Diabetic Macular Edema
Conditions
Brief summary
The purpose of this research study is to determine if a Treat and Extend regimen (increasing the time between visits when the disease is stable and not getting worse) of Ranibizumab 0.3 mg injections inside the eye is safe and effective at treating patients with swelling of the retina from diabetes.
Detailed description
This research study will compare the visual outcomes between a group of patients who are treated with monthly injections of Ranibizumab 0.3 mg and two groups of patients who are treated with the Treat and Extend regimen. One of the Treat and Extend groups will also receive laser therapy to determine if this has any additional beneficial effects.
Interventions
DRUGRanibizumab 0.3 mg intravitreal injection
DEVICEGuided Laser Photocoagulation
Sponsors
Palmetto Retina Center, LLC
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Ability to provide written informed consent and comply with study assessments for the full duration of the study * Age \> 18 years of age Patient related considerations * For sexually active women of childbearing potential, agreement to the use of an appropriate form of contraception (or abstinence) for the duration of the study * Although no birth control method is 100% effective, the following are considered effective means of contraception: surgical sterilization, use of oral contraceptives, barrier contraception using either a condom or diaphragm with spermicidal gel, an intrauterine device, or contraceptive hormone implant or patch. A patient's primary care physician, obstetrician, or gynecologist should be consulted regarding an appropriate form of birth control. * Ability and willingness to return for all scheduled visits and assessments Disease related considerations * The presence of center-involving diabetic macular edema on clinical exam and SDOCT * Best corrected visual acuity in the study eye, using ETDRS testing, between 20/25 and 20/320 (Snellen equivalent), inclusive. * Clear ocular media and adequate pupillary dilation to permit good quality fundus imaging.
Exclusion criteria
* General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Vision at 24 Months | 2 Years | Mean change in ETDRS (Early Treatment in Diabetic Retinopathy Study) visual acuity at 24 months (week 92-week 107) from Day 0. Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard. A higher letter score represents better functioning |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Intravitreal Injections | 2 years | Total number of intravitreal injections required during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period. |
| Number of Office Visits | 2 years | Total number of office visits and imaging studies performed during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period. |
| Change in Retinal Thickness | 2 years | Mean change in central foveal thickness per SDOCT (Spectral Domain Optical Coherence Tomography) from randomization to 12 months (week46 - week 57) and randomization to 24 months (week 92 - week 107) study period.Change at month 24 reported. |
| Number of Participants With Adverse Events | 2 years | Number of Participants with Adverse Events, ocular and non-ocular, in each of the study groups |
| Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy | 2 years | The percentage of eyes which show progression of proliferative diabetic retinopathy requiring panretinal photocoagulation and/or pars plana vitrectomy over the 24-month study period. |
| Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit. | 2 years | The percentage of eyes in the TREX (Treat and Extend) and GILA (Guided Laser) cohorts who are eligible to begin the extension phase prior to week 104 end-point visit. |
| Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness | 2 years | For TREX and GILA Cohorts, the time to achieve a Secondary or Tertiary Baseline retinal thickness. |
| Percentage of Eyes Gaining or Losing Vision | 2 years | Percentage of eyes gaining or losing 3 lines of vision or more and 1 line of vision at 24 months (week 92 - week 107) from Day 0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Monthly Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection | 30 |
| Monthly Monthly Cohort (30 eyes) - Study eyes will receive intravitreal injections of 0.3 mg ranibizumab every 4 weeks for 24 months.
Ranibizumab 0.3 mg intravitreal injection | 30 |
| TREX (60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection | 60 |
| TREX (60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits. At the fourth visit (Week 12), if the central foveal thickness is ≤ 325 μm then the eye will receive 0.3 mg ranibizumab and begin the extension phase of the study. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD (Spectral Domain)-OCT criteria. Treatment is rendered at every visit. The time between visits is individualized based on each subject's response to treatment. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study.
Ranibizumab 0.3 mg intravitreal injection | 60 |
| GILA (60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study. | 60 |
| GILA (60 eyes) - Monthly intravitreal injections of 0.3 mg ranibizumab for four visits combined with guided laser photocoagulation to all microaneurysms in the area of DME at visit 2 (Week 4) and then again every 3 months, if leakage is present on fluorescein angiography. If the central foveal thickness is ≤ 325 μm at visit 4 (Week 12), eyes will receive 0.3 mg ranibizumab and the extension phase will begin. For all subsequent visits in the extension phase, appropriate changes to the treatment interval with 0.3 mg ranibizumab (i.e. extend, maintain, reduce) will be made based on pre-specified SD-Optical coherence tomography criteria. If the central foveal thickness is \> 325 μm at week 12, then the patient will continue to receive monthly intravitreal injections of 0.3 mg ranibizumab and possible guided laser every 3 months until the central foveal thickness is ≤ 325 μm. Once the central foveal thickness is ≤ 325 μm, then the study eye will begin the extension phase of the study. | 60 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 5 | 2 |
| Overall Study | Lost to Follow-up | 4 | 10 | 7 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | TREX | Monthly | GILA |
|---|---|---|---|---|
| Age, Continuous | 59.5 Years | 59.4 Years | 58.7 Years | 59.9 Years |
| Body-Mass Index | 31.6 Units of measure kg/m^2 | 31.9 Units of measure kg/m^2 | 32.2 Units of measure kg/m^2 | 30.9 Units of measure kg/m^2 |
| Central Retinal Thickness (microns) | 452 Microns | 452 Microns | 415 Microns | 484 Microns |
| Mean Best Corrected Visual Acuity (ETDRS Letters) | 66.5 units on a scale | 65.5 units on a scale | 67.5 units on a scale | 67.0 units on a scale |
| Mean Duration of Diabetes | 14 Years | 13.5 Years | 15 Years | 13.5 Years |
| Phakic Status | 117 participants | 48 participants | 23 participants | 46 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 51 Participants | 21 Participants | 12 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 7 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) White | 74 Participants | 31 Participants | 12 Participants | 31 Participants |
| Region of Enrollment United States | 150 participants | 60 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 72 Participants | 32 Participants | 16 Participants | 24 Participants |
| Sex: Female, Male Male | 78 Participants | 28 Participants | 14 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 30 | 5 / 60 | 2 / 60 |
| other Total, other adverse events | 30 / 30 | 60 / 60 | 60 / 60 |
| serious Total, serious adverse events | 11 / 30 | 30 / 60 | 46 / 60 |
Outcome results
Primary
Mean Change in Vision at 24 Months
Mean change in ETDRS (Early Treatment in Diabetic Retinopathy Study) visual acuity at 24 months (week 92-week 107) from Day 0. Visual function of the study eye was assessed using the ETDRS protocol, which is a widely accepted international standard. A higher letter score represents better functioning
Time frame: 2 Years
Population: For those lost to follow-up, last observation carried forward
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monthly | Mean Change in Vision at 24 Months | 72.5 units on a scale |
| TREX | Mean Change in Vision at 24 Months | 75.0 units on a scale |
| GILA | Mean Change in Vision at 24 Months | 75.0 units on a scale |
Secondary
Change in Retinal Thickness
Mean change in central foveal thickness per SDOCT (Spectral Domain Optical Coherence Tomography) from randomization to 12 months (week46 - week 57) and randomization to 24 months (week 92 - week 107) study period.Change at month 24 reported.
Time frame: 2 years
Population: For those not reaching week 104 end-point, last observation carried forward
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monthly | Change in Retinal Thickness | 149 Microns |
| TREX | Change in Retinal Thickness | 151 Microns |
| GILA | Change in Retinal Thickness | 196 Microns |
Secondary
Number of Intravitreal Injections
Total number of intravitreal injections required during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period.
Time frame: 2 years
Population: Multiple imputation model for eyes lost to follow-up prior to week 104 visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monthly | Number of Intravitreal Injections | 25.0 Injections |
| TREX | Number of Intravitreal Injections | 19.0 Injections |
| GILA | Number of Intravitreal Injections | 17.0 Injections |
Secondary
Number of Office Visits
Total number of office visits and imaging studies performed during the first 12 months (week 46 - week 57) and the entire 24-month (week 92 - week 107) study period.
Time frame: 2 years
Population: Multiple imputation model for eyes not reaching week 104 end-point visit.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Monthly | Number of Office Visits | 25.0 Visits |
| TREX | Number of Office Visits | 19.0 Visits |
| GILA | Number of Office Visits | 17.0 Visits |
Secondary
Number of Participants With Adverse Events
Number of Participants with Adverse Events, ocular and non-ocular, in each of the study groups
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Headache | 6 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Fatigue | 3 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperkalemia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hypothyroidism/nodule | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hyperphosphatemia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Acute Myocardial Infarction | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hyperuricemia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperglycemia | 7 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Testosterone deficiency | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Vitamin D Deficiency | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hyperparathyroidism | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Weight Gain | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Arthritis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Abrasion | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Fractured Bone | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Musculoskeletal Pain | 12 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Congestive Heart Failure | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Osteoporosis | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hernia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Skin burn | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Colon Cancer | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Prostate Cancer | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Skin Cancer | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Cranial Nerve Palsy | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Lung Cancer | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Cerebrovascular Accident | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Decreased Hearing | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hypo/hypercalcemia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Depression/Anxiety | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Dizziness | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Neuropathy | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Paresthesia | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Insomnia | 7 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Seizure | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Tinnitus | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreomacular Traction | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Transient Ischemic Attack | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Pericardial Effusion | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Kidney Stone | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Syncope/Presyncope | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Renal Insufficiency | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Cough | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Acute Respiratory Failure | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Dyspnea | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Lung Nodule | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Pneumonia | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Pulmonary Embolism | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Rhinorrhea | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Incontinence | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Sleep apnea | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Orthostatic Hypotension | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Peripheral Edema | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Peripheral Vascular Disease | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Poor dentition | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Worsening Hypertension | 10 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Appendicitis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Diverticulitis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Epistaxis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Gastrointestinal infection | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Parotitis | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Diarrhea | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Skin Infection | 6 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Respiratory Infection | 12 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Retinal Hemorrhage | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Sinusitis | 5 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Elevated liver enzymes | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Urinary Tract Infection | 4 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Elevated Creatinine | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Blepharitis | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Blurred Vision/Vision Loss | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Nausea/emesis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Chalazion | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctivitis | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Gallstones | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Edema | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous Hemorrhage | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Diplopia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Esophageal Reflux | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Dysphotopsia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hemorrhoids | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Elevated IOP | 3 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Epiretinal Membrane | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Eye discomfort/discharge | 6 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Eyelid Swelling | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Cataract Progression | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Glaucoma Progression | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Throat Irritation | 3 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Hollenhorst Plaque | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Vitritis | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Macular Hole | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Anemia | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Optic Neuropathy | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Photophobia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Pingueculum | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hematoma | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Secondary Cataract | 3 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous floaters | 7 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctival hemorrhage | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Punctate Keratitis | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Thrombocytopenia | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Angina Pectoris | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Ocular Adverse Events : Worsening Retinopathy | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Arrhythmia | 2 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Allergy | 5 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Cardiomyopathy | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Coronary Artery Disease | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Constipation | 0 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Graves disease | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hyperammonemia | 1 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Hyperlipidemia | 5 Participants |
| Monthly | Number of Participants With Adverse Events | Nonocular AE: Fever | 2 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Punctate Keratitis | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hypo/hypercalcemia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Eye discomfort/discharge | 9 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Appendicitis | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperkalemia | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Fatigue | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Poor dentition | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hypothyroidism/nodule | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctival hemorrhage | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hyperlipidemia | 4 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hyperphosphatemia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Fever | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Diverticulitis | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hyperuricemia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Eyelid Swelling | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Gastrointestinal infection | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Testosterone deficiency | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperglycemia | 12 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Cataract Progression | 5 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Vitamin D Deficiency | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Peripheral Edema | 6 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Parotitis | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Weight Gain | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hyperparathyroidism | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Elevated Creatinine | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Arthritis | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Glaucoma Progression | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Skin Infection | 18 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Fractured Bone | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Diarrhea | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Musculoskeletal Pain | 16 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Allergy | 9 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Respiratory Infection | 22 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Osteoporosis | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Acute Myocardial Infarction | 5 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Hollenhorst Plaque | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Skin burn | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hernia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Lung Cancer | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Sinusitis | 9 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Thrombocytopenia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Prostate Cancer | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Colon Cancer | 3 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hyperammonemia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Skin Cancer | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Congestive Heart Failure | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Urinary Tract Infection | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Cranial Nerve Palsy | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Elevated liver enzymes | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Macular Hole | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Cerebrovascular Accident | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Abrasion | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Angina Pectoris | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Decreased Hearing | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Blepharitis | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Retinal Hemorrhage | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Depression/Anxiety | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Headache | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Constipation | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Dizziness | 3 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Blurred Vision/Vision Loss | 6 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Neuropathy | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Coronary Artery Disease | 2 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Optic Neuropathy | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Paresthesia | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Nausea/emesis | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Anemia | 4 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Seizure | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Insomnia | 7 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Worsening Retinopathy | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Tinnitus | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctivitis | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Chalazion | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Transient Ischemic Attack | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Photophobia | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Gallstones | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Kidney Stone | 2 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Vitritis | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Edema | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Renal Insufficiency | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Syncope/Presyncope | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Arrhythmia | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Cough | 5 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Pingueculum | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Diplopia | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Dyspnea | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Acute Respiratory Failure | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Graves disease | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Lung Nodule | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Pericardial Effusion | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Epistaxis | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Pneumonia | 4 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Esophageal Reflux | 4 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Dysphotopsia | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Pulmonary Embolism | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreomacular Traction | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Secondary Cataract | 2 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Rhinorrhea | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hematoma | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Elevated IOP | 4 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Sleep apnea | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Incontinence | 0 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Hemorrhoids | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Orthostatic Hypotension | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Cardiomyopathy | 1 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Epiretinal Membrane | 1 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Peripheral Vascular Disease | 0 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous Hemorrhage | 4 Participants |
| TREX | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous floaters | 6 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Worsening Hypertension | 21 Participants |
| TREX | Number of Participants With Adverse Events | Nonocular AE: Throat Irritation | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Worsening Hypertension | 26 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Chalazion | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Punctate Keratitis | 6 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreomacular Traction | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous Hemorrhage | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Vitritis | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Worsening Retinopathy | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Cardiomyopathy | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Congestive Heart Failure | 4 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Coronary Artery Disease | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Pericardial Effusion | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Constipation | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Diverticulitis | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Diarrhea | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Elevated liver enzymes | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Nausea/emesis | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Gallstones | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hemorrhoids | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Poor dentition | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Throat Irritation | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Anemia | 7 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hematoma | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Thrombocytopenia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Epistaxis | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Fatigue | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hyperammonemia | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hyperparathyroidism | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Fractured Bone | 9 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Colon Cancer | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Dizziness | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Headache | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Insomnia | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Paresthesia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Acute Respiratory Failure | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Esophageal Reflux | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Incontinence | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Allergy | 5 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Appendicitis | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Fever | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Gastrointestinal infection | 4 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Parotitis | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Skin Infection | 20 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Respiratory Infection | 14 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Sinusitis | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Urinary Tract Infection | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Blepharitis | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Blurred Vision/Vision Loss | 5 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Cataract Progression | 7 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctivitis | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Conjunctival hemorrhage | 2 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Abrasion | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Corneal Edema | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Diplopia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Dysphotopsia | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Elevated IOP | 3 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Epiretinal Membrane | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Eye discomfort/discharge | 15 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Eyelid Swelling | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Glaucoma Progression | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Hollenhorst Plaque | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Macular Hole | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Optic Neuropathy | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Photophobia | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Pingueculum | 0 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Secondary Cataract | 2 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Vitreous floaters | 7 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Elevated Creatinine | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Acute Myocardial Infarction | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Angina Pectoris | 5 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Arrhythmia | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Peripheral Edema | 8 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Graves disease | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperglycemia | 14 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hyperlipidemia | 6 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hypo/hypercalcemia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hypo/hyperkalemia | 5 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hypothyroidism/nodule | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hyperphosphatemia | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hyperuricemia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Testosterone deficiency | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Vitamin D Deficiency | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Weight Gain | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Arthritis | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Hernia | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Musculoskeletal Pain | 18 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Osteoporosis | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Skin burn | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Lung Cancer | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Prostate Cancer | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Skin Cancer | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Cranial Nerve Palsy | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Cerebrovascular Accident | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Decreased Hearing | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Depression/Anxiety | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Neuropathy | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Syncope/Presyncope | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Seizure | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Tinnitus | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Transient Ischemic Attack | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Kidney Stone | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Renal Insufficiency | 6 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Cough | 5 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Dyspnea | 2 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Lung Nodule | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Pneumonia | 3 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Pulmonary Embolism | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Rhinorrhea | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Sleep apnea | 1 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Orthostatic Hypotension | 0 Participants |
| GILA | Number of Participants With Adverse Events | Nonocular AE: Peripheral Vascular Disease | 1 Participants |
| GILA | Number of Participants With Adverse Events | Ocular Adverse Events : Retinal Hemorrhage | 0 Participants |
Secondary
Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit.
The percentage of eyes in the TREX (Treat and Extend) and GILA (Guided Laser) cohorts who are eligible to begin the extension phase prior to week 104 end-point visit.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Monthly | Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit. | 0 Eyes |
| TREX | Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit. | 49 Eyes |
| GILA | Percentage of Eyes Able to Begin Extension Phase Prior to Week 104 End-point Visit. | 55 Eyes |
Secondary
Percentage of Eyes Gaining or Losing Vision
Percentage of eyes gaining or losing 3 lines of vision or more and 1 line of vision at 24 months (week 92 - week 107) from Day 0.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| Monthly | Percentage of Eyes Gaining or Losing Vision | 1-line vision gainers | 13 Eyes |
| Monthly | Percentage of Eyes Gaining or Losing Vision | 1-line vision losers | 5 Eyes |
| Monthly | Percentage of Eyes Gaining or Losing Vision | 3-line vision gainers | 6 Eyes |
| Monthly | Percentage of Eyes Gaining or Losing Vision | 3-line vision losers | 0 Eyes |
| TREX | Percentage of Eyes Gaining or Losing Vision | 3-line vision losers | 0 Eyes |
| TREX | Percentage of Eyes Gaining or Losing Vision | 1-line vision gainers | 28 Eyes |
| TREX | Percentage of Eyes Gaining or Losing Vision | 3-line vision gainers | 12 Eyes |
| TREX | Percentage of Eyes Gaining or Losing Vision | 1-line vision losers | 1 Eyes |
| GILA | Percentage of Eyes Gaining or Losing Vision | 3-line vision losers | 0 Eyes |
| GILA | Percentage of Eyes Gaining or Losing Vision | 1-line vision losers | 3 Eyes |
| GILA | Percentage of Eyes Gaining or Losing Vision | 3-line vision gainers | 15 Eyes |
| GILA | Percentage of Eyes Gaining or Losing Vision | 1-line vision gainers | 32 Eyes |
Secondary
Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy
The percentage of eyes which show progression of proliferative diabetic retinopathy requiring panretinal photocoagulation and/or pars plana vitrectomy over the 24-month study period.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Monthly | Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy | 1 Eyes |
| TREX | Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy | 2 Eyes |
| GILA | Percentage of Eyes Which Progress to Proliferative Diabetic Retinopathy | 2 Eyes |
Secondary
Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness
For TREX and GILA Cohorts, the time to achieve a Secondary or Tertiary Baseline retinal thickness.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Monthly | Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness | 0 Eyes |
| TREX | Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness | 2 Eyes |
| GILA | Percentage of Eyes With a Secondary or Tertiary Baseline Retinal Thickness | 2 Eyes |