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1.  Incidence of cataract development by 6 months’ corrected age in the Early Treatment for Retinopathy of Prematurity study 
Purpose
To report the incidence of cataract development by 6 months’ corrected age in preterm children who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) study.
Methods
Infants who developed prethreshold ROP in one or both eyes and were determined by the RM-ROP2 model to have a high risk of poor structural outcome without treatment were randomized to receive early treatment (ET), defined as laser photocoagulation at high-risk prethreshold ROP, or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Data on eyes developing a cataract by 6 months’ corrected age was analyzed.
Results
Of 401 randomized infants, 366 survived patients were followed, and 8 eyes of 7 patients (1.9%) developed cataracts by 6 months’ corrected age. Among these patients, mean birth weight was 754 g, and mean gestational age was 25.7 weeks. Mean gestational age at treatment was 36.3 weeks for ET patients and 39.5 weeks for CM patients. Three ET eyes and 5 CM eyes developed a cataract. Of the CM eyes, 3 with and 2 without laser treatment developed a cataract. All 6 treated eyes had plus disease when treated. Three eyes had ROP in zone 1, whereas the other 3 had ROP in zone 2. All eyes were treated using a diode laser.
Conclusions
By 6 months’ corrected age, a small number of both ET and CM eyes developed cataracts following diode laser treatment for retinopathy of prematurity. Absence of obvious intraoperative complications does not preclude subsequent cataract development, which can occur without laser treatment.
doi:10.1016/j.jaapos.2012.10.011
PMCID: PMC3577978  PMID: 23352719
2.  Effects of sequential injections of hepatocyte growth factor and insulin-like growth factor-I on adult rabbit extraocular muscle 
Purpose
To determine whether hepatocyte growth factor (HGF) and insulin-like growth factor-I (IGF-I) have synergistic effects in promoting extraocular muscle fiber growth and force generation.
Methods
A superior rectus muscle of adult rabbits was treated with either a single injection of HGF or sequential injections of HGF followed 1 week later by IGF-I. One week after HGF alone and 1 week after the IGF-I injection, the superior rectus muscles from treated and control orbits were examined for alterations in force generation as well as changes in myofiber size.
Results
Injection of HGF alone did not result in changes to muscle force, specific tension, or myofiber cross-sectional area; however, it did result in a significant increase in numbers of satellite cells. Sequential injection of HGF and IGF-I resulted in significantly increased force, specific tension, and myofiber cross-sectional areas as well as increased numbers of satellite cells.
Conclusions
Preinjection with HGF augments the treatment effect of IGF-I. This is likely a result of HGF-induced activation of satellite cells. This synergistic effect should allow a reduction in IGF-I dosing required to produce a given increase in extraocular muscle force generation.
doi:10.1016/j.jaapos.2012.05.002
PMCID: PMC3431511  PMID: 22929450
3.  Effects of the Sustained Release of IGF-1 on Extraocular Muscle of the Infant Non-Human Primate: Adaptations at the Effector Organ Level 
Sustained IGF-I treatment of both MR muscles in infant monkeys results in bilateral increases in myofiber size and nerve density in treated MR and in the antagonist but untreated LR. As alignment is maintained, central adaptive mechanisms must control compensatory changes in the yoked muscles.
Purpose.
The authors have demonstrated that prolonged exposure of adult rabbit extraocular muscle (EOM) to insulin-like growth factor-1 (IGF-1) results in significantly increased cross-sectional area and muscle force generation lasting over 3 months. Here the authors assess the effects on EOM of sustained IGF-1 treatment on normal binocular infant Macaca mulatta.
Methods.
Sustained-release IGF-1 pellets were implanted bilaterally in each medial rectus (MR) muscle of two normal infant non-human primates. Eye position was examined using corneal light reflex testing. After 3 months, morphometric analyses of myofiber cross-sectional area and innervation density in treated MR muscles were compared with an age-matched control and with antagonist lateral rectus (LR) muscles.
Results.
After 3 months, the slow-release pellets remained at the implantation site in all four MR muscles treated. The treated MR showed pronounced increases in cross-sectional area and nerve density, mirrored in the untreated antagonist LR.
Conclusions.
Three months of bilateral sustained IGF-1 release in infant non-human primate MR resulted in increased muscle size and innervation density, mirrored in the untreated antagonist LR. It appears that bilateral MR treatment resulted in slow adaptation of both treated MR and contralateral LR muscles over time such that functional homeostasis and near-normal alignment were maintained. Further work is needed to determine what signaling mechanisms maintain proportional innervation when EOMs are forced to adapt to an externally applied perturbation.
doi:10.1167/iovs.11-8356
PMCID: PMC3292383  PMID: 22125277
4.  Expansion of the CHN1 Strabismus Phenotype 
Hyperactivating mutations in the CHN1 gene can cause supraduction deficits in the absence of Duane retraction syndrome.
Purpose.
Hyperactivating CHN1 mutations have been described in individuals with Duane retraction syndrome with or without vertical gaze abnormalities. This was a study of five family members with distinctive ocular dysmotility patterns that co-segregated with a novel hyperactivating CHN1 mutation.
Methods.
Participating members of a family segregating pleomorphic incomitant strabismus underwent ophthalmic examinations, and several underwent high-resolution magnetic resonance imaging (MRI) of the orbits and brain stem. Participant DNA was extracted and amplified for haplotype analysis encompassing the CHN1 region on chromosome 2q31.1, and mutation analysis of the CHN1 gene, which encodes the Rac-GAP signaling protein α2-chimaerin. In vitro functional studies of the co-inherited mutation were performed, including a Rac-GTP activation assay, quantification of α2-chimaerin translocation, and co-immunoprecipitation.
Results.
All five clinically affected family members exhibited monocular or binocular supraduction deficits, three in the absence of Duane retraction syndrome. MRI in four affected individuals demonstrated small or absent abducens nerves in all four, small oculomotor nerve in one, and small optic nerves in three. Superior oblique muscle volume was also decreased in three of the individuals, supporting trochlear nerve hypoplasia. Strabismus segregated with the CHN1 locus and affected individuals harbored a c.443A>T CHN1 mutation (p.Y148F). In vitro, this novel mutation behaved similarly to previously reported CHN1 mutations underlying familial Duane syndrome, hyperactivating α2-chimaerin by enhancing its dimerization and membrane association and lowering total intracellular Rac-GTP.
Conclusions.
Analysis of the current pedigree expands the phenotypic spectrum of hyperactivating CHN1 mutations to include vertical strabismus and supraduction deficits in the absence of Duane retraction syndrome.
doi:10.1167/iovs.11-7950
PMCID: PMC3175992  PMID: 21715346
5.  Classifying Stability of Misalignment in Children with Esotropia using Simulations 
Archives of ophthalmology  2010;128(12):1555-1560.
Objective
To determine sensitivity and specificity of several classification rules for stability and instability of angle in childhood esotropia.
Methods
We conducted 10,000 Monte Carlo simulations of subjects with no actual change in angle of esotropia over follow-up, where “observed” changes in ocular alignment were sampled from a distribution of measurement errors for the prism and alternate cover test. Additional simulations were conducted for a range of true changes (1, 2.5, 4.2, 5.0, 7.5, and 10 prism diopters (PD) per visit) with up to 10 follow-up visits. We then estimated sensitivities and specificities for specific rules for retrospectively classifying stability (all measurements within 0, 5, 10 or 15 PD) and instability (at least 2 measurements differing by 10 PD or more, etc.) over a fixed number of visits. Results were extended to classifying ocular alignment stability and instability prospectively based on a varying number of measurements.
Results
For a series of 4 measurements, the rules that optimized sensitivity and specificity were ‘all measurements within 5 PD’ as the rule for stability, and ‘at least 2 measurements differing by 15 PD or more’ as the rule for instability. For a series of 3 measurements, all 3 measurements needed to be identical to confirm stability.
Conclusions
We derived definitions of stability and instability in childhood esotropia using estimates of actual measurement error that may be useful for clinical practice and for future clinical studies of esotropia.
doi:10.1001/archophthalmol.2010.293
PMCID: PMC3142011  PMID: 21149779
6.  Sustained Release of Bone Morphogenetic Protein-4 in Adult Rabbit Extraocular Muscle Results in Decreased Force and Muscle Size: Potential for Strabismus Treatment 
Adult rabbit extraocular muscles respond to sustained release of bone morphogenetic protein-4 by significant decrease in muscle force output and muscle cross-sectional area. This suggests that it may be possible to use a biological, nonsurgical approach to reducing extraocular muscle strength for the treatment of strabismus.
Purpose.
To assess the effect of a sustained-release preparation of bone morphogenetic protein-4 (BMP-4) on EOM force generation and muscle size.
Methods.
Sustained-release pellets, releasing 500 nanograms/day of BMP-4 for a maximum of 3 months, were implanted beneath the superior rectus muscle (SR) belly in anesthetized adult rabbits. The contralateral side received a placebo pellet as a control. After 1, 3, and 6 months, SRs were removed, and force generation at twitch and tetanic frequencies as well as fatigue resistance were determined in vitro. Myofiber size, myosin heavy chain isoform expression, and satellite cell density were assessed histologically.
Results.
SR force generation was significantly decreased by BMP-4 compared with the contralateral controls. Force generation was decreased by 25–30% by 1 month, 31–50% by 3 months, and at 6 months, after 3 BMP-4–free months, force was still decreased by 20–31%. No change in fatigue was seen. Significant decreases in muscle size were seen, greatest at 3 months. At all time points Pax7- and MyoD-positive satellite cell densities were significantly decreased.
Conclusions.
The decreased force generation and muscle size caused by sustained release of BMP-4 suggests that myogenic signaling factors may provide a more biological method of decreasing muscle strength in vivo than exogenously administered toxins. Treating antagonist-agonist pairs of EOM with titratable, naturally occurring myogenic signaling and growth factors may provide safe, efficacious, nonsurgical treatment options for patients with strabismus.
doi:10.1167/iovs.10-6878
PMCID: PMC3175951  PMID: 21357389
7.  Effects of Recession versus Tenotomy Surgery without Recession in Adult Rabbit Extraocular Muscle 
The EOMs are particularly adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression and also with changes in antagonist and contralateral muscles. These results suggest the possibility that these processes are manipulated immediately after surgery to improve surgical success rates.
Purpose.
Surgical recession of an extraocular muscle (EOM) posterior to its original insertion is a common form of strabismus surgery, weakening the rotational force exerted by the muscle on the globe and improving eye alignment. The purpose of this study was to assess myosin heavy chain (MyHC) isoform expression and satellite cell activity as defined by Pax7 expression in recessed EOMs of adult rabbits compared with that in muscles tenotomized but not recessed and with that in normal control muscles.
Methods.
The scleral insertion of the superior rectus muscle was detached and sutured either 7 mm posterior to its original insertion site (recession surgery) or at the same site (tenotomy). One day before euthanatization, the rabbits received bromodeoxyuridine (BrdU) injections. After 7 and 14 days, selected EOMs from both orbits were examined for changes in fast, slow, neonatal, and developmental MyHC isoform expression, Pax7 expression, and BrdU incorporation.
Results.
Recession and tenotomy surgery resulted in similar changes in the surgical EOMs. These included a decreased proportion of fast MyHC myofibers, an increased proportion of slow MyHC myofibers, and increased BrdU-positive satellite cells. Similar changes were seen in the non-operated contralateral superior rectus muscles. The ipsilateral inferior rectus showed reciprocal changes to the surgical superior rectus muscles.
Conclusions.
The EOMs are extremely adaptive to changes induced by recession and tenotomy surgery, responding with modulations in fiber remodeling and myosin expression. These adaptive responses could be manipulated to improve surgical success rates.
doi:10.1167/iovs.10-5523
PMCID: PMC3061502  PMID: 20538996
8.  Myogenic Growth Factors Can Decrease Extraocular Muscle Force Generation: A Potential Biological Approach to the Treatment of Strabismus 
PURPOSE
Future pharmacologic treatment of strabismus may be optimized if drugs that are less potentially toxic to patients can be developed. Prior studies have shown that direct injection of extraocular muscles (EOMs) with insulin growth factor or fibroblast growth factor results in significant increases in the generation of EOM force. The purpose of this study was to examine the morphometric and physiological effects of direct EOM injection with the growth factors BMP4, TGFβ1, Shh, and Wnt3A.
METHODS
One superior rectus muscle of normal adult rabbits was injected with BMP4, TGFβ1, Shh, or Wnt3A. The contralateral muscle was injected with an equal volume of saline to serve as a control. After 1 week, the animals were euthanatized, and both superior rectus muscles were removed and assayed physiologically. The muscles were stimulated at increasing frequencies to determine force generation. A separate group of treated and control superior rectus muscles were examined histologically for alterations in total muscle cross-sectional area and myosin heavy chain isoform (MyHC) composition.
RESULTS
One week after a single injection of BMP4, TGFβ1, Shh, or Wnt3A, all treated muscles showed significant decreases in generation of force compared with control muscles. BMP4, TGFβ1, Shh, and Wnt3A significantly decreased the mean myofiber cross-sectional area of fast MyHC-positive myofibers. BMP4 resulted in a conversion of fast-to-slow myofibers and a significant decrease in the percentage of developmental and neonatal MyHC-positive myofibers. Alterations in mean cross-sectional area and proportion of MyHCs were seen after injection with TGFβ1, Shh, and Wnt3A. TGFβ1 and BMP4 injections resulted in increased Pax7-positive satellite cells, whereas BMP4, TGFβ1, and Wnt3A resulted in a decrease in MyoD-positive satellite cells.
CONCLUSIONS
These results suggest that, rather than using toxins or immunotoxins, a more biological approach to decrease muscle strength is possible and demonstrate the potential utility of myogenic signaling factors for decreasing EOM strength. Ongoing drug-delivery studies will elucidate means of extending treatment effect to make such agents clinically useful.
doi:10.1167/iovs.07-0600
PMCID: PMC3039281  PMID: 18172096
9.  Increased Extraocular Muscle Strength with Direct Injection of Insulin-like Growth Factor-I 
Purpose
Previous work has demonstrated the effectiveness of insulin-like growth factor (IGF)-II in increasing force generation in extraocular muscle (EOM). Studies in the literature have suggested that IGF-I would be even more effective than IGF-II. This study was performed to assess the effects on muscle mass and force generation of IGF-I injection in adult rabbit superior rectus muscle.
Methods
Adult rabbits received a single injection of IGF-I at one of several doses into one superior rectus muscle. One week after treatment, the rabbits were euthanatized, and the superior rectus muscle from each orbit was removed. Force generation was measured using an in vitro apparatus, and injected muscles were compared with the contralateral control. A second group of animals were injected similarly, and the muscles were examined at 1 week for changes in cross-sectional area of individual myofibers.
Results
EOMs demonstrate significant numbers of cells expressing the IGF receptor. After the EOMs were injected with IGF-I, there were significant increases both in muscle force generation and cross-sectional area at all doses tested in this study. Doses of 10 and 25 μg IGF-I were most effective.
Conclusions
Direct muscular injection of IGF-I effectively increases EOM force generation without the potential biomechanical hazards of surgery such as permanently altered muscle length or insertional position on the globe.
doi:10.1167/iovs.05-1416
PMCID: PMC3039316  PMID: 16723457
10.  Increasing Muscle Strength as a Treatment for Strabismus: Sustained Release of Insulin-like Growth Factor-1 in Rabbit Extraocular Muscle 
PURPOSE
Currently, no drug treatment is available for strengthening underacting extraocular muscles (EOM) in strabismus. We showed previously that single injections of insulin-like growth factor (IGF-1) result in significant but short-term increases in muscle force generation. This study examined the effects of sustained release of IGF-1 on force generation in rabbit superior rectus muscles.
METHODS
In adult rabbits, slow-release pellets containing IGF-1 were implanted on the global side of one superior rectus muscle. After 1 week, or 1, 2, 3, or 6 months, treated and control muscles were examined for force generation using an in vitro physiology apparatus. All muscles were prepared for histology and mean myofiber cross-sectional areas were determined.
RESULTS
One and 3 months after pellet implantation, treated muscles generated significantly greater force than contralateral control muscles, whereas at 2 months, no significant difference was found. Force per cross-sectional area (mN/cm2) at 3 months also increased significantly in the treated muscles. Mean muscle cross-sectional area increased significantly after 1, 2, and 3 months of sustained exposure to IGF-1 compared with controls. After an additional 3 months without IGF-1 exposure, mean cross-sectional areas were significantly greater than controls but significantly reduced compared with areas at 1, 2, and 3 months.
CONCLUSIONS
IGF-1 appears to be highly effective in increasing muscle force generation. Because slow release of IGF-1 results in sustained increases in EOM force generation, it may be a potentially useful alternative to surgical resection procedures because it avoids many of the potential long-term biomechanical hazards of resection surgery.
doi:10.1016/j.jaapos.2006.06.011
PMCID: PMC3034355  PMID: 17070477
11.  The Relationship Between Preoperative Alignment Stability and Postoperative Motor Outcomes in Children with Esotropia 
Purpose
To examine the effect of preoperative alignment stability on postoperative motor outcomes in children who underwent surgery for esotropia.
Methods
167 subjects (68 with infantile esotropia and 99 with acquired esotropia) aged less than 6 years had surgery after completing 18 weeks of follow up as part of an observational study. Preoperative alignment was classified as stable, uncertain, or unstable, based on measurements taken at baseline and every 6 weeks for 18 weeks. If the absolute value of the difference between the largest and smallest of the four measurements was within 5 PD inclusive, preoperative alignment was classified as stable; if the difference was 15 PD or greater, alignment was classified as unstable; and if neither of these criteria were met, alignment was classified as uncertain. Distance alignment measured by prism and alternate cover test was compared among stability classification groups at 6 weeks and 6 months after surgery.
Results
Among subjects with infantile esotropia, median 6-week postoperative deviation was 2 prism diopters (PD), 6 PD, and 2 PD for subjects with stable, uncertain, and unstable preoperative alignment, respectively (P = 0.73 for stable vs. unstable). Median 6-month postoperative deviation was 1 PD, 9 PD, and 1 PD for stable, uncertain, and unstable, respectively (P = 1.00 for stable vs. unstable). Among subjects with acquired esotropia, median 6-week postoperative deviation was 6 PD, 4 PD, 4 PD for subjects with stable, uncertain, and unstable preoperative alignment, respectively (P = 0.69 for stable vs. unstable). Median 6-month postoperative deviation was 8 PD, 4 PD, 6 PD, for stable, uncertain, and unstable, respectively (P = 0.22 for stable vs. unstable).
Conclusions
Postoperative alignment at 6 weeks and 6 months appears similar in children with stable versus unstable preoperative esotropia. Nevertheless, our finding should be interpreted with caution due to small sample size.
doi:10.1016/j.jaapos.2009.04.013
PMCID: PMC2728701  PMID: 19683184
12.  Botulinum toxin pretreatment augments the weakening effect of injection with ricin-mAb35 in rabbit extraocular muscle 
Purpose
To examine force generation and duration of effect of botulinum toxin pretreatment, followed by injection of ricin-mAb35 in extraocular muscle (EOM).
Methods
In normal adult rabbits, one superior rectus muscle was injected with either 5 units botulinum toxin or 1/50 maximally tolerated dose for rats (rMTD) of ricin-mAb35. Additional rabbits were first injected with 5 units botulinum toxin, and after one, two, or four weeks the same muscle was injected with either 1/10 or 1/50 rMTD ricin-mAb35. In each treatment group, the contralateral muscle was injected with an equal volume of saline. After 12 weeks (1/50 rMTD) or 6 months (1/10 rMTD), the rabbits were euthanized. Both superior rectus muscles were removed and assayed physiologically, using an in vitro apparatus.
Results
Twelve weeks after treatment with either botulinum toxin or immunotoxin alone, only ricin-mAb35 treated muscles were weaker than control muscles at tetanic stimulation frequencies. Pretreatment with botulinum toxin prior to injection with immunotoxin, especially at shorter intervals between injections, resulted in significant decreases in twitch and tetanic force generation compared to controls and muscles treated with ricin-mAb35 only or botulinum toxin only. At 6 months, force generation was decreased from control only in muscles treated with the higher dose of ricin-mAb35. Botulinum toxin pretreatment did not augment this effect at 6 months.
Conclusions
Upregulation of postsynaptic nicotinic acetylcholine receptors caused by botulinum toxin pretreatment amplifies the reduction of force generation in EOM following secondary injection of the immunotoxin ricin-mAb35 within three months of treatment.
doi:10.1016/j.jaapos.2007.11.001
PMCID: PMC2394737  PMID: 18258470
immunotoxin; extraocular muscles; strabismus; botulinum toxin; muscle physiology
13.  Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane’s retraction syndrome 
Science (New York, N.Y.)  2008;321(5890):839-843.
The RacGAP molecule α2-chimaerin is implicated in neuronal signaling pathways required for precise guidance of developing corticospinal axons. We now demonstrate that a variant of Duane’s retraction syndrome, a congenital eye movement disorder in which affected individuals show aberrant development of axon projections to the extraocular muscles, can result from gain-of-function heterozygous missense mutations in CHN1 that increase α2-chimaerin RacGAP activity in vitro. A subset of mutations enhances α2-chimaerin membrane translocation and/or α2-chimaerin’s previously unrecognized ability to form a complex with itself. In ovo expression of mutant CHN1 alters the development of ocular motor axons. These data demonstrate that human CHN1 mutations can hyperactivate α2-chimaerin and result in aberrant cranial motor neuron development.
doi:10.1126/science.1156121
PMCID: PMC2593867  PMID: 18653847
14.  Botulinum Toxin Treatment of Extraocular Muscles in Rabbits Results in Increased Myofiber Remodeling 
Purpose
Botulinum toxin A (Botox) is commonly used for strabismus treatment. Although other muscles atrophy after intramuscular injection with Botox, extraocular muscles (EOMs) do not. A continuous process of myonuclear addition in normal uninjured adult myofibers in rabbit EOMs was studied. In this study, the effect of Botox-induced muscle paralysis on myofiber remodeling in adult EOMs was examined.
Methods
The superior rectus muscles of adult rabbits were each injected with 5 units of Botox. The contralateral muscle received injections of saline only. Bromodeoxyuridine (BrdU) was administered for various periods after Botox treatment, followed by various BrdU-free periods. Myonuclear addition, the number of BrdU-positive satellite cells, and the number of MyoD-positive satellite cells were quantified, as were alterations in expression of immature myosins.
Results
Intramuscular injection of Botox resulted in a significant increase in both the number of BrdU-positive myonuclei and satellite cells. MyoD expression in both satellite cells and myonuclei was significantly increased after Botox injection in EOMs. In Botox-treated EOMs, an increased number of myofibers positive for the neonatal myosin heavy chain (MyHC) isoform was detected in the orbital layer.
Conclusions
Botox-induced EOM paralysis resulted in a significant short-term increase in satellite cell activation and myo-nuclear addition in single myofibers in adult rabbit EOMs compared with control muscles. The appearance of MyoD-positive myonuclei suggests that protein synthesis becomes upregulated after Botox injection, and this, in turn, may help explain the minimal effects on myofiber size in EOMs after Botox injection. Understanding the effect of Botox on satellite cell activation and myonuclear addition in existing myofibers may suggest new ways to maximize the clinical effectiveness of Botox in patients with strabismus.
doi:10.1167/iovs.05-0549
PMCID: PMC1847582  PMID: 16249488
15.  Extraocular Muscle Force Generation after Ricin-mAb35 Injection: Implications for Strabismus Treatment 
Purpose:
Ricin-mAb35 is an immunotoxin targeted against skeletal muscle. Previously, we have shown that injection of ricin-mAb35 into rabbit extraocular muscle results in long-term muscle loss, and we have proposed this as a potential treatment for strabismus. In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation.
Methods:
Ricin-mAb35, 0.2 μg/kg in a volume of 0.1 mL, was injected into 1 superior rectus muscle in 16 adult rabbits. The contralateral superior rectus was injected with an equal volume of normal saline. Muscle force generation was assessed in vivo at 1, 6, and 12 weeks. Isometric length-tension curves were developed. Single-twitch tension, peak tetanic force generation, and fatigue rate were determined at optimal preload. Data from treated and control muscles were compared with the paired t test.
Results:
Force generation declined in ricin-mAb35 treated muscles at each postinjection interval. At 12 weeks, mean tetanic tension (200 Hz) in treated muscles was 13.8 mN/cm3 compared with 27.7 mN/cm3 in saline-injected controls (P = .02), a reduction of 50%. Single-twitch tension at 12 weeks was reduced 33% compared to controls (P = .04). Similar effects were noted at 1 and 6 weeks. Fatigue rate was not greater in treated muscles at any postinjection intervals.
Conclusions:
Injection of ricin-mAb35 results in sustained weakness in extraocular muscle, although additional studies will be required to determine the duration of physiologic effect. These results confirm our histological analysis and suggest that ricin-mAb35 may be a more long-term alternative to botulinum toxin A for the treatment of strabismus.
doi:10.1016/S1091-8531(03)00056-9
PMCID: PMC1796847  PMID: 12690362
16.  The Effect of Resection on Satellite Cell Activity in Rabbit Extraocular Muscle 
Purpose
A common treatment for motility disorders of the extraocular muscles (EOMs) is a resection procedure in which there is surgical shortening of the muscle. This procedure results in rotation of the globe toward the resected muscle, increased resting tension across the agonist–antagonist pair, and stretching of the elastic components of the muscles. In the rabbit, due to orbital constraints and limited rotation, resection results in more significant stretch of the surgically treated muscle than the antagonist. This surgical preparation allows for the examination of the effects of surgical shortening of one rectus muscle and passive stretch of its ipsilateral antagonist.
Methods
The insertional 6 mm of the superior rectus muscles of adult rabbits were resected and reattached to the original insertion site. After 7 and 14 days, the animals were injected intraperitoneally with bromodeoxyuridine (BrdU) every 2 hours for 12 hours, followed by a 24-hour BrdU-free period. All superior and inferior rectus muscles from both globes were examined for BrdU incorporation, MyoD expression, neonatal and developmental myosin heavy chain (MyHC) isoform expression, and myofiber cross-sectional area alterations.
Results
In the resected muscle and in the passively stretched antagonist muscle, there was a dramatic increase in the number of myofibers positive for neonatal MyHC and in the number of BrdU- and MyoD-positive satellite cells. The addition of BrdU-positive myonuclei increased from 1 per 1000 myofibers in cross sections of control muscles to 2 to 3 per 100 myofibers in the resected muscles. Single myofiber reconstructions showed that multiple BrdU-positive myonuclei were added to individual myofibers. Addition of new myonuclei occurred in random locations along the myofiber length of single fibers. There was no correlation between myofibers with BrdU-positive myonuclei and neonatal MyHC isoform expression.
Conclusions
Both active and passive stretch of the rectus muscles produced by strabismus surgery dramatically upregulated the processes of satellite cell activation, integration of new myonuclei into existing myofibers, and concomitant up-regulation of immature myosin heavy chain isoforms. Understanding the effects of strabismus surgery on muscle cell biological reactions and myofiber remodeling may suggest new approaches for improving surgical outcomes.
doi:10.1167/iovs.05-1069
PMCID: PMC1780261  PMID: 16431957
17.  GLAUCOMA FOLLOWING CATARACT SURGERY IN CHILDREN: SURGICALLY MODIFIABLE RISK FACTORS 
Purpose
To determine the incidence of glaucoma following cataract surgery in children and to identify surgically modifiable risk factors that may influence the development of glaucoma in these eyes.
Methods
All lensectomies performed in patients 18 years old or younger over a 7-year period (1995 through 2001) were identified by conducting a database search. A retrospective chart review was performed for every patient identified. Data extraction included patient’s age at surgery, intraocular lens implantation at cataract extraction, date of glaucoma onset, and length of follow-up. Statistical methods included risk ratio calculations and Kaplan-Meier analyses for the “time to glaucoma” for eyes undergoing lensectomy.
Results
We identified 116 eyes of 79 children in whom lensectomy was performed. The median age at cataract surgery was 178 days (~6 months). Mean follow-up time was 2.7 years. The overall incidence of glaucoma was 11%. Kaplan-Meier analysis demonstrated that eyes operated on at less than 30 days of age were statistically more likely to develop glaucoma than eyes operated on at age 30 days or older (P < .001). For those operated on at less than 30 days of age, the risk ratio was 11.8 for subsequent glaucoma development compared with those operated on at 30 days of age or older. Forty-nine eyes (42%) had primary intraocular lens implantation, and none of these developed glaucoma (P = .001).
Conclusions
Timing of surgery at less than 30 days of age and lack of implantation of an intraocular lens at lensectomy were both associated with an increased risk of subsequent glaucoma. Knowledge of modifiable risk factors is essential to allow ophthalmic surgeons to make cogent decisions regarding the care of children with cataracts.
PMCID: PMC1447558  PMID: 17057787

Results 1-17 (17)