Clinical trial NCT04334499: Mitochondrial DNA in Vitreous Fluid and Blood in Patients With Eye Disease or Ocular Trauma.
Official title: Investigation of the Relationship Between Mitochondrial DNA in Vitreous Fluid and Blood in Patients With Eye Disease or Ocular Trauma.
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Eye Diseases
Ophthalmic Trauma
Mitochondrial DNA
Age Related Macular Degeneration
Glaucoma
Diabetic Retinopathy
Keywords: mitochondrial DNA
opthalmic trauma
age related macular degeneration
glaucoma
inflammation
inflammatory marker
diabetic retinopathy
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2020-04-06
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects suffering eye disease or ocular trauma and healthy subjects undergoing ocular surgery which may include the discard of vitreous humor.

Brief summary: This study is to characterize mitochondrial DNA (mtDNA) populations in adults with eye injuries and eye diseases. The eye exam is often hindered by the clouding of tissues involved in injury or disease. This protocol examines the use of mtDNA populations as indicators of developing inflammation and resolution of injury. This may be used to provide proactive treatment or define appropriate treatment needs beyond the indications of an ophthalmological exam.

Detailed description: The study aim to test correlation between the presence of the mitochondrial DNA in vitreous fluid and blood in patients that are admitted to UTMB's Eye clinic. The goal of the study is to analyze 4 groups of 30 samples of each major ocular disease and injury: age-related macular degeneration, glaucoma and diabetic retinopathy and ocular trauma. Up to 300 subjects may be consented to this study in order to meet recruitment goals. In this study we will use only otherwise discarded eye's vitreous together with a blood sample that is collected during surgery. Patients with ophthalmic surgery scheduled that may result in discarded vitreal fluid will be identified from the clinic schedule or by physician in the emergency room. The possibility of vitreous collection in a surgery may be uncertain. If a subject does not have discarded vitreous from a given surgery they will be screen failed prior to blood draw or data collection from electronic medical record from that moment forward. Subjects will be approached when appropriate for interest in participation in the study by their clinical faculty surgeon. An informed consent briefing will be provided by the clinical research coordinator with an opportunity to ask questions of both the coordinator, the clinical faculty surgeon and the principle investigator. Copies of the consent will be provided for the patient to take home. Additional opportunity for questions the morning of surgery will be provided. Consent signature will be obtained prior to any medication administration the upon admission for surgery. Samples if available will be collected during the eye surgery. Up to 1ml of vitreous fluid and up to 10 ml of blood will be collected from each patient. Samples will be stored at room temperature and transferred directly to Dr. Szczesny's laboratory. Vitreous fluid will be frozen for further analysis and blood plasma will be processed using histopaque and centrifugation prior freezing. Two types of analysis will be conducted with collected biospecimens.1) Total DNA will be isolated, follow by analysis with real-time quantitative polymerase chain reaction (RTq-PCR) using set of primers to identify the presence of the mitochondrial DNA and nuclear DNA as a control. 2) Extracellular vesicles will be isolated using ultracentrifugation or commercially available kit followed by analysis of the mitochondrial and nuclear DNA and/or plasma membrane markers using RTq-PCR and/or Western blot. Electronic medical records will be accessed to collect demographics and ophthalmologic diagnostic information and information on other comorbidity diagnoses.

These data points will include age in years, gender, race, ethnicity, presence of age related macular degeneration(AMD) (y/n), type and stage of AMD, use of AREDs vitamins, treatments of AMD, Glaucoma(y/n), type and stage of glaucoma, diabetes, blood glucose, diabetic retinopathy (y/n), type and stage of diabetic retinopathy, treatments of diabetic retinopathy and amount of time prior to this planned surgery, hypertension type and stage, renal disease type and stage, smoking history, cancer, cancer type, treatment or surgery, viral diagnoses (HIV, CMV, HCV), blunt eye trauma history, cataract history, lens removal surgery, cause of vitrectomy, concomitant medications and procedures, eye exam observations relevant to inflammatory processes, Optical coherence tomography data. IOP, visual field \[VF\] data, visual acuity, gonioscopic findings,.

Eligibility criteria: Inclusion Criteria:

* a) Target group

  1. Age ≥ 20 years old
  2. Subjects must not be nursing, pregnant or planning to become pregnant. Subjects of child bearing potential must have a documented negative pregnancy test at the time of preoperative assessment or not be of child bearing potential. Identified eye disease including but not limited to age-related macular degeneration, glaucoma and/or diabetic retinopathy.
  3. Scheduled ophthalmic surgery with expected vitreal humor discard.
  4. Subject has provided written informed consent to participate in this protocol. b) Control group

  <!-- -->

  1. Age ≥ 20 years old
  2. Subjects must not be nursing, pregnant or planning to become pregnant. Subjects of child bearing potential must have a documented negative pregnancy test at the time of preoperative assessment or not be of child bearing potential.
  3. Lack of identified eye disease.
  4. Scheduled ophthalmic surgery with expected vitreal humor discard.
  5. Subject has provided written informed consent to participate in this protocol.

Exclusion Criteria:

* a) Target group

  1. Age \< 20 years old
  2. Subject is nursing, pregnant, planning to become pregnant or of child bearing potential and does not agree to the use of reliable method of contraception during their participation in the study. A pregnancy test must be administered to women of childbearing potential at the time of preoperative assessment.
  3. Identified eye disease including but not limited to age-related macular degeneration, glaucoma and/or diabetic retinopathy.
  4. Subject has not completed informed consent to participate in this protocol. b) Scheduled ophthalmic surgery with expected vitreal humor discard Control group

  <!-- -->

  1. Age \< 20 years old
  2. Subject is nursing, pregnant, planning to become pregnant or of child bearing potential and does not agree to the use of reliable method of contraception during their participation in the study. A pregnancy test must be administered to women of childbearing potential at the time of preoperative assessment.
  3. Lack of identified eye disease.
  4. Subject has not completed informed consent to participate in this protocol. Scheduled ophthalmic surgery with expected vitreal humor discard.

Primary outcomes:
measure: Quantitation of mitochondrial DNA in vitreous humor and serum samples
timeFrame: 1 day
Secondary outcomes:
measure: Evaluation of mtDNA quantitation versus ocular comorbidities as described in electronic medical record.
timeFrame: 1 month
Other outcomes:
Locations:
Study officials:
affiliation: University of Texas
name: Bartosz Szczesny, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: