Age-related Macular Degeneration, Central Serous Retinopathy, Choroidal Ischemia, Retinitis Pigmentosa, Vitelliform Macular Dystrophy
Conditions
Keywords
Sildenafil, Viagra, Revatio
Brief summary
The hypothesis of this study is to determine if there is a benefit afforded by the use of systemic Sildenafil to patients with choroidal and retinal degenerations and dystrophies, such as vitelliform degeneration, dry and reticular age-related macular degeneration (AMD) as well as patients with hereditary and acquired retinal dystrophies such as retinitis pigmentosa and central serous retinopathy.
Detailed description
Age-Related Macular Degeneration (AMD) is a sight-threatening visual disturbance that affects the macula in older ages. It is irreversible if the pigment epithelium is lost (dry AMD), but wet AMD can be arrested or delayed with the use of intraocular injections of one of 3 different compounds. All three drugs are injected into the eye in minute doses of usually 0.1 ml. These are usually injected at 4 to 6 week intervals and treatment may be extended for several years. Different patterns of injection times are followed but usually are monthly for 12 or more months, or monthly for 3 months and then extended observation at one to two month intervals unless vision (visual acuity) declines or Optical Coherence Tomography-angiography (OCT-A) shows recurrence of fluid or increase in size or amount of drusen (deposits of lipofuscin) in the retina. Vitelliform macular degeneration is a disorder that causes visual loss due to drusen in the macula, which have been shown to be identical to the deposits seen in macular degeneration. The goal of therapy in this proposal is to use sildenafil to increase choroidal blood flow to treat dry AMD and slow the progression of visual loss in vitelliform and age-related dry AMD as well as other macular, retinal and choroidal degenerations and dystrophies, as well as reduce or eliminate the number of injections required by slowing down transformation of dry AMD to wet AMD in treated patients.
Interventions
DRUGSildenafil
Initial Sildenafil dosage will be weight dependent. Participants will start at 40 mg daily (20mg in the morning, 20 mg in the evening) or 60 mg daily (40mg in the morning and 20 mg in the evening). Sildenafil dosage may be increased to up to 80mg daily (20-40mg in the morning and 20-40mg in the evening) based on the response to lower doses. If the participant has not had improvement after initial treatment, the dose may be increased, at the discretion of the study physician.
OTHERStandard of Care Sildenafil
Medical record review of participants that receive Sildenafil as part of standard of care.
DIAGNOSTIC_TESTOcular Coherence Tomography-Angiography (OCT-A)
Retinal photographs will be taken at each study visit.
OTHERVisual Acuity (VA)
Visual acuity will be measured with Snellen Eye Chart at each study visit.
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are assigned to the investigational sildenafil arm with a dose of 40-80mg daily, or the records review arm when taking sildenafil off-label.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of retinal and choroidal degenerations (reticular or vitelliform AMD or vitelliform-type subretinal drusen) or hereditary or acquired retinal dystrophies (retinitis pigmentosa or central serous retinopathy)
Exclusion criteria
* Diagnosis of heart disease requiring use of nitrates * Inability to be examined monthly or bi-monthly
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Acuity (Sildenafil Group) | Up to 63 months | Patients are evaluated for progression of disease/dystrophy via visual acuity (improved/stable/worsened) and appearance of fluid layer and drusen on OCT testing. |
| Change in Visual Acuity (Medical Record Review Group) | 22 months | Patients are evaluated for progression of disease/dystrophy via visual acuity (improved/stable/worsened) and appearance of fluid layer and drusen on OCT testing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Participants are prescribed sildenafil 40-80 mg daily. | 21 |
| Medical Record Review Medical record review for participants that are prescribed Sildenafil off-label as part of standard of care treatment for disease. | 1 |
| Total | 22 |
Baseline characteristics
| Characteristic | Sildenafil | Medical Record Review | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 7 Participants | 0 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 1 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 1 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) White | 11 Participants | 1 Participants | 12 Participants |
| Region of Enrollment United States | 21 participants | 1 participants | 22 participants |
| Sex: Female, Male Female | 11 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 0 |
| other Total, other adverse events | 0 / 21 | 0 / 0 |
| serious Total, serious adverse events | 0 / 21 | 0 / 0 |
Outcome results
Primary
Change in Visual Acuity (Medical Record Review Group)
Patients are evaluated for progression of disease/dystrophy via visual acuity (improved/stable/worsened) and appearance of fluid layer and drusen on OCT testing.
Time frame: 22 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sildenafil | Change in Visual Acuity (Medical Record Review Group) | Right eye | 0.00 logMAR |
| Sildenafil | Change in Visual Acuity (Medical Record Review Group) | Left eye | 0.00 logMAR |
Primary
Change in Visual Acuity (Sildenafil Group)
Patients are evaluated for progression of disease/dystrophy via visual acuity (improved/stable/worsened) and appearance of fluid layer and drusen on OCT testing.
Time frame: Up to 63 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sildenafil | Change in Visual Acuity (Sildenafil Group) | Right eyes | 0.00 logMAR | Standard Deviation 0.21 |
| Sildenafil | Change in Visual Acuity (Sildenafil Group) | Left eyes | -0.03 logMAR | Standard Deviation 0.36 |