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4.How is ROP classified?

The International Classification of Retinopathy of Prematurity (ICROP) is the system used for describing the findings in ROP. ICROP defines the location of disease in the retina and the extent of involvement of the developing vasculature. It also specifies the stage of involvement with levels of severity ranging from 1 (least affected) to 5 (severe disease).

For the purpose of defining location, the retina is divided into three zones, with the optic nerve as the center because vascularization starts from the optic nerve and progresses peripherally (Fig. 44-1). Zone I consists of a circle, the radius of which subtends an angle of 30 degrees and extends from the disc to twice the distance from the disc to the center of the macula (twice the disc-to- fovea distance in all directions from the optic disc). Zone II extends from the edge of zone I peripherally to a point tangential to the nasal ora serrata and around to an area near the temporal anatomic equator. Zone III is the residual temporal crescent of retina anterior to zone II.

Staging pertains to the degree of abnormal vascular response observed. Staging for the eye as a whole receives the stage of the most severe manifestation present. Stage 1 (demarcation line) is defined as a thin but definite structure that separates avascular retina anteriorly from the vascularized retina posteriorly. Abnormal branching of vessels can be seen leading up to the line. It is flat and white and is in the plane of the retina. Stage 2 (ridge) is present when the line of stage 1 has height and width and occupies a volume extending out of the plane of the retina. The ridge may be pink or white. Vessels may leave the plane of the retina to enter it. Small tufts of new vessels may be seen on the surface of the retina posterior to the ridge. These vessels do not constitute fibrovascular growth. Stage 3 (ridge with extraretinal fibrovascular proliferation) is present when fibrovascular proliferation is added to the ridge of stage 2 (Fig. 44-2 ). Stage 4 ROP exists when there is subtotal retinal detachment. Retinal detachments in ROP are concave, tractional retinal detachments. Stage 4A ROP is a subtotal retinal detachment that does not involve the central macula. Typically, it is present in the temporal region of zones II and III. Stage 4B ROP is a subtotal retinal detachment that involves the central macula. Lastly, stage 5 ROP is a total retinal detachment. These retinal detachments are funnel-shaped but may have an open or closed configuration in their anterior and posterior areas. The old term for ROP, ‘‘retrolental fibroplasia,’’ was coined because of the most severe form of retinal detachment in which the retina is totally detached and drawn up into a fibrous mass behind the lens.

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Figure 44-1. The zones of retinopathy of prematurity are shown schematically.

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Improved imaging techniques have allowed for more detailed clinical examination of premature infants’ eyes. This has resulted in a refinement of the ICROP. The committee added the concept of a more virulent retinopathy usually observed in the lowest-birth– weight infants, which they called aggressive posterior ROP (AP-ROP). This form of ROP is posteriorly located and has prominent plus disease with ill-defined retinopathy. The plus disease is out of proportion to the peripheral retinopathy and usually progresses rapidly to stage 5 disease. AP-ROP typically extends circumferentially and is associated with a circumferential vessel.

5.What is plus disease?

Plus disease is indicative of progressive vascular incompetence and is a strong risk factor for development of more severe ROP. Anteriorly, plus disease manifests itself as iris vascular engorgement and pupillary rigidity. Posteriorly, plus disease appears as

retinal venous dilation and arterial tortuosity in the posterior pole. It is

graded as mild, moderate, or severe (Fig. 44-3). When plus disease is present in the posterior pole, a plus sign (i.e., þ) is added to the number stage of the disease, for example, stage 3þ. Before the appearance of plus disease, increasing dilation and tortuosity of the posterior vessels manifests increasing activity of ROP. Pre–plus disease is present when there are vascular abnormalities of the posterior pole that are insufficient for the diagnosis of plus disease, but that demonstrate more venous dilation and arterial tortuosity than normal.

6.When should acute ROP be treated?

Because ROP can lead to blindness from retinal detachment, treatment to prevent progression to retinal detachment is indicated. However, 90% of infants who develop acute ROP undergo spontaneous regression. Treatment should therefore only be performed for those infants who have a high risk of developing retinal detachment. The Cryotherapy for Retinopathy of Prematurity (Cryo-ROP) study set out to determine whether or not treatment for ROP would prevent poor outcomes. For the purposes of that study, a level of disease (called threshold disease) was chosen at which 50% of infants were predicted to go blind without treatment. This prediction was appropriate for the Cryo-ROP study and remains the level of clinical disease at which treatment is recommended.

Threshold disease is defined as the presence of at least five contiguous or eight cumulative 30-degree sectors (clock hours) of stage 3 ROP in zone I or II, in the presence

of plus disease (Fig. 44-4). Thus, prethreshold ROP is defined as zone I, any stage; zone II, stage 2 with plus disease; or zone II with extraretinal fibrovascular proliferation less than threshold. When ROP reaches prethreshold, examinations should be performed weekly.

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Figure 44-4. The Cryo-ROP definition of threshold disease is shown schematically.

Analysis of natural history data from the Cryo-ROP study indicated that certain infants are at high risk for an unfavorable outcome. Infants with zone I ROP are included as infants at high risk for an unfavorable outcome. The Early Treatment for Retinopathy of Prematurity

(ETROP) study used a risk model (RM-ROP2) based on the natural history data from the Cryo-ROP study to identify infants at high risk for an unfavorable outcome. The model used demographic characteristics of the infants and clinical features of ROP to classify eyes with prethreshold ROP at high or low risk. High-risk prethreshold eyes that received conventional management had a much higher likelihood of unfavorable structural outcome (10% versus 1% at 6 months).

Using the RM-ROP2 computer model and an analysis of the visual fields from those treated within the ETROP study, a clinical algorithm for which eyes should be treated was developed. High-risk eyes (termed type 1 ROP) were those with the following findings: zone I, any stage ROP with plus disease; zone I, stage 3 ROP with or without plus disease; and zone II, stage 2 or 3 ROP with plus disease. Plus disease requires that there be at least two quadrants of dilation and tortuosity of the posterior pole vessels. With these criteria to apply laser treatment to the anterior avascular zone of affected high-risk prethreshold eyes, there was a reduction from 19.5% to 14.5% in an unfavorable grating visual acuity measurement and from 15.6% to 9.1% in an unfavorable structural outcome at 9 months compared to the control group that was not treated until threshold was reached. Less severely advanced, low-risk prethreshold eyes (termed type 2 ROP) included the following: zone I, stage 1 or 2 ROP without plus disease; and zone II, stage 3 ROP without plus disease. It was recommended that infants with type 2 ROP should be monitored closely and treated if they progress to type 1 ROP or to threshold disease. The recommendation to treat type 1 eyes and adopt a ‘‘wait-and-watch’’ approach for type 2 eyes (treat if the eyes progress to type 1 or threshold) was supported by the final results of the ETROP study.

7.How do you treat acute ROP?

Cryotherapy was the standard of care for treating acute ROP. More recently, multiple

studies have reported on the efficacy of treating ROP with laser photocoagulation delivered by the indirect ophthalmoscope. Indirect laser has become the most common form of treatment for acute ROP.

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Indirect laser can be delivered in the intensive care nursery without having to take the infant to an operating room. An ‘‘isolation room’’ in the nursery is a desirable location because it allows for others to be shielded from the laser energy. Intravenous sedation is administered at the discretion of the neonatologist, who should be immediately available to manage any possible systemic complications. The pupils are dilated and an eyelid speculum is inserted. Diode or argon laser is then applied to the entire peripheral avascular zone, with the use of a laser indirect ophthalmoscope. The peripheral retina

is brought into view with the aid of a pediatric scleral depressor. The laser spot desired is a dull white or gray spot, and the spots are placed approximately 1–1.25 lesion-widths apart (Fig. 44-5). With the IRIS Medical (Mountain View, CA) diode laser, it is advisable to start with a power of 200 milliwatts and duration of 200 milliseconds. Critical focus on the retina is essential. If the desired lesion is not obtained, increase the power in 50-milliwatt increments until you get the desired result.

8.How is cryotherapy applied?

Cryotherapy is still preferred by some ophthalmologists for managing acute ROP. As for laser treatment, intravenous sedation can be administered at the discretion of the neonatologist. Some ophthalmologists prefer general anesthesia because of the greater stress on the infant and the greater risk of cardiopulmonary complications with cryotherapy than with laser photocoagulation. The pupils are dilated and an eyelid speculum is inserted. Cryotherapy is applied to the entire peripheral avascular zone using a hand-held cryo-pencil. The peripheral retina is brought into view using the cryo-pencil as a scleral depressor. A white freeze spot seen for 1–2 seconds is the desired endpoint. The lesions are placed contiguously.

9.Does posterior ROP respond to treatment?

Zone I and posterior zone II disease have a worse prognosis than more anterior ROP. In the Cryo-ROP study the beneficial effect of treatment for zone I threshold ROP was limited to a reduction in unfavorable anatomic outcome rate from 92% to 75% at 3 months’ follow-up.

Studies have shown that 100% of eyes with any amount of extraretinal fibrovascular proliferation in zone I and approximately 70% of eyes with vascularization limited to zone I or posterior zone II and stage 1 or stage 2 ROP will progress to threshold disease. Investigations have shown that laser photocoagulation for posterior disease can limit the likelihood of an unfavorable anatomic outcome to approximately 20%. Applying the criteria of the ETROP noted previously will result in a better prognosis for zone I disease.

10.What is the expected result after laser treatment for ROP?

Various reports have quoted a regression rate of approximately 90% after laser photocoagulation for threshold ROP. If regression is to occur, plus disease is usually less on the first week’s follow-up visit. There may not be much change in the extraretinal fibrovascular proliferation (ERFP). By 2 weeks, one should start to see a reduction in the ERFP.

11.When should you consider re-treatment for ROP?

Laser photocoagulation for threshold ROP is successful at inducing regression of the acute disease in approximately 90% of cases. Occasionally (approximately 10% of the time),