Retinopathy of Prematurity

Retinopathy of prematurity affects about 1,500 premature babies each year in the United States, and about 500 premature babies very severely.

The mechanism of this retinopathy is mainly ischemic and appears mainly in premature babies and in newborns with low birth weight. Retinopathy of prematurity affects about 1,500 premature babies each year in the United States, and about 500 premature babies very severely.

Therefore, the current recommendations at the time of writing this article are that every newborn who was born at a weight of less than 1.5 kg or at week 30 and lower should undergo at least two fundus examinations by an ophthalmologist. These guidelines are also valid for newborns who were born between a weight of 1.5 kg and 2 kg or above 30 weeks who are more suspected of developing the disease according to the opinion of a neonatologist (a physician for premature babies). One examination can be sufficient only on the condition that it demonstrates that the entire retina has undergone a normal and complete process of vascularization in both eyes.

When are these examinations performed?

The first examination is performed between week 4-6 after birth or between weeks 31 and 33 of the gestational age (according to the last cycle before the pregnancy in question) when choosing the later of the two. There is a better correlation between the gestational age and the development of retinopathy of prematurity than the age of the newborn. After the first examination, an examination is performed every week to three weeks, according to the grade of the retinopathy (as detailed below), until the retina undergoes full vascularization. Signs of the disease can be identified in 2/3 of the newborns with a weight below 1.25 kg and in 80% of those who were born at a weight of less than 1 kg.

An anatomical division makes it possible to distinguish between three different zones in the retina:

1. Zone 1 – posterior retina bounded within a circle of 60 degrees with the optic disc within the center of the circle. It can also be defined that the radius of the circle is twice the distance between the disc and the macula.
2. Zone 2 – an additional circle whose center is the optic disc, which begins from the borders of Zone 1 with the nasal edge defined as the nasal Ora Serrata (it does not reach the edge of the temporal side).
3. Zone 3 – what remains of the temporal retina that is not covered by Zone 2.

The degree of severity is determined according to 5 stages:

1. Stage 1 – a demarcation line that distinguishes between a retina with vascularization and a retina without vascularization.
2. Stage 2 – a demarcation line with height, width and volume such that a ridge is formed.
3. Stage 3 – a ridge with fibrovascular proliferation of various degrees (mild, moderate, severe).
4. Stage 4 – incomplete retinal detachment (Stage 4A– macula attached, Stage 4B– macula detached).
5. Stage 5 – complete retinal detachment with a funnel – it is possible to specify whether the anterior and/or posterior part are narrow or open.

Plus Disease – the presence of dilated and tortuous retinal blood vessels in the posterior pole – marks active disease. Involvement of Zone 1 or posterior Zone 2 combined with Plus marks a chance for a disease that will progress very quickly, "Rush" disease.

Threshold Disease – involvement of more than 5 consecutive hours or a total of 8 hours + Plus Disease.

* V Sign – when a demarcation line is formed at the edges of the two arcades it looks as if there is a triangle with the sharp edge passing between them and the Ora Serrata as the base. It is thought that this structure may perhaps encourage the formation of folds in the center of vision.

The fibrovascular proliferation causes contractions of the vitreous which is firmly attached to the retina, which causes tractional retinal detachment (stages 4 and 5). There may be bleeding in the vitreous in stages 3-5.

Frequency of examinations according to the severity of the disease:

1. Less than a week – these conditions are also an indication to receive ablation treatment (cryotherapy or photocoagulation) within 72 hours.
2. Grade 1 in Zone 1.
3. Grade 3 in Zone 2.
4. A week to two weeks
5. Abnormal vascularization in Zone 1 (without a grade) or in regression.
6. Grade 2 in Zone 2.
7. Two weeks
8. Grade 1 in Zone 2 or in regression in Zone 2.
9. Two to three weeks
10. Abnormal vascularization in Zone II (without a grade).
11. Grade 1 in Zone 3 or regression in Zone 3.

The process of normal vascularization begins at the area of the optic disc and advances to the periphery of the retina such that it ends around week 36 on the nasal side and at week 40 on the temporal side. The theory is that two separate processes occur in different areas and respond differently to treatment:

1. Zone 1 – new formation of blood vessels by precursor cells – called vasculogenesis. This process responds less well to treatment.
2. Zone 2 – budding of every blood vessel from existing blood vessels – called angiogenesis – this process responds better to treatment.

What are the risk factors for retinopathy of prematurity?

a. Exposure to excessive amounts of oxygen.

b. Genetics

c. Low birth weight

d. Small birth age

The following factors were found to be in association with the disease but were found to be non-significant in multivariable regression: accompanying systemic diseases of prematurity, blood transfusions, exposure to carbon dioxide and more..

Additional conditions in which retinopathy of prematurity can be found:

a. Rarely in full-term newborns

b. Stillborn newborns

c. In anencephalic newborns (born with a lack of brain or without a brain)

d. In newborns with a heart defect with the creation of a right-to-left shunt with a smooth pressure of arterial oxygen that did not exceed 50-60.

The natural course of the disease:

In most newborns the disease resolves spontaneously (85% of the eyes). Initially one sees clearing of the area beyond the demarcation and afterward one sees straight blood vessels crossing the demarcation. About 7% of the newborns with a weight below 1.25 kg develop threshold ROP and progress to the cicatricial/scar stage, which is expressed in fibrosis, shrinkage of the tissues including the vitreous, and detachment or traction of different areas of the retina.

There are several eye diseases in association with retinopathy of prematurity: myopia, anisometropia, strabismus, amblyopia, formation of cataract, glaucoma, tractional retinal detachment.

Treatment

Cryotherapy in eyes with threshold disease reduces by half the amount of tractions/detachments. Note that 5% of the patients develop apnea or cardiac arrest.

The Early Treatment for Retinopathy of Prematurity Randomized Trial demonstrated an advantage to ablation in the following cases:

1. Zone 1 + Plus Disease
2. Grade 3 in Zone 1.
3. Grade 2 in Zone 2 + Plus Disease.

The aforementioned study demonstrated that it is preferable to wait and not to treat in the following cases:

1. Grade 2 in Zone 1 without Plus Disease.
2. Grade 3 in Zone 2 without Plus Disease.

Many ophthalmologists today prefer to use laser rather than cryoablation. It is believed that this treatment is less traumatic and gives better results.

In grades 4 or 5, the use of vitrectomy demonstrated an ability to achieve anatomical success in 30% of the cases, when only a quarter of them (8.5%) will remain attached after 5 years, and of those only 10% (3% in total) will have ambulatory vision.