Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT03076697 |
| Other study ID # |
HUM00097907 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 16, 2015 |
| Est. completion date |
August 30, 2028 |
Study information
| Verified date |
August 2023 |
| Source |
University of Michigan |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
To validate new screening instruments for eye disease, increase eye care access in
underserved communities, and provide a scientifically implemented method to set up programs
for eye disease screening.
Description:
Millions of Americans are at risk for sight-threatening diseases and are either unable to
access eye care services or unaware that eye care screening could reduce their risk of vision
loss. In addition, there is a national shortage of eye care providers. Primary care providers
lack resources to effectively screen for sight-threatening conditions. Of the three leading
causes of permanent vision loss and blindness in adults in the United States (namely,
diabetic retinopathy, glaucoma, and age-related macular degeneration), all three diseases
largely affect structures in what is referred to as the "posterior part of the eye." This
encompasses the retina and the optic nerve, as well as accompanying vasculature. The
posterior part of the eye requires advanced instrumentation, training, and technological
advances to visualize pathology and optimize examination in the posterior part of the eye,
and accordingly screen for sight-threatening eye diseases in a manner that was not feasible
previously. However this is still largely restricted to eye care-specific settings that have
the training and resources available to invest in these technologically-advanced instruments.
Thus, there remains a critical need to develop safe, effective, readily available, and
efficient methods and tools to optimize examination and screening for sight threatening
diseases. In addition, these tools should be applicable in a variety of eye care settings,
including inpatient and outpatient clinical contexts in order to optimize eye care. In the
absence of such tools, patients will continue to have limited access to eye care and remain
at risk for sight-threatening eye conditions that otherwise could be prevented and managed
appropriately.
Diabetes mellitus is a leading cause of death and disability worldwide. The World Health
Organization estimates that more than 346 million people worldwide have DM and it is
estimated that 552 million people may be affected by 2030. Diabetic retinopathy is the most
common microvascular complication of diabetes, affecting nearly all patients with a history
of diabetes for 15 years or more. Among US adults aged 40 or older, an estimated 28.5%-40.3%
of diabetics have diabetic retinopathy and 4.4%-8.2% have vision-threatening retinopathy,
with higher estimates among non-Hispanic black individuals. Epidemiological studies from the
National Eye Institute reveal that diabetes is the leading cause of vision loss in
working-age adults in the U.S., and guidelines recommend that patients with diabetes undergo,
at minimum, a yearly dilated examination of the posterior part of the eye. This is
particularly important to detect and treat diabetes-associated eye conditions, as patients
are often asymptomatic until an advanced stage, at which point vision recovery may be
limited. Despite the absence of visual symptoms in those patients with no or with early
diabetic eye complications, conditions such as diabetic retinopathy have a recognizable
latent stage, which is readily diagnosed and graded by retinal imaging (fundus photography).
Given its prevalence and clinically-silent (but examination-apparent) progression, diabetic
retinopathy is an ideal screening disease. Furthermore, visual outcome favors early detection
and treatment.. There are effective, universally agreed-upon treatments for diabetic
retinopathy which include laser photocoagulation for proliferative retinopathy, intravitreal
injections and focal photocoagulation for diabetic macular edema, and improved glucose and
blood pressure control. Despite guidelines for annual screening and benefits of early
detection as it relates to vision outcomes and overall diabetic disease control, there is a
substantial gap in care in regards to annual retinal screening for diabetics. It is estimated
that nearly half of adults with DM in the US do not receive recommended screenings. Screening
may be even more sporadic in areas of the world with a shortage of ophthalmologists.
This study seeks to determine whether a smartphone camera and an attachable device with
optics and illumination specific for imaging the posterior part of the eye is an effective
screening tool that could be used to optimize the posterior eye exam, and to improve access,
ease of diagnosis, and early intervention in eye diseases.
Glaucoma is another disease affecting the posterior part of the eye, specifically the optic
nerve, and is the second leading cause of blindness worldwide. In particular, open-angle
glaucoma is a chronic, insidious disease with progressive loss of peripheral to central
vision. When diagnosed and treated early, however, permanent vision loss, which manifests in
later stages of the disease, may be prevented. The diagnosis of glaucoma typically relies on
both structural changes to the optic nerve and functional visual field deficits. Diagnosing
and screening glaucoma in resource-poor settings can be challenging. For example, a study of
the Frequency Doubling Technique (FDT) perimetry in rural India found very low sensitivity
for this test (7%), whereas studies in industrialized settings have found much higher
sensitivity (59%). Furthermore, many structural testing modalities such as OCT of the retinal
nerve fiber layer and stereoscopic optic nerve photography require both specialized equipment
and expert analysis in order to be effectively used in diagnosis.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the
developed world. Worldwide, 14 million people are blind due to wet AMD. By 2020, an estimated
196 million people will suffer from AMD worldwide. The US population with AMD will double by
2050. Dry AMD accounts for 90% of AMD patients, but wet AMD causes the majority of visual
impairment. Dry AMD is characterized by drusen of various size and characteristics and
pigmentary changes with a classification system. Fundus photography is an established method
of performing this characterization. Patients with dry AMD are at risk for progression to wet
AMD, which occurs at a rate of 13% within 5 years. When dry AMD progresses to wet AMD,
changes occur in the fundus appearance including the presence of retinal fluid and bleeding.
Wet AMD requires prompt treatment to prevent vision loss. The visual acuity at initiation of
anti-VEGF therapy is the best predictor for final visual acuity 2 years after therapy.
Treatment of wet AMD with anti-VEGF therapy results in improvement or stabilization of vision
in over 90% of wet AMD patients. Currently patients with dry AMD are evaluated annually for
possible progression and then are instructed to monitor their vision daily at home and
approximately half of cases of wet AMD come through patient symptoms and half through
asymptomatic physician follow-up. Several home monitoring systems have been developed,
including Amsler grid and Foresee Home monitoring using Vernier hyperacuity. Fundus
photography is another method for monitoring due to the visually apparent changes that can
occur, and utilization of a low-cost, smartphone-based fundus photography system would
greatly increase access.
Additionally, within pediatric populations, there is a similarly critical need to develop
effective, efficient, and child-friendly methods to evaluate for pediatric eye (particularly
intraocular/posterior eye) diseases. Pediatric patients can pose a challenging exam, where
general anesthesia is sometimes needed if a child is unable to tolerate a complete eye exam.
Refined instrumentation and technological advances that are more comfortable for the
pediatric patient may make it possible to explore novel, noninvasive photographic tools to
optimize eye care in this special patient population within a wider range of established care
settings and minimize the need for exam under anesthesia or distress to the patient. For
example, leukocoria (or a white red reflex) can be an important referral to ensure that a
patient does not have an eye cancer called retinoblastoma. Given the difficulty in examining
some patients, providers at times have to take these patients to the operating room for exams
under anesthesia, which has risks of anesthesia along with high cost.
Importantly, Retinopathy of prematurity (ROP) occurs when abnormal blood vessels grow over
the retina and cause blindness in premature babies. ROP happens more often because more
babies are surviving at younger ages due to advances in neonatal care. Screening for ROP is
challenging because many hospitals do not have children's eye specialists on staff or nearby.
This is a much larger public health problem in developing countries where the neonatal care
has improved but ophthalmic expertise in pediatric eye diseases is lacking. ROP telemedicine
program allows physicians to send images to be interpreted at larger medical centers, like
the U-M Kellogg Eye Center. Babies born before 31 weeks and weighing less than 1,500 grams
undergo repeated screenings to monitor for ROP. Photographs of the babies' eyes are taken
using a pediatric retinal camera. Kellogg team routinely evaluates images together or
remotely to make follow up and treatment decisions.
As the above examples indicate, there is a need for cheap, reliable, and user-friendly
diagnostic modality for screening for posterior eye disease, particularly in resource-poor
communities and internationally, in order to prevent blindness. Increasing the accessibility
and portability of the eye exam holds great promise in improving the reach of ophthalmic
care, in both the remote community and inpatient settings. Ophthalmology is uniquely suited
for remote screening and evaluation given the optical transparency of the eye and the
importance of the ocular examination in diagnosing eye disease. This study evaluates a
smartphone-based camera capable of capturing high quality, wide field images of the retina.
This is a multi-site, cross-sectional diagnostic study being conducted at multiple sites . At
each site, patients will be approached in the clinic, inpatient, and operating room settings.
Photographs will be taken with our smartphone-based camera along with the standard of care,
including traditional desktop fundus photography. The feasibility and accuracy of a
smartphone-based camera for diagnosing eye diseases will be tested.
Several ophthalmology specialists will grade the smartphone fundus photographs, the
traditional retinal photographs, and the documented eye examination for eye disease in
question (such as diabetic retinopathy, age related macular degeneration, glaucoma,
retinopathy of prematurity, etc.). The agreement between the graders for the diagnosis of eye
disease will be assessed. The sensitivity and specificity of diabetic retinopathy or glaucoma
diagnoses with the smartphone will also be assessed, using traditional retinal imaging as the
reference standard and in a separate analysis using the ophthalmologist's examination as the
reference standard. The following are the aims of the project:
Aim 1: to assess the sensitivity and specificity of diagnosis of posterior eye disease (e.g.,
diabetic retinopathy, glaucoma, macular degeneration) with a smartphone camera relative to
(A) ophthalmologist examination in outpatient and inpatient care settings and (B) traditional
fundus photography when feasible.
Aim 2: to assess the feasibility of our smartphone-based camera as a pediatric-friendly
approach for imaging of posterior eye disease (retina and optic nerve head) in the
outpatient, inpatient, and operative care settings, and to assess sensitivity and specificity
of diagnosis in screening for important pediatric conditions (e.g. leukocoria and retinopathy
of prematurity).
Aim 3: to assess the agreement between masked graders in diagnosis of different diseases
involving the posterior eye as imaged by our smartphone-based camera.
