Localization of laminin to retinal vessels of the rat and mouse using whole mounts

Using a whole mount procedure in adult and neonatal mice and adult rats, we have developed an immunohistochemical method for the localization of laminin-like immunoreactivity (LLIR) to the retinal vessels. LLIR was localized to the vascular basement membrane, permitting a clear three-dimensional view of the retinal vasculature. Positive stain was seen in the inner limiting membrane, in retracted capillaries, encasing pericytes, and in a banding pattern on retinal arterioles. The major findings with the whole mount preparations were confirmed using paraffin-embedded material, with the additional observation of LLIR in the lens capsule. In whole mounts of retinas from neonatal mice, LLIR was present from the earliest stages of capillary growth, indicating that laminin is likely to be secreted by endothelial cells during retinal angiogenesis. LLIR within the retinal nerve fiber layer does not precede capillary ingrowth, so no evidence was found that laminin acts as a tracker signal for retinal angiogenesis

Anterior segment mesenchymal dysgenesis in a large Australian family is associated with the recurrent 17 bp duplication in PITX3

Purpose: A recurrent 17 bp duplication (c.657ins17bp) of a segment of the paired-like homeodomain transcription factor 3 (PITX3) gene on human chromosome 10 has been reported in seven families with autosomal dominant posterior polar cataracts with or without anterior segment mesenchymal dysgenesis (ASMD). ASMD can include Peters anomaly with corneal clouding, iridolenticular corneal adhesions, displaced Schwalbe's line, and cataract as described previously in a large Australian family. This study reports the examination of PITX3 in this Australian family. Methods: Clinical examinations of the proband and her relatives were performed as part of routine follow up. A polymerase chain reaction (PCR) based test for the duplication in PITX3 was developed, and DNA from 21 members of the proband's family was tested. Results: All clinically affected members of the family had the same 17 bp duplication of PITX3. There was no difference in the size of the duplication between the severely affected individuals and the more mildly affected individuals. Prenatal diagnosis was performed for two offspring of one affected person. In the first pregnancy, the fetus was shown to carry the duplication while in the second pregnancy, the fetus was shown to be homozygous for the normal allele. Conclusions: The results show that in some individuals within one family, duplication of this segment of PITX3 can result in severe symptoms leading to functional blindness while in other individuals in the same family or in other families, the same duplication leads to treatable cataract with minimal visual impairment

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

The effect of amblyopia on fine motor skills in children

PURPOSE. In an investigation of the functional impact of amblyopia in children, the fine motor skills of amblyopes and agematched control subjects were compared. The influence of visual factors that might predict any decrement in fine motor skills was also explored.--- METHODS. Vision and fine motor skills were tested in a group of children (n 82; mean age, 8.2 1.7 [SD] years) with amblyopia of different causes (infantile esotropia, n 17; acquired strabismus, n 28; anisometropia, n 15; mixed, n 13; and deprivation n 9), and age-matched control children (n 37; age 8.3 1.3 years). Visual motor control (VMC) and upper limb speed and dexterity (ULSD) items of the Bruininks-Oseretsky Test of Motor Proficiency were assessed, and logMAR visual acuity (VA) and Randot stereopsis were measured. Multiple regression models were used to identify the visual determinants of fine motor skills performance. RESULTS. Amblyopes performed significantly poorer than control subjects on 9 of 16 fine motor skills subitems and for the overall age-standardized scores for both VMC and ULSD items (P 0.05). The effects were most evident on timed tasks. The etiology of amblyopia and level of binocular function significantly affected fine motor skill performance on both items; however, when examined in a multiple regression model that took into account the intercorrelation between visual characteristics, poorer fine motor skills performance was associated with strabismus (F1,75 5.428; P 0.022), but not with the level of binocular function, refractive error, or visual acuity in either eye.--- CONCLUSIONS. Fine motor skills were reduced in children with amblyopia, particularly those with strabismus, compared with control subjects. The deficits in motor performance were greatest on manual dexterity tasks requiring speed and accuracy

Effect of amblyopia on self-esteem in children

Purpose: In an investigation of the psychosocial impact of amblyopia on children, the perceived self-esteem of children who had been treated for amblyopia was compared with that of age-matched controls. The influence of amblyopia condition or treatment factors that may impact self-perception scores was also explored.----- Methods: Children with a history of treatment for amblyopia (n = 47; age 9.2 +/- 1.3 years) and age-matched controls (n = 52; age 9.4 +/- 0.5 years) completed a standardized age-appropriate questionnaire based evaluation of perceived self-esteem (Harter Self Perception Profile for Children). Their vision characteristics and treatment regimen were also recorded. Bivariate correlation analysis was used to investigate the amblyopic characteristics and treatment factors that may have influenced self-perception scores in the amblyopic group.----- Results: Children treated for amblyopia had significantly lower social acceptance scores than age-matched control children. In other areas related to self-esteem, including scholastic competence, physical appearance, athletic competence, behavioral conduct and global self worth, amblyopic children gave scores similar to those of control children. Within the amblyopic group, a lower social acceptance score was significantly correlated with a history of treatment with patching but not with a history of strabismus or wearing of glasses.----- Conclusions. Self-perception of social acceptance was lower in children treated for amblyopia compared with agematched controls. A reduction in these scores was associated with a history of patching treatment but not with a history of strabismus or spectacle wear

Partial Jensen's procedure for the treatment of myopic strabismus fixus

Myopic strabismus fixus (MSF) is a rare strabismus entity of uncertain etiology. The most recent explanation of etiology was provided by Yokoyama et al,(1) who noted that the enlarged globe in high myopia herniates superotemporally and retroequatorially through the muscle cone. In a typical case, the eye is fixed in depression and adduction. We report the use of a partial Jensen's procedure (superior arm only) for the treatment of MSF