[Skip to Content]
[Skip to Content Landing]
Views 522
Citations 0
Original Investigation
November 7, 2019

Secondary 12-Month Ocular Outcomes of a Phase 1 Dosing Study of Bevacizumab for Retinopathy of Prematurity

Author Affiliations
  • 1Virginia Pediatric Eye Center, Virginia Beach
  • 2Jaeb Center for Health Research, Tampa, Florida
  • 3Department of Ophthalmology, Indiana University School of Medicine, Indianapolis
  • 4Mayo Clinic, Rochester, Minnesota
  • 5Wilmer Institute, Baltimore, Maryland
  • 6Dean A. McGee Eye Institute, University of Oklahoma, Oklahoma City
  • 7Now with Connecticut Children's Medical Center, Hartford, Connecticut
  • 8Pediatric Ophthalmology Associates Inc, Columbus, Ohio
  • 9Cincinnati Children’s Hospital, Cincinnati, Ohio
  • 10Texas Children's Hospital, Houston
JAMA Ophthalmol. Published online November 7, 2019. doi:https://doi.org/10.1001/jamaophthalmol.2019.4488
Key Points

Question  What were ocular outcomes at 12 months’ corrected age for eyes that received a dose of 0.625 mg to 0.031 mg of bevacizumab for type 1 retinopathy of prematurity?

Findings  In this cohort study of 46 infants (87 eyes), 12 eyes had myopia greater than −5.00 D spherical equivalent, and 2 eyes had hyperopia greater than 5.00 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye, 3 eyes, and 3 eyes, respectively.

Meaning  Ocular abnormality rates at 1 year were consistent with those reported in other studies with higher bevacizumab dosages.

Abstract

Importance  Lower bevacizumab dosages are being used for type 1 retinopathy of prematurity, but there are limited data on long-term ocular outcomes with lower doses.

Objective  To evaluate ocular outcomes at 12 months’ corrected age for eyes that received a dose of 0.625 mg, 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab for type 1 retinopathy of prematurity.

Design, Setting, and Participants  This prospective cohort study used a masked, multicenter, phase 1 dose de-escalation study design and was conducted from April 2016 to October 2017. Study eyes were treated with a dose of 0.25, 0.125, 0.063, or 0.031 mg of bevacizumab; fellow eyes were treated with a dosage 1 level higher than the study eye. Additional treatment after 4 weeks was at investigator discretion. Data analysis occurred from November 2018 to March 2019.

Interventions  Intravitreous bevacizumab injections of 0.625 mg to 0.031 mg.

Main Outcomes and Measures  Visual fixation, amblyopia, alignment, nystagmus, cycloplegic refraction, and ocular examinations were assessed at 12 months’ corrected age as preplanned secondary outcomes. The primary outcome 4 weeks after treatment and secondary outcomes after 6 months’ corrected age have been previously reported.

Results  Forty-six of 61 infants (75%) had a 12-month follow-up examination (46 study eyes and 43 fellow eyes; median [interquartile range] birth weight, 650 [590-760] g). Of 87 eyes with a cycloplegic refraction, 12 (14% [95% CI, 7%-27%]) had myopia of more than −5.00 D spherical equivalent; 2 (2%; [95% CI, 0%-8%]) had hyperopia greater than 5.00 D spherical equivalent; and 5 infants (11% [95% CI, 4%-24%]) had anisometropia greater than 1.50 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye (1% [95% CI, 0%-6%]), 3 eyes (3% [95% CI, 1%-10%]), and 3 eyes (3% [95% CI, 1%-10%]), respectively. Optic nerve atrophy was identified in 11 eyes (13% [95% CI, 6%-26%]), and 1 eye (1% [95% CI, 0%-6%]) had total retinal detachment. Strabismus was reported in 13 infants (30% [95% CI, 17%-45%]), manifest nystagmus in 7 infants (15% [95% CI, 6%-29%]), and amblyopia in 3 infants (7% [95% CI, 1%-18%]). Overall, 98% of infants had central fixation in each eye (44 of 45 eyes).

Conclusions and Relevance  In this study of low-dose bevacizumab, the secondary outcomes of high myopia, strabismus, retinal detachment, nystagmus, and other ocular abnormalities at 1 year were consistent with rates reported in other studies with higher dosages.

Trial Registration  ClinicalTrials.gov identifier: NCT02390531

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×