Development and Maintenance of Binocular Vision (EY005236)

描述(申请人提供)：先天性和早发性双眼不平衡，包括内斜视(ET)和白内障，影响美国2-4%的婴儿。视觉发育过程中的双眼不平衡可能导致弱视和双眼视觉异常。超过90%的先天性和早发性双眼不平衡患者需要遮盖治疗、眼镜矫正和/或手术，许多患者需要反复干预。双眼感觉功能异常与多眼肌肉手术、分离性垂直偏斜、潜伏性眼球震颤和弱视的风险较高相关。因此，早发性双眼不平衡的代价是巨大的。在目前的授权期内，我们发现双眼视觉最初在婴儿ET中发育正常，但被异常的双眼经验所干扰。这一结果表明，早期手术可能会预防立体视缺陷，但尽管我们发现非常早期手术后立体视的发生率更高，正常的立体视却很少见。我们建议通过研究以下假设来追求这一令人惊讶的结果：婴儿ET与粗大的外周视差敏感性最初的正常发展有关，但中心视野的视差敏感性先天缺失或不可逆转的异常。此外，我们将调查先天性中心视差敏感度缺陷是否与婴儿ET的收敛异常有关。在目前的拨款期间，我们的几项研究支持双眼功能障碍和弱视之间的联系。我们将测试以下假设：不对称的双眼相互作用使一些内斜视婴儿和儿童容易患上内斜性弱视，脱离遮盖治疗可减少不对称性，以及持续性残余弱视是由于拒绝治疗的不对称性造成的。对3岁儿童弱视的了解相对较少。在即将到来的赠款期间，我们将描述弱视在生命的前3年的自然历史，确定在这个年龄段是否存在不同的治疗反应模式和与治疗相关的不同风险，并评估检测和监测婴幼儿弱视的新方法。虽然我们对单眼剥夺性弱视的影响和致密先天性单眼白内障的治疗方案有了很好的了解，但其他类型的白内障对发育中的视觉系统的影响仍然存在一些重要的问题。我们建议定义致密性先天性双眼白内障视力结局的关键期，观察部分性白内障对视力成熟的影响，并评估致密性先天性白内障儿童眼运动发育的临界期(S)。这五个目标加在一起，直接解决了NEI国家计划的一个明确目标，即“调查弱视和斜视高危儿童的视觉功能发展，确定潜在的机制，并开发和传播有关检测方法和治疗干预的信息，以恢复正常视力。”公共卫生相关性：例如，由于内斜视和白内障导致的先天性和早发性双眼不平衡在美国影响2-4%的婴儿。超过90%的先天性和早发性双眼不平衡患者需要遮盖治疗、眼镜矫正和/或手术，并且许多需要反复干预。拟议研究的目的是确定正常双眼视觉发展的充分必要条件，并改善与先天性和早发性双眼不平衡相关的疾病患者的治疗结果。

Description (provided by applicant): Congenital and early onset binocular imbalance, including esotropia (ET) and cataracts affect 2-4% of infants in the U.S. Binocular imbalance during visual development has the potential to cause amblyopia and abnormalities in binocular vision. Over 90% of patients with congenital and early onset binocular imbalance require occlusion therapy, spectacle correction, and/or surgery, and many require repeated interventions. Abnormal binocular sensory function is associated with higher risk for multiple eye muscle surgeries, dissociated vertical deviation, latent nystagmus, and amblyopia. Thus, the cost of early onset binocular imbalance is significant. During the current grant period, we found that binocular vision initially develops normally in infantile ET but is disrupted by abnormal binocular experience. This result suggested that very early surgery might prevent the deficit but, although we found a higher prevalence of stereopsis after very early surgery, normal stereoacuity was rare. We propose to pursue this surprising result by investigating the hypothesis that infantile ET is associated with initially normal development of the coarse, peripheral disparity sensitivity but a congenital absence or irreversible abnormality of the disparity sensitivity in the central visual field. Furthermore, we will investigate whether a congenital deficit in central disparity sensitivity is associated with vergence abnormalities in infantile ET. Several of our studies during the current grant support a link between binocular dysfunction and amblyopia. We will test the hypotheses that asymmetric binocular interactions predispose some esotropic infants and children to develop amblyopia, that weaning from occlusion therapy acts to diminish asymmetry, and that persistent residual amblyopia results from asymmetry that resists treatment. Relatively little is known about amblyopia in children <3 years of age. In the upcoming grant period, we will characterize the natural history of amblyopia during the first 3 years of life, determine whether different patterns of response to treatments and different risks associated with treatments are present in this age range, and evaluate new approaches to the detection and monitoring of amblyopia in infants and young children. While we have a good grasp on the effects of unilateral deprivation amblyopia and treatment protocols for dense congenital unilateral cataracts, a number of important questions remain about the effects of other types of cataracts on the developing visual system. We propose to define the critical period for visual acuity outcome in dense congenital bilateral cataracts, examine the effects of partial cataracts on visual maturation, and evaluate the critical period(s) for ocular motor development in children with dense congenital cataracts. Taken together, these five Aims directly address a stated goal of the NEI National Plan, namely "to investigate the development of visual function in children at high risk for amblyopia and strabismus, determine underlying mechanisms, and develop and disseminate information about detection methods and therapeutic interventions for restoring normal vision." PUBLIC HEALTH RELEVANCE: Congenital and early onset binocular imbalance due, for example, to esotropia and cataracts affect 2-4% of infants in the U.S. Over 90% of patients with congenital and early onset binocular imbalance require occlusion therapy, spectacle correction, and/or surgery, and many require repeated interventions. The aim of the proposed studies is to define the necessary and sufficient conditions for the development of normal binocular vision and to enhance treatment outcomes of patients with conditions that are associated with congenital and early onset binocular imbalance.