Behind the Lab Door

Trials from Jules Stein Eye Institute – UCLA; National Eye Institute; Neuro Kinetics; and University of Pennsylvania with National Eye Institute

Rapid, non-invasive, regional functional imaging of the retina (Diabetic retinopathy diagnosis device)

Institution: Jules Stein Eye Institute – UCLA; National Eye Institute; Neuro Kinetics

Principal investigator: Michael B. Gorin, MD, PhD

Abstract/statement of the trial’s goals:

The instrument or pupillometer consists of a commercially available set of goggles that monitors the eye positions and pupils using infrared light and small cameras. The signals from the monitoring cameras are collected in a computer that records how the pupils have responded to each lighting condition.

We will analyze latency, constriction velocity and amplitude of the pupillary response. The measurements will be taken after initiation of the light stimulus. These functions will be determined for each eye of each subject using both the central and annular stimuli. Each set of experimental conditions will yield a unique relative luminance ratio that can be used to compare the relative functional integrity of the peripheral retina with respect to the central macula.

ClinicalTrials.gov identifier: NCT01546766

Study population: 95 control subjects, 170 adults with diabetic retinopathy and 50 adults with retinal conditions

Inclusion criteria:

All subjects must be older than 18 years of age and capable of understanding informed consent.
All subjects must be willing to tolerate the placement of a set of goggles on their face.
All subjects must have visual acuities of 20/60 or better in at least one eye.
Control subjects must have a history of a normal eye examination within 1 year prior to participation in this study.
Normal subjects must have no history of ocular disease and no history of diabetes.
Diabetic subjects must be diagnosed with diabetes upon prior clinical examination.
Retinal conditions subjects must be diagnosed with a retinal pathology, hereditary or acquired.

Exclusion criteria:

Subjects with glaucoma and high myopia are specifically excluded.
Diabetic subjects may not have had laser (panretinal photocoagulation) in both eyes.

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

Jules Stein Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90005
Neuro Kinetics, Pittsburgh, PA 15238

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

This observational and prospective clinical trial is testing a modification of existing technology for monitoring the responses of the pupil to light as a method for detecting regional losses of retinal function.

The long-term objective of this program is to develop a noninvasive screening device for the early detection and quantification of mid-peripheral retinal ischemia associated with diabetic retinopathy.

Early detection and monitoring of retinal microvascular damage in diabetics could facilitate intervention at a stage that may prevent or lessen permanent damage from the disease, in turn improving patient quality of life and reducing lifetime treatment costs. By monitoring changing retinal function before the onset of severe retinal damage and neovascularization, one can also assess therapies intended to control the development and progression of diabetic retinopathy. Diabetic retinopathy is one of the more debilitating potential outcomes of diabetes, posing a major threat to the quality of life of diabetics.

Phase 1 trial of gene vector to patients with retinal disease due to RPE65 mutations (LCA)

Institution: University of Pennsylvania with National Eye Institute

Author/principal investigator: Samuel G. Jacobson, MD, PhD

Abstract/statement of the trial’s goals:

The goal of this clinical trial is to determine the safety of uniocular subretinal administration of rAAV2-CBSB-hRPE65 in individuals with RPE65-associated retinal disease. Ocular and systemic toxicity will be assessed prior to and following vector administration to determine if there are adverse changes that may be associated with vector administration.

ClinicalTrials.gov identifier: NCT00481546

Inclusion criteria:

RPE65-associated retinal disease (two disease-causing RPE65 mutations)
Clinical diagnosis of Leber congenital amaurosis (LCA)/early-onset retinal degeneration and of severely impaired visual and retinal function, and best corrected visual acuity of 20/40 or worse in the study eye
Ability to perform tests of visual and retinal function
Visible photoreceptor layer on a standard optical coherence tomography scan
Good general health
Ability to comply with research procedures
Specific for cohorts 1, 2 and 4: 18 years of age and older
Specific for cohorts 3 and 5: Between 8 and 17 years of age, inclusive.

Exclusion criteria:

AAV antibody titers greater than two standard deviations above normal at baseline
Humoral immune deficiency as evidenced by low tetanus toxoid IgG antibody titers
Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or surgical complications
Complicating systemic diseases
Use of anti-platelet agents that may alter coagulation within 7 days prior to study agent administration
Use of immunosuppressive medications
Pregnancy or breastfeeding
Individuals (males and females) of childbearing potential who are unwilling to use effective contraception
Any condition that would prevent a subject from completing follow-up examinations during the course of the study
Any condition that makes the subject unsuitable for the study
Current or recent participation in any other research protocol involving investigational agents or therapies
Recent receipt of an investigational biologic therapeutic agent

Enrollment status: Currently recruiting participants