Improved Vision and Contact Lens Wear Time With Piggy-Back Contact Lens Systems in Children After Penetrating Corneal Trauma.

OBJECTIVE: Consecutive case series of children treated successfully with "piggy-back" (PB) contact lens systems after corneal trauma. METHODS: We reviewed the medical record of all children ages 4 to 14 years treated at the Emory Eye Center between January 11, 2003 and January 11, 2013 with PB contact lens systems. RESULTS: Four children with a history of corneal penetrating trauma were treated with a PB lens system, with a mean age of 7±0.08 (range: 6-8) years. Best-corrected spectacle vision was count fingers in two children and logMAR +0.70 (Snellen equivalent 20/100) and logMAR +0.6 (Snellen equivalent 20/80) in the remaining two. The PB lens system was introduced with a mean of 15.7±6.5 (range: 9-22) months after the injury. All patients were initially fitted with gas-permeable (GP) lenses. Each child achieved 11 or more hours of daily contact lens wear time in PB systems. The mean best-corrected logMAR visual acuity using the PB system was 0.26±0.21 (Snellen equivalent 20/36). The mean improvement in best-corrected logMAR between GP and PB lens systems was +0.21±0.11, which corresponds to an improvement of greater than two lines on the Snellen chart. CONCLUSION: Piggy-back contact lens systems can be helpful to improve vision and contact lens wearing time in children with irregular astigmatism after corneal trauma, who are intolerant of GP contact lenses.

The handy eye chart: a new visual acuity test for use in children.

OBJECTIVE: To design a simple matching acuity test based on hand gestures that is minimally dependent on familiarity with symbols and letters. The visual acuity results obtained from children using the Handy Eye Chart were compared with results obtained with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: Sixty children aged 6 to 16 years were recruited consecutively from the Pediatric Ophthalmology section of the Emory Eye Center. METHODS: Monocular visual acuity was tested using both the new eye chart and the ETDRS chart, alternating the order of administration between subjects. Testing was performed on the subject's eye with the poorest acuity. MAIN OUTCOME MEASURES: Outcome measures were monocular logarithm of the minimum angle of resolution (logMAR) visual acuity scores for each chart. RESULTS: The acuities were shown to have a strong linear correlation (r = 0.95) and a mean difference in acuity of -0.03 (95% confidence interval, -0.05 to -0.01) logMAR, equivalent to approximately 1.5 letters, with the new eye chart underestimating the vision as determined by the ETDRS chart. The 95% limits of agreement were ±1.6 lines. CONCLUSIONS: This study supports the validity of the new eye chart as a measure of visual acuity in pediatric patients aged 6 to 18 years with vision ranging from 20/16 to 20/200.

A reduction in Pten tumor suppressor activity promotes ErbB-2-induced mouse prostate adenocarcinoma formation through the activation of signaling cascades downstream of PDK1.

Loss of function at the Pten tumor-suppressor locus is a common genetic modification found in human prostate cancer. While recent in vivo and in vitro data support an important role of aberrant ErbB-2 signaling to clinically relevant prostate target genes, such as cyclin D1, the role of Pten in ErbB-2-induced prostate epithelial proliferation is not well understood. In the Pten-deficient prostate cancer cell line, LNCaP, restoration of Pten was able to inhibit ErbB-2- and heregulin-induced cell cycle progression, as well as cyclin D1 protein levels and promoter activity. Previously, we established that probasin-driven ErbB-2 transgenic mice presented with high-grade prostate intraepithelial neoplasia and increased nuclear cyclin D1 levels. We show that mono-allelic loss of pten in the probasin-driven-ErbB-2 model resulted in increased nuclear cyclin D1 and proliferating cell nuclear antigen levels and decreased disease latency compared to either individual genetic model and, unlike the probasin-driven-ErbB-2 mice, progression to adenocarcinoma. Activated 3-phosphoinositide-dependent protein kinase-1 was observed during cancer initiation combined with the activation of p70S6K (phospho-T389) and inactivation of the 4E-binding protein-1 (phosphorylated on T37/46) and was primarily restricted to those cases of prostate cancer that had progressed to adenocarcinoma. Activation of mTOR was not seen. Our data demonstrates that Pten functions downstream of ErbB-2 to restrict prostate epithelial transformation by blocking full activation of the PDK1 signaling cascade.

ErbB-2 induces the cyclin D1 gene in prostate epithelial cells in vitro and in vivo.

The receptor tyrosine kinase ErbB-2 plays an important role in the regulation of growth factor-induced signal transduction cascades in the epithelium, and ErbB-2 is frequently overexpressed in epithelial tumors. Our previous studies on clinical prostate cancer specimens indicated that ErbB-2 expression was increased in patients undergoing hormone ablation therapy. We had also shown that the critical cell cycle regulatory gene cyclin D1 and its promoter were targets of proliferative signaling in prostate cancer cell lines, and that cyclin D1 was required for ErbB-2-induced mammary tumorigenesis. In the current studies, we found that increased ErbB-2 membrane expression correlated with increased nuclear cyclin D1 staining in clinical prostate cancer specimens, and that expression of ErbB-2 was capable of inducing cell cycle progression in human prostate cancer cell lines. We further showed that ErbB-2 induced the cyclin D1 promoter in DU145 cells, and that small interfering RNA knockdown of cyclin D1 protein levels blocked a significant proportion of the heregulin-induced cell cycle progression in LNCaP cells. Probasin promoter-targeted expression of an activated ErbB-2 isoform induced cyclin D1 expression in the mouse prostate, commensurate with prostate intraepithelial neoplasia. Together, these in vitro and in vivo studies identify cyclin D1 as a critical downstream target of ErbB-2 in the prostate epithelium, both of which are possible therapeutic targets for cancer intervention. Furthermore, our novel mouse model provides a useful platform for ongoing in vivo investigations of ErbB-2 signaling in the prostate epithelium.

Association of Contact Lens Adherence With Visual Outcome in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Although contact lenses have been used for decades to optically correct eyes in children after cataract surgery, there has never been a prospective study looking at contact lens adherence in children with aphakia, to our knowledge. Objective: To evaluate contact lens adherence and its association with visual outcome in a cohort of children treated for unilateral cataract surgery. Design, Setting, and Participants: Secondary analysis of a multicenter randomized clinical trial of 57 infants born from August 22, 2004, to April 25, 2008, who were randomized to 1 of 2 treatments and followed up to age 5 years. Data analysis was performed from August 9, 2016, to December 7, 2017. Interventions: Unilateral cataract extraction and randomization to implantation of an intraocular lens vs contact lens to correct aphakia. Main Outcomes and Measures: Contact lens adherence was assessed by a 48-hour recall telephone interview that was administered every 3 months starting 3 months after surgery to age 5 years. A traveling examiner assessed visual acuity in patients at aged 4.5 years. Adherence to prescribed contact lens use was estimated as the mean percentage of waking hours as reported in 2 or more interviews for each year of life. Results: Of 57 infants who were randomized to contact lens treatment, 32 (56%) were girls, and 49 (86%) were white. A total of 872 telephone interviews were completed. In year 1, a median of 95% participants wore their contacts lenses nearly all waking hours (interquartile range [IQR], 84%-100%); year 2, 93% (IQR, 85%-99%); year 3, 93% (IQR, 85%-99%); year 4, 93% (IQR, 75%-99%); and year 5, 89% (IQR, 71%-97%). There was a tendency for poorer reported adherence at older ages (F = 3.86, P < .001). No differences were identified when the results were analyzed by sex, insurance coverage, or age at cataract surgery. Using linear regression, children who wore the contact lens for a greater proportion of waking hours during the entire study period tended to have better visual acuity at age 4.5 years, even after accounting for adherence to patching (partial correlation = -0.026; P = .08). Conclusions and Relevance: These results confirm that it is possible to achieve a high level of aphakic contact lens adherence over a 5-year period in children. Trial Registration: clinicaltrials.gov Identifier: NCT00212134.

ErbB-2 induces bilateral adrenal pheochromocytoma formation in mice.

Pheochromocytoma (PCC) is a rare catecholamine-producing tumor that arises from the adrenal medulla and is often familial. The genetic basis for familial PCC involves mutations of RET, VHL, SHDx or NF-1 in more than 20% of cases. Additional genes may be important in pathogenesis of both familial and sporadic PCC. ErbB-2/Her2/Neu is a growth factor receptor tyrosine kinase that is frequently overexpressed in tumors and there is clinical evidence suggesting that enhanced ErbB-2 growth factor receptor signaling may play a role in PCC. In the present study, ectopic expression of an activated ErbB-2 transgene resulted in bilateral adrenal PCC. Analyses of tumor samples and normal adrenal tissue revealed that levels of the Pten tumor suppressor protein were greatly reduced in PCCs, while levels of the cell cycle regulatory protein cyclin D1 were usually increased. In addition, levels of phospo-AKT were increased in PCCs versus normal adrenal tissue. Biochemical analyses established that PCC's were functionally active, producing abundant levels of the catecholamines, epinephrine and norepinephrine. These data establish that increased ErbB-2 growth factor receptor signaling in the adrenal medulla can lead to PCC through combined influences on Pten, AKT andcyclin D1.