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PURPOSE: To describe the clinical course of untreated intermittent exotropia (IXT) in children 12 to 35 months of age followed for three years. METHODS: We enrolled 97 children 12 to 35 months of age with previously untreated IXT who had been randomly assigned to the observation arm of a randomised trial of short-term occlusion versus observation. Participants were observed unless deterioration criteria were met at a follow-up visit occurring at 3 months, 6 months, and 6-month intervals thereafter for three years. The primary outcome was deterioration of the IXT by three years, defined as (1) a constant exotropia ≥10 prism dioptres (∆) at distance and near (i.e., motor deterioration) or (2) treatment prescribed despite not having met motor deterioration. The primary analysis used the Kaplan-Meier method to determine the cumulative proportion of participants meeting deterioration by three years and 95% confidence interval (CI). RESULTS: The cumulative probability of deterioration by three years was 28% (95% CI = 20% to 39%). Of the 24 participants meeting the primary outcome of deterioration, seven met motor deterioration and 17 were prescribed treatment without meeting motor deterioration. The cumulative probability of motor deterioration by three years was 10% (95% CI = 5% to 19%). CONCLUSIONS: Given the modest rate of motor deterioration over three years, watchful waiting may be a reasonable management approach in 12- to 35-month-old children with IXT. To confirm this recommendation would require a long-term randomised trial of immediate treatment versus observation followed by deferred treatment if needed.

International audience; Melphalan is an efficient chemotherapeutic agent that is currently used to treat retinoblastoma (Rb); however, the inherent risk of immunogenicity and the hazardous integration of this drug in healthy cells is inevitable. MicroRNAs are short non-coding single-stranded RNAs that affect a vast range of biological processes. Previously, we focused on the regulatory role of miR-181a during cancer development and progression. In this manuscript, 171 nm switchable lipid nanoparticles (LNP) co-delivered melphalan and miR-181a with en-capsulation efficiencies of 93%. Encapsulation of melphalan in LNP significantly improved its therapeutic efficiency. Gene analysis shows that miR-181a decreases the expression of anti-proliferative gene MAPK1 and anti-apoptotic gene Bcl-2, but significantly increased the expression of pro-apoptotic gene BAX. Our results suggest that the two agents have a complementary effect in reducing the viability of cultured Rb cells (primary and cell line) and decreasing Rb cell counts in an in-vivo xenograft Rb model in rats. Our results suggest that the proposed co-delivery technique significantly increases the therapeutic impact, allows for lower administration of melphalan, and consequently, could minimize the cytotoxic side-effects of this drug.

This study had 3 objectives: (i) to characterize clinical profiles of adults with consecutive exotropia (CXT), intermittent exotropia (IXT), and sensory exotropia (SXT); (ii) to correlate immediate postoperative target angles with successful long-term ocular alignment; and (iii) to compare the efficacy of adjustable versus nonadjustable medial rectus resection ± advancement.Retrospective, observational, and interventional cohort study.A total of 133 adult exotropic patients treated surgically at 3 different hospitals between July 2012 and June 2013.The patients were divided according to clinical profiles (CXT, IXT, and SXT) based on ophthalmic and orthoptic assessments. Two treatment groups were established: group I-adjustable medial rectus resection ± advancement and adjustable lateral rectus recession; group II-nonadjustable medial resection ± advancement and adjustable lateral rectus recession. Measurements of immediate postadjustment alignment (target angle) and 4-6 months of follow-up alignment were performed and compared between groups. Surgical success was defined as distance primary position alignment within 10 prism diopters (PD) of orthotropia 4-6 months postoperatively.Comparison of clinical profile groups showed that CXT patients had more hyperopia and amblyopia and smaller preoperative deviations; IXT patients had more diplopia and larger preoperative deviations (neardistance); and SXT patients had poor vision in the deviating eye and larger preoperative deviations. Immediate postoperative alignment was 5.2 PD of esodeviation in group I and 3.2 PD of esodeviation in group II. Overall success rates for ocular alignment at 4-6 months postoperatively were comparable with both surgical techniques (74.6% for group I and 74.3% for group II). Patients with a preoperative deviation ≥40 PD had a lower surgical success rate (63.8%) than patients with a deviation40 PD (80%). Patients presenting with a significant (-1 or worse) abduction deficit in the operated eye at their first visit after surgery had a better success rate at 4-6 months' follow-up (83.3% vs 67.8%).Adjustable and nonadjustable medial rectus surgeries seem equally successful. Creation of an abduction deficit in the early postoperative period seems predictive of a better outcome. Larger preoperative angles (≥40 PD) were associated with more exotropic drift and a lower percentage of surgical success. Future studies will continue to search for surgical strategies and the ideal target angle that will produce the best long-term alignment stability.

OBJECTIVE: Two strategies were compared for managing moderate hyperopia without manifest strabismus among 1- and 2-year-old children: 1) immediate prescription of glasses vs 2) observation without glasses unless reduced distance visual acuity (VA), reduced stereoacuity, or manifest strabismus. DESIGN: Prospective randomized clinical trial PARTICIPANTS: 130 children 1 to 2 years old with hyperopia between +3.00 diopters (D) and +6.00D spherical equivalent (SE) in at least one eye, anisometropia ≤1.50D SE and astigmatism ≤1.50D based on cycloplegic refraction, and no manifest strabismus. METHODS: Participants were randomly assigned to glasses (1.00D less than full cycloplegic hyperopia) versus observation and followed every 6 months for 3 years. Glasses were prescribed to those assigned to observation if they met pre-specified deterioration criteria of distance VA or near stereoacuity below age norms, or development of manifest strabismus. MAIN OUTCOME MEASURE: At the 3-year primary outcome examination, participants were classified as failing the randomized management regimen if distance VA or stereoacuity were below age norms, or manifest strabismus was observed (each with and without correction in trial frames, confirmed by masked retest, irrespective of whether deterioration had occurred previously), or if strabismus surgery had been performed. RESULTS: Of the 106 (82%) participants completing the 3-year primary outcome examination, failure occurred in 11 (21%) of 53 in the glasses group and 18 (34%) of 53 in the observation group (difference = −13%; 95% CI = −31% to 4%; p=0.14). The reasons for failure in the glasses and observation groups were reduced stereoacuity in 6 (11%) and 16 (30%) respectively, reduced VA in 3 (6%) and 4 (8%), and manifest strabismus in 5 (9%) in each group. Fifty-eight percent (95% CI = 46% to 70%) in the observation group, and 33% (95% CI = 22% to 46%) in the glasses group met deterioration criteria (requiring glasses if not wearing). CONCLUSION: For 1- and 2-year-olds with uncorrected moderate hyperopia (+3.00D to +6.00D SE), our estimates of failure, after 3 years of 6-monthly follow-up, are inconclusive, and consistent with either a small to moderate benefit or no benefit of immediate prescription of glasses compared with careful observation (with glasses only if deteriorated).

A total of 27 children with esotropia (mean age, 3.9 years; range, 9 months to 13.8 years) were enrolled in a 9-month observational study following botulinum toxin A (BTX-A) injection of one (n = 7) or both (n = 20) medial rectus muscles. BTX-A dosage ranged from 3.0 to 6.0 units per muscle. Three participants developed tonic pupil, noted at the first follow-up visit, occurring 12-19 days after injection. All 3 cases occurred in the left eye of participants who underwent bilateral BTX-A injection by the same surgeon. Anisocoria diminished from a maximum of 4 mm at the 2-week visit to 1–2 mm in all patients over the 9-month postinjection data collection period. No adverse visual outcomes were noted. Tonic pupil is an infrequently reported complication of BTX-A injection for strabismus. The experience of our investigator group suggests the need for careful injection technique and thorough preinjection counseling.

Objective Both genetic and environmental factors are thought to play a role in the pathogenesis of strabismus and subsequent ocular dominance and amblyopia. Our purpose was to compare the characteristics of sensory visual function in 2 adult monozygotic (genetically identical) twins who presented with esotropia at different ages. Methods Monocular and binocular visual function was measured in the twins. Contrast sensitivity was used to assess monocular function. Suppressive and stereoscopic measurements were undertaken to assess binocular function. All tests were run using a 2-alternative forced choice psychophysical procedure. Eighteen short tandem repeats (STR) were genotyped across the genome in both twins to determine their exact relationship. Results Twin 1 (nondominant eye OD) was diagnosed with esotropia at 6 months of age, whereas twin 2 (nondominant eye OS) was diagnosed with esotropia at 5 years of age. They underwent a similar corrective surgical intervention soon after diagnosis to correct their esodeviations. Monocular contrast sensitivity was poorer for twin 1, particularly at intermediate spatial frequencies. In addition, twin 1 demonstrated complete suppression and unmeasurable stereoscopic function (>300 seconds). On the other hand, twin 2 demonstrated fusion, exhibited only mild suppression, and had near-normal (28 seconds) stereoscopic function. All STR alleles were identical in the twins, proving monozygosity. Conclusions Sensory measurements of monocular and binocular visual function in these genetically proven monozygotic twins were significantly different, with the earlier onset of esotropia associated with reduced visual function. Twin 2, whose esotropia was diagnosed at the age of 5 years, had near-normal visual function, both monocularly and binocularly. To the best of our knowledge, this represents the first study of a genetically identical sibling pair with strabismus. By eliminating the genetic differences between these patients, we are able to make powerful observations about the effect of environment on visual function in strabismus.

To determine the relationships between stereoacuity, control of exotropia, and angle of deviation in children with intermittent exotropia (IXT).Data collected for 652 participants 3 to11 years of age with IXT meeting eligibility criteria for enrollment into one of two multicenter, randomized clinical trials were used to evaluate relationships between stereoacuity, control, and angle of deviation at enrollment.Any level of stereoacuity and angle of deviation could be accompanied by any level of control. Worse distance exotropia control was weakly associated with poorer distance stereoacuity (R = 0.26; 99% CI, 0.17-0.36) and larger angles of deviation at distance (R = 0.27; 99% CI, 0.17-0.36). Worse near exotropia control was weakly associated with poorer near stereoacuity (R = 0.17; 99% CI, 0.07-0.27) and moderately associated with larger angles of deviation at near (R = 0.37; 99% CI, 0.28-0.45). There was no association between stereoacuity and angle of deviation at distance (R = 0.07; 99% CI, -0.03 to 0.17) or at near (R = 0.02; 99% CI, -0.08 to 0.12).Although weak and moderate associations were found between stereoacuity, control, and angle of deviation, a child may exhibit any combination of stereoacuity, control, and angle of deviation. The specific roles of control, stereoacuity, and angle of deviation in the diagnosis, management, and pathogenesis of IXT are unclear, and each appears to yield somewhat independent information.

Giant cell arteritis (GCA) is a systemic vasculitis of medium and large arteries often with ophthalmic involvement, including ischemic optic neuropathy, retinal artery occlusion, and ocular motor cranial nerve palsies. This last complication occurs in 2%-15% of patients, but typically involves only 1 cranial nerve. We present 2 patients with biopsy-proven GCA associated with multiple cranial nerve palsies.

BACKGROUND AND OBJECTIVE: Bevacizumab intravitreal injection, a vascular endothelial growth factor inhibitor, is used to treat retinopathy of prematurity (ROP). However, concerns have been raised regarding its systemic absorption and effect on developing tissues including brain. This study compared neurodevelopment at 18 months’ corrected age in preterm infants of METHODS: Data from the Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network databases were retrospectively reviewed. Infants born at RESULTS: Of 125 treated infants, 27 received bevacizumab and 98 laser. The bevacizumab group, compared with laser, obtained a median Bayley Scales of Infant and Toddler Development Third Edition motor composite score of 81 (interquartile range, 70–91) versus 88 (79–97), a language composite score of 79 (65–97) versus 89 (74–97), and a cognitive score of 90 (80–100) versus 90 (85–100). Difference was detected on the motor score only (P = .02). Odds of severe neurodevelopmental disabilities (Bayley scores CONCLUSIONS: Preterm infants treated with bevacizumab versus laser had higher odds of severe neurodevelopmental disabilities. Further investigation on the long-term safety of antivascular endothelial growth factor treatment of ROP is needed.

The authors report two cases of retinoblastoma with extension along the optic nerve sheath with negative surgical margins, a pattern not considered in current classifications but suggesting a high risk of metastasis. Both patients were treated with adjuvant chemotherapy alone and remain free of extraocular disease 15 and 22 months later. [ J Pediatr Ophthalmol Strabismus . 2016;53:e51–e53.]

Purpose To study the efficacy of propranolol in the treatment of periocular infantile hemangiomas (IHs). Design Retrospective interventional case series. Participants Eighteen children presenting periocular IH with occlusion of the pupil, anisometropic astigmatism, proliferating eyelid IH, or cosmetically disfiguring periocular IH. Methods All patients received treatment with propranolol started at 0.5 mg/kg/day with an incremental increase by 0.5 mg/kg/day every 4 days, up to a maximum of 2 to 3 mg/kg/day. Complete eye examinations and serial photographs were obtained before, during, and after treatment. Doppler ultrasound and magnetic resonance imaging performed pre- and post-treatment were compared when available. Main Outcome Measures Evolution of the treated IH was evaluated with respect to astigmatism, amblyopia, and size of the lesion. Results The IH size decreased in 17 of 18 patients. We noted a greater reduction when treatment was administered during the proliferative phase of growth of IHs. At the conclusion of treatment, none of our patients had amblyopia. The mean value of amblyogenic astigmatism (n = 7) decreased from 2.71 diopters (D) pretreatment to 1.03 D post-treatment. On radiology, 8 patients had significant regression of the lesion size of their IH and 1 patient had a limited progression. Propranolol had to be temporarily discontinued in only 1 patient because of symptomatic hypotension. Conclusions Propranolol seems to be an effective modality of treatment for periocular IH. It seems to be most efficacious when initiated in the proliferative phase of IH but may be beneficial even in the later stage. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinoblastoma (Rb) is an aggressive childhood cancer of the developing retina. This disease is associated with epigenetic deregulation of several cancer pathways including upregulation of the proto-oncogene spleen tyrosine kinase (SYK). We have previously demonstrated that lymphocyte-derived microparticles (LMPs) possess strong cytotoxic effect on cancer cells. This report demonstrated that LMPs have potent pro-apoptotic properties on human Rb cells, which was associated with a strong reduction of SYK expression. Perturbing SYK activity in Rb cells induced cell apoptosis and upregulated expression of p53 and p21. Interestingly, inhibition of p53 or knockdown of p21, abolished LMP-induced caspase-3 activity and cell death. Blocking oxidized phospholipid-rich LMPs with a specific antibody significantly prevented LMP-induced Rb apoptosis and reversed the expression patterns of SYK, p53, p21. In summary, our results suggest that LMPs are important pro-apoptotic regulators for Rb cells through reduction of SYK expression and upregulation of the p53-p21 pathway which ultimately activates caspase-3. These data may open unexpected avenues for the development of LMPs as a novel therapeutic strategy that would be particularly useful and relevant for the treatment of Rb.

To evaluate postoperative refractive changes in aphakic and pseudophakic children in a comparative case series.The medical records of pediatric patients with aphakia and pseudophakia were reviewed retrospectively. The mean change in refractive error from one postoperative examination to the next was calculated at each age to give aggregate curves of postoperative refractive change for each group.A total of 233 aphakic and 92 pseudophakic eyes were studied. The median age at the time of surgery was 0.8 years (range, 0.0-16 years) for patients with aphakia and 7.3 years (range, 1.5-19.9 years) for patients with pseudophakia (P.0001). The postoperative refraction curves at comparable ages of 2 to 20 years showed a total mean myopic shift of 1.5 D for patients with pseudophakia and 7.8 D for patients with aphakia. An age-matched subset of patients with aphakia also showed more myopic shift than those with pseudophakia.Pseudophakic eyes show less postoperative myopic shift than aphakic eyes. Selecting intraocular lens powers aimed at producing initial emmetropic refractions has been a good strategy in our cohort of patients with pseudophakia. However, our data are insufficient for conclusions regarding children with pseudophakia younger than 2 years, in whom larger myopic shifts may occur.

This review article will attempt to guide ophthalmologists in deciding the indications for cataract surgery. It will consider this year's visual function questionnaires, ancillary vision tests, and postoperative outcome measures to assess visual function. Cultural factors, age, and gender are a few of the confounding variables in trying to assess visual function. The indications for cataract surgery in the 21st century have evolved dramatically since cataract surgery was first performed in the 1700s. The physicians' dictum in the Hippocratic oath of "do no harm" has determined the indications for cataract surgery over time. Today, doing no harm means operating on cataracts earlier than previously, as this is technically easier than in previous years, when poorer surgical techniques prevailed. However, are we operating on cataracts too early? This review will attempt to highlight the relevant factors that will help to determine the indications for cataract surgery.

Orbital cellulitis is a rare complication of strabismus surgery. We report a case of a 4-year-old boy with bilateral orbital cellulitis after uneventful surgery to correct esotropia. Concomitant sinusitis was the likely source of infection. To our knowledge, this is the first case of bilateral orbital cellulitis following strabismus surgery.

Purpose: To quantify cataract patients' functional visual complaints and correlate them with their objective glare disability and spatial contrast sensitivity (SCS) scores. Setting: Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada. Methods: Thirty patients scheduled for cataract surgery with a visual acuity of 20/70or better at the time of patient selection and no other ocular pathology were evaluated objectively and subjectively for visual function preoperatively and within 3 months postoperatively. Objective measures of SCS and visual acuity in the presence and absence of glare were obtained with the Optec 3000 vision tester. Subjective visual function was evaluated with the Activities of Daily Vision Scale (ADVS), a questionnaire that evaluates patients' visual function by assessing the degree of difficulty they experience in performing tasks involving distance vision, near vision, and glare conditions. Results: Preoperatively, patients had decreased visual acuity and SCS in the presence of glare. The ADVS scores were correlated with visual performance. Postoperatively, there was a statistically significant improvement in all dependent measures (i.e., visual acuity and SCS in the presence of glare) as well as in the subjective report of visual performance assessed by the ADVS. Conclusion: Spatial contrast sensitivity, glare disability, and the ADVS questionnaire should be considered as adjuncts to visual acuity testing in evaluating certain cataract patients.

Importance The Intermittent Exotropia Questionnaire (IXTQ) is a patient, proxy, and parental report of quality of life specific to children with intermittent exotropia. We refine the IXTQ using Rasch analysis to improve reliability and validity. Observation Rasch analysis was performed on responses of 575 patients with intermittent exotropia enrolled from May 15, 2008, through July 24, 2013, and their parents from each of the 4 IXTQ health-related quality-of-life questionnaires (child 5 through 7 years of age and child 8 through 17 years of age, proxy, and parent questionnaires). Questionnaire performance and structure were confirmed in a separate cohort of 379 patients with intermittent exotropia. One item was removed from the 12-item child and proxy questionnaires, and response options in the 8- to 17-year-old child IXTQ and proxy IXTQ were combined into 3 response options for both questionnaires. Targeting was relatively poor for the child and proxy questionnaires. For the parent questionnaire, 3 subscales (psychosocial, function, and surgery) were evident. One item was removed from the psychosocial subscale. Resulting subscales had appropriate targeting. Conclusions and Relevance The Rasch-revised IXTQ may be a useful instrument for determining how intermittent exotropia affects health-related quality of life of children with intermittent exotropia and their parents, particularly for cohort studies.

An 85-year-old man developed an anterior dislocation of a posterior chamber intraocular lens (IOL) after blunt trauma. The dislocated IOL was exchanged for an anterior chamber IOL. Visual acuity was 20/40 at the 6 month follow-up. This case presents an unusual sequela of trauma to a pseudophakic eye and discusses management issues that should be considered.

Purpose: To determine whether brightness-induced glare decreases spatial contrast sensitivity and visual acuity in preoperative cataract patients with functional visual complaints and to compare preoperative with postoperative results. Setting: Sir Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada. Methods: Twenty patients with a visual acuity of 20/70 or better at the time of chart selection and no other ocular pathology who were referred for cataract surgery were evaluated with the Optec 3000 vision tester to assess contrast sensitivity and visual acuity in the presence and absence of glare. Testing was done preoperatively and 1 and 3 months postoperatively. Results: An analysis of variance indicated that there were statistically significant double interactions between the preoperative/postoperative and glare/no-glare variables and between the preoperative/postoperative and spatial frequency variables. Postoperatively, visual acuity and contrast sensitivity improved to within normal limits. There were no statistically significant differences in visual acuity and spatial contrast sensitivity between 1 and 3 months postoperatively. Conclusion: Spatial contrast sensitivity and glare testing provided objective assessment of patients who had good visual acuity yet also had functional complaints.