Genetic Polymorphism and Retinopathy of Prematurity: Correlation of Clinical Presentations and Severity

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Brief Title

Genetic Polymorphism and Retinopathy of Prematurity: Correlation of Clinical Presentations and Severity

Official Title

Genetic Polymorphism and Retinopathy of Prematurity: Correlation of Clinical Presentations and Severity

Brief Summary

      Study Aim and Goals

        1. Evaluate the correlation between genetic polymorphism and ROP development

        2. To study the possibility if there are any specific genetic polymorphisms that lead to
           poor outcome or recurrence of ROP after treatment.
    

Detailed Description

      Background:

      The preterm neonate, especially the low birth weight infant, is at a greater risk to develop
      disorders in multiple organ systems because of immaturity. Retinopathy of prematurity (ROP)
      is a disorder of the developing retina of low birth weight preterm infants that has the
      potential to lead to blindness. Although the pathogenesis and etiology of ROP remains
      unclear, many causative factors have been proposed. Vascular endothelial growth factor (VEGF)
      is an important regulator of angiogenesis in fetal life. In humans, polymorphisms in the VEGF
      gene have been reportedly associated with proliferative diabetic retinopathy and age-related
      degeneration. These retinal diseases might share the disease process of vasculopathy with
      ROP. Besides risk factors specifically associated with preterm birth, the activation of
      pro-inflammatory cytokines has been suggested to contribute to ROP development. Tumor
      necrosis factor (TNF)-α is one of the major cytokines in inflammation. Its expression was
      up-regulated in retinal neovascularization in animal models and proliferative eye diseases in
      humans. Many researchers suggest that TNF-α may affect retinal angiogenesis and predispose
      preterm infants for later development of ROP. Recent studies showed the possible correlation
      between ROP and polymorphism in VEGF (-460 T/C, +936 C/T, -634 G/C, and -2578 C/A), or TNF-α
      (-308 G/A). However, these studies focused on western populations. In our study, we will
      analyze the relationships among severity, treatment outcomes, and genetic polymorphism
      findings in ROP.

      Study Aim and Goals

        1. Evaluate the correlation between genetic polymorphism and ROP development

        2. To study the possibility if there are any specific genetic polymorphisms that lead to
           poor outcome or recurrence of ROP after treatment.

      Study Design Participants: We plan to recruit the children born at Linkou and Taipei branches
      of Chung Gung Memorial Hospital in 2009-2018, who are willing to undergo series of
      ophthalmologic examinations.

      Study period: April, 2021 to March, 2024. A prospective cohort study Inclusion criteria: All
      children who were born at Linkou and Taipei branches of Chung Gung Memorial Hospital during
      the period of 2009 to 2018.

      Exclusion criteria: If the parents were not willing to participate the study, or the medical
      records were not complete, or the follow period was less than 6 months.

      Estimated patients' numbers: about 500 babies/3 years Methods: Participants will receive
      series of ocular exams, including: cycloplegic refractions, strabismus exams, exams of
      intraocular pressure, slit lamp exam, fundus exam, axial length measurement, etc. After the
      parent's and the participant's agreement, we will have a blood test of 3 ml and undergo DNA
      collection (Oragene-DNA; DNA-Genotek, Ottawa, Canada) by study personnel. We will analyze
      around 10 SNPs from each of candidate genes in our study.

      According to patients' previous records and images, subjects will be classified as cases and
      controls. "Cases" will be infants with severe treatment-requiring ROP (defined as type-1 ROP
      [zone I, any stage, with plus disease; zone I, stage 3, without plus disease; or zone II,
      stage 2 or 3, with plus disease] or worse). "Controls" will be full-term babies without other
      retinal disorder, infants with no ROP or with mild ROP less severe than type-1 ROP, who are
      within the same birth weight group (e.g., <1000 grams or ≥1000 grams). After matching genetic
      results and structural outcomes, we will analyze whether any specific genetic polymorphism
      had higher presentations in treatment-requiring ROP patients. Also, secondary analysis will
      focus on the difference between recurrent/poor outcome cases and other cases.

      Statistical Analysis: Continuous variables will be analyzed with independent-t or paired-t
      test. One-way ANOVA will be used to compare three or more groups. Ordinal variables will be
      analyzed with Wilcoxon rank sum test (two independent samples) or Wilcoxon signed rank test
      (tow paired samples). Categorical variables will be analyzed with Chi-square test or Fisher's
      exact test. A multivariable logistic regression model will be constructed to assess the
      association between myopia prevalence and all studied risk factors. P value <0.05 will be
      considered statistically significant.
    


Study Type

Observational [Patient Registry]


Primary Outcome

SNP Selection, Detection, and Genotyping


Condition

Retinopathy of Prematurity

Intervention

Severe ROP

Study Arms / Comparison Groups

 PM No-ROP
Description:  Premature without retinopathy of prematurity. Prematurity was defined as birth at < 37 weeks gestation.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Procedure

Estimated Enrollment

500

Start Date

April 1, 2021

Completion Date

March 31, 2024

Primary Completion Date

March 31, 2024

Eligibility Criteria

        Inclusion Criteria:

        1. Infants born at Linkou and Taipei branches of Chang Gung Memorial Hospital during the
        study period.

        Exclusion Criteria:

          1. Parents unwilling to participate in the study

          2. Incomplete medical records.

          3. Folllow-up period less than 6 months

          4. Other ocular diagnosis including glaucoma, cataract, FEVR, etc.
      

Gender

All

Ages

3 Years - 12 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Wu WeiChi, M.D., PhD., 886-3-3281200, [email protected]

Location Countries

Taiwan

Location Countries

Taiwan

Administrative Informations


NCT ID

NCT05132257

Organization ID

202001715A3


Responsible Party

Sponsor

Study Sponsor

Chang Gung Memorial Hospital


Study Sponsor

Wu WeiChi, M.D., PhD., Principal Investigator, Chang Gung Memorial Hospital


Verification Date

April 2021