glaucoma. Older children and adults with a history of ROP require periodic ophthalmic examinations throughout their lifetime, due to the risk for late complications including retinal detachment [14]. Screening Guidelines In the United States, dilated funduscopic examination by a qualified ophthalmologist using binocular indirect ophthalmoscopy is recommended for all infants with a birth weight of less than 1,500 g or gestational age of 30 weeks or less. Screening is also recommended for infants with a birth weight between 1,500 g and 2,000 g or a gestational age greater than 30 weeks who have had an unstable clinical course or who are otherwise believed to be at high risk by the attending neonatologist. Examination of the eyes is performed after dilation of the pupils (often with a 0.2% cyclopentolate and 1.0% phenylephrine solution). Sterile instruments are used, including an eyelid speculum and scleral depressor. A nurse or other qualified assistant should be present in order to swaddle the infant and stabilize the head as well as to intervene if the infant experiences apnea or bradycardia during the examination [7]. The first examination is performed between 4 and 6 weeks’ postnatal age or 31 weeks’ postmenstrual age, whichever is later. After each examination, the follow-up interval is determined based on the presence or absence of ROP and the disease features, as outlined in Table 2. More severe disease indicates a need for shorter follow-up intervals. Retinal screening exams may be discontinued when zone III retinal vascularization is attained without previous zone I or II ROP or with complete regression of ROP. Exams may also be discontinued at post-menstrual age of 50 weeks if no prethreshold disease (or worse ROP) is present. Caregivers must be educated about ROP prior to their baby’s discharge from the neonatal intensive care unit, as it is not uncommon for infants to be sent home from the hospital before their ROP has resolved or before their retinal vasculature is mature. These infants require continued screening exams on an outpatient basis [7]. Digital retinal photography has been shown to be accurate for detecting clinically significant ROP. Telemedicine involving retinal image-based ROP screening has been used, largely in areas where a qualified ophthalmologist is not available to perform conventional screening examinations [15]. It is important to note that affected infants in developing countries are generally larger and of older gestational age than infants in the United States in whom ROP develops. Screening criteria for ROP should be modified in developing countries [1]. Treatment In 1988, the CRYO-ROP study demonstrated that cryoablation of the peripheral avascular retina in eyes with threshold ROP resulted in a 50% reduction of unfavorable outcomes, including macular dragging and retinal detachment [3]. Diode laser ablation was used in later studies following the same guidelines as those in the CRYO-ROP trial, and was shown to be equally effective in inducing regression of ROP and more effective in preventing adverse visual and structural sequelae (see Figures 3 and 4) [16]. The ETROP trial in 2003 demonstrated that earlier treatment for high risk eyes (type 1) resulted in better structural and visual outcomes than conventional treatment for threshold ROP. Laser treatment is recommended for eyes with type 1 ROP, while eyes with type 2 ROP should be closely observed for progression. Clinical judgment and consideration of other risk factors for progression are required for optimal management [17]. The Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity study evaluated the use of antiangiogenic medication injected into the vitreous for the treatment of zone I or posterior zone II stage 3 ROP with plus disease. Compared with conventional laser therapy, a statistically significant treatment benefit for bevacizumab was demonstrated for zone I ROP, whereas zone II disease had similar outcomes with either treatment. Normal peripheral retinal vascularization continued after treatment with table 2. Recommended Intervals of Follow-Up Eye Examinations for ROP 1 week or less Immature vascularization in zone I or posterior zone II Stage 1 or 2 ROP in zone I Stage 3 ROP in zone II Suspected or present aggressive posterior ROP 1 to 2 weeks Immature vascularization in posterior zone II Stage 2 ROP in zone II Unequivocally regressing ROP in zone I 2 weeks Stage 1 ROP in zone II Immature vascularization in zone II Unequivocally regressing ROP in zone II 2 to 3 weeks Stage 1 or 2 ROP in zone III Regressing ROP in zone III NCMJ vol. 78, no. 2 127 ncmedicaljournal.com intravitreal bevacizumab, whereas laser therapy produced permanent destruction of the peripheral avascular retina. However, recurrence of ROP requiring retreatment occurred on average 16 weeks after treatment with bevacizumab, and late-onset retinal detachments have been reported [18]. In addition, a reduction in serum VEGF has been demonstrated in infants after intravitreal injections, which raises concerns for the effects of antiangiogenic drugs on the developing vasculature in other areas of the body [19]. Eyes with stage 4 or 5 ROP require additional surgical intervention such as scleral buckling and/or vitrectomy to alleviate the vitreoretinal traction that causes retinal detachment. More favorable outcomes are noted in eyes undergoing surgery at stage 4A (macula attached) than at stage 4B (macula detached) [20]. For eyes with stage 5 ROP (total retinal detachment), vitrectomy has been successful in reattaching the retina in approximately 30% of eyes, and 25% remain attached 5 years later. Unfortunately, only 10% of these patients have ambulatory vision (able to see large objects at close range) [21]. Conclusion The most important risk factors for the development and progression of ROP are extremely low birth weight and gestational age 30 weeks and under. Therefore, preventing ROP begins with preventing prematurity through optimal prenatal care. Reducing subsequent post-natal risk factors depends on optimal perinatal and postnatal care, as well as adhering to strict ROP screening