Posterior Vitreous Detachment (PVD) Assessment During Dual Retinal Vein Occlusion (RVO) Lucentis Evaluations

Several retinovascular diseases have been shown to be VEGF dependent including retinal vein
occlusion, wet age-related macular degeneration, and diabetic retinopathy. The role of the
vitreous or composition of the vitreous cavity has been examined in diabetic retinopathy on
many occasions in the past and clinically it has been felt that a posterior vitreous
separation leads a quieting and involution of diabetic retinopathy, both proliferative as
well as pre-proliferative retinopathy. This clinical observation has never had any basic
science data to support it. However, it has recently been shown that in cat eyes with
posterior vitreous separation the vitreous cavity has a much lower VEGF concentration than in
cat eyes with an attached posterior vitreous. This may be due to the fact that flow of oxygen
from the retinal vasculature is increased by PVD. Vitreous oxygen levels are inversely
associated with vitreous VEGF levels. As oxygen tension increases, VEGF levels will decline.
This suggests if higher amounts of VEGF are present in the eye without PVD perhaps a powerful
anti-VEGF drug, such as ranibizumab, may be of greater benefit to treat VEGF dependent
retinovascular disease. To try and answer this question clinically, we have suggested that an
analysis of the vitreous status in treatment naive eyes with retinal vein occlusion beginning
ranibizumab therapy be undertaken to see if eyes without a posterior vitreous separation
would achieve greater improvement in vision and a return to more normal retinal physiology
compared to eyes with a posterior vitreous separation. No study has assessed PVDs in RVO
patients receiving potential treatment.

Inclusion Criteria:

- Ability to provide written informed consent and comply with study assessments for the
full duration of the study

- Subjects of either gender, Age > 18 years

- Best corrected visual acuity in the study eye between 20/40 and 2/200 inclusive.

- Retinal venous occlusive disease (BRVO or CRVO)

- Clear ocular media and adequate papillary dilation to permit good quality stereoscopic
fundus photography, scheimpflug photography and high resolution OCT

- Ability to return for all study visits

Exclusion Criteria:

- Pregnancy (positive pregnancy test) or lactation.

- Premenopausal women not using adequate contraception. The following are considered
effective means of contraception: surgical sterilization or use of oral
contraceptives, barrier contraception with either a condom or diaphragm in conjunction
with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

- Prior RVO in the study eye

- Duration of RVO greater than 6 months

- Laser photocoagulation for macular edema within 3 months of Day 0

- Patients prior eye treatment including anti-VEGF therapy (within 3 months) or,
intravitreal corticosteroid therapy (within 6 months)

- Prior vitreoretinal surgery.

- Had ocular surgery within the past 60 days in the study eye.

- Concurrent use of more than two therapies for glaucoma.

- Uncontrolled glaucoma in the study eye (defined as intraocular pressure >30 mm Hg
despite treatment with anti-glaucoma medication).

- Neovascular glaucoma

- Concurrent use of systemic anti-VEGF agents

- Has active infection in the study eye.

- Inability to obtain photographs.

- Has received investigational therapy within 60 days prior to study entry.

- Patients with significantly compromised visual acuity in the study eye due to
concomitant ocular conditions.

- Has other conditions the investigator considers to be sound reasons for exclusion
(e.g., lack of motivation, history of poor compliance, concomitant illnesses,
personality disorder, mental condition, drug abuse, use of neuroleptics, physical or
social condition predicting difficulty in long-term follow-up).

- Has an allergy to fluorescein sodium dye.

- Inability to comply with study or follow-up procedures.