Cystoid Macular Edema, Uveitis
Conditions
Keywords
uveitis, cystoid macular edema
Brief summary
According to a recent estimate more than 280,000 people in the United States are affected by uveitis each year. This report, also estimated that uveitis is the reason for 30,000 new cases of blindness/year and up to 10 percent of all cases of blindness. The purpose of this trial is to determine the effectiveness of VEGF blockade with intravitreal pegaptanib in patients with uveitic CME.
Detailed description
1. Cystoid macular edema is a common complication of uveitic intraocular inflammatory diseases and is characterized by intraretinal edema involving the outer plexiform layer. Intraocular inflammation or uveitis may be associated with non infectious or infectious etiologies. The early symptoms of CME include a decrease or blurry central vision. With long standing CME there is a substantial risk of photoreceptor degeneration and ensuing long term decrease in the quality and level of visual acuity (VA). Furthermore it has been shown that in patients with uveitis, the morphologic features of macular edema and macular thickness correlated with final VA. Current therapeutic interventions have had at best modest results in patients with CME who have had decreased VA. This may the case with systemic interventions also. 2. Vascular endothelial growth factor is a very strong inducer of blood vessel permeability and has been linked to the ocular manifestations of uveitis including CME by experienced researchers both in experimental and clinical settings. In animal tests, VEGF has been shown to be 50,000 times more potent than histamine, the molecule commonly associated with blood vessel leakage related to allergies. Also in animal tests, it has been shown that VEGF is required for the blood vessel permeability associated with neovascular AMD and diabetic retinopathy that have been shown to have an inflammatory component. In addition to its anti-angiogenic property of inhibiting abnormal blood vessel growth, pegaptanib has been shown in animal tests to inhibit blood vessels from leaking into the retina. Uveitis has been shown to be associated with ocular neovascularization both clinically and well as in the clinical studies. Thus, by preventing blood vessel leakage as well as abnormal blood vessel growth pegaptanib may be a viable approach for the treatment of CME. Although pegaptanib use has been associated with mild transient anterior segment inflammation CME itself has not been linked to its use. Besides, pegaptanib has been demonstrated to effect a sustainable decrease the macular edema in maculopathies, both age related and diabetic. 3. There is currently a need for considering alternative forms of local (ocular) therapy for CME to triamcinolone (sub tenon and intraocular). The serious adverse effects with intraocular corticosteroid use are well documented and include cataracts (nuclear and subcapsular), glaucoma, endophthalmitis (may be significantly higher than pegaptanib in patients who are treated exactly as per protocol) as well as sterile inflammatory reactions.
Interventions
DRUGPegaptanib
Five patients will receive intravitreous injections of Macugen 0.3 mg every 6 weeks as needed for a total of no more than five.
Sponsors
Wake Forest University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female adults (\>18 years of age) with non infectious uveitis. 2. Demonstrable (FA and/or OCT) bilateral or unilateral CME associated with uveitis of greater than 3 months but less than 1 years duration that is documented by two independent qualified observers. 3. Best corrected VA between 20/40 and 20/200 as measured by the ETDRS chart attributable to CME in the study eye. 4. Patients may be receiving systemic therapy for the treatment of their intraocular inflammation or cystoid macular edema, or may have been treated for the cystoid macular edema in the past. 5. Anterior chamber inflammation equal to or greater than 1+ and vitreous inflammation equal to or greater than 1+ cell and 1+ haze as per the 'Standardization of Uveitis' working group definition. 6. Females of child bearing potential must agree to utilize effective contraception during the study and two months after the last dose of study medication. 7. Male study patients will agree to use effective contraception. 8. Ability to give informed consent.
Exclusion criteria
1. Allergy to pegaptanib or any of its components 2. Diabetic retinopathy, macular degeneration or any other ocular condition affecting the study eye that may cause vision loss or in the opinion of the study investigator would interfere with the evaluation of the efficacy of Macugen for the treatment of uveitis associated CME. 3. Refusal to try the therapeutic alternative pegaptanib 4. Lack of understanding of the consent or protocol 5. Suspicion/proved history or current diagnosis, (clinical or otherwise) of infectious uveitis. 6. Need for intraocular surgery within 30 weeks of study duration. 7. Periocular steroids to the study eye less than 6 weeks prior to study enrollment 8. History of any prior intravitreal injections in study eye 9. Systemic immunomodulatory agent(s) added or increased in dosage (\>20%) within the last two months prior to study enrollment, or potential need for any increase during the study. 10. Requirement for systemic corticosteroids in the equivalent of oral prednisone \> 30mg/day 11. Topical prostaglandin analog use 12. Severe debilitating disease or medical problems that make consistent follow-up over the treatment period unlikely (e.g. liver impairment, stroke, severe myocardial infarction, terminal cancer). 13. History of hypersensitivity to fluorescein or multiple drug allergies that may increase the chance of a drug reaction to Macugen. 14. Unclear media that precludes assessment of cystoid macular edema in eligible eye(s), such as a cataract or vitreal opacity. 15. Evidence of a macular hole in the study eye. 16. Prior or current retinal detachment in the study eye. 17. Concurrent treatment with any new investigational drug. 18. Pregnant or lactating women (Pregnant and lactating women are excluded since pregnancy may have some effect on CME). 19. Inability to comply with the study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in VA ETDRS >/= 15 Letters | 32 weeks | The primary outcome was an improvement in VA greater than or equal to fifteen letters on the EDTRS chart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Experiencing > 0 Letter Vision Gain and a < 15 Loss | 32 weeks | Patients best corrected visual acuity was measured at each visit to monitor gain or loss of letters on the EDTRS chart. |
| Decrease in CME as Evidenced by Imaging (Fluorescein Angiography and 50 Micron Change in OCT) | 32 weeks | Patients retinal thickness was measured at each visit bu imaging to monitor increase or decrease in thickness. |
| A Decrease in Anterior Chamber Cells or Vitreous Cells or Haze in Injected Eye | 32 weeks | The degree of cell and flare was recorded at each visit during the course of the trial in the injected eye. In uveitis, severely inflamed vessels leak protein which clouds the normally clear aqueous. This looks hazy with the slit lamp. If severe, it disperses the light beam, causing flare. White or red blood cells may be observed: the presence of inflammatory cells in the anterior chamber suggests inflammation of the iris and ciliary body. Blood cells: grading of blood cells in the anterior chamber is as follows: * 0 - None. * 1+ - faint (barely detectable). * 2+ - moderate (clear iris and lens details). * 3+ - moderate (hazy iris and lens details). * 4+ - intense (fibrin deposits, coagulated aqueous). |
| Change in Immunomodulatory Medications (Topical, Periocular or Systemic) After the Initiation of Macugen Therapy | 32 weeks | No changes were to be made in immunodulatory medications of the patients unless needed for safety after in initiation of Macugen therapy. |
Countries
United States
Participant flow
Recruitment details
Five patients with non-infectious uveitis, ongoing for greater than three months but less than twelve months with associated CME. Patients were identified in the PI's regular medical clinic and received five intravitreal pegaptanib doses over the course of thirty weeks.
Pre-assignment details
Five consecutive adult patients with non-infectious uveitis associated CME were chosen for this study. Only patients with a baseline best corrected VA between 20/40 and 20/200, attributable to CME, were selected for the study. In qualified patients with bilateral disease, the eye with the worse visual acuity was selected for the study eye.
Participants by arm
| Arm | Count |
|---|---|
| Macugen Single arm pilot trial
Pegaptanib (Macugen) : Five patients will receive intravitreous injections of Macugen 0.3 mg every 6 weeks as needed for a total of no more than five. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Macugen |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 50.8 years STANDARD_DEVIATION 19.05781 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Improvement in VA ETDRS >/= 15 Letters
The primary outcome was an improvement in VA greater than or equal to fifteen letters on the EDTRS chart.
Time frame: 32 weeks
Population: Five consecutive adult patients with non-infectious uveitis associated CME were chosen from the PI's regular medical clinic. Patients demonstrated, on fluorescein angiogram and/or optical tomography, bilateral or unilateral CME with non-infectious uveitis for greater than three months, but less than twelve.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macugen | Improvement in VA ETDRS >/= 15 Letters | 1 participants |
Secondary
A Decrease in Anterior Chamber Cells or Vitreous Cells or Haze in Injected Eye
The degree of cell and flare was recorded at each visit during the course of the trial in the injected eye. In uveitis, severely inflamed vessels leak protein which clouds the normally clear aqueous. This looks hazy with the slit lamp. If severe, it disperses the light beam, causing flare. White or red blood cells may be observed: the presence of inflammatory cells in the anterior chamber suggests inflammation of the iris and ciliary body. Blood cells: grading of blood cells in the anterior chamber is as follows: * 0 - None. * 1+ - faint (barely detectable). * 2+ - moderate (clear iris and lens details). * 3+ - moderate (hazy iris and lens details). * 4+ - intense (fibrin deposits, coagulated aqueous).
Time frame: 32 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macugen | A Decrease in Anterior Chamber Cells or Vitreous Cells or Haze in Injected Eye | 0 participants |
Secondary
Change in Immunomodulatory Medications (Topical, Periocular or Systemic) After the Initiation of Macugen Therapy
No changes were to be made in immunodulatory medications of the patients unless needed for safety after in initiation of Macugen therapy.
Time frame: 32 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macugen | Change in Immunomodulatory Medications (Topical, Periocular or Systemic) After the Initiation of Macugen Therapy | 0 participants |
Secondary
Decrease in CME as Evidenced by Imaging (Fluorescein Angiography and 50 Micron Change in OCT)
Patients retinal thickness was measured at each visit bu imaging to monitor increase or decrease in thickness.
Time frame: 32 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macugen | Decrease in CME as Evidenced by Imaging (Fluorescein Angiography and 50 Micron Change in OCT) | 2 participants |
Secondary
Proportion of Patients Experiencing > 0 Letter Vision Gain and a < 15 Loss
Patients best corrected visual acuity was measured at each visit to monitor gain or loss of letters on the EDTRS chart.
Time frame: 32 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Macugen | Proportion of Patients Experiencing > 0 Letter Vision Gain and a < 15 Loss | 5 paticipants |