18.1 Goals

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  Induce regression of active retinopathy of prematurity (ROP).

  
  
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  Avoid complications including macular dragging and tractional retinal detachment.

18.2 Advantages

The treatment options for Type I ROP include laser photocoagulation, which has largely replaced cryotherapy, and anti-VEGF therapy. Although it has been the standard of care for many years, laser photocoagulation has its drawbacks. Very posterior disease requires retinal ablation near the fovea and macula, and infants with aggressive posterior ROP (AP-ROP) can rapidly progress despite laser treatment. Laser photocoagulation also has known complications including visual field loss and increased rates of strabismus and high myopia.

Anti-VEGF agents have more recently been used to treat ROP without the destruction of retinal tissue. Specifically, it can be used to treat posterior disease to avoid laser treatment near the macula, and it may induce regression of AP-ROP more quickly than laser photocoagulation. In addition, it has been used as an adjunctive treatment in ROP that progresses despite laser therapy. Numerous case reports and case series on using anti-VEGF agents for ROP have been published, and the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) and RAnibizumab Compared with Laser Therapy for the Treatment of INfants BOrn Prematurely With Retinopathy of Prematurity (RAINBOW) randomized controlled trials showed the benefit of bevacizumab and ranibizumab, respectively, for the treatment of ROP. ¹

BEAT-ROP was the first prospective, randomized, multicenter trial that compared monotherapy with intravitreal bevacizumab to conventional diode laser for infants with stage 3 ROP with Plus disease in zone I or posterior zone II. Eyes treated with 0.625 mg intravitreal bevacizumab had lower rates of recurrence, although this was significant only in eyes with zone I disease (6% vs. 42% at 54 weeks), not those with zone II disease. It was also noted that recurrence after treatment with bevacizumab typically occurred later than after laser treatment (mean 16 weeks vs. 6.2 weeks), with recurrence after the 54-week follow-up visit not uncommon. ²

The RAINBOW trial compared intravitreal ranibizumab to laser therapy for the treatment of ROP. Primary outcome measures included the absence of active ROP and unfavorable structural outcome at 24 weeks. Data from this study showed that 80% of patients who received 0.2 mg ranibizumab met criteria for success, compared to 66% who received laser. Ranibizumab led to higher success rates for ROP in both zone I and zone II disease. ³

Although both laser photocoagulation and intravitreal injection require well-trained ophthalmologists, treatment with intravitreal anti-VEGF medication is arguably easier and relies less on the skill of the ophthalmologist once the medication is in the eye. It can be administered quickly at the bedside with local anesthesia, using less equipment compared too laser therapy. In addition, neonates most at risk for ROP requiring treatment may be too unstable to undergo a longer procedure with sedation, which is typically required for laser treatment. Intravitreal injections can also be administered in patients with small pupils or a dense vitreous hemorrhage, which may render laser treatment difficult or impossible to perform. Additionally, by avoiding laser treatment, the area of viable retinal tissue may be increased, reducing the incidence of peripheral visual field loss and laser-associated myopia.

18.3 Expectations

Successful anti-VEGF therapy in patients with Type I ROP includes:

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  Complete regression of active ROP:

  
  
  
  
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    Without retinal detachment or distortion of posterior pole anatomy.

  
  
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  Continued growth of retinal vasculature anteriorly into zone II in more posterior disease and toward the retinal periphery.

Expectations of anti-VEGF therapy should be discussed in detail with the patient’s family. Although there has been success in the treatment of ROP with anti-VEGF agents, infants must be monitored weekly for disease recurrence and additional treatment that may be needed. Incomplete retinal vascularization and late recurrence are not uncommon, and compliance with follow-up may be a factor when considering which treatment option best suits the patient and also the patient’s family.

18.4 Key Principles

There is currently no universal protocol for intravitreal injection in the prematurely born neonatal population, and there are no definitive recommendations on sclerotomy placement due to uncertainty and variation of the location of the ora serrata in these patients.

There is a high risk of touching the lens with intravitreal injection in an infant compared to adult patients, as well as a risk of inadvertent traction on the vitreous base.

18.5 Indications

The treatment of ROP with anti-VEGF therapy is not standardized and can vary between treating ophthalmologists.

Infants who may benefit the most from anti-VEGF therapy include those with:

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  Posterior disease (zone I or posterior zone II) (Fig. 18.1).

  
  
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  AP-ROP (Fig. 18.2).

  
  
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  Persistent active ROP despite laser therapy (Fig. 18.3).

As well as infants:

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  Who may be too unstable to undergo laser therapy with sedation.

  
  
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  With an inadequate view for laser therapy.