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Purpose: To investigate the results of patients undergoing surgical treatment for strabismic diplopia in thyroid eye disease (TED) following teprotumumab., Design: Multicenter, retrospective, case series., Methods: We report 28 patients who underwent extraocular muscle surgery for strabismic diplopia after treatment with teprotumumab at 7 different academic centers. Elapsed time from last teprotumumab dose to the date of surgery, previous orbital decompression, primary preoperative horizontal and vertical deviation, surgical procedure, and 2-month postoperative results were collected from the patient records., Results: Sixteen (57%) patients were diplopia-free after 1 surgery. Three (11%) chose prism spectacles to correct residual diplopia, 2 (7%) used compensatory head posture to resolve diplopia, and 1 (4%) had intermittent diplopia and was functionally improved (choosing no prisms or further surgery). These were considered treatment successes. Three (11%) patients required reoperation, and all were diplopia-free after their second procedure., Conclusions: Most patients requiring surgery for strabismic diplopia following teprotumumab achieve good outcomes with success rates comparable to series published before the availability of teprotumumab., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: As the rate of post-traumatic stress disorder (PTSD) among military personnel and military veterans continues to rise, occupational therapists are increasingly concerned with the impact of this disorder on health, occupational performance, and quality of life. However, the literature on occupational therapy for military personnel and military veterans with PTSD has not been summarised., Method: The objective was to identify what is known from the published, peer-reviewed literature, about the services provided by occupational therapists to military personnel and military veterans experiencing PTSD. Arksey and O'Malley's five steps for scoping reviews were utilised. A search of three databases identified 27 articles., Results: Of the 27 papers reviewed, 13 papers discussed military personnel, 13 for military veterans, and 1 reported on both populations. Of these 27, 9 research papers provided data to support the efficacy of interventions, whereas 2 papers reported occupational performance issues. Eight opinion and eight service description papers were included. The most commonly mentioned interventions across the reviewed papers were stress and anger, or coping skills (n = 11), returning to duty (n = 9), physical training (n = 7), and sleep hygiene (n = 6)., Conclusion: Occupational therapists provide services to military personnel who are vulnerable to PTSD from combat and operational stress. Rarely did publications address intervention efficacy for military personnel. Additionally, there is a paucity of literature that addresses occupational therapy interventions following transition from military service for veterans with PTSD specific to facilitating reintegration to civilian life. Despite this, occupational therapists are well suited to enable military veterans to build upon their existing strengths, skills, and professional identities to minimise the impact of PTSD on daily life and to reach their full potential., (© 2020 Occupational Therapy Australia.)

Purpose: To evaluate the effect of age at primary intraocular lens (IOL) implantation on rate of refractive growth (RRG3) during childhood., Methods: A retrospective chart review was performed for children undergoing primary IOL implantation during cataract surgery. RRG3 was calculated for one eye from each patient using the first postoperative refraction, last refraction that remained stable (< 1.00 diopters [D] change/2 years), and the corresponding ages. RRG3 values for pseudophakic patients operated on from ages 0 to 5 months were compared with values for patients operated on at ages 6 to 23 months and 24 to 72 months. Patients with refractive errors that stabilized were grouped by age at surgery to compare age at refractive plateau., Results: Of 296 eyes identified from 219 patients, 46 eyes met the inclusion criteria. There was a statistically significant difference in RRG3 among age groups. The mean RRG3 value was -19.82 ± 5.23 D for the 0 to 5 months group, -22.32 ± 7.45 D for the 6 to 23 months group (0 to 5 months vs 6 to 23 months, P = .43), and -9.64 ± 11.95 D for the 24 to 72 months group (0 to 5 months vs 24 to 72 months, P = .01)., Conclusions: Age at primary IOL implantation affects the RRG3, especially for children 0 to 23 months old at surgery. Surgeons performing primary IOL implantation in infants may want to use age-adjusted assumptions, because faster refractive growth rates can be expected in young children. [J Pediatr Ophthalmol Strabismus. 2020;57(4):264-270.]., (Copyright 2020, SLACK Incorporated.)

The authors describe a case of unilateral abducens nerve palsy following perinatal stroke of the middle cerebral artery. A 1-year-old boy presented with left eye esotropia but no other ocular abnormalities. The patient's history, examination, and diagnostic tests were consistent with abducens nerve palsy. He underwent left medial rectus recession of 5.5 mm and left lateral rectus resection of 7 mm followed by patching. At 15 months after surgery, primary gaze by prism alternate cover testing revealed a 4 prism diopter (PD) esophoria (small angle in left gaze with essentially no action of lateral rectus) and 2 PD right hyperphoria. Ophthalmologic management of abducens nerve palsy entails addressing neurological sequelae in a timely manner, treating the esotropia and strabismic amblyopia to optimize visual system development. [J Pediatr Ophthalmol Strabismus. 2020;57:e30-e33.]., (Copyright 2020, SLACK Incorporated.)

Background: Rectus muscle restriction is a common finding in thyroid eye disease (TED). Typically, restricted muscles are recessed to address strabismus and diplopia. However, some patients have residual strabismus following maximal recession of a restricted muscle. The purpose of this study was to report outcomes following resection of the lateral rectus muscle after maximal recession of the medial rectus muscle in patients with TED., Methods: The medical records of patients with TED who underwent lateral rectus resection between 1998 and 2015 were reviewed retrospectively. Information regarding thyroid disease history and surgical treatment, including history of orbital decompressions, rectus muscle recessions, rectus muscle resections, and pre- and postoperative alignment was collected. Adjustable suture was used in all cases. Success was defined as a postoperative orthotropia with ≤2 Δ of phoria at distance and a phoria at near., Results: A total of 11 patients were included. Of these, 10 (91%) required postoperative adjustment. A successful outcome was achieved in 10 cases (91%)., Conclusions: Lateral rectus muscle resection to address residual esotropia and diplopia was effective at reducing residual esotropia following medial rectus recession in our study cohort., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel., Methods: Heparan-N-sulfatidase enzyme function testing in skin fibroblasts and white blood cells and SGSH gene sequencing were obtained. Clinical office examinations, examinations under anesthesia, electroretinogram, spectral domain optical coherence tomography (SD-OCT), and fundus photography were performed over a 5-year period., Results: Fundus examination revealed a progressive breadcrumb-like pigmentary retinopathy with perifoveal pigmentary involvement. SD-OCT showed loss of normal neuroretinal lamination and cystic macular changes responsive to treatment with carbonic anhydrase inhibitors. Electroretinography exhibited complex characteristics indicative of a generalized retinal rod > cone dysfunction with significant ON > OFF postreceptoral response compromise. Sequencing revealed compound heterozygous mutations in the SGSH gene, the novel c.88G > C (p.A30P) change and a second, previously reported one (c.734G > A, p.R245H)., Conclusions: We have identified ocular features of a patient with Sanfilippo syndrome type IIIA harboring a novel SGHS mutation that were not previously known to occur in this disease - namely, a progressive retinopathy with distinctive features, cystic macular changes responsive to carbonic anhydrase inhibitors, and complex electroretinographic abnormalities consistent with postreceptoral dysfunction. SD-OCT imaging revealed retinal lamination changes consistent with previously reported histologic studies. Both the SD-OCT and the electroretinogram changes appear attributable to intraretinal deposition of heparan sulfate.

Background: Approximately 30% of patients with metastatic (stage M) neuroblastoma present with periorbital ecchymosis from orbital osseous disease. Though locoregional disease is staged by imaging, the prognostic significance of metastatic site in stage M disease is unknown. We hypothesize that, compared to nonorbital metastasis, orbital metastasis is associated with decreased survival in patients with stage M neuroblastoma, and that periorbital ecchymosis reflects location and extent of orbital disease., Procedure: Medical records and imaging from 222 patients with stage M neuroblastoma seen at St. Jude Children's Research Hospital between January 1995 and May 2009 were reviewed. Thirty-seven patients were <18 months of age at diagnosis and 185 were ≥18 months of age. Overall survival (OS) and 5-year survival (5YS) were compared for patients with and without orbital, calvarial and nonorbital osseous metastasis, and with and without periorbital ecchymosis (log-rank test). Associations of periorbital ecchymosis with orbital metastasis location/extent were explored (Fisher's exact test, t-test)., Results: In patients ≥18 months of age, only orbital metastasis was associated with decreased 5YS (P = 0.0323) and OS (P = 0.0288). In patients <18 months of age, neither orbital, calvarial, or nonorbital bone metastasis was associated with OS or 5YS. Periorbital ecchymosis was associated with higher number of involved orbital bones (P = 0.0135), but not location or survival., Conclusions: In patients ≥ 18 months of age with stage M neuroblastoma, orbital metastatic disease is associated with decreased 5YS and OS. In future clinical trials, orbital disease may be useful as an imaging-based risk factor for substratification of stage M neuroblastoma., Competing Interests: None., (© 2015 Wiley Periodicals, Inc.)

Purpose: To report our experince in establishing a sustainable pediatric surgical outreach mission to an underserved population in Guatemala for treatment of strabismic disorders., Methods: A pediatric ophthalmic surgical outreach mission was established. Children were evaluated for surgical intervention by 3 pediatric ophthalmologists and 2 orthoptists. Surgical care was provided at the Moore Pediatric Surgery Center, Guatemala City, over 4 days. Postoperative care was facilitated by Guatemalan physicians during the second year., Results: In year 1, patients 1-17 years of age were referred by local healthcare providers. In year 2, more than 60% of patients were prescreened by a local pediatric ophthalmologist. We screened 47% more patients in year 2 (132 vs 90). Diagnoses included congenital and acquired esotropia, consecutive and acquired exotropia, congenital nystagmus, Duane syndrome, Brown syndrome, cranial nerve palsy, dissociated vertical deviation, and oblique muscle dysfunction. Overall, 42% of the patients who were screened underwent surgery. We performed 21 more surgeries in our second year (58 vs 37), a 57% increase. There were no significant intra- or postoperative complications., Conclusions: Surgical outreach programs for children with strabismic disorders in the developing world can be established through international cooperation, a multidisciplinary team of healthcare providers, and medical equipment allocations. Coordinating care with local pediatric ophthalmologists and medical directors facilitates best practice management for sustainability., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Autopsy studies have described definitive traumatic avulsion of the oculomotor nerve from the brainstem; however, detailed characterization of mechanisms and localization of traumatic nerve injury has yet to be definitively described in vivo. We report the case of a 13-year-old girl in whom high-resolution magnetic resonance imaging confirmed irreversible injury to the left oculomotor nerve after trauma., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether overcorrection shifts occur after vertical rectus recession on adjustable suture in the absence of thyroid eye disease., Methods: The medical records of patients without thyroid eye disease who underwent vertical rectus recession surgery from 2001 to 2008 were retrospectively reviewed for shifts in alignment between suture adjustment at postoperative day 1 and 2 months' follow-up. Superior rectus and inferior rectus recessions were compared. In addition, we compared the use of a nonabsorbable polyester suture to an absorbable polyglactin 910 suture in nonthyroid patients undergoing inferior rectus recessions., Results: A total of 59 patients were included (superior rectus, 30; inferior rectus, 29). We found a mean undercorrection shift of 1.1 (range, 17.5(Δ) undercorrection to 16(Δ) overcorrection) and 1.0(Δ) (range, 12(Δ) undercorrection shift to 6(Δ) overcorrection shift) for superior and inferior rectus recessions, respectively, between 1 day and 2 months postoperatively., Conclusions: There was no trend toward overcorrection following unilateral vertical rectus adjustable suture recessions in patients without thyroid eye disease, suggesting that thyroid myopathy may account for overcorrection shifts seen with this surgery., (Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified., Methods: Detailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period., Results: At presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function., Conclusions: The p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.

Background: Children with brain neoplasms often develop cranial nerve palsies (CNP) affecting ocular ductions. Duction deficits may improve or resolve with treatment of their intracranial disease. However, these children may be left with residual strabismus., Methods: We identified 104 children with third, fourth, and/or sixth cranial nerve palsies who were treated for central nervous system (CNS) neoplasms. A retrospective chart review was conducted to determine the presence or absence of residual strabismus following resolution of duction deficits., Results: Of the 104 children with CNP secondary to an intracranial neoplasm, forty-five had improvement or resolution of their duction deficit with treatment of their CNS lesion. Of these forty-five children, one had a third cranial nerve palsy, six had fouth cranial nerve palsies (one was bilateral), thirty-seven had sixth cranial nerve palsies (thirteen were bilateral), and one had two different cranial nerve palsies in the same eye (fourth and sixth). Of the eighteen children with improved (but not resolved) duction deficits, only three (17%) experienced resolution of their strabismus. Of the twenty-seven children with resolved duction deficits, nine (33%) experienced resolution of their strabismus. For the children with residual strabismus, the average angle of strabismus before duction deficits improved or resolved was 33.2Δ; while for those children without residual strabismus, it was 20Δ., Conclusions: Our findings indicated that the majority of children with improved or resolved duction deficits from CNP after treatment for CNS neoplasms are left with residual strabismus. Therefore, we suggest children with CNP secondary to CNS neoplasms need ophthalmic care after duction deficits resolve, as they are likely to have residual strabismus., (© 2015 Board of regents of the University of Wisconsin System, American Orthoptic Journal, Volume 65, 2015, ISSN 0065-955X, E-ISSN 1553-4448.)

We and others have previously shown that the neuropeptide galanin modulates neurite outgrowth from adult sensory neurons via activation of the second galanin receptor; however, the intracellular signalling pathways that mediate this neuritogenic effect have yet to be elucidated. Here, we demonstrate that galanin decreases the activation state in adult sensory neurons and PC12 cells of Rho and Cdc42 GTPases, both known regulators of filopodial and growth cone motility. Consistent with this, activated levels of Rho and Cdc42 levels are increased in the dorsal root ganglion of adult galanin knockout animals compared with wildtype controls. Furthermore, galanin markedly increases the activation state of cofilin, a downstream effector of many of the small GTPases, in the cell bodies and growth cones of sensory neurons and in PC12 cells. We also demonstrate a reduction in the activation of cofilin, and alteration in growth cone motility, in cultured galanin knockout neurons compared with wildtype controls. These data provide the first evidence that galanin regulates the Rho family of GTPases and cofilin to stimulate growth cone dynamics and neurite outgrowth in sensory neurons. These findings have important therapeutic implications for the treatment of peripheral sensory neuropathies., (© 2013 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.)

Purpose: To characterize the phenotype of Bardet-Biedl syndrome (BBS) patients homozygous for the BBS1 M390R mutation., Methods: Three patients [PT1, F, 27 years old (yo) at last examination, 14-year follow-up (F/U) PT2, F, 15-yo PT3, M, 15-yo, both 1-year F/U] underwent eye exams, Goldmann visual fields (GVFs), dark- (DA) and light-adapted (LA) electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). Vision and systemic history were also collected., Results: All patients had night blindness, hyperopic astigmatism, ptosis or mild blepharospasm, foot polydactyly, 5th finger clinodactyly, history of headaches, and variable, diet-responsive obesity. Two had asthma, PT1 was developmentally delayed, PT2 had Asperger-like symptoms, and PT3 had normal cognition. At age 14, acuity was 20/100 in PT1, who had nystagmus since age 2, 20/40 in PT2 and 20/30 in PT3. By 27yo PT1 progressed to 20/320, by 15 yo PT2 was 20/60 and PT3 remained stable. PT1 had well preserved peripheral GVFs, with minimal progression over 10 years of F/U. PT2 and PT3 presented with ring scotomas and I4e<5°. All patients had severe generalized visual sensitivity depression. ERGs were consistently recordable (also rod ERG in PT3 after 60 min DA), but progressed to non-recordable in PT1. Mixed DA ERGs exhibited electronegativity. In PT3, this was partly due to a bleaching effect during bright-flash DA averaging, partly to ON≫OFF LA response compromise. PT2 and 3 had, on SD-OCTs, generalized macular thinning, normal retinal lamination, and widespread photoreceptor outer/inner segment attenuation except foveally, and multiple rings of abnormal FAF configuring a complex bull's eye-pattern. PT1 had macular atrophy. All patients also had peripapillary nerve fiber layer thickening., Conclusions: The observed phenotype matches very closely that reported in patients by Azari et al. (IOVS 2006) and in the Bbs1-M390R knock-in mouse model, and expands it to the characterization of important ERG response characteristics that provide insight in the pathogenesis of retinopathy in these patients. Our findings confirm the consistent pathogenicity of the BBS1 M390R mutation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: To assess visual outcome prospectively after conformal radiation therapy (CRT) in children with optic pathway glioma., Methods and Materials: We used CRT to treat optic pathway glioma in 20 children (median age 9.3 years) between July 1997 and January 2002. We assessed changes in visual acuity using the logarithm of the minimal angle of resolution after CRT (54 Gy) with a median follow-up of 24 months. We included in the study children who underwent chemotherapy (8 patients) or resection (9 patients) before CRT., Results: Surgery played a major role in determining baseline (pre-CRT) visual acuity (better eye: P=.0431; worse eye: P=.0032). The visual acuity in the worse eye was diminished at baseline (borderline significant) with administration of chemotherapy before CRT (P=.0726) and progression of disease prior to receiving CRT (P=.0220). In the worse eye, improvement in visual acuity was observed in patients who did not receive chemotherapy before CRT (P=.0289)., Conclusions: Children with optic pathway glioma initially treated with chemotherapy prior to receiving radiation therapy have decreased visual acuity compared with those who receive primary radiation therapy. Limited surgery before radiation therapy may have a role in preserving visual acuity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Overcorrection of hypotropia subsequent to adjustable suture surgery following inferior rectus recession is undesirable, often resulting in persistent diplopia and reoperation. I hypothesized that overcorrection shift after suture adjustment may be unique to thyroid eye disease, and the use of a nonabsorbable suture may reduce the occurrence of overcorrection., Methods: A retrospective chart review of adult patients who had undergone eye muscle surgery with an adjustable suture technique was performed. Overcorrection shifts that occurred between the time of suture adjustment and 2 months postoperatively were examined. Descriptive statistics, linear regression, Anderson-Darling tests, generalized Pareto distributions, odds ratios, and Fisher tests were performed for two overcorrection shift thresholds (>2 and >5 prism diopters [PD])., Results: Seventy-seven patients were found: 34 had thyroid eye disease and inferior rectus recession, 30 had no thyroid eye disease and inferior rectus recession, and 13 patients had thyroid eye disease and medial rectus recession. Eighteen cases exceeded the 2 PD threshold, and 12 exceeded the 5 PD threshold. Statistical analyses indicated that overcorrection was associated with thyroid eye disease (P=6.7E-06), inferior rectus surgery (P=6.7E-06), and absorbable sutures (>2 PD: OR=3.7, 95% CI=0.4-35.0, P=0.19; and >5 PD: OR=6.0, 95% CI=1.1-33.5, P=0.041)., Conclusions: After unilateral muscle recession for hypotropia, overcorrection shifts are associated with thyroid eye disease, surgery of the inferior rectus, and use of absorbable sutures. Surgeons performing unilateral inferior rectus recession on adjustable suture in the setting of thyroid eye disease should consider using a nonabsorbable suture to reduce the incidence of postoperative overcorrection.

Objectives: To report a child with early-onset autosomal recessive Best vitelliform macular dystrophy and compound heterozygous BEST1 mutations, the management of a choroidal neovascular membrane with intravitreal bevacizumab in the proband, the benefits of amblyopia therapy in the fellow eye, and the findings in the parents, carriers of heterozygous BEST1 mutations., Methods: A 5-year-old white girl presented with monocular visual acuity loss and bilateral vitelliform macular lesions. Her parents were also examined. Examinations included electro-oculograms (EOGs), electroretinograms, imaging studies, and BEST1 gene testing. Interventions included off-label treatment with intravitreal bevacizumab in the left eye and amblyopia therapy in the right eye., Results: The proband presented with visual acuity of 20/200 OD with an atypical subfoveal vitelliform scar and 20/16 OS with asymptomatic vitelliform deposits. Subfoveal choroidal neovascularization developed at age 6 years, causing marked vision loss (20/200 OS). Visual acuity recovered to 20/20 OS after serial intravitreal bevacizumab injections. Amblyopia therapy improved visual acuity to 20/50 OD. The proband showed subnormal EOG Arden ratios and mild electroretinogram changes. Molecular testing showed missense BEST1 mutations (R141S and R141H) in the proband. Unlike dominant Best vitelliform macular dystrophy, in the heterozygous parents EOGs were normal and minimal autofluorescence changes were seen., Conclusions: Choroidal neovascularization treatment with bevacizumab was associated with vision restoration. Amblyopia treatment also yielded significant benefit. Patients presenting with vitelliform lesions should be screened for BEST1 mutations, even when parents have normal EOG and imaging results., Clinical Relevance: Prompt recognition and treatment of choroidal neovascularization and amblyopia management effectively restores vision. Awareness and recognition of recessive inheritance permits correct diagnosis and counseling.

Introduction and Purpose: We evaluated the impact of developmentally-at-risk status on the results of photorefractive screening with iScreen®., Patients and Methods: We sequentially recruited 169 children (aged 2-5 years) to participate in a blinded, prospective study of a photoscreening device. The principle investigator examined the children after photoscreening. Using established standards for amblyogenic factors, the principle investigator and photoscreen interpreters separately made a determination of "normal" or "needs referral" for each child. Sensitivity, specificity, positive predictive value, and negative predictive value for the photoscreening device were determined., Results: Overall, sensitivity was 85% with a positive predictive value of 98%, and specificity was 87% with a negative predictive value of 47%. Developmentally-at-risk status in 34 children (three refused imaging) did not reduce sensitivity (89%) or specificity (100%) when compared with 130 children (two refused imaging) who did not have developmentally-at-risk factors (sensitivity = 84% and specificity = 80%)., Conclusion: The efficacy of photorefractive screening in young children with developmentally-at-risk status is comparable to results found in normal children.

Background and Purpose: To review the surgical management of five vertical strabismus syndromes secondary to anatomical abnormalities. These syndromes are: 1) craniosynostosis; 2) "heavy eye syndrome" of high myopia; 3) Brown syndrome; 4) upshoot-downshoot in Duane retraction syndrome (DRS); and 5) antielevation syndrome after inferior oblique anteriorization., Methods: The syndromes are presented from evolving to well-accepted surgical management practices based on review of the current literature., Results: Surgical management techniques discussed include: 1) excyclotorsion of the muscle cones inducing elevation in adduction craniosynostosis, and surgery to stabilize the globe vertically in adduction in this situation; 2) loop myopexy to prevent prolapse of the elongated, highly myopic eye posteriorly between the superior and lateral recti; 3) superior oblique tenotomy and lengthening procedures to address inability to elevate the adducted eye in Brown syndrome; 4)Y-splitting of the lateral rectus to stabilize the adducted globe vertically in Duane retraction syndrome; and 5) re-recession of the anteriorized inferior oblique to a position posterior to the inferior rectus insertion in anti-elevation syndrome., Conclusions: The surgeon can, through careful surgical management techniques, alter the form of anatomy in these conditions and thereby provide more normally functioning binocular systems.

The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems and is involved in many diverse biological functions. There is a substantial data set that demonstrates galanin is upregulated after injury in the DRG, spinal cord and in many brain regions where it plays a predominantly antinociceptive role in addition to being neuroprotective and pro-regenerative. To further characterise the role of galanin following nerve injury, a novel transgenic line was created using the binary transgenic tet-off system, to overexpress galanin in galaninergic tissue in a suppressible manner. The double transgenic mice express significantly more galanin in the DRG one week after sciatic nerve section (axotomy) compared to WT mice and this overexpression is suppressible upon administration of doxycycline. Phenotypic analysis revealed markedly attenuated allodynia when galanin is overexpressed and an increase in allodynia following galanin suppression. This novel transgenic line demonstrates that whether galanin expression is increased at the time of nerve injury or only after allodynia is established, the neuropeptide is able to reduce neuropathic pain behaviour. These new findings imply that administration of a galanin agonist to patients with established allodynia would be an effective treatment for neuropathic pain.

Background: An expected side effect of external beam radiation therapy for retinoblastoma is cataract formation, which impairs a child's visual development and an ophthalmologist's ability to examine the eye. When surgery is indicated, the potential complications can be vision-or life-threatening. Here we report the results of cataract extraction with intraocular lens placement in young children with retinoblastoma., Methods: A retrospective chart review of all patients at St. Jude's Children's Research Hospital who had undergone external beam radiation therapy for retinoblastoma during a 25-year period was performed. Patients who required cataract extraction with IOL placement were included. Preoperative and postoperative visual acuity and ocular complications were recorded., Results: The chart review identified 40 patients (53 eyes) with cataracts, of whom 15 (19 eyes) had surgery. Of the 19 eyes, 2 (10.5%) developed a vitreous hemorrhage (one of which was subsequently enucleated secondary to phthisis, whereas the other resolved without further complications). A total of 12 eyes (63.2%) required Nd:YAG laser capsulotomies (mean, 3.6 months; range, 1-7 months). None developed recurrence or spread of disease. Thirteen eyes (68.4%) had improved visual acuity after cataract extraction and intraocular lens placement, 4 of which (30.8%) subsequently lost vision as the result of other complications of retinoblastoma treatment. Visual acuity outcomes were 20/20 to 20/60 in 3 eyes (15.8%); 20/70 to 20/200 in 4 (21.1%); and 20/400 or less in 10 (52.6%). One patient (5.2%) required enucleation., Conclusions: Patients who underwent cataract extraction after treatment for retinoblastoma had few postoperative adverse outcomes, and visual acuity improved in most patients immediately after surgery. However, some patients who showed initial improvement subsequently lost vision as the result of other complications from retinoblastoma treatment.

The neuropeptide galanin is widely, but not ubiquitously, expressed in the adult nervous system. Its expression is markedly up-regulated in many neuronal tissues after nerve injury or disease. Over the last 10 years, we have demonstrated that the peptide plays a developmental survival role to subsets of neurons in the peripheral and central nervous systems with resulting phenotypic changes in neuropathic pain and cognition. Galanin also appears to play a trophic role to adult sensory neurons following injury, via activation of GalR2, by stimulating neurite outgrowth. Furthermore, galanin also plays a neuroprotective role to the hippocampus following excitotoxic injury, again mediated by activation of GalR2. Most recently, we have shown that galanin expression is markedly up-regulated in multiple sclerosis (MS) lesions and in the experimental autoimmune encephalomyelitis (EAE) model of MS. Over-expression of galanin in transgenic mice abolishes disease in the EAE model, whilst loss-of-function mutations in galanin or GalR2 increase disease severity. In summary, these studies demonstrate that a GalR2 agonist might have clinical utility in a variety of human diseases that affect the nervous system.

The expression of voltage-gated sodium channels is regulated at multiple levels, and in this study we addressed the potential for alternative splicing of the Na(v)1.2, Na(v)1.3, Na(v)1.6 and Na(v)1.7 mRNAs. We isolated novel mRNA isoforms of Na(v)1.2 and Na(v)1.3 from adult mouse and rat dorsal root ganglia (DRG), Na(v)1.3 and Na(v)1.7 from adult mouse brain, and Na(v)1.7 from neonatal rat brain. These alternatively spliced isoforms introduce an additional exon (Na(v)1.2 exon 17A and topologically equivalent Na(v)1.7 exon 16A) or exon pair (Na(v)1.3 exons 17A and 17B) that contain an in-frame stop codon and result in predicted two-domain, truncated proteins. The mouse and rat orthologous exon sequences are highly conserved (94-100% identities), as are the paralogous Na(v)1.2 and Na(v)1.3 exons (93% identity in mouse) to which the Na(v)1.7 exon has only 60% identity. Previously, Na(v)1.3 mRNA has been shown to be upregulated in rat DRG following peripheral nerve injury, unlike the downregulation of all other sodium channel transcripts. Here we show that the expression of Na(v)1.3 mRNA containing exons 17A and 17B is unchanged in mouse following peripheral nerve injury (axotomy), whereas total Na(v)1.3 mRNA expression is upregulated by 33% (P=0.003), suggesting differential regulation of the alternatively spliced transcripts. The alternatively spliced rodent exon sequences are highly conserved in both the human and chicken genomes, with 77-89% and 72-76% identities to mouse, respectively. The widespread conservation of these sequences strongly suggests an additional level of regulation in the expression of these channels, that is also tissue-specific.

There is increasing evidence that a number of cytokines and their receptors are involved in the processes that lead to the development and maintenance of neuropathic pain states. Here we demonstrate that levels of CX3CR1 (the receptor for the chemokine fractalkine) mRNA in lumbar dorsal root ganglia (DRG) increase 5.8-fold 7 days after sciatic nerve axotomy, and 1.7- and 2.9-fold, 3 and 7 days respectively, after the spared nerve injury (SNI) model of neuropathic pain. In contrast, no significant change in the levels of fractalkine mRNA is apparent in the DRG after axotomy or SNI. The increase in CX3CR1 mRNA is paralleled by a 3.9- and 2.1-fold increase in the number of CX3CR1-positive macrophages in the DRG 7 days after axotomy and SNI, respectively. Expression of CX3CR1 in macrophages is also markedly increased in the sciatic nerve proximal to site of injury, by 25.7-fold after axotomy and 16.2-fold after SNI, 7 days after injury. Intra-neural injection into the sciatic nerve of 400 ng or 100 ng of fractalkine in adult 129OlaHsd mice significantly delayed the development of allodynia for 3 days following SNI. Further, CX3CR1 knockout (KO) mice display an increase in allodynia for three weeks after SNI compared to strain-matched Balb/c controls. Taken together, these results suggest an anti-allodynic role for fractalkine and its receptor in the mouse.

The neuropeptide galanin is widely, but not ubiquitously, expressed in the adult nervous system. Its expression is markedly upregulated in many neuronal tissues after nerve injury or disease. Over the last 10 years we have demonstrated that the peptide plays a developmental survival role to subsets of neurons in the peripheral and central nervous systems with resulting phenotypic changes in neuropathic pain and cognition. Galanin also appears to play a trophic role to adult sensory neurons following injury, via activation of GalR2, by stimulating neurite outgrowth. Furthermore, galanin also plays a neuroprotective role to the hippocampus following excitotoxic injury, again mediated by activation of GalR2. In summary, these studies demonstrate that a GalR2 agonist might have clinical utility in a variety of human diseases that affect the nervous system.

Galanin expression markedly increases in the dorsal root ganglion (DRG) after sciatic nerve axotomy and modulates pain behavior and regeneration of sensory neurons. Here, we describe transgenic mice expressing constructs with varying amounts of sequence upstream of the murine galanin gene marked by LacZ. The 20 kb region upstream of the galanin gene recapitulates the endogenous expression pattern of galanin in the embryonic and adult intact DRG and after axotomy. In contrast, 1.9 kb failed to drive LacZ expression in the intact DRG or after axotomy. However, the addition of an additional 2.7 kb of 5' flanking DNA (4.6 kb construct) restored the expression in the embryonic DRG and in the adult after axotomy. Sequence analysis of this 2.7 kb region revealed unique 18 and 23 bp regions containing overlapping putative Ets-, Stat-, and Smad-binding sites, and adjacent putative Stat- and Smad-binding sites, respectively. Deletion of the 18 and 23 bp regions from the 4.6 kb construct abolished the upregulation of LacZ expression in the DRG after axotomy but did not affect expression in the embryonic or intact adult DRG. Also, a bioinformatic analysis of the upstream regions of a number of other axotomy-responsive genes demonstrated that the close proximity of putative Ets-, Stat-, and Smad-binding sites appears to be a common motif in injury-induced upregulation in gene expression.

Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with little or no expression reported postnatally. We report here the expression of Nav1.5 mRNA isoforms in adult mouse and rat DRG. The major isoform of mouse DRG is Nav1.5a, which encodes a protein with an IDII/III cytoplasmic loop reduced by 53 amino acids. Western blot analysis of adult mouse DRG membrane proteins confirmed the expression of Nav1.5 protein. The Na+ current produced by the Nav1.5a isoform has a voltage-dependent inactivation significantly shifted to more negative potentials (by approximately 5 mV) compared to the full-length Nav1.5 when expressed in the DRG neuroblastoma cell line ND7/23. These results imply that the alternatively spliced exon 18 of Nav1.5 plays a role in channel inactivation and that Nav1.5a is likely to make a significant contribution to adult DRG neuronal function.

Osteopontin expression has previously been demonstrated in the adult rat dorsal root ganglion, although its function remains unclear. Here, we demonstrate, using real-time reverse transcription-polymerase (RT-PCR) chain reaction, that osteopontin mRNA expression is increased 1 and 3 weeks following sciatic nerve section (axotomy). Further, immunohistochemical staining suggests that this increase is restricted to neurons already expressing the protein. Osteopontin knock-out animals have significantly increased mechanosensory thresholds in the intact adult compared with the wild-type controls; however no differences in allodynia are noted between genotypes using a model of neuropathic pain. Lastly, exogenous recombinant osteopontin has no effect on neurite outgrowth from adult wild-type sensory neurons, nor were differences in neurite outgrowth observed in osteopontin knock-out animals compared with wild-type controls.

Expression of the neuropeptide galanin is markedly up-regulated within the adult dorsal root ganglia (DRG) following peripheral nerve injury. We have previously demonstrated that galanin knockout (Gal-KO) mice have a developmental loss of a subset of DRG neurons. Galanin also plays a trophic role in the adult animal, and the rate of peripheral nerve regeneration and neurite outgrowth is reduced in adult Gal-KO mice. Here we describe the characterization of mice with an absence of GalR2 gene transcription (GalR2-MUT) and demonstrate that they have a 15% decrease in the number of calcitonin gene-related peptide (CGRP) expressing neuronal profiles in the adult DRG, associated with marked deficits in neuropathic and inflammatory pain behaviours. Adult GalR2-MUT animals also have a one third reduction in neurite outgrowth from cultured DRG neurons that cannot be rescued by either galanin or a high-affinity GalR2/3 agonist. Galanin activates extracellular signal-regulated kinase (ERK) and Akt in adult wild-type (WT) mouse DRG. Intact adult DRG from GalR2-MUT animals have lower levels of pERK and higher levels of pAkt than are found in WT controls. These data suggest that a lack of GalR2 activation in Gal-KO and GalR2-MUT animals is responsible for the observed developmental deficits in the DRG, and the decrease in neurite outgrowth in the adult.

We report a child with persistent fevers, arthritis, and parvoviral infection who subsequently developed unilateral orbital pseudotumor, lytic bone lesions, bilateral anterior uveitis, band keratopathy, and migratory polyarthritis. Our working diagnosis was systemic-onset juvenile rheumatoid arthritis, although pseudotumor of the orbit and lytic bone lesions are not found in this disease.

Brown's Syndrome was initially described as a superior oblique tendon sheath syndrome-a short anterior tendon resulting in a restricted elevation of the globe in the nasal field. Brown believed that a congenital paralysis of the inferior oblique muscle resulted in this secondary shortening of the anterior sheath of the superior oblique tendon. The definition of Brown's Syndrome has changed over time. It is currently defined as the inability to elevate the eye in the adducted position, both actively and passively on force duction testing, and can be acquired. The pathophysiology of acquired Brown's Syndrome may involve an abnormality of the superior oblique trochlea/tendon complex. However, it may also result from other causes unrelated to the superior oblique tendon or muscle, such as tumors of the superior nasal orbit, inferior orbital mechanical restriction, or an inferiorly displaced lateral rectus muscle and pulley. We present two cases in which a Brown's Syndrome was diagnosed after the superior oblique muscle had been disinserted or removed.

Purpose of Review: The purpose of this review is to examine current trends in vision screening for children., Recent Findings: Literature within the past year regarding children's vision screening has been dominated by clinical validation studies of autorefractors or photoscreeners that allow the detection of amblyogenic refractive errors, misalignment of the eyes, or media opacities. New technologies reported include wave-front analysis for amblyogenic factors and a visual evoked potentials-based screening tool for the preverbal child. Studies evaluating the goals of the screening program, the target population, and the physical limitations of the screening environment have prompted multipronged or hybrid studies designed to more accurately detect vision problems, particularly in the preschool child, in whom cooperation and cognitive development affect reliability of results. State and federal legislation in the United States has been proposed or adopted to regulate and partially fund pediatric vision screening and comprehensive examinations., Summary: Through improvements and new developments in technology, study design, the efforts of organized medicine, and legislative initiatives, vision screening for children continues toward the goal of bringing all children with eye disease or vision problems to treatment in a timely fashion.

We report the natural history of acquired retinal oxalosis in a child with chronic renal failure. The clinical manifestations were characterized by a transient crystalline retinopathy, but stable, diffuse, flecked retina-like changes and focal hypertropic retinal pigment epithelial lesions. The pathophysiology and previous reports of retinal oxalosis are reviewed.

Background: Fat adherence syndrome (FAS) is a permanent restrictive strabismus that can occur after periocular surgery or trauma. The pathophysiology is poorly characterized., Methods: Under varying conditions, fat autografts were secured with dissolvable sutures between the inferior rectus and the periosteum of the inferior orbital rim in both eyes of 15 New Zealand white rabbits. Sutures without fat autografts were placed in both eyes of three control rabbits. The force required to move the eyeball superiorly 4, 6, or 8 mm was measured with a digital strain gauge preoperatively and 6 weeks after surgery. Twelve of the 15 rabbits with autografts were then sacrificed, and exenteration specimens were taken. The three remaining rabbits (six eyes) were observed for 6 months after placement of fat autografts., Results: Analysis of variance allowed rejection of the null hypothesis that there was no difference among the postsurgical groups for all deflection points when 6 weeks postoperative was compared to baseline (preoperative) measurements (P < or = 0.05). Regression analyses showed that stiffness at each deflection was dependent on the amount of fat placed in the orbit. In three rabbits observed for 6 months, restriction tended to be stable over the 6-month observation period and was not alleviated by lysis of adhesions or removal of the fat grafts., Conclusion: A fat autograft introduced into an extraocular wound in rabbits will produce a permanent restrictive strabismus. This model may prove useful in the study of FAS.

The voltage-gated sodium channel Na(v)1.8 is only expressed in subsets of neurons in dorsal root ganglia (DRG) and trigeminal and nodose ganglia. We have isolated mouse partial length Na(v)1.8 cDNA clones spanning the exon 17 sequence, which have 17 nucleotide substitutions and 12 predicted amino acid differences from the published sequence. The absence of a mutually exclusive alternative exon 17 was confirmed by sequencing 4.1 kilobases of genomic DNA spanning exons 16-18 of Scn10a. A novel cDNA isoform was identified, designated Na(v)1.8c, which results from alternative 3'-splice site selection at a CAG/CAG motif to exclude the codon for glutamine 1031 within the interdomain cytoplasmic loop IDII/III. The ratio of Na(v)1.8c (CAG-skipped) to Na(v)1.8 (CAG-inclusive) mRNA in mouse is approximately 2:1 in adult DRG, trigeminal ganglion, and neonatal DRG. A Na(v)1.8c isoform also occurs in rat DRG, but is less common. Of the two other tetrodotoxin-resistant channels, no analogous alternative splicing of mouse Na(v)1.9 was detected, whereas rare alternative splicing of Na(v)1.5 at a CAG/CAG motif resulted in the introduction of a CAG trinucleotide. This isoform, designated Na(v)1.5c, is conserved in rat and encodes an additional glutamine residue that disrupts a putative CK2 phosphorylation site. In summary, novel isoforms of Na(v)1.8 and Na(v)1.5 are each generated by alternative splicing at CAG/CAG motifs, which result in the absence or presence of predicted glutamine residues within the interdomain cytoplasmic loop IDII/III. Mutations of sodium channels within this cytoplasmic loop have previously been demonstrated to alter electrophysiological properties and cause cardiac arrhythmias and epilepsy.

The neuropeptide galanin is expressed in the dorsal root ganglia (DRG) and spinal cord and is thought to be involved in the modulation of pain processing. However, its mechanisms of action are complex and poorly understood, as both facilitatory and inhibitory effects have been described. To understand further the role played by galanin in nociception, we have generated two transgenic lines that overexpress galanin in specific populations of primary afferent DRG neurons in either an inducible or constitutive manner. In the first line, a previously defined enhancer region from the galanin locus was used to target galanin to the DRG (Gal-OE). Transgene expression recapitulates the spatial endogenous galanin distribution pattern in DRG neurons and markedly overexpresses the peptide in the DRG after nerve injury but not in the uninjured state. In the second line, an enhancer region of the c-Ret gene was used to constitutively and ectopically target galanin overexpression to the DRG (Ret-OE). The expression of this second transgene does not alter significantly after nerve injury. Here, we report that intact Ret-OE, but not Gal-OE, animals have significantly elevated mechanical and thermal thresholds. After nerve damage, using a spared nerve-injury model, mechanical allodynia is attenuated markedly in both the Gal-OE and Ret-OE mice compared with WT controls. These results support an inhibitory role for galanin in the modulation of nociception both in intact animals and in neuropathic pain states.

Purpose: To report the severity of ocular injury in seven children with traumatic hyphemas resulting from the accidental striking of the child in the face with a belt during the administration of corporal punishment., Design: Observational case series., Methods: We retrospectively reviewed the records of all patients (n = 7, aged 4 to 14 years) with traumatic hyphemas secondary to belt injuries evaluated by the senior author between 1989 to 2002 at Le Bonheur Children's Medical Center, a regional pediatric referral hospital in Memphis, Tennessee., Results: Anterior segment injuries ranged from small hyphemas with normal intraocular pressure and no vision loss to injuries with severe elevations of intraocular pressure and permanent, significant loss of vision., Conclusions: Ocular injury to a child can result from trauma inflicted with a belt by a parent or caretaker during corporal punishment and may result in permanent loss of vision.

The purposes of this investigation were to determine: (a) if visual evoked potential (VEP) abnormalities could be identified in children with neurofibromatosis type 1 (NF1) with no evidence of optic pathway or brain neoplasias on MRI; and (b) if VEP abnormalities could be explained by the presence of hyperintense T2-weighted foci on MRI testing, known as unidentified bright objects (UBOs). To answer these questions, VEPs were recorded from 16 children with NF1 and compared to 13 normal subjects in the same age range tested with the same protocol. Pattern-reversal VEPs were recorded at four stimulus sizes both monocularly and binocularly, the latter to hemi-field stimuli. Flash VEPs were recorded in dark- and light-adapted conditions. VEP measurements and MRI readings for UBOs were conducted in a masked fashion. Ten of the 16 children with NF1 had abnormal VEPs to at least one of the four types of stimuli. Abnormalities included delayed responses (n=6), absent flash VEP P2 component (n=3), or both (n= 1). Abnormalities of the P2 component of the dark-adapted flash VEP were the most common finding (n=7), although no single testing strategy was able to identify all children with abnormal VEPs. UBOs were present in all children, demonstrating that their presence does not fully account for VEP abnormalities in children with NF1. This study also demonstrates that VEP abnormalities are present also in the absence of neoplasias of the optic pathways or of the brain. Our results are suggestive of a primary abnormality of visual processing in children with NF1.

To determine the visual results of conservative (non- surgical) therapy, we reviewed all our patients with genetic ectopia lentis, with and without Marfan's Syndrome. Of these patients, 50% had significant permanent (or potentially so) ametropic functional amblyopia (visual acuity 20/50 to 20/200) in spite of good conservative management. This was especially true (100%) if the amount of lens dislocation was such that the lens edge was approaching the center of the pupil (vision still primarily phakic). The worst amblyopia was noted when the lens was still covering the visual axis and the lens edge was 1.3 mm from the center of the pupil (range of 0.3 to 2.3 mm). With regard to the most serious complication of ectopia lentis and its treatment, retinal detachment, when it occurred in our patients it was more strongly related to axial high myopia than surgery, per se. Since the axial high myopia which characteristically develops in ectopia lentis is probably the result of the amblyopia or the amblyopiagenic optics of ectopia lentis, lentectomy may be indicated early in this condition, before the axial high myopia develops, to prevent both axial high myopia and the attendant risks of retinal detachment as well as functional amblyopia. If the refractive error cannot be corrected well and the resultant ametropic amblyopia does not respond to conservative management, early surgery should be considered. If the lens is subluxated so that the edge of the lens approaches to within 0.3 to 2.3 mm of the center of the pupil (with best correctable vision still phakic), this is highly probable.

Objective: Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes associated with an autoimmune response to type II collagen (CII), a cartilage-specific protein. To test the hypothesis that down-regulation of autoimmunity to CII can be accomplished in JRA by oral administration of CII, an open-label study of CII was performed in 9 patients with JRA., Methods: Seven rheumatoid factor-negative JRA patients with polyarticular disease and 2 JRA patients with pauciarticular disease (1 with early onset and 1 with late onset) were treated for 3 months with oral bovine CII. Patients were examined for disease activity and underwent routine laboratory testing at monthly intervals. Two of the patients had flares of disease when treatment was discontinued, and these patients were re-treated for an additional 3 months. To test the hypothesis that oral tolerance induces an immune deviation of T cells, peripheral blood mononuclear cells from patients were collected before and after treatment and cultured with CII. Supernatants and RNA were collected and analyzed for the presence of various cytokines., Results: Eight patient trials met the criteria for clinical improvement outlined by Giannini and coworkers in 1997. None of the patients had any side effects from the treatment. In 6 of the 8 patients who improved, interferon-gamma production decreased after oral CII therapy, correlating with clinical improvement, while 6 patients had increases in levels of transforming growth factor beta3., Conclusion: These results are encouraging. The possible beneficial effect of oral CII in JRA merits further investigation.

Purpose: Sixth nerve palsies in children with brain tumors have a low rate of spontaneous recovery. Botulinum toxin has been used to treat sixth nerve palsies. In this study, we review outcomes for children with brain tumors and sixth nerve palsies, some of whom were treated with botulinum toxin., Methods: To determine whether botulinum toxin effected the outcome of children with sixth nerve palsies and brain tumors, a retrospective review of charts was conducted for patients identified as having brain tumors and sixth nerve palsies after evaluation at the St Jude Children's Research Hospital Eye Clinic between 1992 and 1999. Of 48 charts identified, 19 met our inclusion criteria, having a record of brain tumor associated with sixth nerve palsy and 2 or more eye clinic visits at least 6 months apart. Children were considered recovered if they had an esotropia of less than 10 PD in primary gaze at the last follow-up visit and did not require surgical correction., Results: Of the 19 children included in the study, 10 were managed conservatively (no botulinum toxin or surgery for at least 6 months after diagnosis). Nine children received one or more botulinum toxin injections. Two (20%) of the 10 children in the conservatively managed group recovered without surgical intervention. Two (22%) of the 9 children in the botulinum toxin treatment group recovered without surgical intervention., Conclusions: Treatment with botulinum toxin did not improve the rate of recovery in our series of children with brain tumors and sixth nerve palsies.

Galanin-like peptide (GALP) was recently purified on the basis of its preferential activation of galanin receptor subtype 2 (GALR2) compared with galanin receptor subtype 1 (GALR1). Using in situ hybridization of adult rat brain, pituitary and dorsal root ganglia (DRG) we demonstrate that GALP mRNA expression is restricted to the arcuate nucleus and median eminence of the hypothalamus, and to the posterior lobe of the pituitary. No expression was detected elsewhere in brain, or in the DRG. In adult mouse, no expression was detected in brain or in DRG either before or after axotomy, suggesting that GALP has no apparent role in the axotomy response of DRG.

The neuropeptide galanin is expressed developmentally in the dorsal root ganglion (DRG) and is rapidly up-regulated 120-fold after peripheral nerve section in the adult. Here we report that adult mice carrying a loss-of-function mutation in the galanin gene have a 13% reduction in the number of cells in the DRG associated with a 24% decrease in the percentage of neurons that express substance P. These deficits are associated with a 2.8- and 2.6-fold increase in the number of apoptotic cells in the DRG at postnatal days 3 and 4, respectively. After crush injury to the sciatic nerve, the rate of peripheral nerve regeneration is reduced by 35% with associated long-term functional deficits. Cultured DRG neurons from adult mutant mice demonstrate similar deficits in neurite number and length. These results identify a critical role for galanin in the development and regeneration of sensory neurons.

Purpose: To describe a patient with infantile osteopetrosis and optic atrophy secondary to optic canal stenosis who demonstrated optic canal enlargement after bone marrow transplant., Methods: Case report. A 3-month-old infant with infantile "malignant" osteopetrosis underwent ophthalmic examination, including visual evoked potentials, electroretinogram, and computed tomography (CT). Bone marrow transplant was performed at 8 months of age., Results: Examination revealed visual loss and optic atrophy, left eye greater than right eye, secondary to optic canal stenosis. Flash visual evoked potentials revealed a normal waveform in both eyes with increased latency in the left eye. Electroretinogram was normal in both eyes. CT after bone marrow transplant showed enlargement of the optic canals. Vision remains stable 43 months after bone marrow transplant., Conclusions: Bone marrow transplant in infantile osteopetrosis may be followed by reversal of optic canal stenosis and preservation of vision.