Behind the Lab Door

Ozurdex with rescue Lucentis for treating macular edema secondary to retinal vein occlusion

Institution: Mid Atlantic Retina, the Retina Service of Wills Eye Institute

Author/principal investigator: Julia A. Haller, MD

Abstract/statement of the trial’s goals:

This study seeks to compare dexamethasone implant with rescue intravitreal ranibizumab to monthly intravitreal ranibizumab for the treatment of macular edema secondary to branch or central retinal vein occlusion. This is based on the null hypothesis that dexamethasone implant with rescue ranibizumab has inferior best corrected visual acuity at 6 months compared to monthly ranibizumab alone.

ClinicalTrials.gov identifier: NCT01581151

Study population: 30

Inclusion criteria:

Signed informed consent form.
18- to 90-year-old men or women.
Women must be postmenopausal for at least 12 months before study enrollment or surgically sterile. Potential childbearing women must have a negative serum pregnancy test within 14 days prior to the first treatment and practice effective contraception during and at least 120 days following the last dose of injection.
Patient of the Wills Eye Institute Retina service, including all Mid Atlantic Retina offices.
Healthy enough to participate in the study.
Willing and able to consent to participation in the study.
Retinal vein occlusion:

Must be diagnosed within 2 weeks of onset of symptoms.
Best corrected visual acuity on initial presentation between 20/40 and 20/320.
No contraindications to intravitreal injection of dexamethasone implant or ranibizumab.
Central foveal thickness greater than 250 µm on spectral-domain OCT.

Exclusion criteria:

Unknown duration of symptoms prior to diagnosis.
Patients with any history of prior intravitreal dexamethasone or anti-VEGF or grid laser.
Patients with diabetic retinopathy.
Patients with age-related macular degeneration.
Patients with an optic neuropathy.
Patients with a retinal detachment or history of retinal detachment.
Patients with a significant epiretinal membrane.
Patients with a history of choroidal neovascularization.
Patients with glaucoma with visual field loss documented on a Humphrey visual field test or ocular hypertension requiring more than two medications to control IOP in the study eye.
Patients with a clinically significant media opacity.
Patients using or anticipating using systemic steroids.
Patients with any uncontrolled systemic disease.
Patients with aphakia or anterior-chamber IOL.
Patients with active neovascularization of the iris, disc or retina

Enrollment status: Currently recruiting participants:

Wills Eye Retina Service, Philadelphia

A note from the institution regarding the value of this trial:

Retinal vein occlusion (RVO) is the second most common retinal vascular disease, and associated macular edema is an important and treatable cause of vision loss in these eyes. The pathogenesis of this condition is multifactorial. We know that VEGF is an important mediator; VEGF is upregulated in RVO eyes, and exogenous VEGF injections into primate eyes causes a RVO-like appearance with intraretinal hemorrhages, venous dilation and venous tortuosity. Moreover, anti-VEGF injections have been shown in multiple large, multicenter clinical trials (eg, BRAVO and CRUISE) to effectively reduce macular edema secondary to RVO and improve visual acuity. However, VEGF does not act alone but with known contributions from other inflammatory mediators. As such, the ideal treatment would target the broader inflammatory milieu. Intraocular corticosteroids are one such approach and inhibit multiple inflammatory pathways in addition to direct inhibition of VEGF. The SCORE trial and Ozurdex Geneva Study Group demonstrated the efficacy of intravitreal triamcinolone and the dexamethasone implant, respectively.

Moving forward, the next advancements in treatment will include novel therapies as well as refinements in treatment algorithms, including combination therapy. The high frequency of anti-VEGF re-treatments necessary to maintain efficacy is burdensome for the patient, leads to higher costs, and puts patients at greater risk of endophthalmitis. A more robust or less frequent treatment regimen that provides equal efficacy is needed. This prospective pilot study is designed to compare the effect of combination therapy using the intravitreal dexamethasone implant with adjunctive ranibizumab with monthly intravitreal ranibizumab in the treatment of macular edema secondary to RVO. Our specific aims are to evaluate the efficacy of these regimens regarding visual acuity, OCT macular thickness as well as number of injections over the duration of the trial.

Acupuncture for the treatment of vision loss due to retinitis pigmentosa

Institution: Johns Hopkins University

Abstract/statement of the trial’s goals:

Retinitis pigmentosa (RP) patients are interested in trying alternative therapies to attempt to slow, halt or reverse the retinal disease process and claim success with some approaches such as acupuncture, but this potential treatment has not been put to the test of objective, rigorous scientific study conducted in Western society. In this pilot study, the investigators aim to evaluate an acupuncture treatment tailored to the RP population for its feasibility to improve visual function, specifically visual field and dark adaptation. The study results may provide a basis for eye care providers’ recommendations to RP patients regarding whether to consider acupuncture as a potential treatment modality. If our hypotheses regarding improvements in vision beyond typical test variability are supported, our future research goals include the conduct of a larger clinical trial involving randomization and a placebo control for acupuncture in RP.

ClinicalTrials.gov identifier: NCT01604356

Study population: 12

Inclusion criteria:

Age: at least 10 years.
Diagnosis of retinitis pigmentosa.
Best corrected visual acuity better than 20/400 in at least one eye.
More than 20% loss of Goldmann visual field area (III4e) in at least one eye.
Able and willing to participate in all study visits in Baltimore for the 8-week program.
Provide informed consent.

Exclusion criteria:

Very severe vision losses in both eyes (eg, hand motions or light perception only) with difficulty performing the proposed vision tests.
Vision loss due to ocular diseases other than RP, cystoid macular edema or cataracts.
Schedules do not permit participation in all study visits.
Previous acupuncture treatment in the last 6 months.
Inability to understand study procedures or communicate responses to visual stimuli in a consistent manner (cognitive impairment).
Dementia; long- or short-term memory loss.
Unable to read or speak English.
Smoking, substance abuse or illegal drug use.
Receiving current psychiatric care (ie, unstable emotional and mental health status).
History of excessive bleeding.

Enrollment status: Currently recruiting participants:

Johns Hopkins University, Baltimore

A note from the institution regarding the value of this trial:

This is an innovative, integrative pilot study to evaluate a 2-week electroacupuncture treatment protocol specifically developed for retinitis pigmentosa. We hope to advance management options for RP, which are currently limited to nutritional supplements (as well as some off-label drugs, some with potentially serious side effects) attempting to slow disease progression. After being diagnosed with a disabling, chronic disease such as RP, there is nothing more disheartening for the patient than to hear that nothing can be done to treat it. Many RP patients consider alternative treatments such as acupuncture, and some who have tried it report improved vision, but there are no previous publications of rigorously conducted placebo-controlled studies to test acupuncture for its potential to improve vision in RP. The goal of this pilot study is to provide a basis for recommendations to RP patients regarding safety and potential for vision changes, by identifying the proportion of patients who respond to the treatment, types of vision improvements, as well as the duration and magnitude of the effects.

Using optical coherence tomography to capture retinal microvascular changes associated with multiple sclerosis

Institution: Oregon Health and Science University

Author/principal investigator: Rebecca Spain, MD, MSPH

Abstract/statement of the trial’s goals:

People with multiple sclerosis (MS) who also have diseases related to vascular health such as high cholesterol, high blood pressure, diabetes, cardiovascular disease and others may end up more disabled than people with MS who do not have those diseases. This has led to a growing interest in the role of vascular diseases in MS because they may provide another avenue of MS treatment. Sophisticated OCT techniques of the retina allow visualization of both the appearance of blood vessels and measurement of the rates of retinal blood flow. Blood flow changes are thought to come before the changes in physical appearance of the blood vessels, and so may be able to detect problems even earlier than routine examination by eye doctors. Retinal blood flow has never been carefully studied in MS. Given that MS affects the retina due to the late effects of inflammation of the optic nerve, or optic neuritis, we expect to see altered blood flow in the retinal blood vessels of people with MS compared to healthy control subjects. If so, we can then use retinal blood flow as a way to measure therapies that target vascular diseases in the MS population and determine if those therapies can alter the course of disease.

ClinicalTrials.gov identifier: NCT01596881

Study population: 80

Inclusion criteria (Subjects with MS):

Physician-confirmed diagnosis of MS (any subtype acceptable, eg, relapsing-remitting, secondary progressive, primary progressive).
Age: 18 to 70 years.
Able to comply with study procedures.
Corrected visual acuity at least 20/200 in either eye.

Inclusion criteria (healthy subjects):

Age: 18 to 70 years.
Able to comply with study procedures.
Able to maintain stable fixation for OCT imaging.
Corrected visual acuity of at least 20/40 in either eye.

Exclusion criteria (all participants):

Intravenous or oral steroids in the prior 30 days.
Evidence on ophthalmological exam within the last year of other ocular diseases or pathology that would confound the assessment of MS and optic nerve head (eg, glaucoma, diabetic or hypertensive retinal disease, amblyopia).
Previous intraocular surgery except for uncomplicated cataract surgery.
Inability to maintain stable fixation for OCT imaging.
Refractive error greater than +3 D or –7 D.
MS exacerbation in the prior 60 days.

Enrollment status: Currently recruiting participants:

Oregon Health and Science University, Portland, Ore.

A note from the institution regarding the value of this trial:

There is growing interest in vascular risk factors as a cause of disability, including visual dysfunction, in MS as well as an avenue of therapeutic treatment. Even just one vascular risk factor is associated with a 6-year shorter interval between MS diagnosis and need for use of a cane to walk. Vascular risk factors are thought to cause structural damage to the central nervous system and may also result in a vasculopathy wherein blood vessels, including those in the retina, do not demonstrate a compensatory flow to increased demand.

As retinal microvascular changes correlate with those seen on brain MRI, novel OCT techniques that can capture retinal changes may provide a direct in vivo assessment reflecting more widespread microvascular changes in MS. OCT is a new technique that can perform cross-sectional imaging of tissue structure in real time. An ultrahigh-speed swept-source OCT prototype system is used in this study that is able to cover wider areas and deeper locations of the retina than standard OCT. Measurements include retinal layer thicknesses, total blood flow and the compensatory blood flow response to visual stimulation using an angiography algorithm.

We hypothesize that OCT will detect abnormalities in retinal blood flow and compensatory blood flow response to visual stimuli in people with MS compared to healthy controls. The results of this pilot study will be used to estimate sample size for a larger study of vascular risk factors in MS and the ability of OCT to predict disability progression.