunostained to determine the presence of fast, slow, and neonatal myosin heavy-chain isoforms. To determine alterations in myofiber number, differential counts of myofiber number and the cross-sectional areas of the muscle fibers were performed with the use of computerized morphometry. RESULTS: The orbicularis oculi muscle in the palpebral portion of the eyelids from hyperthyroid rabbits had significantly fewer myofibers compared with control eyelids, predominantly as the result of a loss of myofibers in the preseptal region. The remaining fibers showed continued expression of fast myosin but upregulated coexpression of slow myosin isoform. CONCLUSIONS: Hyperthyroidism led to reduced orbicularis oculi muscle in the rabbit model and an alteration in the myosin heavy-chain isoform composition. This finding may help explain the clinical finding of eyelid retraction in patients with Graves orbitopathy.     

The electromyographic analysis of orbicularis oculi muscle in epiphora

Purpose:Functional epiphora is a clinical condition that presents with the complaint of watery eyes, but without anatomical stenosis in the lacrimal drainage system. Although the mechanism is not clear, there are various possibilities involving the movement of the orbicularis oculi muscle, especially its deeper segment (Horner’s muscle). We aimed to evaluate the function of the orbicularis oculi muscle in patients with patent, but dysfunctional lacrimal drainage system using a quantitative motor unit potential (MUP) analysis.Methods:Twenty-eight patients with functional epiphora (mean age = 59 years) and a control group of 28 volunteers were included in the study. Inclusion criteria were persistent and symptomatic epiphora or wiping >10 times per day and diagnosis confirmation by lacrimal irrigation test. Electromyography (EMG) was performed on the deeper segment of the orbicularis oculi muscle (medial and lateral parts). MUP parameters (duration time, amplitude, number of phases, number of turns, area, rise time, and thickness) were evaluated in both groups. Any increase in amplitude, prolongation time (>14 ms), number of turns, and satellite potential was taken as characteristic of the neurogenic type of epiphora, whereas shortened motor unit duration time, increased phase number, and low amplitude are the features of myopathic type.Results:Upon MUP analysis of the medial and lateral orbicularis oculi muscle, the increase in duration and thickness values in the medial part and the increase in duration, amplitude, area, and thickness values of the lateral part were found to be statistically significant in the patient group compared to the control group (P < 0.001). In the evaluation of the patients’ medial and lateral orbicularis oculi muscle, the increase in phase values and decrease in amplitude, area, and rise time values were found to be statistically significant (P = 0.024, P < 0.001, P < 0.001, and P = 0.010, respectively).Conclusion:These data show that functional epiphora is due to neurogenic damage of the orbicularis oculi muscle and should be investigated in more detail.     

The effects of tetanus toxin on the orbicularis oculi muscle

PURPOSE: Tetanus toxin can cause localized neuromuscular weakness, but it also can produce systemic tetany. The action of tetanus toxin on the orbicularis muscle has not been studied in animals immunized to prevent systemic tetany. Our objective was to determine whether tetanus toxin could be used to treat orbicularis oculi muscle spasms. METHODS: We analyzed the clinical, electrophysiologic, and histopathologic effects of tetanus toxin injected into the orbicularis oculi muscle of rabbits with passive immunity to tetanus toxin. In six rabbits, the orbicularis oculi function in both eyes was assessed clinically, and the baseline orbicularis oculi muscle action potential was measured physiologically with electromyography (EMG). The rabbits then were immunized against tetanus toxin with tetanus immunoglobulin for immediate and definitive immunity. Tetanus toxin was injected into the left orbicularis oculi muscles, leaving the right eyes as controls. Ten days later, the rabbits were again assessed by clinical examination and with EMGs on both the injected side and the noninjected side. The animals were killed at 14 days, and the orbicularis muscle was removed from both sides. The injected and control tissues were examined microscopically for signs of neuromuscular denervation. RESULTS: All six rabbits showed weakness in eye closure on the side injected with tetanus toxin. In addition, four rabbits developed complete ear ptosis on the tetanus toxin injected side because of spread of the toxin to adjacent ear muscles. EMGs showed both a denervation of the orbicularis oculi muscle and a poor blink potential on the side injected with tetanus toxin. Histopathologic studies of the orbicularis oculi muscle injected with tetanus toxin showed angulation of both slow and fast types of muscle fibers compatible with neuromuscular denervation. CONCLUSIONS: Tetanus toxin can cause localized orbicularis oculi weakness, as documented clinically, physiologically, and microscopically, without producing systemic tetany in immunized rabbits. Tetanus toxin may have a potential application in the treatment of blepharospasm and hemifacial spasm.     

睑袋成形术后眼轮匝肌功能状态的临床研究

目的探讨睑袋成形术后眼轮匝肌的功能状态及其影响因素。方法用肌皮瓣法矫正下睑袋32例（64眼）,分别在术前和术后5d、14d、1个月、3个月和6个月,以结膜囊染料消失法进行泪囊排泄功能测试。结果术后5d、14d和1个月结膜囊染料消失时间较术前明显延长（P〈0．001）,3个月和6个月检测结果与术前相比差异无统计学意义（P〉0．05）。结论肌皮瓣法睑袋成形术,术后早期眼轮匝肌泵作用明显减弱;但术中精细操作,减少对组织的损伤,有利于术后眼轮匝肌泵功能的恢复。     

眼轮匝肌切除联合眼轮匝肌缩短下睑缩肌复位术治疗老年性下睑内翻

目的：探究眼轮匝肌切除联合眼轮匝肌缩短下睑缩肌复位术治疗老年性下睑内翻患者疗效。

方法：回顾性分析。选取2019-06/2021-06我院收治老年性下睑内翻患者97例175眼,依据治疗方式分两组：对照组47例82眼接受眼轮匝肌切除术进行治疗,联合组50例93眼接受眼轮匝肌切除联合眼轮匝肌缩短下睑缩肌复位术进行治疗。比较两组患者近期疗效、围手术相关指标、手术前后症状与体征评分、手术前后睑裂宽度、睫毛朝向、泪阜显露率、并发症、患者满意度。

结果：术后3mo联合组患者总有效率显著高于对照组(95% vs 80%,P=0.004); 联合组患者手术出血量、手术时间以及住院时间均明显高于对照组(P<0.001); 联合组术后流泪、异物感、畏光以及刺激感症状体征评分均低于对照组(均P<0.001); 联合组患者手术后睑裂宽度、睫毛朝向、泪阜显露率均高于对照组(均P<0.001); 联合组患者术后并发症发生率低于对照组(8% vs 18%,P=0.032); 联合组患者术后舒适度、倒睫矫正、瘢痕外观、双眼对称以及外形美观患者满意度评分均高于对照组(均P<0.001)。

结论：应用眼轮匝肌切除联合眼轮匝肌缩短下睑缩肌复位术治疗老年性下睑内翻患者安全有效,可以满足患者美容要求。     

No histological evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon

Background: To analyse the microscopic anatomy of the orbicularis oculi muscle in patients with congenital epiblepharon and to determine whether hypertrophy of the orbicularis oculi muscle, which is considered as a possible cause of this eyelid malposition, exists. Methods: Sixty‐seven eyelids with congenital epiblepharon of 41 Japanese patients, as well as 30 control eyelids of 24 Japanese patients with other eyelid pathologies (upper eyelid: fourteen blepharoptosis, one trichiasis and two retractions; lower eyelid: five involutional entropions, one trichiasis and seven retractions) were analysed. These controls contained no orbicularis pathology such as cicatrization or orbitopathy. The muscle specimens were obtained from the central part of the pretarsal orbicularis oculi muscle during surgery. The specimens were stained with haematoxylin & eosin. Only specimens with cross‐sectional areas that included large muscle fibres were selected. In each section, 10 muscle fibres were measured across their smallest diameter, thereby avoiding inaccurate measurements of muscle kinking occurring during the processing or by any obliquity of the plane of section. Measurements of the muscle fibre diameter were made with a digital measure. Results: There were no significant differences in the average diameter of the muscle fibres between the patients with congenital epiblepharon and the control group. Conclusions: There was no evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon.     

Clinical research: Ragged-red fibres in the orbicularis oculi muscle and their significance

Neuropathologic examination of the orbicularis oculi muscle (OOM) obtained from patients undergoing blepharoplasty for ectropion (n=10), entropion (n=7) and biopsies taken from patients with a clinical diagnosis of chronic progressive external ophthalmoplegia (n=3) revealed ragged-red fibres (RRF) as demonstrated by increased sub-sarcolemmal staining with haematoxylin & eosin, Gomori's trichrome and reduced nicotinamide adenine dinucleotide (NADH) in all except one specimen (95%). A control group consisting of ten patients with normal eyelids underwent OOM biopsy during the course of an enucleation or cosmetic facial surgery. Similar findings were seen in 90% of these specimens, RRF'S were quantified in all specimens which were more abundant in the group with eyelid abnormalities (mean 7.05%). The mean number of RRF'S in the control group was 3.40%.     

Efficacy of tightening of orbicularis oculi muscle in patients with functional nasolacrimal duct obstruction

Purpose: To evaluate the efficacy of tightening of lateral portion of orbicularis oculi muscle in patients with functional nasolacrimal duct obstruction (FNLDO).Methods: This is an interventional cross-section study for evaluation of effect of orbicularis oculi tightening procedure in patients with FNLDO. Patients with unexplained epiphora, open lacrimal system in syringing and evidences of lacrimal pump weakness in lacrimal scintigraphy underwent surgery. In this procedure, a stripe of preseptal and pretarsal orbicularis muscle was dissected, slightly resected and secured to the periosteum of lateral orbital rim. Each subject completed a questionnaire about the intensity of epiphora before surgery and 1, 3 and 6 months after surgery. Furthermore, fluorescein dye disappearance test (FDDT) was performed before surgery and repeated in the follow-up visits. At last visit, the pre- and post-operative data were analyzed and compared.Results: Fifteen eyes of 12 patients (5 males and 7 females) with the mean age of 56.7 years included in the study. Severity of epiphora and tearing effect on daily life were significantly improved following the operation. FDDT result was improved significantly after 1 month follow-up in all eyes (15 eyes), at 3 months follow-up in 80% of eyes (12 eyes) and at the end of the 6th month in 66.7% of eyes (10 eyes). Subjective and objective success rates were 87% and 80%, respectively. No significant complications or side-effects were observed.Conclusion: Tightening of lateral portion of preseptal and pretarsal orbicularis muscle seems an effective, safe, and easy procedure to decrease epiphora in patients with FNLDO.     

A new approach to the correction of involutional entropion by pretarsal orbicularis oculi muscle fixation

A new surgical technique to repair involutional entropion involves fixation of a strip of dissected and displaced pretarsal orbicularis oculi muscle. In 112 patients followed up for an average of 14 months, this technique was successful. The procedure is easy to perform and complications were minimal.     

Doxorubicin chemomyectomy: injection of monkey orbicularis oculi results in selective muscle injury

Doxorubicin was injected into the preseptal portion of the orbicularis oculi of one lower eyelid in each of two cynomolgus monkeys at a dose of 2 mg. One monkey was observed for 4 days and the other for 68 days after doxorubicin injection. Although some skin ulceration was seen, it was completely healed by 3 weeks postinjection. The preseptal portion of the orbicularis oculi in both monkeys showed extensive signs of injury. At 4 days after doxorubicin injection many necrotic muscle fibers could be seen. Very few muscle fibers in the preseptal portion of the muscle remained by 68 days after injection. The pretarsal portion of the injected orbicularis oculi was relatively normal, with little evidence of injury. It appears that doxorubicin injection into the lower lid resulted in a gradient of muscle injury, with increasing severity at decreasing distances from the injection site. The extent of muscle injured is related to the dose and injection site and indicates the ability to selectively control the injury within a muscle. The ramifications of this effect on the use of doxorubicin for permanent treatment of blepharospasm and other related diseases are discussed in this first report of the injection of this drug into the eyelids of nonhuman primates.     

Innervation zone of orbicularis oculi muscle and implications for botulinum A toxin therapy.

Motor points (areas of maximal sensitivity to electrical stimulation) were found in constant locations over orbicularis oculi when measured in both eyes of six normal subjects. All subjects had a motor point at the lateral terminus of the upper lid crease and the medial extent of the lower lid crease. A study of the innervation zone [distribution of neuromuscular junctions (NMJ)] was conducted on strips of pretarsal and preseptal portions of the upper eyelid orbicularis that had been removed routinely during involutional ptosis surgery. There was no significant difference in NMJ concentration between the medial and lateral sections, as determined by cholinesterase staining. Therefore, we concluded that the innervation zone is diffuse for the orbicularis muscle within this portion of the upper eyelid. Single-point injections of botulinum toxin were then compared to the conventional multiple injection sites on separate eyes in 10 patients with benign essential blepharospasm. Eight of the 10 patients reported greater relief on the side given injections into multiple points; the other two patients experienced no difference between the two methods. Both histologic data and clinical observation of response to botulinum toxin injection suggest the innervation zone for the upper orbicularis is diffuse. Thus, we conclude that multiple injections are superior to the injection of a single motor point.     

Doxil-induced chemomyectomy: effectiveness for permanent removal of orbicularis oculi muscle in monkey eyelid

PURPOSE. To test the safety and effectiveness of Doxil chemomyectomy in monkey eyelids using treatment schedules and doses similar to those proposed for the human blepharospasm patients in Phase I and II trials. METHODS. Bupivacaine/hyaluronidase and Doxil were injected sequentially into the eyelids of five Cynomolgus monkeys. Eyelids received 1, 2, or 3 sets of injections. The monkeys were euthanatized at a minimum of 2 months and a maximum of 12 months after the final treatment. The eyelids were prepared for histologic examination, and muscle fiber loss was quantified. RESULTS. All Doxil injections resulted in a significant loss of myofibers. No bruising, ulceration, or other skin injuries occurred, even after a third injection regimen within a single treated eyelid. Two-day preinjury with a bupivacaine/hyaluronidase mixture had a significant adjuvant effect. CONCLUSIONS. Doxil chemomyectomy is an effective protocol to permanently remove muscle from injected eyelids in nonhuman primates. Serial injections over the course of several months using the preinjury protocol combined with Doxil treatment significantly increased Doxil's myotoxic effects. Additionally, the injection of the liposome-encapsulated form of doxorubicin did not result in skin injury or ulceration. Species differences demonstrated the importance of testing these drugs in nonhuman primates. Thus, repeated doses of Doxil may prove to be as clinically effective as free doxorubicin injections in reducing muscle spasms in blepharospasm patients but with increased safety to the skin and tissue around the injection site.     

Myotoxic effects of the skeletal muscle-specific immunotoxin, ricin-mAb35, on orbicularis oculi muscle after eyelid injections in rabbits

PURPOSE: The authors recently demonstrated that a single injection of the immunotoxin ricin-mAb35 has potent and long-lasting myotoxic effects in extraocular muscles. The myotoxicity of injected ricin-mAb35 was tested in the eyelids of rabbits to determine its potential for use in the treatment of benign essential blepharospasm and other dystonias. METHODS: The immunotoxin ricin-mAb35 was injected in one eyelid of adult rabbits. After 1 week, 1 month, or 6 months, the rabbits were euthanized, and the eyelids were prepared for histologic examination of inflammatory cell infiltrate with immunohistochemical localization of cd11b and myosin heavy chain isoform expression. Muscle loss was quantified by analysis of muscle fiber cross-sectional area and total myofiber number. RESULTS: Within the first week after a single injection of ricin-mAb35, some edema developed, which resolved by the second week. Otherwise, the eyelids were normal in appearance. A short-lived inflammatory response was seen at 1 week, but this resolved 1 month after treatment. One week after injection, there was a significant decrease in the total number of orbicularis oculi myofibers in the ricin-mAb35-treated eyelids. This myofiber loss remained significant 1 month later and was maintained 6 months after the initial injection. CONCLUSIONS: Direct injection of the immunotoxin ricin-mAb35 resulted in significant, acute muscle loss in the orbicularis oculi of rabbits that was maintained for up to 6 months. Physiologic studies are needed to demonstrate concomitant loss of muscle strength, but these results suggest that ricin-mAb35 injection holds promise as a muscle-weakening agent in the eyelid.     

Pretarsal and marginal orbicularis oculi muscle fiber changes in trachomatous cicatricial entropion: histopathological evaluation.

PURPOSE: To evaluate the histopathological changes of pretarsal and orbicularis muscle fibers in trachomatous cicatricial entropion. METHODS: Orbicularis muscle tissue specimens were histopathologically evaluated in 17 eyes of 11 cases in which anterior lamellar reposition and/or wedge-shaped tarsal resection or Wies procedure were performed. RESULTS: Degeneration of orbicularis muscle fibers, atrophy, connective tissue increase between muscle fibers and edema were observed in 13 tissue specimens. Muscle fiber changes were more commonly observed in cases with severe entropion, in which Wies procedure was performed. CONCLUSIONS: These histopathological changes, which may develop secondary to other structural changes that can cause entropion in the eyelid and weaken the orbicularis muscle, may be a co-factor influencing the severity of entropion more than causing entropion alone.     

松弛皮肤切除加眼轮匝肌缩短术治疗老年性下睑内翻的临床疗效

目的：：观察松弛皮肤切除联合眼轮匝肌缩短术与单纯眼轮匝肌缩短术治疗老年性下睑内翻的临床疗效,为临床治疗提供参考。方法：研究我科就诊的临床诊断为下睑内翻的老年患者82例126眼,采用随机数字表法将其随机分为松弛皮肤切除加眼轮匝肌缩短术治疗组与单纯眼轮匝肌缩短术治疗组,对两组患者一般资料进行比较,并对其短期疗效与长期疗效进行比较。结果：观察组与对照组患者在年龄、病程、性别及首次手术患者的比例方面的差异无统计学意义(P>0.05),观察组的短期有效率为95.2％,而对照组的短期有效率为77.8％,两组短期有效率之间的差异有统计学意义(χ2=4.100,P=0.043);观察组的长期治愈率为82.5％(34例52眼),未愈或复发率为17.5％(7例11眼),对照组的治愈率为60.3％(25例38眼),未愈或复发率为39.7％(16例25眼),两组患者的长期治愈率之间的差异具有统计学意义(P<0.05)。结论：松弛皮肤切除联合眼轮匝肌缩短术治疗老年性下睑内翻的临床疗效较单纯眼轮匝肌缩短术好,推荐在临床上应用。