Micropulse for Suppression of Diabetic Macular Edema

This is a randomized, controlled clinical trial comparing subthreshold micropulse laser
versus sham laser treatment for eyes with diabetic macular edema with good visual acuity of
20/32 or better.

Subjects will be randomized to receive either subthreshold micropulse laser treatment or no
treatment (sham). Randomization will occur as a ratio of 2:1 and will take place during the
clinic visit.

Subjects selected for the study will undergo a complete ophthalmic examination, including
measurements of best corrected visual acuity, low luminance visual acuity, contrast
sensitivity (using ETDRS testing with a masked coordinator), intraocular pressure, slit lamp
exam including documentation of lens status, and dilated funduscopic exam with standard
dilating agents used at the UC Davis Eye Center. Subjects will then undergo baseline imaging
including Spectral Domain Ocular Coherence Tomography (SD-OCT), fundus autofluorescence (FAF)
and microperimetry testing. Both the use of OCT, FAF, and microperimetry testing are within
the standard of care for the management of DME.

The duration of an individual subject's participation in the study will be two years which
will include at least 10 total visits at various time points including on the day of
enrollment, followed by 1, 3, 6, 9, and 12, 15, 18, 21, 24 months after the day of
enrollment.

The subjects in the treatment arm will be treated on the day of randomization by SML
photocoagulation using the Iridex IQ577 laser unit with TxCell scanning laser delivery
system.

Subjects in the sham treatment arm will undergo the same set up procedures as those receiving
the laser treatment, however, no actual laser treatment will occur.

Subjects will then return to the clinic for repeat ophthalmic exam, OCT imaging, and
microperimetry at 1 month, 3 month, 6 month, 9 month, 12 month, 15 month, 18 month, 21 month
and 24 month time points, which is similar in frequency as standard of care.

Patients in the treatment arm are eligible for repeat SML laser at any subsequent visit if
there is any decline in vision (1 or more ETDRS lines) or worsening in edema (>10% increase),
at the discretion of the treating physician. If vision declines to 20/40 or worse at any
study visit, patients in the treatment arm will undergo repeat treatment with SML laser,
while those in the sham arm will undergo repeat sham laser.

Inclusion Criteria:

1. Age >=18 years

2. Type 1 or type 2 diabetes mellitus

3. Clinical evidence of center-involved DME confirmed on OCT, and defined by OCT

Central Subfield (CSF) thickness at the time of randomization by the following:

1. Zeiss Cirrus: 275μ in women, and 290μ in men

2. Heidelberg Spectralis: 290μ in women, and 305μ in men

4. Best corrected visual acuity of 20/32 or better on ETDRS testing

Exclusion Criteria:

1. Macular edema from causes other than DME

2. An ocular condition is present such that in the opinion of the investigator, visual
acuity would not improve from resolution of macular edema (i.e/foveal atrophy, pigment
abnormalities, dense hard exudates)

3. An ocular condition is present other than DME which may contribute to macular edema
(i.e/vein occlusion, ERM, uveitis, RP, etc…).

4. Cataract that in the opinion of the investigator may alter visual acuity throughout
the course of the study

5. History of prior laser or other surgical, intravitreal, or peribulbar treatment for
DME in the study eye within the prior 6 months.

6. More than 4 prior intraocular injections for treatment of DME at any time

7. More than 1 prior focal/grid macular photocoagulation session for treatment of DME at
any time

8. History of topical steroid or NSAID treatment within 30 days prior to randomization

9. History of PRP within 4 months prior to randomization or anticipated need for PRP in
the 6 months following randomization.

10. Any history of vitrectomy.

11. History of major ocular surgery (cataract extraction, scleral buckle, any intraocular
surgery, etc.) within prior 4 months or anticipated within the next 6 months following
randomization

12. History of YAG capsulotomy performed within 2 months prior to randomization.

13. Aphakia

14. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or
significant blepharitis