ROP is a disorder of the developing retinal vasculature that occurs with interruption of the forming retinal vessels. Constriction and obliteration of the advancing capillary bed are followed by neovascularization of the retina, which can extend into the vitreous. The most serious and feared complication of ROP is retinal detachment. ROP has previously been known as RLF- Retrolental Fibroplasia, a very advanced form or ROP with end stage fibrosis and scarring behind the lens.
 
 

Incidence — The Cryotherapy for ROP trial, a prospective cohort study that observed 4000 infants of birth weight < 1251g, demonstrated that ROP occurred in 47% of infants 1000- 1251g, in 78% of those 750-999g, and in 90% of those <750 g. 6-10% of all infants with ROP will develop severe vision loss or blindness.
 
 

Development of ROP: It is postulated that there are two events that occur

1. Vasoconstriction and obliteration of the capillary network in response to a vascular insult ( possibly high supplemental O2 concentration)
2. Vasoproliferation- possibly a response by the hypoxic retina to an angiogenic factor released by the insult — thought that hypoxia can cause an overexpression of VEGF that can induce abnormal retinal angiogenesis.

Etiology of ROP: multifactorial and still unclear

1. Oxygen administration originally was thought to contribute to the development of ROP. This is now being debated. The STOP ROP- Supplemental Therapeutic Oxygen to Prevent ROP study investigated whether supplemental therapeutic oxygen for premature infants reduces the proportion of infants that progress to threshold ROP. The study found that the more liberal use of oxygen actually decreased the risk of progression to threshold ROP in these infants from 48% to 41%. Threshold ROP is defined as disease progression to the point of necessitating peripheral retinal ablation therapy.
2. Prematurity- birth weight < 1250g have a 65% risk of developing ROP, if < 1000g at birth, an 81% risk of ROP. Those at < 28 weeks gestational age have increased risk of ROP.

Risk Factors for development of ROP:

1. Extreme Prematurity — the most significant risk factor
2. Thought to be related to oxygen administration
3. Other possible risk factors: apnea, sepsis, hypoxia, hyper or hypocapnia, IVH, Caucasian race

International Classification of ROP (ICROP)

Three components used to determine the extent of disease: the zone in which ROP occurs, the stage of ROP, and the presence or absence of plus disease.

Zone 1- the most posterior — an area within twice the distance from the optic nerve head to the fovea

Zone 2- ROP outside of zone 1

Zone 3- ROP only present on the temporal side of the eye

• Stage 1- a line of demarcation develops from the vascularized region of the retina and the avascular zone
• Stage 2- the line becomes a ridge that protrudes into the vitreous. Histological evidence of an A-V shunt
• Stage 3- Extra-retinal vascular proliferation occurs with the ridge. Neovascular tufts can be found posterior to the ridge.
• Stage 4- Scarring and fibrosis can occur when the neovascularization extends into the vitreous. This can cause traction on the retina, leading to retinal detachment.
• Stage 5 — Indicates total retinal detachment.
• Plus Disease — can occur when vessels posterior to the ridge become dilated and tortuous.

National (AAPOS, AAP, AAO) recommendations for ROP screening exams in premature infants:

1. Infants <1500 g or < 28 weeks, or > 1500g with poor clinical course — dilated eye exams at 4-6 weeks of age. Exams are to continue every 2-4 weeks until retinal maturity is reached.
2. Infants with ROP or immature retinal vessels are to have exams every 1-2 weeks until vessels are mature.

1. Cryotherapy- an attempt the prevent further progression of the disease by destroying the cells that may release angiogenic factors. If both eyes have threshold ROP, only one eye is treated due to the risk of vitreous hemorrhage. If there is a very high risk of bilateral retinal detachment, the procedure can be performed in both eyes.
2. Photocoagulation — laser photocoagulation procedure done to destroy cells that could lead to disease progression. In a meta analysis of four photocoagulation trials, this procedure was found to be at least as effective as cryotherapy.
3. Retinal reattachment — an attempt to treat stage 5 disease, has a low success rate.

References:

1. An International Classification of Retinopathy of Prematurity. The Committee for the Classification of Retinopathy of Prematurity. Archives of Opthalmology 1984; 102: 1130.
2. Gomella, Ed., Retinopathy of Prematurity, Neonatology, 520-524, 1999, A & L.
3. Good, W, Gendron, RL, Retinopathy of Prematurity Opthalmology Clinics of North America, 2001; Vol 14, No. 3
4. Palmer, EA, Flynn, Jt, Hardy RJ et al. Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Opthalmology 1991; 981:628.
5. Screening examination of premature infants for retinopathy of prematurity. A joint statement by the American Academy of Pediatrics, the American Association for Pediatric Opthalmology and Strabismus, and the American Academy of Opthalmology. Pediatrics 1997; 100:273.
6. Supplemental Theraputic Oxygen for Prethreshold Retinopathy of Prematurity (STOP ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics 2000; 105:295.
7. Yanoff, Opthalmology 1^st ed., Vascular Disorders — Retinopathy of Prematurity. Section 8, 19.1-19.7, 1999, Mosby International.