Macular Edema, Cystoid Macular Edema, Uveal Melanoma, Radiation Maculopathy, Radiation Retinopathy
Conditions
Keywords
Plaque radiotherapy, Brachytherapy, Macular edema, Cystoid macular edema, Uveal melanoma, Radiation maculopathy, Radiation retinopathy, Ozurdex, Dexamethasone intravitreal implant
Brief summary
To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex) and compare it with safety and efficacy of intravitreal bevacizumab in eyes with macular edema after plaque radiotherapy of uveal melanoma.
Detailed description
Plaque radiotherapy is a commonly used method for treatment of small and medium-sized uveal melanomas. Macular edema is one of the most common causes of visual loss after plaque radiotherapy and has been reported in up to 70% of patients with posterior uveal melanoma. Different methods have been proposed for treatment of post-radiation macular edema and include periocular steroid, intravitreal steroid, intravitreal vascular endothelial growth factor (VEGF) inhibitors, photodynamic therapy, and macular laser photocoagulation. Injection of intravitreal triamcinolone (a form of steroid) has been found to be useful for treatment of different forms of macular edema but is associated with considerable rates of increased intraocular pressure (glaucoma). Dexamethasone is more potent than triamcinolone and can be safely injected directly into the vitreous cavity (intravitreal injection) but unfortunately its use in the form of intravitreal injection is not practical due to the short half-life of intraocular dexamethasone (about 3 hours). Within the past several years, tiny drug delivery systems have been developed that allow sustained release of minute amounts of steroid into the back part (vitreous cavity) of the eye, when they are implanted into the vitreous cavity. Ozurdex is a biodegradable dexamethasone intravitreal implant that has been shown to be well-tolerated and effective for up to 6 months in reducing vision loss and improving visual outcome in eyes with different types of macular edema including those secondary to diabetic retinopathy and retinal vein occlusion. In this study the investigators would like to evaluate the safety and effectiveness of Ozurdex (dexamethasone intravitreal implant) for treatment of macular edema developing after plaque radiotherapy of uveal melanoma.
Interventions
DRUGOzurdex
Eyes in the Ozurdex group can have a maximum total of three Ozurdex insertions in the first 12 months after enrolling into the study. The criteria for retreatment with Ozurdex are: i.The study eye must have shown initial favorable response to prior Ozurdex implant (\>10% decrease in central macular thickness with maintenance \[change in BCVA of \<=1 line\] or improvement of visual acuity \[increase of BCVA of \>1 line\]) ii. Interval since last Ozurdex implant should be \> 4 and \< 12 months. iii. The study eye must show definite evidence of recurrence of macular edema.
DRUGBevacizumab
Eyes in the Bevacizumab group can have a maximum total of twelve bevacizumab injections in the first year after enrolling into the study. All patients will receive 6 monthly injections after entering the study. After the sixth injection (at month 5) the interval between injections will be extended to 6 weeks if the study eye has shown initial favorable response to prior intravitreal bevacizumab.
Sponsors
Allergan
Arman Mashayekhi
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria: 1. Patient age 18 years or more. 2. Uveal melanoma treated with I-125 plaque radiotherapy. 3. Visual acuity between 20/40 to 20/400 secondary to post-radiation macular edema. 4. Central subfield retinal thickness \> 300 micron. 5. Duration of macular edema \< 12 months. 6. No potential contributing causes of decreased vision other than macular edema. *
Exclusion criteria
1. Visual acuity worse than 20/400 or better than 20/40. 2. Monocular patient or poor vision in the non-study eye (\<20/80). 3. History of vitrectomy surgery. 4. Panretinal photocoagulation or intraocular surgery within 3 months of enrollment. 5. Concomitant or previous radiation optic neuropathy. 6. Use of periocular, intravitreal, or systemic steroids within 6 month of enrollment in the study eye. 7. Use of intravitreal VEGF antagonist within 6 weeks of enrollment. 8. History of ocular hypertension or glaucoma, or intraocular pressure (IOP)\>21 mmHg. 9. History of steroid-induced glaucoma in either eye. 10. Active ocular infection or history of herpetic eye infection. 11. Clinically significant epiretinal membrane in the study eye. 12. Iris neovascularization in the study eye. 13. Clinically significant media opacity preventing acquisition of good-quality optical coherence tomography (OCT) in the study eye. 14. Aphakia or anterior chamber intraocular lens. 15. Poorly controlled diabetes (Hemoglobin A1c level \>13%). 16. Poorly controlled hypertension (Systolic pressure \> 160 mm Hg or diastolic pressure \> 90 mm Hg). 17. Pregnancy (women of childbearing age should have negative pregnancy test and use contraception). 18. Presence of any ocular condition that in the opinion of one of the investigators will prevent at least 2 lines of improvement in best-corrected visual acuity. 19. Interval between plaque radiotherapy for uveal melanoma and intended date of dexamethasone intravitreal implant of less than 6 months. 20. Evidence of activity or inadequate regression of the treated uveal melanoma after plaque radiotherapy (based on the judgment of the study investigators). 21. Known allergy or hypersensitivity to any of the study medications or their components. 22. History of prior myocardial infarction or stroke.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity | At 12 months | The number of participants that developed 2 or more lines of visual acuity improvement in the study eye. Visual acuity was measured with Snellen eye chart placed 10 feet away from the patient. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Central Subfield Retinal Thickness | At 12 months | Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement |
| Development of Glaucoma | At 12 months | Intraocular pressure more than 21 mm Hg as measured with applanation tonometry. |
| Development of Cataract | At 12 months | Development of visually-significant lens opacity based on judgement of examining physician. |
| Development of Retinal Detachment | At 12 months | Development of rhegmatogenous retinal detachment in the study eye. |
| Development of Vitreous Hemorrhage | At 12 months | Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ozurdex Patients will be followed at 1 week after Ozurdex insertion (0.7 mg) and then at 1,2, 3,4, 5, and 6 months. Afterwards, patients will be seen every 2 months. At each visit patients will undergo measurement of BCVA, complete eye examination, fundus photography, and optical coherence tomography. Fluorescein angiography will be repeated at 6 and 12 months. Each eye in the Ozurdex group can have a maximum total of three Ozurdex insertions at minimum of 4-month intervals in the first year of study.
The criteria for retreatment with Ozurdex are:
i.The study eye must have shown initial favorable response to prior Ozurdex implant (\>10% decrease in central macular thickness with maintenance \[change in BCVA of \<=1 line\] or improvement of visual acuity \[increase of BCVA of \>1 line\]) ii. Interval since last Ozurdex implant should be \> 4 and \< 12 months. iii. The study eye must show definite evidence of recurrence of macular edema. | 5 |
| Bevacizumab Patients will be followed at 1 week after the initial bevacizumab injection and then at 1,2, 3,4, 5, and 6 months. Afterwards, the patients will be examined every 4-8 weeks. At each visit patients will be checked for side effects of treatment, measurement of BCVA, complete eye examination, fundus photography, and optical coherence tomography. Fluorescein angiography will be repeated at 6 and 12 months. Eyes in the Bevacizumab group can have a maximum total of twelve (12) bevacizumab injections at minimum of 4-week intervals in the first year after enrolling into the study.
All patients will receive 6 monthly injections after entering the study. After the sixth injection (at month 5) the interval between injections will be extended to 6 weeks if the study eye has shown initial favorable response to prior intravitreal bevacizumab. | 1 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated prematurely | 4 | 0 |
Baseline characteristics
| Characteristic | Total | Ozurdex | Bevacizumab |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 60 years | 66 years | 30 years |
| 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 1 Participants |
| Region of Enrollment United States | 6 participants | 5 participants | 1 participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 1 |
| other Total, other adverse events | 0 / 5 | 0 / 1 |
| serious Total, serious adverse events | 0 / 5 | 0 / 1 |
Outcome results
Primary
Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity
The number of participants that developed 2 or more lines of visual acuity improvement in the study eye. Visual acuity was measured with Snellen eye chart placed 10 feet away from the patient.
Time frame: At 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ozurdex | Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity | 2 participants |
| Bevacizumab | Number of Participants for Whom Study Eye Showed >=2 Lines of Improvement in Best-corrected Visual Acuity | 0 participants |
Secondary
Change in Central Subfield Retinal Thickness
Increase or decrease in central subfield retinal thickness in microns based on spectral-domain optical coherence tomography measurement
Time frame: At 12 months
Population: We were not able to measure central macular thickness at 12 months in one patient in the Ozurdex group due to advanced cataract.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Ozurdex | Change in Central Subfield Retinal Thickness | -120 micron | Standard Deviation 231 |
| Bevacizumab | Change in Central Subfield Retinal Thickness | -4 micron | — |
Secondary
Development of Cataract
Development of visually-significant lens opacity based on judgement of examining physician.
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ozurdex | Development of Cataract | 3 Participants |
| Bevacizumab | Development of Cataract | 0 Participants |
Secondary
Development of Glaucoma
Intraocular pressure more than 21 mm Hg as measured with applanation tonometry.
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ozurdex | Development of Glaucoma | 3 Participants |
| Bevacizumab | Development of Glaucoma | 0 Participants |
Secondary
Development of Retinal Detachment
Development of rhegmatogenous retinal detachment in the study eye.
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ozurdex | Development of Retinal Detachment | 0 Participants |
| Bevacizumab | Development of Retinal Detachment | 0 Participants |
Secondary
Development of Vitreous Hemorrhage
Development of hemorrhage in the vitreous cavity detectable with slit lamp examination or dilated funduscopy.
Time frame: At 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ozurdex | Development of Vitreous Hemorrhage | 0 Participants |
| Bevacizumab | Development of Vitreous Hemorrhage | 0 Participants |