Macular Degeneration, Retinal Drusen
Conditions
Brief summary
This is a randomized controlled study of non-damaging photothermal macular grid laser versus sham laser therapy in patients with dry age-related macular degeneration (AMD) and large high-risk drusen. The goal of the study is to determine if this treatment will reduce macular drusen volume and also whether this might improve visual acuity or reduce the risk of conversion to advanced age-related macular degeneration defined as development of choroidal neovascularization or geographic atrophy.
Interventions
DEVICEPascal Retinal Laser Photocoagulator
Sub-threshold macular laser treatment with Pascal laser Endpoint Management System
Sponsors
Bascom Palmer Eye Institute
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Older than 60 years of age. 2. Male or female patients with nonexudative AMD with a drusen volume of of at least 0.03mm3 in the central 3mm circle 3. Adequate pupil dilatation and clear media to perform colour, red-free imaging and fundus fluorescein angiography, fundus autofluorescence imaging and OCT. 4. Able to give an informed consent.
Exclusion criteria
1. Presence of signs of advanced AMD, such as CNV, haemorrhages or macular atrophy based on OCT and fundus autofluorescence photography (FAF). 2. Previous macular laser treatment. 3. Any previous ocular condition that may be associated with a risk of developing macular oedema. 4. Vitreomacular traction determined clinically and /or by OCT, which in the opinion of the investigator, contributes to the macular oedema (associated or causing a detachment of the fovea). 5. Presence of other macular disease such as epiretinal membrane, macular telangiectasia. 6. Important known allergies to sodium fluorescein dye used in angiography. 7. Ocular or periocular infections. 8. Planned intra-ocular surgery within one year. 9. Patient is unavailable for follow-up visits.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Macular Drusen Volume | baseline, 6, 12, and 24 months | Mean change in macular drusen volume as measured on high-resolution spectral domain ocular coherence tomography (SD-OCT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Acuity | baseline, 6, 12, and 24 months | Mean change in best-corrected visual acuity as measured using early treatment diabetic retinopathy study (ETDRS) chart - average number of letters seen on chart |
| Development of Geographic Atrophy (GA) or Choroidal Neovascularization (CNV) | 2 years | Count of eyes that develop geographic atrophy or choroidal neovascularization by 24 months. |
Countries
United States
Participant flow
Recruitment details
Participants recruited from January 2016 until May 2018, at which time interim analysis revealed futility.
Pre-assignment details
19 participants signed informed consent; 2 participants failed screening, and 17 participants started the study. Participants may have contributed one or both eyes to the study. If both eyes were enrolled the first eye would be randomly assigned to treatment or sham, and the fellow eye would be assigned to the opposite treatment arm. Participants who contributed more than one eye are counted in more than one reporting group.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants receive sub-threshold macular laser photocoagulation and/or sham treatment with power setting at zero | 17 |
| Total | 17 |
Baseline characteristics
| Characteristic | All Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 15 Participants | — |
| Age, Categorical Between 18 and 65 years | 2 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 17 Participants | — |
| Sex: Female, Male Female | 11 Participants | — |
| Sex: Female, Male Male | 6 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 1 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Change in Macular Drusen Volume
Mean change in macular drusen volume as measured on high-resolution spectral domain ocular coherence tomography (SD-OCT)
Time frame: baseline, 6, 12, and 24 months
Population: Participants who contributed more than one eye are counted in more than one reporting group. Data for the participant who did not complete the study are included using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sub-threshold Macular Laser Photocoagulation | Change in Macular Drusen Volume | Baseline volume | 0.05 mm^3 |
| Sub-threshold Macular Laser Photocoagulation | Change in Macular Drusen Volume | 6 month change | 20.0 mm^3 |
| Sub-threshold Macular Laser Photocoagulation | Change in Macular Drusen Volume | 12 month change | 42.2 mm^3 |
| Sub-threshold Macular Laser Photocoagulation | Change in Macular Drusen Volume | 24 month change | 80.0 mm^3 |
| Sham Laser | Change in Macular Drusen Volume | 24 month change | -4.5 mm^3 |
| Sham Laser | Change in Macular Drusen Volume | Baseline volume | 0.11 mm^3 |
| Sham Laser | Change in Macular Drusen Volume | 12 month change | 27.2 mm^3 |
| Sham Laser | Change in Macular Drusen Volume | 6 month change | 9.0 mm^3 |
Secondary
Change in Visual Acuity
Mean change in best-corrected visual acuity as measured using early treatment diabetic retinopathy study (ETDRS) chart - average number of letters seen on chart
Time frame: baseline, 6, 12, and 24 months
Population: Participants who contributed more than one eye are counted in more than one reporting group. Data for the participant who did not complete the study are included using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sub-threshold Macular Laser Photocoagulation | Change in Visual Acuity | Baseline vision | 81.7 Letters | Standard Deviation 8.6 |
| Sub-threshold Macular Laser Photocoagulation | Change in Visual Acuity | 6 month change | -0.7 Letters | Standard Deviation 4.24 |
| Sub-threshold Macular Laser Photocoagulation | Change in Visual Acuity | 12 month change | -2.7 Letters | Standard Deviation 324 |
| Sub-threshold Macular Laser Photocoagulation | Change in Visual Acuity | 24 month change | -3.6 Letters | Standard Deviation 6.1 |
| Sham Laser | Change in Visual Acuity | 24 month change | -6.3 Letters | Standard Deviation 6.96 |
| Sham Laser | Change in Visual Acuity | Baseline vision | 79.4 Letters | Standard Deviation 5.19 |
| Sham Laser | Change in Visual Acuity | 12 month change | -0.9 Letters | Standard Deviation 3.95 |
| Sham Laser | Change in Visual Acuity | 6 month change | -3.4 Letters | Standard Deviation 4.67 |
Secondary
Development of Geographic Atrophy (GA) or Choroidal Neovascularization (CNV)
Count of eyes that develop geographic atrophy or choroidal neovascularization by 24 months.
Time frame: 2 years
Population: Participants who contributed more than one eye are counted in more than one reporting group. Data for the participant who did not complete the study are included using the Last Observation Carried Forward (LOCF) method.
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Sub-threshold Macular Laser Photocoagulation | Development of Geographic Atrophy (GA) or Choroidal Neovascularization (CNV) | 0 Eyes |
| Sham Laser | Development of Geographic Atrophy (GA) or Choroidal Neovascularization (CNV) | 0 Eyes |