How should retinal vein occlusion be evaluated and managed?

Retinal Vein Occlusion: Evaluation and Management

Anti-VEGF intravitreal injections are the first-line treatment for macular edema causing vision loss in retinal vein occlusion, with ranibizumab or aflibercept as FDA-approved agents, while immediate panretinal photocoagulation is required for neovascularization. 1, 2

Initial Diagnostic Evaluation

Essential History Elements

• Duration and location of vision loss 2
• Current medications 1
• Cardiovascular risk factors: systemic hypertension, diabetes, hyperlipidemia, cardiovascular disease, sleep apnea, coagulopathies, thrombotic disorders 1
• Ocular history: glaucoma, prior injections, laser treatment, cataract or refractive surgery 1

Critical Physical Examination Components

• Visual acuity measurement is mandatory as the strongest prognostic factor 1, 2
• Pupillary assessment for relative afferent pupillary defect (RAPD) corresponds to ischemia level and predicts neovascularization risk 1, 2
• Slit-lamp biomicroscopy examining carefully for fine, abnormal new iris vessels 1
• Intraocular pressure (IOP) measurement 1
• Gonioscopy prior to dilation is essential, especially in ischemic CRVO, elevated IOP, or high iris neovascularization risk 1
• Dilated fundus examination using slit-lamp biomicroscopy with appropriate lenses for posterior pole and midperipheral retina, plus indirect ophthalmoscopy for far peripheral retina 1

Key Funduscopic Findings to Document

• Macular edema (clinical and OCT confirmation) 1
• Signs of ischemia: neovascularization of disc or elsewhere, RAPD, extensive hemorrhages, venous dilation and tortuosity, cotton wool spots 1
• Optic nerve head neovascularization and/or neovascularization elsewhere 1
• Vitreous or preretinal hemorrhage 1

Diagnostic Imaging

Optical Coherence Tomography (OCT)

OCT is essential for detecting and quantifying macular edema, guiding treatment decisions, and monitoring response. 1, 2 Treatment decisions for anti-VEGF re-injection, changing therapeutic agents (intravitreal corticosteroids), initiating laser, or considering vitrectomy are frequently based on both visual acuity and OCT findings. 1 However, retinal thickness measured by OCT is not always consistently correlated with visual acuity. 1

Fluorescein Angiography (FA)

FA evaluates the extent of vascular occlusion, degree of ischemia, and extent of macular edema. 1 It defines ischemic CRVO as eyes with 10 disc areas of capillary non-perfusion on standard FA versus nonischemic. 1 FA distinguishes collateral vessels (no late leakage) from retinal neovascularization (late leakage), identifies macular capillary nonperfusion explaining vision loss, and guides peripheral laser treatment. 1 Wide-field FA evaluates peripheral nonperfusion, though current data on benefits are inconclusive. 1

Optical Coherence Tomography Angiography (OCTA)

OCTA is similar to FA in detecting capillary nonperfusion, enlarged foveal avascular zone, and vascular abnormalities, but is currently limited by image artifacts and limited field of view. 1

Fundus Photography

Fundus photography documents severity of retinal findings, presence of new vessels elsewhere (NVE), extent of intraretinal hemorrhages, new vessels on or near optic disc (NVD), response to treatment, and need for additional treatment. 1

Classification and Prognosis

Types of RVO

• Central retinal vein occlusion (CRVO): obstruction at or posterior to optic nerve head 1
• Branch retinal vein occlusion (BRVO): obstruction at branch or tributary, typically at arteriovenous crossing point, most commonly superior temporal quadrant 1
• Hemiretinal vein occlusion (HRVO): occlusion at disc involving half of venous drainage, behaves like BRVO with visible occlusion near branch point 1
• Hemi-CRVO: occlusion of one hemicentral retinal vein trunk, acts like CRVO with no visible crossing point and increased risk of iris/angle neovascularization 1

Risk Factor Associations

CRVOs and hemi-CRVOs are often associated with glaucoma and have higher risk of anterior segment neovascularization and neovascular glaucoma. 1 BRVOs and HRVOs are more commonly associated with systemic hypertension, diabetes, and lipid disorders, and are more likely to lead to retinal neovascularization. 1

Treatment Algorithm

First-Line Treatment for Macular Edema

Anti-VEGF intravitreal injections are the safest and most effective treatment for macular edema causing vision loss in both CRVO and BRVO. 1, 2, 3 FDA-approved agents include:

• Ranibizumab (Lucentis) 0.5 mg intravitreally 2, 4
• Aflibercept (Eylea) 2 mg intravitreally 2, 3
• Bevacizumab (Avastin) is used off-label 3, 4

Initial treatment consists of 3 monthly injections (upload phase), followed by pro-re-nata (PRN) or treat-and-extend regimens based on OCT findings rather than visual acuity alone. 3

Second-Line Treatment: Intravitreal Corticosteroids

Intravitreal corticosteroids are reserved for patients with contraindications to anti-VEGF therapy, with associated risks of glaucoma and cataract formation. 1, 2 Options include:

• Dexamethasone implant (Ozurdex) 2, 3, 4
• Preservative-free triamcinolone 4

Taking into account the side effect spectrum (particularly cataract progression and increased IOP), dexamethasone implant may be a reasonable alternative. 3

Laser Photocoagulation

Recent clinical trials (BRIGHTER, RETAIN, RELATE) demonstrated no added benefit for macular grid or peripheral scatter laser photocoagulation when combined with anti-VEGF therapy for BRVO. 1 The CVOS showed no value of focal photocoagulation for macular edema in CRVO. 1 However, sectoral panretinal photocoagulation (PRP) remains indicated for neovascularization complications such as vitreous hemorrhage or iris neovascularization. 1

Management of Neovascular Complications

Immediate and complete peripheral PRP is indicated for CRVO patients who develop iris or angle neovascularization. 1, 2 Initial treatment with anti-VEGF agent may provide immediate benefit and improve ability to deliver complete laser treatment. 1, 2 Monthly monitoring for the first 6 months is essential to detect iris or angle neovascularization early, with undilated slit-lamp biomicroscopy and gonioscopy performed before dilation. 1, 2

Systemic Evaluation and Risk Factor Management

Refer patients to primary care physician for cardiovascular risk factor optimization, including control of hypertension, diabetes, serum lipid levels, and IOP for glaucoma. 1, 2 Communicate end-organ damage findings to the primary care provider. 1 Treatment of obesity, obstructive sleep apnea, and smoking cessation counseling are also recommended. 2

Follow-Up Protocol

Monitoring Schedule

Monthly follow-up for the first 6 months is essential with assessment of: 1, 2

• Visual acuity 1, 2
• Undilated slit-lamp biomicroscopy and gonioscopy for early iris or angle neovascularization 1, 2
• Pupillary assessment for RAPD 1
• IOP 1, 2
• Stereoscopic examination of posterior pole after dilation 1
• OCT imaging to monitor macular edema and guide re-treatment decisions 1, 2
• Peripheral retina and vitreous examination when indicated 1

Critical Pitfalls to Avoid

• Do not delay treatment: prognosis for visual acuity and decline in macular edema depend on starting treatment early and continuing consistently 3
• Perform gonioscopy before dilation to avoid missing angle neovascularization 2
• Base re-injection decisions on OCT findings rather than visual acuity alone 3
• Fluorescein angiography is necessary before and during treatment to detect ischemic retinal areas requiring laser coagulation 3
• Early targeted laser coagulation of ischemic retina may reduce frequency of necessary injections and improve edema response 3

Vision Rehabilitation

Patients whose conditions fail to respond to therapy should be offered referral for counseling, vision rehabilitation, or social services. 1 Vision rehabilitation helps restore functional ability in patients with functionally limiting visual impairment. 1