Laser Photocoagulation and Retinopathy of Prematurity

VEGF has received increasing attention, but laser is still the standard.

MICHAEL T. TRESE, MD

The Early Treatment of Retinopathy of Prematurity (ETROP) study, conducted a decade ago, set forth the current standards for treatment of retinopathy of prematurity.

As reports of success with anti-VEGF have proliferated, some researchers have proposed that these drugs may be effective treatments for ROP as well. However, given the evidence currently available, I maintain that laser panretinal photocoagulation intervention is the best treatment for these premature infants.

The ETROP study successfully categorized characteristics of ROP that may help predict which eyes are most likely to benefit from early peripheral retinal ablation, effectively dividing patients into two groups.¹

The authors concluded that all patients with type I ROP should be treated, and all patients with type II ROP should be watched and treated if they progressed to type I characteristics (box).

DIODE LASER PHOTOCOAGULATION

Diode laser treatment of ROP has proved a safe and effective therapy in several studies, with favorable anatomical results occurring in 90% of eyes or more, and favorable refractive outcomes in 55% to 85% of eyes, depending on the study.^2-5

My personal experience has been similar. I have found that I must adjust laser power and duration settings for each patient, based on the area being treated and the child’s pigmentation. However, a near confluent laser treatment promotes the best outcomes with the fewest number of problems universally.

The goal with diode laser treatment is to destroy the tissue that is producing VEGF. This tissue is customarily the RPE located under the retina. To prevent persistent neovascularization or plus disease that initially regresses then recurs, the area must receive complete treatment.

Treatment Area

The treatment area should extend anteriorly up to the ora serrata and posteriorly to the junction of the vascular and avascular retina. Surgeons comfortable performing laser therapy — that is, retinal surgeons — are most likely to accomplish such an area when the child is under general anesthesia.

While these patients can receive treatment without general anesthesia, a tendency exists to commonly under treat them unless the surgeon is very familiar with both laser procedures and premature infants.

Figure 1. Following treatment, fundus image shows a fairly confluent laser application and resolution of ROP

Figure 2. Fundus of an infant born at 28 weeks shows flat neovascularization that may require more than one treatment.

Physicians should also be sensitive to the fact that a patient may need more than one treatment. They should inform the family of this possibility before performing the first treatment (Figure 1).

CASE EXAMPLE

A child born at 28 weeks with a gestational weight of 1,000 g underwent screening at 31 weeks. The screening found immature vessels. At 35 weeks, I found some stage 2 and a minimal stage 3 ROP with plus disease.

I treated him with the Iridex 810 (Mountain View, CA) infrared diode laser, set at 300 mW with a duration of 300 ms and an interval of 300 ms with a fairly confluent pattern covering (Figure 2).

The VEGF was downregulated in the eye. I followed the patient until 50 weeks postmenstrual age (PMA), and he required no additional treatment. At that time I sent him to a pediatric ophthalmologist for continued follow-up.

ALTERNATIVES TO LASER

Interest has increased recently in determining whether anti-VEGF injections could replace laser for ROP. The most frequently cited study is one by the BEAT-ROP Cooperative Group, which found a significant benefit with intravit-real bevacizumab (Avastin, Genentech, South San Francisco, CA) monotherapy, compared to conventional laser therapy for zone I but not zone II disease.⁶

In this study, ROP recurred in 4% of infants in the bevacizumab group and 22% of the laser-therapy group. However, any study requires a close analysis. In this particular study, 67% of the bevacizumab-treated group and 56% of the laser-treated group were Latino, an ethnicity more prone to develop difficult-to-treat cases.

The most significant target organs for damage from VEGF suppression are the alveoli. Infants with ROP are already prone to bronchopulmonary dysplasia.

In addition, the study protocol applied only a single laser treatment, and considered the treatment a failure if patients required a second treatment. Either of these parameters could have caused a failure rate double that of other published studies.

On Anti-VEGF Treatment

For me, the biggest drawback of anti-VEGF treatment is exposing a premature infant to a drug for which we cannot truly evaluate the systemic risk.

The most significant target organs for damage from VEGF suppression are the alveoli. Infants with ROP are already prone to bronchopulmonary dysplasia, which these drugs very possibly aggravate.⁷ Accurately evaluating the risk is difficult, but undoubtedly risk does exists.

In contrast, while the physician must know how to perform laser photocoagulation effectively, and the infant may need multiple treatments, the secondary risks are minimal.

In addition, I follow an infant who received laser treatment until 50 weeks PMA. A child that receives an injection of anti-VEGF drugs must be followed to at least 70 weeks, creating increased hardship for the family and increasing the likelihood of missed appointments.

So while a role might exist for intravitreal anti-VEGF in ROP, I do not believe it is a primary role.

CONCLUSION

The most important step in treating ROP is a good screening program. As the number of pediatric ophthalmologists declines, difficulty in obtaining qualified screeners increases. This lack of screeners is opening doors to telemedicine, as we search for ways to ensure that every child born in the risk guidelines receives effective screening.

Without good screening, we cannot even attempt to treat this disease. For infants that meet the guidelines for treatment, I have great confidence in laser photocoagulation.

Without good screening, we cannot even attempt to treat this disease. For those infants that meet the ETROP guidelines for treatment, I have great confidence in laser photocoagulation. The treatment is contained within the eye, and my success rates are over 90%. RP

REFERENCES

1. Good WV, ETROP Cooperative Group. Final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc. 2004;102:233-250.

2. Axer-Siegel R, Maharshak I, Snir M, et al. Diode laser treatment of retinopathy of prematurity: anatomical and refractive outcomes. Retina. 2008;28:839-846.

3. McLoone E, O’Keefe M, McLoone S, Lanigan B. Long term functional and structural outcomes of laser therapy for retinopathy of prematurity. Br J Ophthalmol. 2006;90:754-759.

4. Kobylarz J, Piwowarczyk A, Romanowska-Dixon B. [Diode laser photocoagulation for retinopathy of prematurity—outcomes in one-year observation]. Klin Oczna. 2006;108:36-38.

5. Li QP, Wang ZH, Zhang S, et al. [Bedside diode laser photocoagulation for 103 cases with serious retinopathy of prematurity in NICU]. Zhonghua Er Ke Za Zhi. 2013;51:12-15.

6. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364:603-615.

7. Compernolle V, Brusselmans K, Acker T, et al. Loss of HIF-2 and inhibition of VEGF impair fetal lung maturation, whereas treatment with VEGF prevents fatal respiratory distress in premature mice. Nat Med. 2002;8:702-710.