Clinical trial NCT03342235: Excimer Laser Surgery for Anisometropic Amblyopia
Official title: Excimer Laser Surgery for Anisometropic Amblyopia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Anisometropic Amblyopia
Refractive Errors
Keywords: Excimer Laser Surgery
Photorefractive Keratectomy
Anisometropic Amblyopia
Visual Acuity
Refractive Surgical Procedures
PRK
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2017-11-14
Enrollment: 0
Sex: ALL
Minimum age (years): 3
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Surgical Group: treatment with PRK and patching prescribed 2 hours per day with continued refractive correction (with spectacles and/or contact lenses) as able.

  o Surgery will be performed within 60 days of randomization
* Non-surgical Control Group: patching prescribed 2 hours per day with continued refractive correction (with spectacles and/or contact lenses) as able.
Primary purpose: TREATMENT

Brief summary: Study Objectives To compare the efficacy and safety of surgical treatment (PRK) versus non-surgical treatment of anisometropic amblyopia in children who have failed conventional treatment due to non-compliance or non-response.

Synopsis of Study Design

The study consists of two phases:

1. A Patching Run-In Phase during which all participants are treated for at least 8 weeks with continued refractive correction (with spectacles and/or contact lenses) and patching prescribed 42 hours per week (averaging 6 hours daily) until no further improvement over 2 consecutive visits at least 4 weeks apart or the vision no longer meets eligibility criteria.
2. A Randomized Trial Phase, beginning after no further VA improvement in the patching run-in phase and qualifying amblyopia is still present, during which the participant is assigned to either surgery with PRK and patching prescribed 2 hours per day or to non-surgical treatment with continued refractive correction (with spectacles and/or contact lenses) and patching prescribed 2 hours per day.

Detailed description: The study is evaluating the efficacy of surgical treatment with PRK versus non-surgical treatment of anisometropic amblyopia in children who have failed conventional treatment. The primary analysis will be a treatment group comparison of the change in BCVA in the amblyopic eye at the 8-month primary outcome visit. For participants wearing a contact lens, the BCVA will be the visual acuity tested in the contact lens rather than in spectacles (or trial frames).

Eligibility criteria: Inclusion Criteria:

1. Age 3 to \<8 years
2. Best-corrected amblyopic-eye VA using the ATS single-surround HOTV letter protocol (ATS-HOTV) meeting the following criteria:

   * If age 3 to \<5 years, 20/80 to 20/800 (a re-test is required if the VA is 20/80)
   * If age 5 to \<8 years, 20/63 to 20/800 (a re-test is required if the VA is 20/63)
   * Note: For participants who require a re-test (as specified above), the better of the test and re-test acuities must meet the eligibility criteria for the amblyopic eye and will serve as the enrollment VA.
3. Best-corrected fellow-eye VA meeting the following criteria by ATS-HOTV:

   * If age 3 years, 20/50 or better
   * If age 4 to 5 years, 20/40 or better
   * If age 6 to 7 years, 20/32 or better
4. Best-corrected inter-ocular acuity difference ≥ 3 logMAR lines by ATS-HOTV
5. Refractive error meeting the following criteria (based on a cycloplegic refraction that is not more than 4 months old):

   * Refractive error in the amblyopic eye must be greater than the fellow eye.
   * If the amblyopic eye is myopic, SE refractive error in the amblyopic eye between -3.00D and -12.00D, inclusive.
   * If the amblyopic eye is hyperopic, SE refractive error in the amblyopic eye between +3.00D and +6.00D, inclusive, if \<=1.00D of astigmatism in the amblyopic eye; and between +3.00D and +5.00D, inclusive, if \>1.00D of astigmatism in the amblyopic eye.
   * Astigmatism less than or equal to 3.50D in the amblyopic eye.
   * SE refractive error in the fellow eye between -4.00D and +3.00D, inclusive, with no astigmatism limits.
   * For participants 3 to \<5 years of age, at least 5.00D of SE anisometropic difference between the two eyes by cycloplegic refraction; for subjects 5 to \<8 years of age, at least 3.00D SE anisometropic difference
   * No more than 3.00D of difference in cylinder power between the two eyes
   * Target postoperative refractive error (if participant becomes eligible for randomization) must be achievable with PRK as defined in Table 3 and must be within 2.00D of the fellow eye.
6. Prior to enrollment into the Patching Run-In Phase, must have had patching and/or optical penalization with atropine or Bangerter filters prescribed for at least 6 months and optical correction of refractive error prescribed for at least 6 months. Prior treatment does not have to be continuous. Compliance with prescribed treatment does not influence eligibility but the best effort at compliance is expected from both the patient and provider.
7. Corneal thickness \>500 microns (\>510 microns within the previous 7 months, or corneal thickness between 500 and 510 microns within the last 2 months).
8. Central corneal thickness must be enough to allow the treatment dose needed while leaving a residual corneal thickness of ≥ 375 microns.
9. IOP ≤ 22 mm Hg within 7 months of enrollment
10. Investigator believes that the participant has achieved maximum improvement in amblyopic-eye VA with conventional treatment.
11. Investigator is willing to prescribe patching, and parent and child are willing to attempt patching for at least 8 weeks for 42 hours per week (averaging 6 hours daily) in the Patching Run-In Phase.
12. No rigid gas permeable lens (including OrthoK) worn in the past 2 months
13. Soft contact lens is currently worn, has been attempted within the past 4 months, or a contact lens fitting exam (paid for by the study) is scheduled or the investigator does the contact lens fitting on the same day as enrollment.
14. Parent understands the protocol and is willing to accept randomization (if child meets eligibility criteria after Patching Run-In Phase).
15. Parent has a phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff during the next 36 months.
16. Relocation outside of area of an active PEDIG site for this study without the next 36 months is not anticipated.

Exclusion Criteria:

1. Non-refractive ocular cause for reduced VA in the amblyopic eye (example: cataract, posterior staphyloma, extensive myelinated nerve fiber layer, optic nerve anomaly, macular scar, corneal opacity); or any cause of previous form deprivation.
2. Prior penetrating ocular surgery or injury
3. Prior strabismus surgery within 60 days preceding enrollment
4. Diagnosis of collagen vascular disease, Marfan syndrome, Ehlers-Danlos syndrome or other disorder of collagen synthesis
5. Previous ocular condition that may predispose the eye to be treated for future complications, for example:

   * Corneal disease (e.g., herpes simplex, herpes zoster keratitis, keratoconus or suspicion of keratoconus based upon family history, slit lamp exam, retinoscopy, or corneal topography (if able), recurrent erosion syndrome, corneal melt, or corneal dystrophy)
   * Established diagnosis of glaucoma
   * Any condition that, in the investigator's opinion, would interfere with or prolong corneal epithelial healing
   * History of significant eye rubbing or dry eye symptoms
6. History of retinopathy of prematurity resulting in macular ectopia
7. Down syndrome (trisomy 21)

Primary outcomes:
measure: Mean Change in Best Corrected Visual Acuity in the Amblyopic Eye
timeFrame: from randomization to the 8-month primary outcome visit
Secondary outcomes:
measure: Randot Preschool Stereoacuity Outcomes by Treatment Group
timeFrame: At 8 months after randomization
measure: Refractive Error Outcomes in Surgery Group
timeFrame: At 7 months after randomization
measure: Visual Acuity Outcomes
timeFrame: At 8 months
measure: Distribution of refractive error outcomes
timeFrame: At 7 months after baseline
measure: Distribution in Randot Preschool stereoacuity level
timeFrame: at baseline and 8 months
measure: Visual Acuity Outcomes at 12 and 24 Months Post-surgery
timeFrame: at 12 and 24 months after surgery
measure: Stereoacuity at 12 and 24 Months Post-surgery
timeFrame: at 12 and 24 months after surgery
measure: Refractive Error at 12 and 24 Months Post-surgery
timeFrame: at 12 and 24 months after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Baylor College of Medicine
name: Evelyn A Paysse, MD
role: STUDY_CHAIR
affiliation: Duke Eye Center
name: David K Wallace, MD, MPH
role: STUDY_CHAIR
References: