Open Angle Glaucoma
Conditions
Keywords
trabeculectomy, mitomycin-C, glaucoma
Brief summary
Trabeculectomy is routinely used as a surgical treatment for open angle glaucoma. Success of trabeculectomy is greatly augmented by the use of antimetabolites to inhibit wound healing, specifically Mitomycin C (MMC). MMC can be applied to the eye at various sites, concentrations and times. This study aims to compare the two application routes that are commonly employed: subconjunctival pre-operative injection and intraoperative direct scleral application in terms of IOP lowering effect, bleb appearance and complications.
Detailed description
Trabeculectomy is widely used as a surgical treatment of uncontrolled open glaucoma. Success of trabeculectomy at halting or slowing glaucoma progression primarily relies on the extent of conjunctival and sclera wound healing. The success rates of trabeculectomy increased dramatically with the introduction of anti-metabolites. For more than two decades mitomycin-c (MMC), a chemotherapeutic agent capable of decreasing fibroblast activity and modulating wound healing at the bleb, has been used with trabeculectomy. The complications of MMC are well known and several studies have described various methods of application based on exposure time, dose and surface area. Numerous retrospective and prospective studies have compared the efficacy of MMC applied beneath the conjunctival flap with soaked sponges versus intrascleral application. In 2008, Lee et al. first described an alternative route of application: subconjunctival injection of MMC directly into the intra-Tenon area. Seventy-six eyes with primary and secondary open angle glaucoma underwent trabeculectomy with this approach and were followed for one year post-operatively. Eighty-six percent of eyes achieved an IOP \<21 mm Hg and 57% an IOP\<14 mm Hg at one year without adjunctive drops. Transient complications included hyphema, bleb leak and choroidal detachment. The advantages of injected MMC are primarily in controlling the exact dosage and area of application and reduced surgical time. Lim et al. retrospectively reviewed the outcomes of trabeculectomy in 57 eyes using sponge application directly to the sclera versus intra-tenon injection. IOP was significantly lower in the injection group at 1 month, 1, 2, and 3 years. Trabeculectomy success (IOP\<21mm Hg or IOP \>20% below baseline without medications or additional surgery) was greater in the injection group at 3 years. The sponge group experienced more encapsulated blebs but complication rates were similar in both groups. To date, there have been no prospective studies comparing the IOP-lowering efficacy and safety of intra-tenon injection versus direct scleral application of MMC.
Interventions
DRUGMitomycin-C injection
MMC delivered by preoperative subconjunctival injection
DRUGMitomycin-C sponge
MMC delivered by intraoperative direct scleral application with impregnated cellulose sponges
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* medically uncontrolled glaucoma * healthy and freely mobile conjunctiva in superior bulbar region
Exclusion criteria
* previous incisional glaucoma surgery * no light perception vision * pregnant or nursing women * iris neovascularization or proliferative retinopathy * iridocorneal endothelial syndrome * chronic or recurrent uveitis * steroid-induced glaucoma * pathologic myopia or refractive error less than -6.00 diopters * unwillingness or inability to give consent * inability to return for scheduled protocol visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | 6 months | Percentage of patients achieving at least a 30% mean intraocular pressure reductions from baseline and with an intraocular pressure \<21 mm Hg. Subjects that met this criteria without the use of intraocular pressure lowering medications were classified as Complete Success. Subjects that met this criteria but required the use of intraocular pressure lowering medications were classified as Qualified Success. Subjects that failed to meet this criteria were classified as Failure. Subjects that failed to meet this criteria and required additional glaucoma surgery were classified as Complete Failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleb Morphology | 6 months | Bleb morphology at 6 months was graded using Indiana Bleb Appearance Grading Scale. Bleb height was graded on a scale of 0 to 3 (0: flat bleb without visible elevation, 1: low bleb elevation, 2: moderate bleb elevation, 3: high bleb elevation). Bleb extent was graded on a scale of 0 to 3 (0: no visible bleb extent to less than 1 clock hour, 1: extent equal to or greater than 1 clock hour but less than 2 clock hours, 2: extent equal to or greater than 2 clock hours but less than 4 clock hours, 3: extent equal to or greater than 4 clock hours). Bleb vascularity was graded on a scale of 0 to 4 (0: avascular/white, 1: avascular/cystic, 2: mild vascularity, 3: moderate vascularity, 4: extensive vascularity). Scales are descriptive and do not necessarily represent better or worse outcomes. |
| Visual Acuity | 6 months | Change in visual acuity from baseline |
| Medications | 6 months | Number of intraocular pressure lowering medications used by the patient at follow up visit. |
| Number of Participants Requiring Additional Surgery | 6 months | Number of eyes requiring additional surgery from each group |
| Postoperative Interventions | 6 months | Mean number of postoperative interventions (needling, antifibrotic injections) performed in each group |
| Number of Participants With Surgical Complications | 6 months | Number of eyes that experienced surgical complications following surgery |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Injection Group MMC delivered by preoperative subconjunctival injection
Mitomycin-C injection: MMC delivered by preoperative subconjunctival injection | 50 |
| Sponge Group MMC delivered by intraoperative direct scleral application with impregnated cellulose sponges
Mitomycin-C sponge: MMC delivered by intraoperative direct scleral application with impregnated cellulose sponges | 50 |
| Total | 100 |
Baseline characteristics
| Characteristic | Sponge Group | Total | Injection Group |
|---|---|---|---|
| Age, Continuous | 74.2 years STANDARD_DEVIATION 9.5 | 72.0 years STANDARD_DEVIATION 11.6 | 69.9 years STANDARD_DEVIATION 13.4 |
| Diagnosis Chronic angle closure glaucoma | 0 Participants | 1 Participants | 1 Participants |
| Diagnosis Other | 3 Participants | 5 Participants | 2 Participants |
| Diagnosis Pigmentary glaucoma | 1 Participants | 1 Participants | 0 Participants |
| Diagnosis Primary open angle glaucoma | 43 Participants | 88 Participants | 45 Participants |
| Diagnosis Pseudoexfoliation glaucoma | 3 Participants | 5 Participants | 2 Participants |
| IOP Goal | 12.7 mm Hg STANDARD_DEVIATION 2.2 | 12.2 mm Hg STANDARD_DEVIATION 1.7 | 11.8 mm Hg STANDARD_DEVIATION 0.9 |
| Number of Medications 1 | 6 Participants | 10 Participants | 4 Participants |
| Number of Medications 2 | 12 Participants | 18 Participants | 6 Participants |
| Number of Medications 3 | 21 Participants | 42 Participants | 21 Participants |
| Number of Medications 4 | 7 Participants | 24 Participants | 17 Participants |
| Number of Medications 5 | 0 Participants | 2 Participants | 2 Participants |
| Number of Medications None | 4 Participants | 4 Participants | 0 Participants |
| Preoperative Intraocular Pressure | 21.8 mm Hg STANDARD_DEVIATION 9.3 | 21.45 mm Hg STANDARD_DEVIATION 8.3 | 21.1 mm Hg STANDARD_DEVIATION 7.2 |
| Preoperative Pattern Standard Deviation | 8.9 decibels STANDARD_DEVIATION 3.2 | 9.15 decibels STANDARD_DEVIATION 3.4 | 9.4 decibels STANDARD_DEVIATION 3.6 |
| Preoperative Visual Field Mean Deviation | -15.87 decibels STANDARD_DEVIATION 8.09 | -16.53 decibels STANDARD_DEVIATION 8 | -17.19 decibels STANDARD_DEVIATION 7.9 |
| Race/Ethnicity, Customized Asian | 7 Participants | 16 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants | 14 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 10 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 28 Participants | 55 Participants | 27 Participants |
| Sex: Female, Male Female | 24 Participants | 50 Participants | 26 Participants |
| Sex: Female, Male Male | 26 Participants | 50 Participants | 24 Participants |
| Visual Acuity | 0.36 logMAR STANDARD_DEVIATION 0.52 | 0.335 logMAR STANDARD_DEVIATION 0.44 | 0.31 logMAR STANDARD_DEVIATION 0.34 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 5 / 50 | 6 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
Primary
Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds
Percentage of patients achieving at least a 30% mean intraocular pressure reductions from baseline and with an intraocular pressure \<21 mm Hg. Subjects that met this criteria without the use of intraocular pressure lowering medications were classified as Complete Success. Subjects that met this criteria but required the use of intraocular pressure lowering medications were classified as Qualified Success. Subjects that failed to meet this criteria were classified as Failure. Subjects that failed to meet this criteria and required additional glaucoma surgery were classified as Complete Failure.
Time frame: 6 months
Population: 14 subjects in the Injection group were lost to follow up at the 6 month postoperative visit. 10 subjects from the Sponge group were lost to follow up at the 6 month postoperative visit.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Injection Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Complete Success | 21 Participants |
| Injection Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Qualified Success | 1 Participants |
| Injection Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Failure | 6 Participants |
| Injection Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Complete Failure | 8 Participants |
| Sponge Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Complete Failure | 7 Participants |
| Sponge Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Complete Success | 21 Participants |
| Sponge Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Failure | 9 Participants |
| Sponge Group | Percentage of Participants Achieving Intraocular Pressure Reduction Thresholds | Qualified Success | 3 Participants |
Secondary
Bleb Morphology
Bleb morphology at 6 months was graded using Indiana Bleb Appearance Grading Scale. Bleb height was graded on a scale of 0 to 3 (0: flat bleb without visible elevation, 1: low bleb elevation, 2: moderate bleb elevation, 3: high bleb elevation). Bleb extent was graded on a scale of 0 to 3 (0: no visible bleb extent to less than 1 clock hour, 1: extent equal to or greater than 1 clock hour but less than 2 clock hours, 2: extent equal to or greater than 2 clock hours but less than 4 clock hours, 3: extent equal to or greater than 4 clock hours). Bleb vascularity was graded on a scale of 0 to 4 (0: avascular/white, 1: avascular/cystic, 2: mild vascularity, 3: moderate vascularity, 4: extensive vascularity). Scales are descriptive and do not necessarily represent better or worse outcomes.
Time frame: 6 months
Population: In the injection group, 14 subjects were lost to follow up and 17 subjects did not undergo bleb assessments at 6 months.In the sponge group, 10 subjects were lost to follow up and 20 subjects did not undergo bleb assessments at 6 months.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Injection Group | Bleb Morphology | Vascularity | 1.5 scores on a scale |
| Injection Group | Bleb Morphology | Height | 1.6 scores on a scale |
| Injection Group | Bleb Morphology | Extent | 2.2 scores on a scale |
| Sponge Group | Bleb Morphology | Height | 1.7 scores on a scale |
| Sponge Group | Bleb Morphology | Extent | 2.0 scores on a scale |
| Sponge Group | Bleb Morphology | Vascularity | 1.5 scores on a scale |
Secondary
Medications
Number of intraocular pressure lowering medications used by the patient at follow up visit.
Time frame: 6 months
Population: In the injection group, 14 subjects were lost to follow up and 1 subject did not have medications documented at 6 months. In the sponge group, 10 subjects were lost to follow up and 2 subjects did not have medications documented at 6 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Injection Group | Medications | 0 | 30 Participants |
| Injection Group | Medications | 1 | 3 Participants |
| Injection Group | Medications | 2 | 1 Participants |
| Injection Group | Medications | 3 | 1 Participants |
| Sponge Group | Medications | 3 | 1 Participants |
| Sponge Group | Medications | 0 | 32 Participants |
| Sponge Group | Medications | 2 | 1 Participants |
| Sponge Group | Medications | 1 | 4 Participants |
Secondary
Number of Participants Requiring Additional Surgery
Number of eyes requiring additional surgery from each group
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Injection Group | Number of Participants Requiring Additional Surgery | Xen | 0 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | Any Surgery | 8 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | GDD | 2 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | CEIOL | 8 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | Trabectome | 0 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | YAG | 0 participants |
| Injection Group | Number of Participants Requiring Additional Surgery | Trab Revision | 8 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | YAG | 1 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | Trab Revision | 5 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | GDD | 1 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | Xen | 1 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | Trabectome | 1 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | Any Surgery | 7 participants |
| Sponge Group | Number of Participants Requiring Additional Surgery | CEIOL | 5 participants |
Secondary
Number of Participants With Surgical Complications
Number of eyes that experienced surgical complications following surgery
Time frame: 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Injection Group | Number of Participants With Surgical Complications | Hypotony Maculopathy | 3 participants |
| Injection Group | Number of Participants With Surgical Complications | Choroidal Effusions | 2 participants |
| Sponge Group | Number of Participants With Surgical Complications | Hypotony Maculopathy | 1 participants |
| Sponge Group | Number of Participants With Surgical Complications | Choroidal Effusions | 5 participants |
Secondary
Postoperative Interventions
Mean number of postoperative interventions (needling, antifibrotic injections) performed in each group
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Injection Group | Postoperative Interventions | 5FU Injection | 3.3 number of procedures |
| Injection Group | Postoperative Interventions | Laser suture lysis | 2.0 number of procedures |
| Sponge Group | Postoperative Interventions | Laser suture lysis | 1.6 number of procedures |
| Sponge Group | Postoperative Interventions | 5FU Injection | 3.2 number of procedures |
Secondary
Visual Acuity
Change in visual acuity from baseline
Time frame: 6 months
Population: In the injection group, 14 subjects were lost to follow up at 6 months. In the sponge group, 10 subjects were lost to follow up at 6 months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Injection Group | Visual Acuity | 0.11 logMAR |
| Sponge Group | Visual Acuity | 0.03 logMAR |