Simultaneous subthreshold retinal-photocoagulation and intravitreal injection of VEGF inhibitors for diabetic macular edema

JRCT ID: jRCTs031180182

Registered date:05/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: diabetic macular edema
• Date of first enrollment: 21/10/2016
• Target sample size: 50
• Study type: Interventional

Intervention(s)

A group: VEGF inhibitors vitreous injection
The 3 times injection are conducted with 4-week intervals. After that, the visit interval is 1 month. When recurrence of DME appears, injection will be conducted within 4 weeks. If no recurrence has occurred, only follow up observation will be done. No recurrence is observed over 16 weeks from the last injection, multiple of 8 weeks are set for further visits.
B group: VEGF inhibitors vitreous injection + subthreshold photocoagulation of retina

Outcome(s)

• Primary Outcome: A period before re-injection : A period before re-injection being necessary after the 3 consecutive monthly intravitreal injection of VEGF inhibitors

Secondary Outcome

1. The number of VEGF inhibitor vitreous injections during the first 12-month in observation period
2. The number of VEGF inhibitor vitreous injections during the first 24-month in observation period
3. Re-injection rate: rate of events, which are defined as indication of re-injection after 3 times series injections, during the first 24-month in observation period
4. Retention rate: Proportion of subjects who do not indicate re-injection at 8 16, 24, 32 and 80weeks after 3 times series injections
5. Number of retinal subthreshold photocoagulation: The number of retinal Subthreshold photocoagulation treatment during 24-month observation period
6. Optical coherence tomography (OCT): foveal thickness at each observation point
7. Acuity: logMAR acuity converted from corrected vision at each measurement point
8. Comparison subjects treated with subthreshold micropulse Laser photocoagulation with those with PASCAL subthreshold photocoagulation: Duration for indicating re-injection, the number of VEGF inhibitor vitreous injections, re-injection rate, retention rate, acuity (at baseline and final measurement, and change from baseline), foveal thickness (at baseline and final measurement, and change from baseline), and the number of subthreshold photocoagulation interventions during the first 12 months and 24 months
9. Eye fundus photograph: Evaluation of the presence/ absence of hemorrhage from mucula and hard spot on mucula at each observation point
10. Fluorescent fundus angiography FA): Evaluation of diapedesis from perimucula vessels at each observation point
11. Fundus perimetry measurement(MAIA): Evaluation of perimucula retina sensitivity at each measurement point

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Japanese male and female >= 18 years with type 1 or 2 diabetes mellitus
2. DME with central involvement in the study eye
3. Decrease in vision determined to be primarily the result of DME in the study eye
4. central macular thickness >= 300 micrometer in the study eye
5. BCVA of 0.7 to 0.05 in the study eye
6. Subject must be competent to understand the information ICF and must sign the form
7. An eye with thicker patina when both eyes meet the above criteria

Exclude criteria

1.Laser photocoagulation (panretinal or macular) in the study eye within 90 days prior to the first dose
2.Previous use of intraocular or periocular corticosteroids in the study eye within 120 days prior to the first dose
3.Previous treatment with anti-angiogenic drugs in the study eye (pegaptanib sodium, bevacizumab, ranibizumab, etc.) within 90 days prior to the first dose
4.Active proliferative diabetic retinopathy (PDR) in the study eye
5.Uncontrolled diabetes mellitus
6.Medical history of vitreoretinal surgery and scleral buckling
7.Medical history of filtering operation for glaucoma treatment and subject is expected to treat that operation in future
8.Medical history of idiopathic or autoimmune uveitis
9.Central vision is significantly affected by existing Vitreous tug syndrome or preretinal membrane
10.Existing iris neovascularization, vitreous hemorrhage and/or traction retinal detachment
11.Preretinal fibrosis extending to macular
12.Structural damage of central macular preventing improvement of visual acuity after regression of macular edema, such as atrophy of retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia, or structural hard spot
13.Posibility of low vision to conduct medical or surgical interventions during the study period, complications which should affect the study result
14.Cataract surgery or other intraocular surgery within 90 days prior to the first dose
15.Capsulotomy after yttrium aluminum garnet (YAG)lesser treatment within 30 days prior to the first dose
16.Three or more times of Macular lesser treatment (excluding direct coagulation for microaneurysm), or judged no responder to lesser treatment
17.Subject has developed symptoms of infectious blepharitis, corneitis, leucitis or conjunctivitis
18.Insufficient degree of clearness of optic media for the fundus imaging and OCT imaging
19.Subject has treated for serious systemic infectious disease
20.Poor controlled hypertension (sitting systolic pressure > 160mmHg and/or diastolic pressure > 95mmHg
21.Renal failure indicating dialysis or renal transplantation
22.An event of cerebrovascular disease or myocardial infarction within 180 days prior to the first dose
23.Systemic treatment of angiogenic inhibitor within 180 days prior to the first dose
24. High risk subject, who will affect study results or develop complications, based on medical records, metabolic dysfunction, or laboratory test findings indicating a disease and/or conditions for that the test drug will be contraindicated
25.Allergy to fluorescein
26.Female subject who is pregnant or breastfeeding, or who hopes to become pregnancy during the study period
27.Subjects judged not to be adequate by the investigator

Related Information

• Primary Sponsor: Tatsumi Tomoaki
• Secondary Sponsor: Yamamoto Shuichi
• Source(s) of Monetary Support: Bayer Yakuhin Ltd.
• Secondary ID(s): UMIN000019635