Rosanne Superstein

Treatment of Periocular Infantile Hemangiomas with Propranolol: Case Series of 18 Children

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.

Real-time Ophthalmoscopic Findings of Intraophthalmic Artery Chemotherapy in Retinoblastoma

Author Affiliations: Vitreoretinal Service, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics (Drs Davis, Folk, Russell, Sohn, Boldt, Stone, and Mahajan), Howard Hughes Medical Institute (Dr Stone), and Omics Laboratory (Dr Mahajan), University of Iowa, Iowa City. Correspondence: Dr Mahajan, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242 (mahajanlab@gmail.com). Financial Disclosure: None reported.

Anti-proliferative and anti-tumour effects of lymphocyte-derived microparticles are neither species- nor tumour-type specific

Background Unregulated cell proliferation or growth is a prominent characteristic of cancer. We have previously demonstrated that LMPs (cell membrane microparticles derived from apoptotic human CEM T lymphoma cells stimulated with actinomycin D) strongly suppress the proliferation of not only human endothelial cells but also mouse Lewis lung carcinoma cells. Methods LMPs were generated either from CEM T cells using different stimuli or from 3 different types of lymphocytes. The effects of LMPs on cancer cell proliferation were examined using cell lines from different species and tissues. The cell cycle kinetics was evaluated by FACS and the expression of cell cycle-related genes was determined using quantitative RT-PCR. The in vivo anti-tumor effect of LMPs was investigated using xenografts and allografts. Results LMPs at doses far above physiological levels dramatically suppressed the proliferation of cancer cells in a non species-specific manner. LMPs selectively target high proliferating cells and their anti-proliferative effect is not dependent on parental cell origin or stimuli. The anti-proliferative effect of LMPs was due to induction of cell-cycle arrest in G0/G1, with associated increases in expression of the cyclin-dependent kinase inhibitors p15INK4b, p16INK4a, and p21Cip1. In vivo, LMPs significantly suppressed tumor growth in animal tumor models. Conclusion These results highlight the potential role of LMPs in modulating the growth of high proliferating cells. Given that cell-based therapies are considered less toxic than pharmacologic approaches and have the potential to target multiple pathways in a synergistic manner, LMPs may serve as a veritable option for cancer treatment.

SYK is a target of lymphocyte-derived microparticles in the induction of apoptosis of human retinoblastoma cells

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.

The effects of the age of onset of strabismus on monocular and binocular visual function in genetically identical twins

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.

Data for: Pediatric ocular injuries: a 3-year review of patients presenting to an emergency department in Canada

BACKGROUND Ocular traumas represent the most common cause of noncongenital blindness in children. Sports are the second most common cause in children less than 14 years old in Canada. To our knowledge, there have not yet been any reports regarding the causes of pediatric ocular trauma in the Quebec population. The goal of our study was to gather data from the Quebec pediatric population to determine high-risk age groups, sports, or other activities. METHODS A retrospective study evaluating all patients younger than 18 years who presented with ocular trauma to the Ste-Justine Hospital emergency department between 2007 and 2010. Data obtained included age, sex, activity at the time of injury, mechanism of injury, and visual outcomes. RESULTS Trauma was more common in males (65%). The mean age was 7.2 years. Injuries occurred more often in the 5-9 year age group, at home, and during free play. Sports-related injuries occurred more often in the 10-18 year age group, with hockey being associated most often with injuries. Visual acuity at presentation was variable, but final acuity was 20/30 or better in 86.7% of cases. In 89% of cases, there was no mention of ocular protection and prevention of injuries in the chart by emergency physicians. CONCLUSION Our study suggests that ocular injuries may be prevented by better supervision and parental education in the younger population and by mandating ocular protection for sports in high school-aged patients.

Two Cases of Retinoblastoma Invading the Optic Nerve Sheath

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.].