Proliferative Diabetic Retinopathy, Tractional Retinal Detachment
Conditions
Keywords
Conbercept, Proliferative diabetic retinopathy, Silicone oil tamponade
Brief summary
To evaluate efficacy of different intravitreal Conbercept injection therapy in the treatment of severe proliferative diabetic retinopathy.
Detailed description
To assess the clinical effects of preoperative, intraoperative or preoperative combined with intraoperative intravitreal conbercept (IVC) injection in pars plana vitrectomy (PPV) with silicone oil tamponade for severe proliferative diabetic retinopathy (PDR). Methods. These patients were randomly assigned to three groups: Group 1 received an IVC injection 3 to 5 days before surgery; Group 2 received an IVC injection at the end of surgery; and Group 3 received an IVC injection 3 to 5 days before PPV as well as an IVC injection at the end of PPV. Follow-up examinations were performed for at least six months after surgery.
Interventions
DRUGConbercept
Conbercept is a humanized soluble fusion protein which has a high binding affinity to the Fc region of human immunoglobulin G1 simultaneously. Prior clinical studies have demonstrated that intravitreal conbercept (IVC) inhibits the process of angiogenesis in vivo and in vitro, and has been recognized as a novel effective treatment strategy for neovascularization, providing an alternative treatment option for ophthalmologists.
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects of either sex aged ≥ 18 years. 2. Diagnosis of diabetes mellitus (type 1 or type 2); 3. Active proliferative diabetic retinopathy was clinically evident; 4. Study eyes required a vitrectomy and silicone oil tamponade due to vitreous hemorrhage with significant fibrous proliferation, tractional retinal detachment in the posterior pole or complicated retinal detachment, which can be detected by B-scan ultrasonography. 5. Ability to give informed consent.
Exclusion criteria
1. Coexistent ocular disease that may interfere with visual outcome; 2. Prior vitreoretinal surgery or anti-vascular endothelial growth factor (VEGF) pharmacotherapy in either eye; 3. A macula-involving retinal detachment for \>6 months in the study eye; 4. Iris or angle neovascularization and neovascular glaucoma; 5. known allergy to any components of conbercept formulation 6. severe external ocular infection; 7. pregnancy or current oral contraceptive intake; 8. usage of anticoagulant or antiplatelet therapy; 9. preoperative or postoperative poor diabetes control \[serum hemoglobin A1c (HbA1c) \>11.0%\]; 10. uncontrolled systemic diseases, such as hypertension, cardiac diseases or presenting abnormal coagulation-associated blood diseases; 11. \<6 months of follow-up post initial surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best-corrected Visual Acuity | 6 months | — |
| Duration of Surgery | during the operation time | To evaluate the influence of these three methods to the final duration of surgery. We carefully estimated the time of the vitrectomy from insertion to extraction of the 23-gauge three-port trocars. |
| Intraoperative Bleeding | Time between the insertion and extraction of three 23-gauge vitrectomy ports | The grading criteria for intraoperative bleeding: Grade 1, spontaneous cessation of minor bleeding or bleeding that stopped by transient elevation of perfusion pressure; Grade 2, moderate bleeding requiring endodiathermy or broad blood clots formed far away from the bleeding site; Grade 3, thick blood clots exceeding half of the posterior pole or affecting the operation field. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Intraoperative Electrocoagulation | during the operation time | The number of times electrocoagulation, which was used to stop bleeding, was carefully counted. |
| Number of Participants With Neovascular Glaucoma (NVG) | follow up period, up to an average of 6 months after the operation | — |
| Postoperative Preretinal Blood | postoperatively, up to 1 week | The grading criteria for postoperative preretinal blood: Grade 1, isolated blood clots within 10 disk area but without covering the posterior pole; Grade 2, broad blood clots exceeding 10 disk area regardless of involvement of the posterior pole; Grade 3, broad blood clots exceeding 10 disk area as well as involving the posterior pole. Maximal extent of preretinal blood within 1 week postoperatively was used for grading the extent of hemorrhage. |
| Need for Reoperation | follow up period, up to an average of 6 months after the operation | due to recurrent retinal detachment or unclear vitreous hemorrhage |
| Recurrent Retinal Detachment | follow up period, up to an average of 6 months after the operation | — |
| Reabsorption Time of Blood | follow up period, up to an average of 6 months after the operation | To monitor the reabsorption time of preretinal blood. |
| Recurrent Vitreous Hemorrhage | follow up period, up to an average of 6 months after the operation | Recurrent vitreous hemorrhage(VH) was referred to any new episode of VH occurring after one week postoperatively, dividing into early stage (≤ 4 weeks) and late stage (\> 4 weeks). |
Countries
China
Participant flow
Recruitment details
The study was performed in the department of Ophthalmology, Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine, between July 2016 and September 2017.
Participants by arm
| Arm | Count |
|---|---|
| IVC Preoperative Group Conbercept injection before vitrectomy
Conbercept: Conbercept is a humanized soluble fusion protein which has a high binding affinity to the Fc region of human immunoglobulin G1 simultaneously. Prior clinical studies have demonstrated that intravitreal conbercept (IVC) inhibits the process of angiogenesis in vivo and in vitro, and has been recognized as a novel effective treatment strategy for neovascularization, providing an alternative treatment option for ophthalmologists. | 34 |
| IVC Postoperative Group Conbercept injection at the end of vitrectomy
Conbercept: Conbercept is a humanized soluble fusion protein which has a high binding affinity to the Fc region of human immunoglobulin G1 simultaneously. Prior clinical studies have demonstrated that intravitreal conbercept (IVC) inhibits the process of angiogenesis in vivo and in vitro, and has been recognized as a novel effective treatment strategy for neovascularization, providing an alternative treatment option for ophthalmologists. | 35 |
| IVC Pre- and Post-operative Group First conbercept injection before vitrectomy and second at the end of operation.
Conbercept: Conbercept is a humanized soluble fusion protein which has a high binding affinity to the Fc region of human immunoglobulin G1 simultaneously. Prior clinical studies have demonstrated that intravitreal conbercept (IVC) inhibits the process of angiogenesis in vivo and in vitro, and has been recognized as a novel effective treatment strategy for neovascularization, providing an alternative treatment option for ophthalmologists. | 29 |
| Total | 98 |
Baseline characteristics
| Characteristic | IVC Pre- and Post-operative Group | Total | IVC Preoperative Group | IVC Postoperative Group |
|---|---|---|---|---|
| Age, Continuous | 52.55 years STANDARD_DEVIATION 14.62 | 52.44 years STANDARD_DEVIATION 14.2 | 50.76 years STANDARD_DEVIATION 13.47 | 53.97 years STANDARD_DEVIATION 14.76 |
| Duration of diabetes (years) | 12.66 years STANDARD_DEVIATION 5.24 | 13.37 years STANDARD_DEVIATION 5.22 | 14.50 years STANDARD_DEVIATION 5.16 | 12.86 years STANDARD_DEVIATION 5.23 |
| Extent of vitreoretinal adhesion grade 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Extent of vitreoretinal adhesion grade 1 | 4 Participants | 33 Participants | 14 Participants | 15 Participants |
| Extent of vitreoretinal adhesion grade 2 | 8 Participants | 29 Participants | 11 Participants | 10 Participants |
| Extent of vitreoretinal adhesion grade 3 | 17 Participants | 36 Participants | 9 Participants | 10 Participants |
| HbA1c at time of surgery | 7.88 % STANDARD_DEVIATION 1.26 | 7.51 % STANDARD_DEVIATION 1.41 | 7.12 % STANDARD_DEVIATION 1.52 | 7.59 % STANDARD_DEVIATION 1.36 |
| Hypertension | 13 Participants | 45 Participants | 15 Participants | 17 Participants |
| Lens status (pseudophakic) | 7 Participants | 14 Participants | 4 Participants | 3 Participants |
| LogMAR Best Corrected Visual Acuity (BCVA) | 1.98 LogMAR STANDARD_DEVIATION 0.44 | 1.96 LogMAR STANDARD_DEVIATION 0.41 | 1.95 LogMAR STANDARD_DEVIATION 0.43 | 1.97 LogMAR STANDARD_DEVIATION 0.37 |
| Preoperative iris neovascularization | 2 Participants | 7 Participants | 2 Participants | 3 Participants |
| Previous history of pan-retinal photocoagulation (PRP) | 13 Participants | 39 Participants | 11 Participants | 15 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — | — |
| Sex: Female, Male Female | 13 Participants | 52 Participants | 20 Participants | 19 Participants |
| Sex: Female, Male Male | 16 Participants | 46 Participants | 14 Participants | 16 Participants |
| Study eye (right eye) | 16 eyes | 54 eyes | 21 eyes | 17 eyes |
| Type 1 diabetes | 3 Participants | 8 Participants | 3 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 35 | 0 / 29 |
| other Total, other adverse events | 0 / 34 | 0 / 35 | 0 / 29 |
| serious Total, serious adverse events | 0 / 34 | 0 / 35 | 0 / 29 |
Outcome results
Primary
Best-corrected Visual Acuity
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IVC Preoperative Group | Best-corrected Visual Acuity | 1.25 LogMAR | Standard Deviation 0.45 |
| IVC Postoperative Group | Best-corrected Visual Acuity | 1.29 LogMAR | Standard Deviation 0.46 |
| IVC Pre- and Post-operative Group | Best-corrected Visual Acuity | 1.16 LogMAR | Standard Deviation 0.44 |
Primary
Duration of Surgery
To evaluate the influence of these three methods to the final duration of surgery. We carefully estimated the time of the vitrectomy from insertion to extraction of the 23-gauge three-port trocars.
Time frame: during the operation time
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IVC Preoperative Group | Duration of Surgery | 55.41 minutes | Standard Deviation 11.24 |
| IVC Postoperative Group | Duration of Surgery | 67.66 minutes | Standard Deviation 15.15 |
| IVC Pre- and Post-operative Group | Duration of Surgery | 57.86 minutes | Standard Deviation 13.23 |
Primary
Intraoperative Bleeding
The grading criteria for intraoperative bleeding: Grade 1, spontaneous cessation of minor bleeding or bleeding that stopped by transient elevation of perfusion pressure; Grade 2, moderate bleeding requiring endodiathermy or broad blood clots formed far away from the bleeding site; Grade 3, thick blood clots exceeding half of the posterior pole or affecting the operation field.
Time frame: Time between the insertion and extraction of three 23-gauge vitrectomy ports
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IVC Preoperative Group | Intraoperative Bleeding | Grade 1 | 15 Participants |
| IVC Preoperative Group | Intraoperative Bleeding | Grade 3 | 7 Participants |
| IVC Preoperative Group | Intraoperative Bleeding | Grade 2 | 12 Participants |
| IVC Postoperative Group | Intraoperative Bleeding | Grade 2 | 16 Participants |
| IVC Postoperative Group | Intraoperative Bleeding | Grade 1 | 7 Participants |
| IVC Postoperative Group | Intraoperative Bleeding | Grade 3 | 12 Participants |
| IVC Pre- and Post-operative Group | Intraoperative Bleeding | Grade 1 | 12 Participants |
| IVC Pre- and Post-operative Group | Intraoperative Bleeding | Grade 3 | 6 Participants |
| IVC Pre- and Post-operative Group | Intraoperative Bleeding | Grade 2 | 11 Participants |
Secondary
Frequency of Intraoperative Electrocoagulation
The number of times electrocoagulation, which was used to stop bleeding, was carefully counted.
Time frame: during the operation time
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IVC Preoperative Group | Frequency of Intraoperative Electrocoagulation | 1.73 events | Standard Deviation 1.26 |
| IVC Postoperative Group | Frequency of Intraoperative Electrocoagulation | 3.00 events | Standard Deviation 1.14 |
| IVC Pre- and Post-operative Group | Frequency of Intraoperative Electrocoagulation | 1.34 events | Standard Deviation 0.81 |
Secondary
Need for Reoperation
due to recurrent retinal detachment or unclear vitreous hemorrhage
Time frame: follow up period, up to an average of 6 months after the operation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVC Preoperative Group | Need for Reoperation | 11 Participants |
| IVC Postoperative Group | Need for Reoperation | 9 Participants |
| IVC Pre- and Post-operative Group | Need for Reoperation | 6 Participants |
Secondary
Number of Participants With Neovascular Glaucoma (NVG)
Time frame: follow up period, up to an average of 6 months after the operation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVC Preoperative Group | Number of Participants With Neovascular Glaucoma (NVG) | 4 Participants |
| IVC Postoperative Group | Number of Participants With Neovascular Glaucoma (NVG) | 5 Participants |
| IVC Pre- and Post-operative Group | Number of Participants With Neovascular Glaucoma (NVG) | 2 Participants |
Secondary
Postoperative Preretinal Blood
The grading criteria for postoperative preretinal blood: Grade 1, isolated blood clots within 10 disk area but without covering the posterior pole; Grade 2, broad blood clots exceeding 10 disk area regardless of involvement of the posterior pole; Grade 3, broad blood clots exceeding 10 disk area as well as involving the posterior pole. Maximal extent of preretinal blood within 1 week postoperatively was used for grading the extent of hemorrhage.
Time frame: postoperatively, up to 1 week
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IVC Preoperative Group | Postoperative Preretinal Blood | Grade 3 | 9 Participants |
| IVC Preoperative Group | Postoperative Preretinal Blood | Grade 1 | 14 Participants |
| IVC Preoperative Group | Postoperative Preretinal Blood | Grade 2 | 11 Participants |
| IVC Postoperative Group | Postoperative Preretinal Blood | Grade 2 | 11 Participants |
| IVC Postoperative Group | Postoperative Preretinal Blood | Grade 3 | 9 Participants |
| IVC Postoperative Group | Postoperative Preretinal Blood | Grade 1 | 15 Participants |
| IVC Pre- and Post-operative Group | Postoperative Preretinal Blood | Grade 1 | 17 Participants |
| IVC Pre- and Post-operative Group | Postoperative Preretinal Blood | Grade 3 | 4 Participants |
| IVC Pre- and Post-operative Group | Postoperative Preretinal Blood | Grade 2 | 8 Participants |
Secondary
Reabsorption Time of Blood
To monitor the reabsorption time of preretinal blood.
Time frame: follow up period, up to an average of 6 months after the operation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IVC Preoperative Group | Reabsorption Time of Blood | 11.24 days | Standard Deviation 4.33 |
| IVC Postoperative Group | Reabsorption Time of Blood | 12.23 days | Standard Deviation 6.19 |
| IVC Pre- and Post-operative Group | Reabsorption Time of Blood | 10.10 days | Standard Deviation 4.07 |
Secondary
Recurrent Retinal Detachment
Time frame: follow up period, up to an average of 6 months after the operation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IVC Preoperative Group | Recurrent Retinal Detachment | 4 Participants |
| IVC Postoperative Group | Recurrent Retinal Detachment | 5 Participants |
| IVC Pre- and Post-operative Group | Recurrent Retinal Detachment | 3 Participants |
Secondary
Recurrent Vitreous Hemorrhage
Recurrent vitreous hemorrhage(VH) was referred to any new episode of VH occurring after one week postoperatively, dividing into early stage (≤ 4 weeks) and late stage (\> 4 weeks).
Time frame: follow up period, up to an average of 6 months after the operation
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IVC Preoperative Group | Recurrent Vitreous Hemorrhage | early vitreous hemorrhage | 6 Participants |
| IVC Preoperative Group | Recurrent Vitreous Hemorrhage | no vitreous hemorrhge | 23 Participants |
| IVC Preoperative Group | Recurrent Vitreous Hemorrhage | late vitreous hemorrhage | 5 Participants |
| IVC Postoperative Group | Recurrent Vitreous Hemorrhage | early vitreous hemorrhage | 7 Participants |
| IVC Postoperative Group | Recurrent Vitreous Hemorrhage | late vitreous hemorrhage | 3 Participants |
| IVC Postoperative Group | Recurrent Vitreous Hemorrhage | no vitreous hemorrhge | 25 Participants |
| IVC Pre- and Post-operative Group | Recurrent Vitreous Hemorrhage | early vitreous hemorrhage | 2 Participants |
| IVC Pre- and Post-operative Group | Recurrent Vitreous Hemorrhage | no vitreous hemorrhge | 25 Participants |
| IVC Pre- and Post-operative Group | Recurrent Vitreous Hemorrhage | late vitreous hemorrhage | 2 Participants |