Retinal vein occlusion (RVO) is a common vascular disorder of the retina and common cause of vision loss. It is also a common cause of blindness from retinal vascular disease, second only to diabetic retinopathy. Retinal Vein Occlusions can be broadly classified as Central Retinal Vein Occlusion (CRVO) and Branch Retinal Vein Occlusions (BRVO).

Risk factors for CRVO are

  • Glaucoma
  • Carotid occlusive disease
  • Sleep Apnoea
  • Elevated homocysteine

DM is more prevalent among patients with CRVO, cardiovascular diseases and, SLE.

Risk factors for BRVO are

  • Hypertension
  • Hyperlipidaemia
  • Diabetes
  • Coronary artery disease

A major symptom of RVO is decreased vision.

Cause of decreased vision include,

  • In the early stage,
    • Haemorrhage
    • Macular oedema
  • In the later stages,
    • Macular ischaemia
    • Vitreo macular traction with or without TRD
    • Vitreous haemorrhage

Natural history: If the systemic factors are not controlled, the risk of developing BRVO in the fellow eye is 10% in the next 3 years; the risk of CRVO is 1% per year.

Management: The systemic and ocular risk factors must be addressed first.
Trials associated with the management of vein occlusions:

LASER: The Branch Vein Occlusion Study (BVOS) and the Central Vein Occlusion Study (CVOS) assessed the role of LASER in the respective conditions.

The conclusions were as follows.
BVOS – Cases with BRVO observed for spontaneous resolution for 3 months. 1/3rd of the cases resolved spontaneously. At the end of 3 months, patients with macular oedema with BCVA <20/40 were subjected to grid LASER. 65% of the treated eyes had >=2 line improvement as compared to 37% of the observed eyes. The authors concluded that grid LASER at the end of 3 months could help in visual improvement. Similarly, scatter photocoagulation in case of new vessels was also found to be clinically beneficial.

CVOS study answered 3 questions.

1: Does grid photocoagulation help in macular oedema?
Reduces angiographic oedema but does not improve visual acuity. Hence Grid laser is not advisable for macular oedema in CRVO.

2: Does early PRP help in eyes with ischaemic CRVO?
NVI develops in 35% of no-treated eyes and 20% of treated eyes. There was no significant benefit of prophylactic treatment.

3: Is early PRP more beneficial than delaying PRP till NVI/NVA develops?
56% of treatment of naïve eyes had NVI regression compared to 22% of treated eyes. It is better to defer till NVI develops.

Triamcinolone acetonide: The SCORE trial studied the efficacy of IntraVitreal Triamcinolone (IVTA) in the management of vein occlusions. The study compared the efficacy of Grid LASER and intravitreal triamcinolone (1mg and 4 mg). The study concluded that the outcome with IVTA was better than natural history but not as good as LASER. Moreover, IVTA also carried the risk of IOP rise and cataract progression.

Ozurdex: It is a 0.7 mg bio erodible dexamethasone intravitreal implant. The GENEVA trial studied the efficacy of OZURDEX in macular oedema with vein occlusions. They found that positive results were noted both with improvement in visual acuity and reduction of foveal thickness after the injection with a peak effect noted after 2 months, with results tapering after that. The visual acuity improvement was noted to be better in eyes with BRVO. However, the associated risk of IOP rise and cataract progression means that the drug must be avoided in patients with the history of glaucoma, steroid responders and phakic patients. However, if the patient has significant cataract and macular oedema, Ozurdex injection can be given followed by cataract surgery after one month which prevents any further perioperative flare-up of macular oedema. There is a possibility of rebound oedema after 3 months which the patient must be explained at the outset.

Anti VEGF agents:

LUCENTIS: The role of anti-LUCENTIS has been studied in various clinical trials.
BRAVO/CRUISE: These studies included cases of BRVO and CRVO with BCVA <6/12 and foveal thickness > 250 microns in the treatment of naive eyes with the problem which was less than 1 year old. 6 monthly injections had to be given followed by monthly follow-ups where retreatment was considered if BCVA was less than 6/ 12 or the foveal thickness was more than 250 microns. At the end of one year, LUCENTIS injections resulted in improvement in visual acuity, reduction in foveal thickness as well as helped in clearing haemorrhage, oedema and reduced vascular leakage. The injections also resulted in an improvement in the quality of vision at the end of 1 month.

HORIZON TRIAL: This trial is a continuation of the BRAVO/CRUISE trial from 12 to 24 months. The patients were followed up once every 3 months and retreatment was done if the foveal thickness was >250 microns. The study found that on an average 0-3 injections were needed in eyes with BRVO and 0-6 injections were need in eyes with CRVO in the second year to maintain the foveal thickness/ visual acuity improvement noted in the first year.

RETAIN: This trial is a continuation of the HORIZON trial from the 24th month to the 48th month. In the first 12 months patients were followed up on a monthly basis, and in the next 12 months, they were followed up on a 1-3 monthly basis based on the presence of intra retinal fluid. The injection was repeated in the presence of intra retinal fluid. Scatter LASER was done to areas of Capillary non-perfusion (noted on FFA) if injection LUCENTIS was needed on 2 consecutive months due to a persistence of intra retinal fluid. At the end of 48 months, complete resolution was seen in 50% of eyes with BRVO as compared to 44% of the eyes in CRVO. In the remaining eyes, 3 injections /year for BRVO and 6 injections /year for CRVO were needed to maintain the gains in visual acuity and foveal thickness. BCVA >= 20/40 was noted in 80% of the eyes in BRVO and 28% of the eyes in CRVO. This study suggests that a sizeable portion of patients will continue to need intravitreal injections long after the onset of the condition. The authors of the study also suggested that it is better to explore the role of LASER/steroids in eyes which continue to need anti-VEGF injections after 2 years.

SHORE TRIAL: This trial compared the efficacy of PRN therapy after 6 months as compared to monthly injections of LUCENTIS. The study found no difference in outcomes between PRN therapy and monthly injections

MARVEL TRIAL: It compared the efficacy of AVASTIN with LUCENTIS. Treatment was given on a PRN basis and rescue LASER if needed was given at the end of 3 months. At the end of 6 months, the trial found no difference in outcomes between the 2 drugs.

RAVE TRIAL: This trial studied the role of LUCENTIS in ischaemic CRVO. The study found that the injection resulted in improvement of BCVA and reduction in foveal thickness. The NVI/NVA/NVE developed after 24 months, suggesting that LUCENTIS injections postpone but do not prevent the formation of new vessels in ischaemic CRVO.

VEGF trap: Aflibercept is a soluble receptor protein with a longer duration of action as compared to other anti-VEGF agents. It also binds to other angiogenic factors like placental growth factor. Its efficacy was studied in some trials.

VIBRANT: It compared the efficacy of VEGF trap with that of LASER and found that VEGF trap was superior to LASER both in terms of increased visual acuity and reduced foveal thickness.

GALILEO/COPERNICUS : These studies compared the efficacy of VEGF trap with that of sham and found that eyes treated with VEGF Trap had better outcomes. Eyes which were initially treated with sham and then shifted to VEGF trap also showed improvement after the switch, but the outcome was never as good as those eyes which were treated from the beginning, suggesting that treatment must be initiated at the earliest for the best results.

Role of combined therapy:

RELATE: This trial studied the role of combining delayed LASER (after 24 weeks) with anti-VEGF and found no added benefit of the combination.

SUMMARY: Retinal vein occlusions have multi-factorial aetiology. Systemic factors need to be addressed along with the ocular management. Treatment can be in the form of LASER, steroid injections and anti-VEGF injections like LUCENTIS and AFLIBERCEPT. The best outcomes with injections are noted in those eyes where treatment is initiated at the earliest. Despite initial success, oedema might recur, and hence the patients must be counselled about the possibility of recurrence and the need for follow up and further management.


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