There are several advantages of using lasers instead of cryotherapy to treat ROP. These are summarized in Table 7.2.

McNamara highlighted the advantages of lasers [27] over cryotherapy emphasizing that cryo is stressful on the infant, leaves large scars, and is more difficult for the surgeon to administer. He predicted early that laser therapy was to become the preferred method for treating threshold retinopathy of prematurity because it is easier for the surgeon to administer and is less traumatic on the infant. Algawi [28] in 1994 was able to demonstrate that eyes with threshold disease treated with diode laser photocoagulation developed significantly less myopia than those treated with cryotherapy. Further studies have also reported that laser photocoagulation provides superior visual acuity and less refractive myopic shift [29–33]. Today, cryotherapy has very limited indications and all efforts should be made to install laser units to treat ROP [33] when peripheral retinal ablation is to be applied.

Tanaka [34] successfully used indirect ophthalmoscope photocoagulation to treat threshold ROP in two premature infants through the transparent wall of an incubator in whom their poor systemic condition would have prevented the use of cryotherapy.

Clearly, laser delivery systems offer advantages over cryotherapy in treating posterior disease. Zone I might be easily reached with a laser but for cryotherapy, conjunctival incisions might be necessary. Nonetheless, it is precisely cases of posterior ROP that remain responsible for the majority of failures of this treatment modality.

A more recent but growing indication is the use of laser photocoagulation of the peripheral retinal in patients who have been treated with anti-VEGF drugs for a posterior disease once the advancing retinal vascularization approaches zone III. This laser application would prevent late recurrences while minimizing the chances of unfavorable results due to loss in the long follow-ups required in these patients. Additionally, this combined treatment modality would still give treated ROP patients the possible benefits of the long-term retinopexy provided by the laser.

Both punctate and transient lenticular opacities have been described after indirect retinal photocoagulation in ROP patients treated with argon [35] and diode lasers [36]. Pogrebniak [37] described a total cataract and Christiansen [38] also described that cataract is a potential vision-threatening complication of argon laser photocoagulation in ROP. Later, in 1998 O´Neil [39] noted that the incidence of cataract formation after argon laser photocoagulation was approximately 1% and may be more likely to occur when persistent hyaloidal vessels are present on the lens.

Other complications included hyphema [40], iris atrophy, hypotony [41], and phthisis [30] most likely secondary to anterior segment ischemia induced by the peripheral ablation with damage to the posterior ciliary arteries [42, 43]. Payse [44] proposed that diode lasers were safer than argon, and they are the recommended type of laser to be used in ROP. To be taken into consideration is that younger postmenstrual age at the time of laser treatment may be related to an increased risk of anterior segment complications [45].

The treatment can be applied in the neonatal intensive care unit (NICU) or in an operating room, with general anesthesia or with sedation.

The best alternative will depend on many issues regarding the particular setting where the baby is treated. Good communication with the neonatologist and anesthesiologist are essential to choosing the best option for every premature.

An indirect diode laser with a wavelength of 810 nm is the most appropriate. A 28D-condensing lens is suitable although other lenses can be used. Proper sizing of the lid speculum and scleral depressors are also very important.

The baby should be placed in a way that allows the surgeon to clearly view the entire peripheral retina. The surgeon moving along the position of the head of the baby while applying the laser normally helps to attain complete treatment with no skipped areas.

Laser spots should be applied trans-pupillary in a nearly confluent pattern, leaving a space of half to 1 laser spot between adjacent burns over the entire avascular retina (Fig. 7.1). More confluent laser treatments would increase the risk of both local and systemic complications. In 2013, Ells [46] proposed additional laser treatment, posterior to the ridge, for eyes with severe stage 3 ROP in zone II (Fig. 7.2). Sixteen out of 18 eyes experienced rapid regression.

Laser burns should produce a dull white lesion. This can be obtained in the majority of cases with a power setting between 150 and 250 mw and a pulse duration of 100 ms. In the areas adjacent to the ridge an increase in the power setting is normally needed. The number of spots can vary greatly between cases, but for a typical zone II case 1000–1500 spots will be needed, whereas for a zone I case the amount of spots can easily increase to over 2000.

Photocoagulation can be performed in repeat mode, but the surgeon must be sure that all spots are being applied to the retina. It is advisable to follow an order, starting where the avascular area is greater and then advancing clockwise all around the avascular area until reaching the starting point again. There should be no skipped areas.

Scleral indentation helps to apply the laser in areas closer to the ora serrata. Excessive pressure must be avoided to prevent decompensation of the corneal epithelium and central vein occlusion.

It is important to note that in the first days post-treatment, the disease might continue to progress. Laser photocoagulation acts on the cells that produce VEGF, but it does nothing to the VEGF already present in the eye. Nonetheless signs of regression should be clearly present by 7–10 days after treatment.

Follow-up must be schedule from 48 h post laser treatment in zone I cases to a maximum of 7 days in zone II cases. Patients should then be followed weekly until complete regression. Retreatments are applied in those cases with persistent plus disease or that continue to progress. In this situation, a careful examination should be conducted to find and treat missed or skipped areas (Fig. 7.3).

Even with the timing of treatment moved to an earlier stage of the disease by the results of the Early Treatment for Retinopathy of Prematurity (ETROP) study and ablation of the peripheral retina by laser reducing the progression of the disease, patients might still show poor anatomical and visual outcomes after treatment, especially for cases with posterior or zone I disease (Fig. 7.4). Progression to retinal detachment occurred in 12% of eyes in the ETROP study with adequate peripheral ablation.

Vitreal VEGF levels are not reduced by retinal laser photocoagulation and thus might be responsible for the lack of the effectiveness of laser therapy for ROP in some cases. Additionally, laser therapy has some complications including such long-term side effects as a significant decrease in peripheral vision due to ablation of peripheral retina and myopia.

Although there is plenty of evidence to support treating ROP with laser photocoagulation and (depending on the severity) vitreoretinal surgery, there is also an increasing amount of clinical work supporting indications for the use of anti-VEGF therapy in some of these patients [47, 48].