Please select the eligibility criteria that correspond to the clinical trial below.
Title: Short-term Evaluation of Combination Corticosteroid+Anti-VEGF Treatment for Persistent Central-Involved Diabetic Macular Edema Following Anti-VEGF Therapy
Brief Summary: Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as treatment for center-involved diabetic macular edema (DME), a substantial proportion of anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of retinal thickening. Indeed, over 50% of ranibizumab-treated eyes did not achieve a 2 or more line improvement in visual acuity from baseline at 2 years in Protocol I, a previous DRCR.net (Diabetic Retinopathy Clinical Research Network) study. Furthermore, 27% of ranibizumab-treated eyes still had central subfield (CSF) thickness on time-domain optical coherence tomography (OCT) ≥ 300 at 1 year, and more than 40% of ranibizumab-treated eyes did not achieve complete resolution of retinal thickening (\< 250 microns) by 2 years. Thus, there is a need for alternative or additional treatments that will improve vision by reducing retinal edema in eyes with persistent DME following previous anti-VEGF therapy. Intravitreal steroid is not as efficacious as ranibizumab in eyes with DME overall, but it has been shown to have a positive effect for DME in some eyes and might add benefit in eyes that are already receiving anti-VEGF.

The main objective of this study is to assess the short-term effects of combination steroid+anti-VEGF therapy on visual acuity and retinal thickness on OCT in comparison with that of continued anti-VEGF therapy alone in eyes with persistent central-involved DME and visual acuity impairment despite previous anti-VEGF treatment. This study will provide important information for the design of a future confirmatory phase III clinical trial on the efficacy of combination steroid and anti-VEGF in eyes with persistent DME and vision impairment following previous anti-VEGF therapy. The primary outcome for efficacy will be the mean change in visual acuity at 24 weeks.

Each study eye is required to complete a 12-week run-in phase. The run-in phase will identify study eyes that truly have persistent DME despite anti-VEGF therapy by requiring an additional 3 injections while also collecting standardized visual acuity and OCT measurements. At the enrollment, 4-week and 8-week visits of the run-in phase, enrolled eyes will receive an intravitreal injection of ranibizumab 3mg. Then at the 12-week run-in visit, if the eye still has persistent DME, it will be randomized to receive either intravitreal sham+intravitreal ranibizumab 0.3 or intravitreal dexamethasone+intravitreal ranibizumab 0.3 injections. The randomized study duration is 24 week, during which a protocol visit takes place every month. The combination injections of sham+ranibizumab or dexamethasone +ranibizumab will be given at the randomization visit (baseline) and at the 12-week visit after randomization. In between, an intravitreal injection of ranibizumab only will be given to study eyes at the 4, 8, 16 and 20 week visits.


Options:
A: Inclusion Criteria:

* case with clear media IOP below 23 mm/Hg female after menopause at least for 12 months or had 2 contraceptive roots visual acuity between 20/50 to 20/320

Exclusion Criteria:

* no PRP or N.d YAG laser in past 6 months no intraocular surgery in past 12 months
* CVA in past 12 months blood sugar above 250
* active infection in extraocular adnexa
B: Inclusion Criteria:

* Age \>= 18 years
* Diagnosis of diabetes mellitus types 1 or 2
* Diabetic macular oedema affecting the fovea in one or both eyes (phakic or pseudophakic) for which laser treatment is unlikely to be helpful in the opinion of the centre chief investigator
* Best corrected visual acuity of 17-72 letters (6/12 -6/120)
* Retinal thickness \> 250 micron in central 1mm subfield on Stratus (time domain) OCT and 300 on Spectral domain OCT
* Previous macular laser treatment, or the investigator believes laser treatment is unlikely to be helpful
* Intraocular pressure \<22mmHg
* Women of childbearing potential must have a negative urine pregnancy test at the screening visit and prior to treatment. A woman is considered of childbearing potential unless she is postmenopausal and without menses for 12 months or is surgically sterilised
* Written informed consent has been obtained.

Exclusion Criteria:

* Known allergy to Ozurdex, Avastin or agents used in the study
* Women who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential and not using reliable means of contraception
* Glaucoma which is uncontrolled or is controlled but with more than one medication or with only one medication and with glaucomatous field defects
* Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration, retinal vein occlusion)
* Macular oedema due to other causes
* An ocular condition that would prevent visual acuity improvement despite resolution of oedema (such as foveal atrophy or substantial premacular fibrosis)
* Treatment with IVTA within the last 6 months or peribulbar TA within the last 3 months or bevacizumab within the last 2 months.
* Cataract surgery within the last 6 months
* Retinal laser treatment within the last 3 months
* History of herpes virus infection in study eye
* Media opacity including cataract that already precludes adequate macular photography and laser treatment, or cataract that is likely to require surgery within 2 years
* Known allergies to dexamethasone or bevacizumab
* Patient is already receiving systemic steroid treatment \> 5mg prednisolone daily or equivalent)
* Intercurrent severe disease such as septicemia, any condition which would affect follow-up or photographic documentation (e.g. geographical, psycho-social)
* History of chronic renal failure requiring dialysis or renal transplant
* Blood pressure \>180/110
* Patient has a condition or is in a situation that in the investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study
C: Inclusion Criteria:

1. Age ≥ 18 years i) Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.
2. Diagnosis of diabetes mellitus (type 1 or type 2)
3. Any one of the following will be considered to be sufficient evidence that diabetes is present:

   1. Current regular use of insulin for the treatment of diabetes
   2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
   3. Documented diabetes by ADA (American Diabetes Association) and/or WHO (World Health Organization) criteria
4. At least one eye meets the study eye criteria listed below.
5. Fellow eye (if not a study eye) meets criteria.
6. Able and willing to provide informed consent.

Meets all of the following ocular criteria in at least the one eye:

1. At least 3 injections of anti-VEGF drug (ranibizumab, bevacizumab, or aflibercept) within the prior 20 weeks.
2. Visual acuity letter score in study eye ≤ 78 and ≥24 (approximate Snellen equivalent 20/32 to 20/320).
3. On clinical exam, definite retinal thickening due to DME involving the center of the macula.
4. OCT CSF thickness, within 8 days of enrollment:

   i) On Zeiss Cirrus ≥ 290 microns in women; ≥ 305 in men ii) On Heidelberg Spectralis: ≥ 305 microns in women; ≥ 320 in men
5. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs.

Exclusion Criteria:

An individual is not eligible if any of the following exclusion criteria are present:

1. History of chronic renal failure requiring dialysis or kidney transplant.
2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
3. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.
4. Participation in an investigational trial within 30 days of enrollment that involved treatment with any drug that has not received regulatory approval for the indication being studied. Note: study participants cannot receive another investigational drug while participating in the study.
5. Known allergy to any component of the study drugs (including povidone iodine prep).
6. Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the individual can become eligible.
7. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month prior to enrollment.
8. Systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment or anticipated use during the study. These drugs cannot be used during the study.
9. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 9 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.
10. Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next 9 months.

The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye unless otherwise specified):

1. Macular edema is considered to be due to a cause other than DME. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema.
2. An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal condition, etc.).
3. An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).
4. Substantial posterior capsule opacity that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., opacity would be reducing acuity to 20/40 or worse if eye was otherwise normal).
5. History of intravitreal anti-VEGF drug within 21 days prior to enrollment.
6. History of intravitreal or peribulbar corticosteroids within 3 months prior to enrollment.
7. History of macular laser photocoagulation within 4 months prior to enrollment.
8. History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the 6 months following enrollment into run-in phase.
9. Any history of vitrectomy.
D: Inclusion Criteria:

* Cases with clinically significant macular edema (CSME) with persistent retinal thickening after initial or supplemental macular photocoagulation

Exclusion Criteria:

* Monocularity,
* History of vitrectomy,
* Glaucoma or ocular hypertension,
* Significant media opacity,
* Existence of traction on the macula

Answer: C