A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema

This study has been completed.
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Catherine Cukras, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01120899
First received: May 8, 2010
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in individuals with diabetic macular edema (DME).


Condition Intervention Phase
Diabetic Macular Edema
Drug: Minocycline
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Number of Study Eyes Demonstrating an Increase or Decrease in Best-corrected Visual Acuity (BCVA) of 15 or More Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 6 Months Compared to Baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."



Secondary Outcome Measures:
  • Change in BCVA in the Study Eye at 6 Months Compared to Baseline [ Time Frame: Baseline and 6 Months ] [ Designated as safety issue: No ]

    Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Change in BCVA in the Study Eye at 12 Months Compared to Baseline [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]

    Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Change in BCVA in the Study Eye at 18 Months Compared to Baseline [ Time Frame: Baseline and 18 Months ] [ Designated as safety issue: No ]
    Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

  • Change in BCVA in the Study Eye at 24 Months Compared to Baseline [ Time Frame: Baseline and 24 Months ] [ Designated as safety issue: No ]
    Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

  • Percentage Change in Retinal Thickness in the Study Eye at 6 Months Compared to Baseline [ Time Frame: Baseline and 6 Months ] [ Designated as safety issue: No ]

    Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Percentage Change in Retinal Thickness in the Study Eye at 12 Months Compared to Baseline [ Time Frame: Baseline and 12 Months ] [ Designated as safety issue: No ]
    Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

  • Percentage Change in Retinal Thickness in the Study Eye at 18 Months Compared to Baseline [ Time Frame: Baseline and 18 Months ] [ Designated as safety issue: No ]
    Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

  • Percentage Change in Retinal Thickness in the Study Eye at 24 Months Compared to Baseline [ Time Frame: Baseline and 24 Months ] [ Designated as safety issue: No ]
    Retinal thickness was assessed by spectral-domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec, Dublin, CA), a non-invasive imaging technique that uses long-wavelength light to capture micrometer-resolution cross-sectional images from biological tissue.

  • Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Study Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline [ Time Frame: 24 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 6 Months Compared to Baseline [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 12 Months Compared to Baseline [ Time Frame: 12 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 18 Months Compared to Baseline [ Time Frame: 18 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."


  • Number of Fellow Eyes Demonstrating a Decrease in the Area of Late Leakage, as Measured by Fluorescein Angiography (FA), at 24 Months Compared to Baseline [ Time Frame: 24 Months ] [ Designated as safety issue: No ]

    Fluorescein angiography (FA) images from both eyes in each participant were obtained via a standard digital imaging system (OIS, Sacramento, CA) at baseline and at Month 6, Month 12, Month 18, and Month 24. Three retinal specialists independently graded the area of late fluorescein leakage (at approximately 10 minutes)in each eye using a region-of-interest tool in an image analysis software package (NIH ImageJ, Bethesda, MD).

    The participant's eye that met the study eye eligibility criteria was selected as the study eye. For cases in which both eyes met the study eye eligibility criteria, the study eye was selected according to the "choice of study eye in cases of bilateral disease" selection criteria outlined in the eligibility criteria. The eye not chosen as the study eye is referred to as the "fellow eye."



Enrollment: 6
Study Start Date: April 2010
Study Completion Date: February 2013
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Minocycline Drug: Minocycline
Participants take 100 mg minocycline pills twice daily for 24 months.
Other Names:
  • Dynacin; serial number 73419626
  • Minocin; serial number 72309825
  • Minocin PAC
  • Myrac; serial number 76589055
  • Solodyn; serial number 78883462
  • Vectrin; serial number 78188505

Detailed Description:

Objective: Diabetic retinopathy (DR) is one of the leading causes of blindness in the United States. A frequent manifestation of diabetic retinopathy is diabetic macular edema (DME) for which the only proven treatment is laser photocoagulation. In the retina, microglia are capable of migrating through the retina to sites of inflammation to associate closely with neurons and the vasculature, and are key cellular players in the mediation of processes of chronic inflammation implicated in DME. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the deleterious inflammatory changes found in DR. The objective of this study is to investigate the safety and efficacy of minocycline as a microglia inhibitor in patients with DME.

Study Population: Eligibility criteria include previous treatment with standard-of-care focal laser photocoagulation, or macular edema not amenable to focal laser treatment; retinal thickness in the central subfield > 250 microns as measured by optical coherence tomography (OCT); and visual acuity between 20/32 and 20/200 in the study eye.

Design: Five participants will be initially enrolled in this open-label pilot study. However, up to an additional three participants may be enrolled to account for participants who withdraw from the study prior to receipt of six months of study treatment. Participants will take an oral dose of 100 mg of minocycline twice daily for 24 months. During each visit, participants will have their visual acuity measured and will undergo OCT testing to measure retinal thickness. Beginning at the Month 6 visit, participants will be eligible for focal laser therapy unless they show marked improvement in retinal thickness and/or visual acuity or if they are not amenable to focal laser treatment. Participants who do not meet the criteria for improvement will also be eligible for anti-vascular endothelial growth factor (VEGF) treatments such as bevacizumab (Avastin®) or ranibizumab (Lucentis®). Additionally, beginning at the Month 4 visit, participants will be assessed for worsening disease defined as loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters of vision compared to baseline or a ≥ 50% increase in total retinal thickness as measured by OCT. Participants deemed to have worsening disease will also be eligible for focal laser and/or anti-VEGF treatments.

Outcome Measures: The primary outcome is the change in best-corrected visual acuity (BCVA) in the study eye at 6 months compared to baseline. Secondary outcomes include the change in retinal thickness as measured by OCT at 6, 12, 18 and 24 months compared to baseline, change in BCVA at 12, 18 and 24 months compared to baseline, as well as changes in fluid leakage in the macula as demonstrated by fluorescein angiography at 6, 12, 18 and 24 months compared to baseline. Safety outcomes include the number and severity of systemic and ocular toxicities, and adverse events.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Participant is 18 years of age or older.
  2. Participant must understand and sign the protocol's informed consent document.
  3. Female participants of childbearing potential (see Appendix 1 for definition) must not be pregnant or breast-feeding, must have a negative urine pregnancy test within 24 hours prior to initiation of study medication and must be willing to undergo urine pregnancy tests throughout the study.
  4. Female participants of childbearing potential (see Appendix 1 for definition) and male participants able to father children must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two acceptable methods of contraception throughout the course of the study and for one week after study medication discontinuation (based on the half life of minocycline which is 11-22 hours). Acceptable methods of contraception include:

    • hormonal contraception (i.e., birth control pills*, injected hormones, dermal patch or vaginal ring),
    • intrauterine device,
    • barrier methods (diaphragm, condom) with spermicide, or
    • surgical sterilization (hysterectomy or tubal ligation). *Oral birth control pills must be used with caution as minocycline decreases the effectiveness of some oral contraceptives. Participants already taking oral contraceptives may continue to use them, but must agree to use at least one other method of birth control while on study.
  5. 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.
  6. Participant must have normal renal function and liver function or have mild abnormalities no greater than grade 1 as defined by the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Refer to Appendix 2 for grading.
  7. Participant has a diagnosis of diabetic mellitus (type 1 or type 2). Any one of the following will be considered to be sufficient evidence that diabetes is present:

    • Current regular use of insulin for the treatment of diabetes
    • Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
    • Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria
  8. Participant has documented hemoglobin A1C 12% or less within one month of baseline.
  9. Participant must agree to minimize exposure to sunlight or artificial UV rays and to wear protective clothing, sunglasses and sunscreen [minimum Sun Protection Factor (SPF) 15] if s/he must be out in the sun.
  10. Participant has at least one eye that meets the study eye criteria listed below.

Exclusion Criteria

  1. Participant is in another investigational study and actively receiving study therapy.
  2. Participant is unable to comply with study procedures or follow-up visits.
  3. Participant has a known hypersensitivity to sodium fluorescein dye.
  4. Participant has a condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control).

    • Patients in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.

  5. Participant has a history of chronic renal failure requiring dialysis or kidney transplant.
  6. Participant has a history of hepatitis or liver failure.
  7. Participant has an allergy or hypersensitivity to minocycline or any drug in the tetracycline family.
  8. Participant is taking any medication that could adversely interact with minocycline such as methoxyflurane.
  9. Participant has a blood pressure of > 180/110 (systolic above 180 OR diastolic above 110).

    • If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.

  10. Participant has a history of treatment with systemic anti-vascular endothelial growth factor (VEGF) agents or steroids within three months prior to study entry.
  11. Participant has a history of thyroid cancer.

Study Eye Inclusion Criteria

  1. Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score between 78 and 39 letters (i.e., between 20/32 and 20/200).
  2. Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula that is not refractory to further therapy as based on the investigator's clinical judgment.
  3. Previous treatment with focal laser photocoagulation following standard-of-care/best practice guidelines, as described by the ETDRS study,6 ≥ 3 months prior to enrollment unless the edema is not responsive to previous laser and/or not amenable to safe laser treatment at the discretion of the investigator. The laser treatment may be performed at the National Eye Institute (NEI) clinical center (CC) or by an outside ophthalmologist at the discretion of the participant and the investigator.
  4. Retinal thickness in the central subfield on baseline optical coherence tomography (OCT) measurement > 250 microns, as measured by Spectral OCT.
  5. Media clarity, pupillary dilation and patient cooperation sufficient for adequate fundus photographs.

Study Eye Exclusion Criteria

  1. Macular edema is considered to be due to a cause other than diabetic macular edema.

    An eye should not be considered eligible if:

    • The macular edema is considered to be related to cataract extraction or
    • Clinical exam and/or OCT suggest that vitreoretinal interface disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of the macular edema.
  2. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, non-retinal condition).
  3. An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
  4. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  5. History of panretinal scatter photocoagulation (PRP) within four months prior to study entry.
  6. History of prior pars plana vitrectomy within six months prior to study entry.
  7. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within three months prior to study entry.
  8. History of yttrium aluminium garnet (YAG) capsulotomy performed within two months prior to study entry.
  9. History of treatment within three months prior to enrollment with any drug that has not received regulatory approval at the time of study entry, such as intravitreal or periocular steroids or intravitreal anti-VEGF agents.

Choice of Study Eye in Cases of Bilateral Disease

If both eyes of a participant meet the study eye inclusion and exclusion criteria listed above, the following will be used to determine the study eye:

  1. If one eye is treatment-naïve and the other is not, the treatment-naïve eye will be chosen as the study eye.
  2. If both eyes are treatment-naïve, the eye with the better visual acuity will be chosen as the study eye.
  3. If both eyes are treatment-naïve and are equivalent, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.
  4. If both eyes have been previously treated, the choice of study eye will be determined at the investigator's discretion after consultation with the participant.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01120899

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
The EMMES Corporation
Investigators
Principal Investigator: Catherine A Cukras, MD, PhD National Eye Institute (NEI)
  More Information

Additional Information:
Publications:
Responsible Party: Catherine Cukras, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01120899     History of Changes
Other Study ID Numbers: 100098, 10-EI-0098
Study First Received: May 8, 2010
Results First Received: August 2, 2012
Last Updated: October 6, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Diabetic Macular Edema
Microglia
Minocycline
Diabetes

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Minocycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 16, 2014