Initial treatment outcomes in chronic sixth nerve palsy.

INTRODUCTION: We conducted a prospective multi-center, nonrandomized, data-collection study of patients with chronic sixth cranial nerve palsy. We evaluated success rates with conservative nonsurgical management, botulinum toxin (botox) treatment, strabismus surgery, and a combination of botox treatment and surgery. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with sixth nerve palsy or paresis of more than 6 months duration over a 2-year period (between March 1998 and February 2000). The botox and surgical groups received intervention within 3 months of enrollment. Success at 6 months from enrollment was defined as absence of diplopia in primary position and no more than 10 prism diopters (pd) distance esotropia in primary position. Patients with no follow-up were excluded. RESULTS: Fifty-six eligible patients were enrolled by 33 investigators. Eighteen (32%) were traumatic in etiology, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were other. Twenty (35%) were managed conservatively without surgery, 10 (18%) with botox treatment, 19 (33%) with surgery, and 8 (14%) with a combination of botox treatment and surgery. Success at 6 months from enrollment was 15% in the conservatively managed cases, 10% with botox alone, 39% with surgery alone, and 25% with a combination of botox and surgery. CONCLUSIONS: This study demonstrates that management of chronic sixth nerve palsy and paresis remains challenging. Spontaneous recovery occurs but is uncommon. Botox treatment alone was rarely successful, and a single surgical procedure had a lower-than-expected success rate. Care should be taken in directly comparing success rates between treatment groups because of bias in patient selection.

Acute effects of the skeletal muscle-specific immunotoxin ricin-mAb 35 on extraocular muscles of rabbits.

PURPOSE: To determine the acute histologic and ultrastructural effects of a recently developed muscle-specific immunotoxin, ricin-mAb 35. METHODS: Graduated doses of ricin-mAb 35, composed of ricin conjugated to a monoclonal antibody against the nicotinic acetylcholine receptor of skeletal muscle, were injected into one superior rectus muscle in rabbits. After 3, 7, and 14 days, both superior rectus muscles were removed and prepared for electron microscopy and histologic examination, by using a number of immunohistochemical markers to identify inflammatory cell infiltration, muscle fiber loss, and muscle regeneration. RESULTS: Myotoxicity of the ricin-mAb 35 was focal and dose related. At the highest dose tested, there was substantial inflammatory cell infiltrate by 3 days, which largely disappeared by 7 days. Significant muscle loss was apparent by 7 days after ricin-mAb 35 treatment. Both the inflammatory reaction and muscle fiber loss were confined to the immediate injection site. Surrounding muscle appeared to be normal. At 14 days after treatment, early signs of muscle regeneration were evident within the tissue sections. No evidence of orbital or systemic toxicity was seen in any animal. CONCLUSIONS: Direct injection of ricin-mAb 35 into the extraocular muscles of rabbits results in a dose-related focal injury to the muscles, with a self-limited inflammatory component and significant muscle fiber loss. This novel immunotoxin may be useful in the treatment of strabismus if chronic studies show a sustained histologic and electrophysiologic effect.

Ocular morbidity in very low birth-weight infants with intraventricular hemorrhage.

PURPOSE: To document ocular outcomes and prevalence of ocular disease in very low birth-weight infants with intraventricular hemorrhage. METHODS: We retrospectively reviewed the records of all surviving very low birth-weight infants (1,500 g or less) admitted to the neonatal intensive care unit of our institution during 1992 and 1993. Of 252 survivors, 74 had complete ophthalmologic examinations at a mean adjusted age of 11 months. Of these 74 infants, 38 had intraventricular hemorrhage. Chi-square and multivariate analysis were used for statistical testing, in controlling for race, sex, and birth weight, and for other disease processes associated with prematurity. RESULTS: Of 38 infants with intraventricular hemorrhage, strabismus occurred in 14 (37%), esotropia in 12 (32%), and exotropia in two (5%). Of the 20 infants with grades III and IV intraventricular hemorrhage, 11 (55%) had esotropia; none had exotropia. Infants with grades III and IV intraventricular hemorrhage were at significantly greater risk for the development of esotropia than were infants with less severe or no hemorrhage (odds ratio, 5.0; P = .04). Mean adjusted age at diagnosis of strabismus was 8.5 months. Infants with periventricular leukomalacia (odds ratio, 6.3; P = .036) and neonatal seizures (odds ratio, 7.3; P = .019) were at significantly greater risk of developing optic atrophy. CONCLUSIONS: Very low birth-weight infants with more severe neurologic morbidity are at significant risk for development of esotropia and optic atrophy. Ophthalmologic screening of all very low birth-weight survivors may allow earlier diagnosis and intervention for these at-risk infants.

Extraocular muscle fiber morphometry following combined recession-resection procedures in rabbits.

PURPOSE: In earlier studies, we have reported extraocular muscle fiber atrophy following recession and fiber hypertrophy following resection of a horizontal rectus muscle. Changes seen in the operated muscle were mirrored in the antagonist and were thought to be a compensatory response to sustained changes in tension across the muscle pair caused by the surgery and by changes in the rotational position of the globe. The purpose of this study is to examine the effects of combined recession-resection on extraocular muscle fiber diameter. METHODS: In 16 anesthetized rabbits, a 6-mm recession of the medial rectus was combined with a 6-mm resection of the lateral rectus in the left orbit. The horizontal rectus muscles were removed from both orbits of four rabbits at 2-, 4-, 8-, and 16-week postoperative intervals. Cross-sections were cut from the midbelly of each muscle, and muscle fiber diameters were measured with a computerized morphometry unit. Mean fiber diameters from the operated orbit of animals at each postoperative interval were pooled and compared with means from the unoperated orbit using the paired-samples t test. RESULTS: No statistically significant change in fiber diameter was seen in either the global or orbital fiber layers at any postoperative interval examined. CONCLUSIONS: Because resection would be expected to increase and recession to decrease the resting tension across an agonist-antagonist pair, our results suggest that a combined recession-resection yields no significant net change in resting tension, and minimizes compensatory changes in extraocular muscle fiber diameter.

Tensile strength of insertional suture techniques in strabismus surgery.

BACKGROUND: The "lost" extraocular muscle is a serious adverse outcome of seemingly uncomplicated strabismus surgery. One potential cause of this complication is suture slippage in the operated muscle or tendon. The purpose of this study was to determine the relative tensile strengths of three suture techniques commonly used in strabismus surgery and to compare the incidence of suture slippage in the tendon or muscle among these techniques. METHODS: The horizontal rectus muscles of 18 adults pigs were assigned to undergo either recession or resection and were randomized to one of three suture techniques studies. Tension applied to the free ends of the suture was incrementally increased until failure occurred. The two techniques were compared in terms of the mean applied tensions at the time of failure and the incidence of slippage. RESULTS: No statistically significant difference in mean tension at failure between the three techniques used in recessed or resected muscles was found. Suture slippage in the tendon or muscle occurred in 25% of the trials and was almost evenly distributed among the techniques. Mean tension at slippage did not differ significantly between the techniques. No failure of any kind occurred at less than 100 g applied tension. CONCLUSION: Each suture technique appeared to adequately secure to tendon or muscle for recession and resection procedures. Changing techniques is unlikely to alter the incidence of lost muscles in strabismus surgery.

Effect of antagonist weakening on developed tension in cat extraocular muscle.

PURPOSE: In a previous study, the authors found that recession of an extraocular muscle resulted in atrophy of both the recessed muscle and its antagonist. To determine if atrophy, caused by weakening of an extraocular muscle, results in changes in developed tension in the antagonist, the authors studied force development of the cat lateral rectus muscle after adductor weakening. METHODS: Tenotomy of the left inferior, medial, and superior rectus muscles was performed in 18 cats. At 3, 6, and 12 weeks after surgery, the right (control) and left lateral rectus muscles were exposed through a lateral orbitotomy and were attached to isometric force transducers. Length-tension curves were obtained by direct muscle stimulation using bipolar contact electrodes at 0.1 Hz and 50% suprathreshold stimulus intensity. In addition, peak tetanic tension was measured at the optimal resting tension using a 5-second stimulus train at 200 Hz. Pooled data from the operative and control muscles at each postoperative interval were compared. RESULTS: Three weeks after adductor weakening, a 28% decrease in maximal single-twitch tension was seen in the left lateral rectus muscle when compared with controls. This difference disappeared at 6 weeks. No statistically significant changes in peak tetanic tension occurred at any time interval after surgery. CONCLUSIONS: Adductor weakening results in a transient decrease in single-twitch tension in the antagonist lateral rectus muscle in the cat.

Cataract in infants treated with argon laser photocoagulation for threshold retinopathy of prematurity.

PURPOSE: Previous studies of lens opacities occurring after argon laser photocoagulation for retinopathy of prematurity indicate that the lens in these laser-treated eyes may be at risk for cataract. We studied the occurrence of permanent, visually significant cataracts in four infants after laser therapy for retinopathy of prematurity. METHODS: The records of 51 consecutive patients (100 eyes) treated only with argon laser photocoagulation for threshold retinopathy of prematurity at our institution were reviewed. Patient characteristics and treatment variables were compared between infants who developed cataracts and those who did not. RESULTS: Complete opacification of the lens nucleus and cortex developed in six eyes of four patients between 19 and 99 days after laser therapy. An additional patient developed a transient, focal, anterior capsular, and subcapsular opacity in one eye that cleared by one month postoperatively. Eyes that developed permanent cataracts were noted to have a prominent anterior tunica vasculosa lentis at the time of treatment. After laser therapy, these eyes developed hyphema, shallowing of the anterior chamber, corneal edema, and progressive opacification of the lens. When compared with eyes that did not develop cataract, no statistically significant difference in number of burns, zone or clock hours of extraretinal proliferation, birth weight, gestational age, or age at treatment was found. CONCLUSIONS: Cataract is a potential vision-threatening complication of argon laser photocoagulation that must be considered before choosing a treatment modality for infants with threshold retinopathy of prematurity.

Lengthening extraocular muscle with autologous muscle transplants.

Increasing extraocular muscle length by regenerative growth has been proposed as a potentially useful means of treating patients with paralytic or multiple re-operation strabismus. This study evaluates the viability and pattern of regeneration of fresh, autologous extraocular muscle and temporalis muscle transplants in the canine orbit. Bilateral grafts of either inferior oblique or temporalis muscle were sewn between host lateral rectus muscles and the globe. Grafts were biopsied and examined by light and electron microscopy at survival times to 56 days. Functional responses to abducens nucleus stimulation were examined in one extraocular muscle and one temporalis muscle graft at 15 weeks post-operatively. During the first week, both graft types were characterized by loss of pre-terminal nerve from neuromuscular junctions, muscle fiber necrosis that spared the central fibers, and inflammatory cell infiltrate. Myoblasts migrated into and fused within the existing basal laminae of degenerating fibers. By 14 days, grafts were populated by immature myofibers. Neuromuscular junctions were seen by 56 days, coinciding with muscle fiber differentiation as seen by enzyme histochemistry. Only two grafts failed to show regeneration. At 15 weeks survival, both types of grafts contracted in response to abducens nucleus stimulation. Free skeletal muscle grafts to extraocular muscle survive and mature with clear evidence of contractility by 15 weeks. These data suggest that muscle graft procedures could be useful in the management of certain types of strabismus where greater muscle length is needed.

Retinal hemorrhage following lensectomy and anterior vitrectomy in children.

Lensectomy and anterior vitrectomy were performed on 13 eyes of 10 consecutive children, aged 10 years or less, with congenital or acquired nontraumatic cataracts or subluxed lenses. Operative eyes were examined prospectively to determine the incidence and natural course of hemorrhagic retinopathy following lens extraction. Flame-shaped retinal hemorrhages occurred in five eyes of four patients within 24 hours of surgery. In addition, a small vitreous hemorrhage was seen in one of these patients. All hemorrhages cleared within 3 weeks postoperatively. No statistically significant correlation was found between the occurrence of hemorrhage and patient age, race, sex, or duration of surgery. We conclude that retinal hemorrhage following lensectomy and anterior vitrectomy in children may occur more commonly than previously recognized.

Type-specific changes in fiber morphometry following denervation of canine extraocular muscle.

To investigate the changes that occur in extraocular muscle morphometry following denervation, 12 beagles were subjected to intracranial section of the left oculomotor nerve. The inferior and medial rectus muscles were removed from both orbits of four dogs killed at each 4-week postoperative interval. Fiber diameters and fiber-type ratios of denervated muscles were compared with those from paired muscles in the normal orbit. We found significant, persistent atrophy of the singly innervated fibers in both the global and orbital layers of denervated extraocular muscle. The multiinnervated fibers were predominantly spared from denervation atrophy. We also found a significant increase in the proportion of multiinnervated fibers in the orbital layer only. These results suggest a relative neurotrophic independence of multiinnervated fibers in extraocular muscle.

Extraocular muscle regeneration in freeze-treated extraocular muscle autografts.

New growth of extraocular muscle has been demonstrated in degenerating peripheral nerve autografts implanted between two extraocular muscles. This suggests that extraocular muscle may be lengthened for therapeutic purposes if a suitable matrix can be found to support this new growth. Investigators of peripheral nerve regeneration have found that the basal lamina of freeze-killed skeletal muscle remains intact and supports axonal regeneration. This study was designed to investigate the feasibility of inducing regenerative growth of extraocular muscle in freeze-treated extraocular muscle autografts. In six beagles the inferior oblique muscle was removed from both orbits, frozen in liquid nitrogen, and allowed to thaw at room temperature. The freeze-thaw cycle was repeated. The freeze-treated grafts were then sewn in an end-to-end fashion between the cut end of the lateral rectus and the globe. At both 4 and 8 weeks postoperatively, three dogs were killed, and the grafts were removed from both orbits. These were prepared for light and electron microscopic examination. This revealed robust growth of mature-appearing, innervated muscle fibers in the proximal graft that could be differentiated by adenosine triphosphatase histochemistry. Rare, immature fibers were seen in the distal graft. These results demonstrate that freeze-treated extraocular muscle autografts support regenerative growth of extraocular muscle.

Limb muscle regeneration in peripheral nerve autografts.

In a previous study we demonstrated regenerative growth of extraocular muscle within transplanted peripheral nerve autografts. The present study addresses the feasibility of inducing regeneration of limb muscle within autologous peripheral nerve implants in the gluteus medius of beagles. In six anesthetized animals, a 2-cm segment of the left infraorbital sensory nerve was removed from the nose and implanted between the cut ends of several muscle fascicles in the left gluteus medius. After 4 weeks, the nerve grafts were removed and examined by light and electron microscopy. Muscle fibers were seen surrounded by the epineurium of the implanted nerve along its entire length, growing in parallel with the long axis of the nerve. The regenerating fibers were closely associated with the basal lamina of degenerating myelinated and unmyelinated axons. This study suggests that limb muscle, like extraocular muscle, is capable of organized regenerative growth within peripheral nerve autografts.

A quantitative assessment of extraocular muscle growth in peripheral nerve autografts.

In previous studies, we have documented new growth of extraocular muscle fibers within axon-depleted motor neurons of denervated muscle. This study was designed to quantitate the regenerative growth of extraocular muscle within autologous peripheral sensory nerve transplants and to determine whether acutely denervated extraocular muscle affects this growth. Fifteen anesthetized beagles were subjected to an intracranial lesion of the left third cranial nerve. Segments of the infraorbital sensory nerve were removed from the nose and implanted between the lateral rectus and inferior oblique muscles in both orbits. At 2, 4 and 8 weeks postoperatively, five dogs were killed and the nerve grafts were removed. Muscle fibers were counted at four levels along each nerve segment. Fiber number increased significantly at each successive postoperative interval in implanted nerve segments on both the denervated and nondenervated side. At 8 weeks, fiber number was significantly greater on the denervated side. These results indicate that autologous peripheral sensory nerve is capable of supporting regenerative growth of extraocular muscle and that denervation has a significant positive influence on muscle fiber growth.

New growth of extraocular muscle in peripheral nerve autografts. Ultrastructural relationships.

We assessed the ultrastructural relationships of extraocular muscle (eom) fibers grown in a nonmuscle, extracellular matrix. Free sections of autogenous, extraorbital, peripheral nerve were implanted between the cut edge of a healthy eom and a denervated eom in four dogs. Light microscopy at 4 and 8 weeks demonstrated muscle fiber growth throughout the length of the implanted segments. Electron microscopy showed muscle fibers surrounded by collagen, frequently beside degenerating myelinated nerve fibers, but never growing within Schwann tubes or completely surrounded by the basal lamina of one nerve or Schwann cell. The muscle fibers were, however, bordered by abundant fibroblast processes (always separated by collagen), which often partially encircled the fiber. All muscle fiber growth occurred in parallel with the nerve axis. These findings indicate that peripheral nerve may contain factors conducive to the growth and orderly alignment of eom fibers. The identification of these factors may be helpful in the development of a synthetic matrix for eom graft growth.