Behind the Lab Door

Effect of Alphagan on retinal blood flow autoregulation and motion detection in patients with normal pressure glaucoma

Institution: Massachusetts Eye and Ear Infirmary

Author/principal investigator: Louis R. Pasquale, MD

Abstract/statement of the trial’s goals:

The investigators have completed a study in which they examined the response of retinal circulation to changes in posture from sitting to lying down in patients with normal tension glaucoma (NTG). This alteration in position produces changes in the local blood pressure at the entrance to the retinal vasculature. In a healthy retina, the vasculature adapts by dilating and constricting in order to maintain a steady blood flow rate. In an eye with NTG, this often does not occur. Upon analysis at the completion of the study, the investigators found that the patients who had been taking Alphagan (brimonidine 0.15%, Allergan) during the study did not exhibit the blood flow increases typical of NTG while lying down; instead, they maintained a steady blood flow rate as did the group of healthy control subjects. The investigators’ primary objective is to demonstrate in a prospective study that Alphagan can restore retinal vascular autoregulatory function in patients with NTG who do not autoregulate. The investigators will also determine the effect of Alphagan treatment on the patient’s ability to detect motion.

ClinicalTrials.gov identifier: NCT01105065

Study population: 40

Inclusion criteria:

Eligible subjects will have no history of IOP higher than 24 mm Hg in either eye.
All subjects will have open angles on gonioscopy with the filtering portion of the trabecular meshwork visible for 360° in both eyes.
Previously or newly diagnosed patients are required to have Humphrey visual fields that are reliable and show loss consistent with nerve fiber layer atrophy.
Patients with glaucoma-like discs (cup-to-disc ratio greater than 0.7 in either eye) and normal/reliable visual fields who the principal investigator has opted to observe without treatment will enter the study if they meet the other study criteria.
In order to facilitate the retinal blood flow measurements, only subjects with refractive error within the range of –10 D to +10 D, no lens opacities greater than 1+ cortical spokes or 2+ nuclear sclerosis, and pupillary dilation of at least 6 mm following mydriasis will be included.

Exclusion criteria:

Patients with evidence of exfoliation or pigment dispersion syndrome in either eye.
Patients with a cup-to-disc ratio greater than 0.8.
Known history of allergy to brimonidine.
Patients already on treatment with brimonidine will be excluded from the study.
Diabetic retinopathy.
History of ocular laser or incisional surgery in either eye.
Use of systemic alpha-2 blockers.
Pregnant or planning to become pregnant.

Enrollment status: Currently enrolling participants

Massachusetts Eye and Ear Infirmary, Boston

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

In this study we prospectively recruit patients with the normal tension variant of primary open-angle glaucoma who are naïve to brimonidine and identify those with retinal vascular dysregulation (RVD). RVD is defined as a more than 30% increase or more than 25% decrease in retinal blood flow while the patient is reclined for 30 minutes vs. the baseline seated position. Blood flow is measured using the Canon Laser Blood Flowmeter in an inferior temporal retinal arteriole just off the optic disc. These patients with optic nerve damage and concomitant RVD also undergo a baseline novel visual function test designed to detect neuronal noise in the retina. Then after an 8-week treatment with brimonidine 0.15% three times daily in both eyes, these patients undergo repeat visual function testing and hemodynamic profiling. This trial is designed to assess whether brimonidine corrects RVD in POAG and whether this translates into reduced neuronal noise in the retina.

Determining the effect of low-dose isotretinoin on proliferative vitreoretinopathy (the DELIVER study)

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

Author/principal investigators: Nikolas J.S. London, MD, and Richard S. Kaiser, MD

Abstract/statement of the trial’s goals:

The DELIVER study is a prospective, non-randomized, controlled study examining the efficacy of a low dose of isotretinoin for both treating and preventing proliferative vitreoretinopathy.

ClinicalTrials.gov identifier: NCT01445028

Study population: 70

Inclusion criteria:

18- to 80-year-old men or 18- to 80-year-old women not of childbearing potential.
Healthy enough to participate in the study.
Willing and able to consent to participation.
Recurrent PVR-associated retinal detachment occurring at least 2 weeks after retinal detachment repair

Primary retinal detachment associated with one or more high-risk features.

Exclusion criteria:

History of hypersensitivity to isotretinoin.
Current use of a corticosteroid (excluding topical).
Any history of depression, anorexia or liver or pancreatic disease.
Patients with closed funnel retinal detachments.
Patients with chronic retinal detachment, defined as longer than 12 weeks.
Any use of an oral retinoid within 6 months.
Systemic chemotherapy within 6 months.
Patients taking supplemental vitamin A.
Corneal opacity sufficient to impair surgical view.
Proliferative diabetic retinopathy.

Enrollment status: Currently recruiting participants

Wills Eye Institute, Philadelphia

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

The pathogenesis of proliferative vitreoretinopathy (PVR) is poorly understood. Following a retinal detachment, retinal pigment epithelial (RPE) cells and retinal glial cells may differentiate and form a fibrocellular matrix that can cover the surface of the retina. This matrix can subsequently contract, leading to a traction retinal detachment with or without a rhegmatogenous component. Untreated, PVR has a uniformly dismal prognosis, with persistent retinal detachment, vision loss and, eventually, phthisis. Currently, surgery is the only treatment available outside of experimental settings. Pharmacologic interventions have been described but have not been widely adopted.

Isotretinoin (13-cis-retinoid acid) is a commonly prescribed systemic medication for recalcitrant nodular cystic acne. Retinoid acid inhibits RPE proliferation in in vitro PVR membranes and reduces PVR in animal models of PVR. Further, we know that the RPE is depleted of retinoids after retinal detachment, leading to a loss of inhibitory control of RPE and potentially allowing the RPE to proliferate, differentiate and form PVR. The efficacy of isotretinoin for PVR has also been shown in clinical trials, but only two have been performed, and only in a handful of patients (Fekrat et al, 1995; Chang et al, 2008). No other studies have been performed, and no studies have looked at the efficacy of isotretinoin for preventing PVR in high-risk eyes.

Functional neuroimaging of cortical plasticity in the human visual system

Institution: Baylor College of Medicine

Author/principal investigator: Stelios M. Smirnakis, MD, PhD

Abstract/statement of the trial’s goals:

The study’s objective is to measure changes in human visual cortex organization that may arise as a result of injury to the visual pathways. Subjects with retinal or cortical injury will be studied and compared to appropriate controls. Functional MRI methods are used to monitor cortical topography in time. The main aims of the study are to determine 1) what are the patterns of cortical reorganization that are seen spontaneously after injury, and 2) whether rehabilitative training can promote adaptive reorganization enhancing recovery.

ClinicalTrials.gov identifier: NCT01062672

Study population: 200

Inclusion criteria:

Stable lesion of the visual pathways resulting in a visual field scotoma.

Exclusion criteria:

Inability to undergo MRI.
Inability to comply with basic instructions.
Inability to perform the behavioral tasks required.
Patients with chronic progressive neurological or psychiatric disorders.
Patients who are pregnant or breast feeding.

Enrollment status: Active, enrolling participants in both study locations:

Baylor College of Medicine, Houston
Max Planck Institute for Biological Cybernetics, Tübingen, Germany