Minocycline to treat central retinal vein occlusion

Institution: National Eye Institute

Author/principal investigator: Catherine A. Cukras, MD

Abstract/statement of the trial’s goals

This study is designed to investigate the safety and potential efficacy of minocycline as a microglia inhibitor in participants with central retinal vein occlusion. Microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in vein occlusions. Minocycline, a second-generation tetracycline, has been shown to exhibit anti-inflammatory properties, including microglial inhibition. This study is a pilot, double-masked, randomized single-center study, using 100 mg minocycline or placebo orally twice daily in addition to standard-of-care anti-VEGF intravitreal injections.

Study population: 20

Inclusion criteria

Age older than 18 years.
Female participants of childbearing potential must not be pregnant or breast-feeding and must be willing to undergo urine pregnancy tests throughout the study.
Female participants of childbearing potential and male participants able to father children must be willing to use contraception.
Participants must agree to notify the study investigator or coordinator if any of their doctors initiate a new medication during the course of this study.
Participant must have normal renal function and liver function or have mild abnormalities not above grade 1, as defined by the Common Terminology Criteria for Adverse Events v4.0.
Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses and sunscreen (minimum SPF 15) if she or he must be out in the sun.
Participant has at least one eye that meets the study eye criteria.
The study eye shows definite retinal thickening due to a CRVO based on clinical examination involving the center of the macula that is not refractory to further therapy as based on the investigator’s clinical judgment.
The study eye has a best corrected ETDRS visual acuity score between 78 and 34 letters (ie, between 20/32 and 20/200).
The study eye has retinal thickness in the central subfield on baseline optical coherence tomography of more than 350 µm, as measured by Cirrus spectral domain OCT (Carl Zeiss Meditec), or an equivalent retinal thickness on a similar OCT machine.
The study eye has media clarity and pupillary dilation sufficient for adequate fundus photographs.

Exclusion criteria

Participant is in another investigational study and actively receiving investigational product for CRVO.
Participant is unable to comply with study procedures or follow-up visits.
Participant has a known hypersensitivity to sodium fluorescein dye.
Participant has a condition that, in the opinion of the investigator, would preclude participation in the study.
Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
Participant has a history of hepatitis or liver failure.
Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
Participant is currently taking a tetracycline medication.
Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
Participant has a blood pressure of more than 180/110 (systolic above 180 or diastolic above 110).
Participant has a history of treatment with systemic anti-VEGF agents or steroids within 3 months before study entry.
Participant had a cerebral vascular event or myocardial infarction within 3 months before study entry.
Participant has a history of thyroid cancer.
Macular edema in the study eye is considered to be due to a cause other than CRVO.
An eye should not be considered eligible if the macular edema is considered to be related to cataract extraction; or clinical examination and/or OCT suggest that vitreoretinal interface disease (eg, a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema; or clinical examination, medical history and/or fluorescein angiography suggest that diabetic retinopathy is the primary cause of the edema.
The study eye has a history of a recurrent RVO.
The study eye has a history of RVO present for more than 18 months.
A brisk afferent pupillary defect is present in the study eye.
An ocular condition (other than RVO) is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (eg, foveal atrophy, pigmentary changes, dense subfoveal hard exudates, laser scar at fovea, non-retinal condition).
An ocular condition (other than RVO) is present that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (eg, vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass syndrome, etc.).
A substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (ie, cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal) is present in the study eye.
The study eye has had panretinal or sectoral scatter photocoagulation within 4 months before study entry.
The study eye has had pars plana vitrectomy within 6 months before study entry.
The study eye has undergone major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within 3 months before study entry.
YAG capsulotomy has been performed on the study eye within 2 months before study entry.
The study eye has had treatment less than 3 months before study entry of intravitreal or periocular steroid injections.
The study eye has had treatment less than 28 days before study entry of intravitreal anti-VEGF agents.

Enrollment status: Currently recruiting participants

A note from the institution regarding the value of this trial

Retinal vein occlusions are a significant source of vision loss, affecting mostly healthy people over 55 years of age. The common source of vision loss is the macular edema accompanying the retinal injury.

The fundamental cause of macular edema associated with RVOs is not understood completely, but it is increasingly clear that its pathophysiology extends beyond microvascular disease to involve immune mediators in the retina. In the aftermath of a RVO, tissue hypoxia induces the expression of several cytokines, including monocyte chemoattractant protein (MCP-1), leading to the activation of inflammatory cells, such as macrophages and microglia, which are then attracted to the hypoxic retinal areas. Activated microglia release a cascade of cytokines, which are thought to speed neurodegeneration and sustain macular edema. As such, there may be a feasible therapeutic rationale to broadly limit and down-regulate the level of microglia-mediated chronic inflammation in the treatment of RVOs, in addition to local anti-VEGF treatments.

We are conducting a similarly designed trial for the treatment of branch retinal vein occlusions (ClinicalTrials.gov identifier: NCT01468831). We are recruiting for both of these studies. Contact cukrasc@nei.nih.gov with referrals or questions.