STUDY SUBJECTS

Major inclusion criteria:

• Central Retinal Vein Occlusion (CVO)
• Less than 1 year in duration with hemorrhage in all 4 quadrants
• At least 10 DD of retinal non perfusion
• No iris or retinal neovascularization
• VA of light perception or better
• IOP of < 30 mm Hg
• Ability to obtain good quality fundus photographs
• Willingness to sign consent form

Major exclusion criteria:

• Previous treatment with laser photocoagulation
• Concurrent ocular disease that may affect VA over study period
• Presence of diabetic retinopathy (either eye)
• New or old BRAO/BRVO in study eye
• Other retinal vascular diseases in study eye
• Vitreous hemorrhage, retinal neovascularization
• Peripheral anterior synechiae in study eye
• Inability to discontinue heparain/warfarin for duration of study

Randomization scheme and interventions:

Randomized 1:1

1. (a) Early PRP before TC-INV/ANV ("early treatment group")
   • Supplemental fill in PRP was performed when TC-INV/ANV developed in a prophylactically treated eye.
2. (b)Delayed PRP after TC-INV/ANV ("no early treatment group")
   • PRP was also permitted for eyes that developed retinal neovascularization in the "no early treatment group."

Method of PRP: The settings were the following: spot size 500-100 microns, moderate intensity, 0.2 second duration, 0.5-1 burn width apart. Treatment was applied in all quadrants and avoided over areas of retinal hemorrhages or retinal vessels. Laser was not done less than 2 DD from the fovea or < 500 microns nasal to the disc

Follow up: Patients were followed monthly with serial slit lamp examinations, gonioscopy, and slit lamp photographs for up to 6 months, 8 months after entry, then q 4 months until the end of the study duration. Fluorescein angiograms were obtained at baseline and then annually. Patients that developed TC-INV/ANV were followed monthly until deemed stable (minimum of 6 months of follow up).

Study Duration: 3 years

PRIMARY ENDPOINT:

• Presence of 2 clock hours of NVI or any angle neovascularization on slit lamp photographs

RESULTS

Study population

• 181 eyes (91 eyes with immediate prophylactic PRP; 90 eyes with delayed PRP after NV developed)

PRIMARY OUTCOME:

• 18% of eyes in early treatment group versus 35% of eyes in the no early treatment group development of TC INV/ANV. However, there was no statistically significant difference among the groups after controlling for VA, non perfusion, and venous tortuosity.
• TC-INV/ANV was four times more likely to regress at 1 month post treatment and subsequent visits in the "no early treatment group" than the "early treatment group" with pretreatment after first laser prophylaxis (56% in no early treatment vs 22% in the early treatment group)

NOTABLE SECONDARY OUTCOMES

• The risk of TC-INV/ANV was highly associated with the degree of nonperfusion: risk of varied from 16% for 10-29 DD of non perfusion to 52% for >75 DD of nonperfusion
• The 4 risk factors for TC-INV/ANV were 30 DD or more of non perfusion, retinal hemorrhages greater than photographic standard #2, RVO duration < 1 month, and male sex.
• Almost all but two patients developed TC-INV/ANV in the first year, usually in the first 3 months (all but two were within 3-8 months of entry).
• No difference in risk of retinal NV development, neovascular glaucoma, or mean change in VA between groups

Adverse events

• Early PRP was associated with 2 retinal hemorrhages and a vitreous hemorrhage; one vitreous hemorrhage and one choroidal hemorrhage was noted in the "no early treatment" group

CONCLUSION

• Panretinal photocoagulation reduces but does not eliminate the risk of anterior segment neovascularization (ANV)
• PRP is highly effective in inducing regression of ANV once it develops in previously untreated eyes
• PRP is recommended therapeutically in patients after the development of ANV
• The highest risk of ANV development is in the first few months (first 3 months, up to 8 months in majority) and patients should be observed closely, especially during this time period