Management of Retinal Vein Occlusion: European Society of Retina Specialists guidelines

Written by Hina Zahid Published On 2019-10-28T19:00:06+05:30 | Updated On 28 Oct 2019 7:00 PM IST

European Society of Retina Specialists have published their latest guidelines on Management of Retinal Vein Occlusion.

Retinal vein occlusion (RVO) is among the leading causes of visual impairment and is often due to an underlying systemic disease. Advances in imaging and therapeutic possibilities with anti-vascular endothelial growth factor (VEGF) agents have revolutionized the diagnosis and treatment of this disease.

Retinal Diagnostics-

Recommendation

Whenever an RVO is suspected, a full ophthalmologic examination in particular including a VA measurement, an iris examination to rule out neovascularization, and a fundus examination should be undertaken. Taking the medical history and the examinations into account, the various possible diagnoses should be considered and the presence of macular edema as well as the extent of the retinal ischemia evaluated. For this last evaluation, establishing the relation between the extent of change in VA and non-perfusion on FA can be helpful. If hemorrhage precludes reliable evaluation of retinal perfusion on FA, this examination can be done after a few injections (if required) as they often clean the fundus significantly. Monitoring of signs of ischemia and neovascularization should continue during follow-up at least by monitoring VA, the iris, and the fundus.

Features in Optical Coherence Tomography and Angiography

Recommendation

OCT is a useful modality to diagnose macular edema due to RVO. Unlike in other retinal diseases, the magnitude of the impact of individual morphologic changes on VA remains unclear. Nevertheless, there are features that seem to play an important role. HRF in the outer plexiform layer have an especially negative impact on VA prognosis. Additionally, CRT is a robust variable because RVO is an acute-onset disease and may not show as many long-term changes as chronic retinal diseases. The photoreceptor status has no direct influence on the VA at the time of the acute onset of the disease but plays an important role in VA prognosis after therapy. OCT angiography is a good addition to monitor the retinal microvasculature over time. It is recommended to use it in addition to regular OCT imaging when available. At baseline, the patient should be imaged with OCT angiography in addition to FA.

The exact impact of each feature in OCT and OCT angiography is still to be determined in large randomized clinical trials; therefore, the recommendation is to monitor disease activity with OCT at regular intervals and retreat based on VA (as the strongest predictor for later VA) and CRT. These recommendations are based on evidence levels I and II.

Therapeutic Strategies

Laser Therapy

PRP is the standard of care for the treatment of neovascular complications associated with RVO. These include retinal and disc neovascularization secondary to BRVO or CRVO as well as iris neovascularization. Laser treatment can be withheld in patients with extensive retinal ischemia who require close follow-up until neovascularization is detected. Otherwise, prophylactic laser photocoagulation should be considered. Laser treatment for macular edema secondary to BRVO has been shown to be effective for visual improvement but in view of the availability of anti-VEGF therapy, focal laser photocoagulation should be considered only as a second-line treatment

Anti-VEGF Agents

Recommendation

Several randomized, controlled studies have proven the efficacy and safety of ranibizumab in macular edema secondary to RVO. An individualized dosing regimen of 0.5 mg ranibizumab, driven by VA stabilization criteria, as recommended by the European Summary of Product Characteristics, has been shown to provide anatomic and functional improvement in both BRVO and CRVO with obvious higher final VA achieved in BRVO.

Moreover, data on patients with longer disease duration suggest the necessity for prompt intravitreal treatment, as also proven by the inferior results in patients injected after a first laser-only period compared with patients injected early. Subsequent monthly injections must be continued until VA stability is reached. Long-term data support a monthly follow-up period for at least 1 year, with subsequent extension upon functional and/or anatomic stability reducing the treatment burden while maintaining functional stability. In fact, it has been proven that although ranibizumab monthly injections suppress the effects of VEGF in most patients, they did not eliminate VEGF production, as shown by the reduction of visual and anatomic benefits at injection interruption points. In addition, cases of late recurrence in the RETAIN study verified the importance of long-term follow-up, particularly in patients with CRVO. First-year follow-up also has the relevant role of allowing individualized treatment for less responsive patients and patients with VA more susceptible to edema persistence or recurrence. Therefore, treatment regimens need to be fitted to each patient’s needs

Aflibercept

Recommendation

Intravitreal aflibercept has proven to be effective in the treatment of macular edema secondary to RVO. Early treatment is important for optimal outcomes. After fixed initial monthly injections, visual gain can largely be maintained, including regimens with extended intertreatment intervals. The PRN regimen in the COPERNICUS and GALILEO studies demonstrated a sustained efficacy at 1 year in patients with CRVO. In the VIBRANT study, the switch to bimonthly treatment in patients with BRVO was shown to preserve visual outcomes, reducing the treatment burden.

A multicenter study (CENTERA) is on-going to evaluate a treat-and-extend regimen of aflibercept in macular edema secondary to CRVO. In any case, long-term close monitoring is advisable to control macular edema, particularly in patients with CRVO, probably because of the continued excessive production of VEGF due to retinal ischemia. Moreover, as in previous ranibizumab studies, aflibercept therapy was shown to be also effective in reducing non-perfused retinal areas as well as posterior and anterior segment neovascularization when patients are monitored adequately.

Bevacizumab

Recommendation

Bevacizumab proved to effectively reduce macular thickness in these comparative, non-inferiority trials and to improve VA in patients with macular edema due to RVO using both monthly and PRN regimens. A very high gain of ETDRS letters was obtained after the first injection compared with AMD and DME [59, 67].

The non-inferiority of bevacizumab to ranibizumab in CRVO was found in the SCORE2 study with a monthly regimen despite less reduction in CRT in the bevacizumab than in the ranibizumab group; longer follow-up with an eventual switch to PRN could confirm this result [67]. The large range of BCVA results in patients with BRVO in the MARVEL study did not reach the non-inferiority limit, but the regimen of treatment was different from the SCORE2 Study, and the population was smaller [59, 60]. The PRN regimen with bimonthly evaluations after the first 6 months of the MARVEL study may have reduced the treatment burden, but because of the limited number of patients and short follow-up, further studies are required to confirm these data [60].

Post hoc analysis of the SCORE2 trial confirmed previous data obtained with other anti-VEGF drugs showing better visual results in shorter duration macular edema, younger patients and lower BCVA at baseline with no statistically significant disparity between groups treated with different drugs [74]. This supports the necessity for an individualized approach to each patient, based on baseline features and treatment response.

Steroids

Recommendation

Based on the data that exist thus far, it is evident that corticosteroids are important in our armamentarium of drugs for treating patients with RVO, but largely on a second-choice level. Hence, switching to a steroid in non-responders who have already been treated with anti-VEGF (after 3–6 injections, depending on the specific response of each patient) is reasonable.

Steroids may be considered as a first-line therapy for patients who have a recent history of a major cardiovascular event as these patients had to be excluded from all major anti-VEGF trials and thus could not receive anti-VEGF as first-line therapy.

Another group of patients in whom corticosteroids may be considered as first-line therapy are those who are unwilling to come for monthly injections (and/or monitoring) in the first 6 months of therapy. However, these patients’ IOP still needs to be monitored every 2 to 8 weeks following injection as in every patient who underwent Ozurdex® implantation. The first cycles after implantation need close monitoring after every 2 weeks to see the patients IOP response.

A complete examination including VA and OCT imaging should be performed 3 months after an Ozurdex® injection and repeated if macular edema is still found present on OCT or VA has decreased. Retreatment with Ozurdex® will generally be performed after 3–4 months, with a mean of approximately 2–3 injections per year. Patients with pseudophakic eyes are preferable for the use of steroids, otherwise patients have to be informed about the high risk for cataract formation leading to cataract surgery.

From the body of data that has been collected to date, it is evident that the effects of Ozurdex® can be sustained for about 4 months. Retreatment therapy with a PRN regimen would necessitate reinjection intervals of substantially less than 6 months for the vast majority of eyes.

Surgical Intervention

Vitrectomy

Recommendation

The use of vitrectomy with or without membrane peeling in the management of macular edema secondary to CRVO requires further randomized trials to establish its efficacy compared with the actual gold standard management, which is the intravitreal injection of anti-VEGF drugs. This is particularly important because vitrectomy increases the intravitreal clearance of these agents, which may reduce the duration of the effect and result in decreased efficacy of further intravitreal pharmacotherapy.

Radial Optic Neurotomy

Recommendation

Evidence for the efficacy of RON in the management of CRVO is limited and currently does not clearly demonstrate a benefit. The use of RON for CRVO has largely been abandoned due to the availability of effective intravitreal pharmacologic agents.

Branch Retinal Vein Occlusion

Vitrectomy

Recommendation

Lack of data and the availability of intravitreal pharmacotherapy do not allow any recommendation for PPV in eyes with macular edema due to BRVO.

Sheathotomy

Recommendation

Alternative therapies such as vitrectomy, ILM peeling, and arteriovenous sheathotomy may play a role in selected cases of BRVO, but the overall evidence for these approaches is limited. Due to the risk of intraoperative complications and the availability of less invasive alternatives, vitrectomy with or without sheathotomy has restricted clinical use as a first-line treatment. Current evidence on comparative therapy across and within drug classes is limited. Robust evidence on combination therapy is also lacking.

New imaging technology, including OCT angiography and ultra-widefield angiography, may in the future play a role in the approach to therapeutics and prognosis. Additional research on these treatment modalities is needed to better explain their role in disease management.

Risk Factors and Systemic Evaluation

Recommendations

It is recommended that the minimum investigation of a patient newly diagnosed with RVO in an eye clinic should include a detailed medical history, measurement of blood pressure and sugar, and basic laboratory tests of the full blood count, erythrocyte sedimentation rate, and c-reactive protein measurement. To avoid nightly non-dipping or over-dipping, 24-h blood pressure measurements as regular follow-up via the general practitioners are recommended. The results will allow urgent treatment of any newly diagnosed or uncontrolled cardiovascular risk factors and help to rule out any rarer conditions such as blood dyscrasias, myeloma, or an inflammatory cause. Further tests as needed are best performed by the general physician based on the history and results of initial investigations. Bilateral presentation or any sign of a vascular disturbance in the other eye suggests an underlying systemic condition. Younger patients with RVO in whom no common risk factors have been identified may require a comprehensive systemic evaluation. They may additionally be screened for thrombophilia including antiphospholipid antibody syndrome, although this association is weak. Women already receiving estrogen-containing hormone replacement therapy may continue with it after an informed decision is made, but such therapy should not be commenced in women with RVO.

For more details click on the link: https://doi.org/10.1159/000502041

AfliberceptEuropean Society of Retina Specialistsischemic retinamacular edemaOCT angiographypanretinal laser photocoagulationretinal diseasesretinal microvasculatureretinal vein occlusion

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Hina Zahid